We have all treated a patient for whom you know you had the diagnosis correct, the medication regimen was working, and the patient adhered to treatment, but something was still “off.” There was something cognitively that wasn’t right, and you had identified subtle (and some overt) errors in the standard psychiatric cognitive assessment that didn’t seem amenable to psychotropic medications. Perhaps what was needed was neuropsychological testing, one of the most useful but underutilized resources available to help fine-tune diagnosis and treatment. Finding a neuropsychologist who is sensitive to the unique needs of patients with psychiatric disorders, and knowing what and how to communicate the clinical picture and need for the referral, can be challenging due to the limited availability, time, and cost of a full battery of standardized tests.

This article describes the purpose of neuropsychological testing, why it is an important part of psychiatry, and how to make the best use of it.

What is neuropsychological testing?

Neuropsychological testing is a comprehensive evaluation designed to assess cognitive functioning, such as attention, language, learning, memory, and visuospatial and executive functioning. Neuropsychology has its own vocabulary and lexicon that are important for psychiatric clinicians to understand. Some terms, such as aphasia, working memory, and dementia, are familiar to many clinicians. However, others, such as information processing speed, performance validity testing, and semantic memory, might not be. Common neuropsychological terms are defined in Table 1.

The neuropsychologist’s role

A neuropsychologist is a psychologist with advanced training in brain-behavior relationships who can help determine if cognitive problems are related to neurologic, medical, or psychiatric factors. A neuro­psychological evaluation can identify the etiology of a patient’s cognitive difficulties, such as stroke, poorly controlled diabetes, or mental health symptoms, to help guide treatment. It can be difficult to determine if a patient who is experiencing significant cognitive, functional, or behavioral changes has an underlying cognitive disorder (eg, dementia or major neurocognitive disorder) or something else, such as a psychiatric condition. Indeed, many psychiatric conditions, including schizophrenia, bipolar disorder, posttraumatic stress disorder (PTSD), and major depressive disorder (MDD), can present with significant cognitive difficulties. Thus, when patients report an increase in forgetfulness or changes in their ability to care for themselves, neuropsychological testing can help determine the cause.

How to refer to a neuropsychologist

Developing a referral network with a neuro­psychologist should be a component of establishing a psychiatric practice. A neuropsychologist can help identify deficits that may interfere with the patient’s ability to adhere to a treatment plan, monitor medications, or actively participate in treatment and therapy. When making a referral for neuropsychological testing, it is important to be clear about the specific concerns so the neuropsychologist knows how to best evaluate the patient. A psychiatric clinician does not order specific neuropsychological tests, but thoroughly describes the problem so the neuropsychologist can determine the appropriate tests after interviewing the patient. For example, if a patient reports memory problems, it is essential to give the neuropsychologist specific clinical data so he/she can determine if the symptoms are due to a neurodegenerative or psychiatric condition. Then, after interviewing the patient (and, possibly, a family member), the neuropsychologist can construct a battery of tests to best answer the question.

Which neuropsychological tests are available?

There is a large battery of neuropsychological tests that require a licensed psychologist to administer and interpret.¹ Those commonly used in research and practice to differentiate neurologically-based cognitive deficits associated with psychiatric disorders include the Wechsler Adult Intelligence Scale-4th edition (WAIS-IV) for assessing intelligence, the California Verbal Learning Test-Third Edition (CVLT-3) for verbal memory and learning, the Brief Visuospatial Memory Test-Revised for visual memory, the Wisconsin Card Sorting Test (WCST) for executive functions, and the Ruff 2&7 Selective Attention Test for sustained attention.² These and other commonly used tests are described in Table 2.¹

Neuropsychological testing vs psychological testing

The neuropsychologist will use psychometric properties (such as the validity and reliability of the test) and available normative data to pick the most appropriate tests. To date, there are no specific tests that clearly delineate psychiatric from nonpsychiatric etiologies, although the Screen for Cognitive Impairment in Psychiatry (SCIP)³ was developed in 2013 to explore cognitive abilities in the functional psychoses; it is beginning to be used in other studies.^4,5 The neuropsychologist will consider the patient’s current concerns, the onset and progression of these concerns, and the pattern in testing behavior to help determine if psychiatric conditions are the most likely etiology.

Continue to: In addition to cognitive tests...

In addition to cognitive tests, the neuropsychologist might also administer psychological tests. These might include commonly used screening tools such as the Patient Health Questionnaire-9 (PHQ-9)⁶ or Geriatric Depression Scale (GDS),⁷ or more comprehensive objective personality measures, such as the Minnesota Multiphasic Personality Inventory-2-Restructured Format (MMPI-2-RF)⁸ or Personality Assessment Inventory (PAI).⁹ These tests, along with a thorough clinical history, can help identify if a psychiatric condition is present. In addition, for the more extensive tests such as the MMPI-2-RF or PAI, there are certain neuropsychological profiles that are consistent with a psychiatric etiology for cognitive difficulties. These profiles are formulated based on specific test scores in combination with complex patient variables.

Understanding the report

While there will be stylistic differences in reports depending on the neuropsychologist’s setting, referral source, and personal preferences, most will include discussion of why the patient was referred for evaluation and a description of the onset and progression of the problem.¹⁰ Reports often also include pertinent medical and psychiatric history, substance use history, and family medical history. A section on social history is important to help establish premorbid functioning, and might include information about prenatal/birth complications, developmental milestones, educational history, and occupational history. Information about current psychosocial support or stressors, including marital status or current/past legal issues, can be helpful. In addition to this history, there is often a section on behavioral observations, especially if anything stood out or might have affected the validity of the data.

There are also objective measures of validity that the neuropsychologist might administer to evaluate whether the results are valid. Issues of validity are monitored through the evaluation, and are used to determine if the results are consistent with known neurologic patterns. If the results are deemed not valid, then low scores cannot be reliably interpreted as evidence of impairment. This is akin to an arm moving during an X-ray, thereby blurring the results. If valid, the results of objective testing are include in the neuropsychologist’s report; this can range from providing raw scores, standard scores, and/or percentiles to a general description of how the patient did on testing.

The section that is usually of most interest to psychiatric clinicians is the summary, which explains the results, might offer a diagnosis, and discusses possible etiologies. This might be where the neuropsychologist discusses if the findings are due to a neurologic or psychiatric condition. From this comes the neuropsychologist’s recommendations. When a psychiatric condition is determined to be the underlying etiology, the neuropsychologist might recommend psychotherapy or some other psychiatric treatment.

Why is neuropsychological testing important?

Schizophrenia, MDD, bipolar disorder, and PTSD produce significant neurobiologic changes that often result in deterioration of a patient’s global cognitive function. Increased emphasis and attention in psychiatric research have yielded more clues to the neurobiology of cognition. However, even though many psychiatric clinicians are trained in cognitive assessments, such as the “clock test,” “serial sevens,” “numbers forward and backward,” “proverb,” and “word recall,” and common scenarios to evaluate judgment and insight, such as “mailing a letter” and “smoke in a movie theatre,” most of these components are not completed during a standard psychiatric evaluation. Because the time allotted to completing a psychiatric evaluation continues to be shortened, it is sometimes difficult to complete the “6 bullets” required by the Centers for Medicare & Medicaid Services as part of the mental status exam (Table 3¹¹).

Continue to: To date, the best evidence...

To date, the best evidence for neuropsychological deficits exists for patients with schizophrenia, bipolar disorder, MDD, and PTSD.^12,13 The Box^2,14-24 describes the findings of studies of neuropsychological deficits in patients with schizophrenia and bipolar disorder.

Box

Continue to: Neuropsychological testing

The following 2 cases illustrate the pivotal role of neuropsychological testing in formulating an accurate differential diagnosis, and facilitating improved outcomes.

Case 1

A veteran with PTSD and memory complaints

Mr. J, age 70, is a married man who spent his career in the military, including combat service in the Vietnam War. His service in Vietnam included an event in which he couldn’t save platoon members from an ambush and death in a firefight, after which he developed PTSD. He retired after 25 years of service.

Mr. J’s psychiatrist refers him to a neuropsychologist for complaints of memory difficulties, including a fear that he’s developing Alzheimer’s disease (AD). Because of the concern for AD, he undergoes tests of learning and memory, such as the CVLT-3, the Brief Visuospatial Memory Test-Revised, and the Logical Memory subtest from the Wechsler Memory Scale–4th Edition. Other tests include a measure of confrontation naming, verbal fluency (phonemic and semantic fluency), construction, attention, processing speed, and problem solving. In addition, a measure of psychiatric and emotional functioning is also administered (the MMPI-2-RF).

The results determined that Mr. J’s subjective experience of recall deficits is better explained by anxiety resulting from the cumulative impact of day-to-day emotional stress in the setting of chronic PTSD.²⁵ Mr. J was experiencing cognitive sequelae from a complicated emotional dynamic, comprised of situational stress, amplified by coping difficulties that were rooted in older posttraumatic symptoms. These emotions, and the cognitive load they generated, interfered with the normal processes of attention and organization necessary for the encoding of information to be remembered.²⁶ He described being visibly angered by the clutter in his home (the result of multiple people living there, including a young grandchild), having his efforts to get things done interrupted by the needs of others, and a perceived loss of control gradually generalized to even mundane circumstances, as often occurs with traumatic responses. In short, he was chronically overwhelmed and not experiencing the beginnings of dementia.

For Mr. J, neuropsychological testing helped define the focus and course of therapy. If he had been diagnosed with a major neurocognitive disorder, therapy might have taken a more acceptance and grief-based approach, to help him adjust to a chronic, potentially life-limiting condition. Because this diagnosis was ruled out, and his cognitive complaints were determined to be secondary to a core diagnosis of PTSD, therapy instead focused on treating PTSD.

Continue to: Case 2

A 55-year-old with bipolar I disorder

Mr. S, age 55, is taken to the emergency department (ED) because of his complaints of a severe headache. While undergoing brain MRI, Mr. S becomes highly agitated and aggressive to the radiology staff and is transferred to the psychiatric inpatient unit. He has a history of bipolar disorder that was treated with lithium approximately 20 years ago. Due to continued agitation, he is transferred to the state hospital and prescribed multiple medications, including an unspecified first-generation antipsychotic (FGA) that results in drooling and causes him to stoop and shuffle.

Mr. S’s wife contacts a community psychiatrist after becoming frustrated by her inability to communicate with the staff at the state hospital. During a 1-hour consult, she reveals that Mr. S was a competitive speedboat racer and had suffered numerous concussions due to accidents; at least 3 of these concussions that occurred when he was in his 20s and 30s had included a loss of consciousness. Mr. S had always been treated in the ED, and never required hospitalization. He had a previous marriage, was estranged from his ex-wife and 3 children, and has a history of alcohol abuse.

The MRI taken in the ED reveals numerous patches of scar tissue throughout the cortex, most notably in the striatum areas. The psychiatrist suspects that Mr. S’s agitation and irritation were related to focal seizure activity. He encourages Mr. S’s wife to speak with the attending psychiatrist at the state hospital and ask for him to be discharged home under her care.

Eventually, Mr. S is referred for a neurologic consult and neuropsychological testing. The testing included measures of attention and working, learning and memory, and executive functioning. The results reveal numerous deficits that Mr. S had been able to compensate for when he was younger, including problems with recall of newly learned information and difficulty modifying his behavior according to feedback. Mr. S is weaned from high doses of the FGA and is stabilized on 2 antiepileptic agents, sertraline, and low-dose olanzapine. A rehabilitation plan is developed, and Mr. S remains out of the hospital.

A team-based approach

Psychiatric clinicians need to recognize the subtle as well as overt cognitive deficits present in patients with many of the illnesses that we treat on a daily basis. In this era of performance- and value-based care, it is important to understand the common neuropsychological tests available to assist in providing patient-centered care tailored to specific cognitive deficits. Including a neuropsychologist is essential to implementing a team-based approach.

Continue to: Bottom Line

Neuropsychological testing can help pinpoint key cognitive deficits that interfere with the potential for optimal patient outcomes. Psychiatric clinicians need to be knowledgeable about the common tests used and how to incorporate the results into their diagnosis and treatment plans.

Related Resources

• The American Academy of Clinical Neuropsychology. www.theaacn.org.
• Schwarz L. Answers to 7 questions about using neuropsychological testing in your practice. Current Psychiatry. 2014;13(3):33-39.

Drug Brand Names

Lithium • Eskalith, Lithobid
Olanzapine • Zyprexa
Sertraline • Zoloft

We have all treated a patient for whom you know you had the diagnosis correct, the medication regimen was working, and the patient adhered to treatment, but something was still “off.” There was something cognitively that wasn’t right, and you had identified subtle (and some overt) errors in the standard psychiatric cognitive assessment that didn’t seem amenable to psychotropic medications. Perhaps what was needed was neuropsychological testing, one of the most useful but underutilized resources available to help fine-tune diagnosis and treatment. Finding a neuropsychologist who is sensitive to the unique needs of patients with psychiatric disorders, and knowing what and how to communicate the clinical picture and need for the referral, can be challenging due to the limited availability, time, and cost of a full battery of standardized tests.

This article describes the purpose of neuropsychological testing, why it is an important part of psychiatry, and how to make the best use of it.

What is neuropsychological testing?

Neuropsychological testing is a comprehensive evaluation designed to assess cognitive functioning, such as attention, language, learning, memory, and visuospatial and executive functioning. Neuropsychology has its own vocabulary and lexicon that are important for psychiatric clinicians to understand. Some terms, such as aphasia, working memory, and dementia, are familiar to many clinicians. However, others, such as information processing speed, performance validity testing, and semantic memory, might not be. Common neuropsychological terms are defined in Table 1.

The neuropsychologist’s role

A neuropsychologist is a psychologist with advanced training in brain-behavior relationships who can help determine if cognitive problems are related to neurologic, medical, or psychiatric factors. A neuro­psychological evaluation can identify the etiology of a patient’s cognitive difficulties, such as stroke, poorly controlled diabetes, or mental health symptoms, to help guide treatment. It can be difficult to determine if a patient who is experiencing significant cognitive, functional, or behavioral changes has an underlying cognitive disorder (eg, dementia or major neurocognitive disorder) or something else, such as a psychiatric condition. Indeed, many psychiatric conditions, including schizophrenia, bipolar disorder, posttraumatic stress disorder (PTSD), and major depressive disorder (MDD), can present with significant cognitive difficulties. Thus, when patients report an increase in forgetfulness or changes in their ability to care for themselves, neuropsychological testing can help determine the cause.

How to refer to a neuropsychologist

Developing a referral network with a neuro­psychologist should be a component of establishing a psychiatric practice. A neuropsychologist can help identify deficits that may interfere with the patient’s ability to adhere to a treatment plan, monitor medications, or actively participate in treatment and therapy. When making a referral for neuropsychological testing, it is important to be clear about the specific concerns so the neuropsychologist knows how to best evaluate the patient. A psychiatric clinician does not order specific neuropsychological tests, but thoroughly describes the problem so the neuropsychologist can determine the appropriate tests after interviewing the patient. For example, if a patient reports memory problems, it is essential to give the neuropsychologist specific clinical data so he/she can determine if the symptoms are due to a neurodegenerative or psychiatric condition. Then, after interviewing the patient (and, possibly, a family member), the neuropsychologist can construct a battery of tests to best answer the question.

Which neuropsychological tests are available?

There is a large battery of neuropsychological tests that require a licensed psychologist to administer and interpret.¹ Those commonly used in research and practice to differentiate neurologically-based cognitive deficits associated with psychiatric disorders include the Wechsler Adult Intelligence Scale-4th edition (WAIS-IV) for assessing intelligence, the California Verbal Learning Test-Third Edition (CVLT-3) for verbal memory and learning, the Brief Visuospatial Memory Test-Revised for visual memory, the Wisconsin Card Sorting Test (WCST) for executive functions, and the Ruff 2&7 Selective Attention Test for sustained attention.² These and other commonly used tests are described in Table 2.¹

Neuropsychological testing vs psychological testing

The neuropsychologist will use psychometric properties (such as the validity and reliability of the test) and available normative data to pick the most appropriate tests. To date, there are no specific tests that clearly delineate psychiatric from nonpsychiatric etiologies, although the Screen for Cognitive Impairment in Psychiatry (SCIP)³ was developed in 2013 to explore cognitive abilities in the functional psychoses; it is beginning to be used in other studies.^4,5 The neuropsychologist will consider the patient’s current concerns, the onset and progression of these concerns, and the pattern in testing behavior to help determine if psychiatric conditions are the most likely etiology.

Continue to: In addition to cognitive tests...

In addition to cognitive tests, the neuropsychologist might also administer psychological tests. These might include commonly used screening tools such as the Patient Health Questionnaire-9 (PHQ-9)⁶ or Geriatric Depression Scale (GDS),⁷ or more comprehensive objective personality measures, such as the Minnesota Multiphasic Personality Inventory-2-Restructured Format (MMPI-2-RF)⁸ or Personality Assessment Inventory (PAI).⁹ These tests, along with a thorough clinical history, can help identify if a psychiatric condition is present. In addition, for the more extensive tests such as the MMPI-2-RF or PAI, there are certain neuropsychological profiles that are consistent with a psychiatric etiology for cognitive difficulties. These profiles are formulated based on specific test scores in combination with complex patient variables.

Understanding the report

While there will be stylistic differences in reports depending on the neuropsychologist’s setting, referral source, and personal preferences, most will include discussion of why the patient was referred for evaluation and a description of the onset and progression of the problem.¹⁰ Reports often also include pertinent medical and psychiatric history, substance use history, and family medical history. A section on social history is important to help establish premorbid functioning, and might include information about prenatal/birth complications, developmental milestones, educational history, and occupational history. Information about current psychosocial support or stressors, including marital status or current/past legal issues, can be helpful. In addition to this history, there is often a section on behavioral observations, especially if anything stood out or might have affected the validity of the data.

There are also objective measures of validity that the neuropsychologist might administer to evaluate whether the results are valid. Issues of validity are monitored through the evaluation, and are used to determine if the results are consistent with known neurologic patterns. If the results are deemed not valid, then low scores cannot be reliably interpreted as evidence of impairment. This is akin to an arm moving during an X-ray, thereby blurring the results. If valid, the results of objective testing are include in the neuropsychologist’s report; this can range from providing raw scores, standard scores, and/or percentiles to a general description of how the patient did on testing.

The section that is usually of most interest to psychiatric clinicians is the summary, which explains the results, might offer a diagnosis, and discusses possible etiologies. This might be where the neuropsychologist discusses if the findings are due to a neurologic or psychiatric condition. From this comes the neuropsychologist’s recommendations. When a psychiatric condition is determined to be the underlying etiology, the neuropsychologist might recommend psychotherapy or some other psychiatric treatment.

Why is neuropsychological testing important?

Schizophrenia, MDD, bipolar disorder, and PTSD produce significant neurobiologic changes that often result in deterioration of a patient’s global cognitive function. Increased emphasis and attention in psychiatric research have yielded more clues to the neurobiology of cognition. However, even though many psychiatric clinicians are trained in cognitive assessments, such as the “clock test,” “serial sevens,” “numbers forward and backward,” “proverb,” and “word recall,” and common scenarios to evaluate judgment and insight, such as “mailing a letter” and “smoke in a movie theatre,” most of these components are not completed during a standard psychiatric evaluation. Because the time allotted to completing a psychiatric evaluation continues to be shortened, it is sometimes difficult to complete the “6 bullets” required by the Centers for Medicare & Medicaid Services as part of the mental status exam (Table 3¹¹).

Continue to: To date, the best evidence...

To date, the best evidence for neuropsychological deficits exists for patients with schizophrenia, bipolar disorder, MDD, and PTSD.^12,13 The Box^2,14-24 describes the findings of studies of neuropsychological deficits in patients with schizophrenia and bipolar disorder.

Box

Continue to: Neuropsychological testing

The following 2 cases illustrate the pivotal role of neuropsychological testing in formulating an accurate differential diagnosis, and facilitating improved outcomes.

Case 1

A veteran with PTSD and memory complaints

Mr. J, age 70, is a married man who spent his career in the military, including combat service in the Vietnam War. His service in Vietnam included an event in which he couldn’t save platoon members from an ambush and death in a firefight, after which he developed PTSD. He retired after 25 years of service.

Mr. J’s psychiatrist refers him to a neuropsychologist for complaints of memory difficulties, including a fear that he’s developing Alzheimer’s disease (AD). Because of the concern for AD, he undergoes tests of learning and memory, such as the CVLT-3, the Brief Visuospatial Memory Test-Revised, and the Logical Memory subtest from the Wechsler Memory Scale–4th Edition. Other tests include a measure of confrontation naming, verbal fluency (phonemic and semantic fluency), construction, attention, processing speed, and problem solving. In addition, a measure of psychiatric and emotional functioning is also administered (the MMPI-2-RF).

The results determined that Mr. J’s subjective experience of recall deficits is better explained by anxiety resulting from the cumulative impact of day-to-day emotional stress in the setting of chronic PTSD.²⁵ Mr. J was experiencing cognitive sequelae from a complicated emotional dynamic, comprised of situational stress, amplified by coping difficulties that were rooted in older posttraumatic symptoms. These emotions, and the cognitive load they generated, interfered with the normal processes of attention and organization necessary for the encoding of information to be remembered.²⁶ He described being visibly angered by the clutter in his home (the result of multiple people living there, including a young grandchild), having his efforts to get things done interrupted by the needs of others, and a perceived loss of control gradually generalized to even mundane circumstances, as often occurs with traumatic responses. In short, he was chronically overwhelmed and not experiencing the beginnings of dementia.

For Mr. J, neuropsychological testing helped define the focus and course of therapy. If he had been diagnosed with a major neurocognitive disorder, therapy might have taken a more acceptance and grief-based approach, to help him adjust to a chronic, potentially life-limiting condition. Because this diagnosis was ruled out, and his cognitive complaints were determined to be secondary to a core diagnosis of PTSD, therapy instead focused on treating PTSD.

Continue to: Case 2

A 55-year-old with bipolar I disorder

Mr. S, age 55, is taken to the emergency department (ED) because of his complaints of a severe headache. While undergoing brain MRI, Mr. S becomes highly agitated and aggressive to the radiology staff and is transferred to the psychiatric inpatient unit. He has a history of bipolar disorder that was treated with lithium approximately 20 years ago. Due to continued agitation, he is transferred to the state hospital and prescribed multiple medications, including an unspecified first-generation antipsychotic (FGA) that results in drooling and causes him to stoop and shuffle.

Mr. S’s wife contacts a community psychiatrist after becoming frustrated by her inability to communicate with the staff at the state hospital. During a 1-hour consult, she reveals that Mr. S was a competitive speedboat racer and had suffered numerous concussions due to accidents; at least 3 of these concussions that occurred when he was in his 20s and 30s had included a loss of consciousness. Mr. S had always been treated in the ED, and never required hospitalization. He had a previous marriage, was estranged from his ex-wife and 3 children, and has a history of alcohol abuse.

The MRI taken in the ED reveals numerous patches of scar tissue throughout the cortex, most notably in the striatum areas. The psychiatrist suspects that Mr. S’s agitation and irritation were related to focal seizure activity. He encourages Mr. S’s wife to speak with the attending psychiatrist at the state hospital and ask for him to be discharged home under her care.

Eventually, Mr. S is referred for a neurologic consult and neuropsychological testing. The testing included measures of attention and working, learning and memory, and executive functioning. The results reveal numerous deficits that Mr. S had been able to compensate for when he was younger, including problems with recall of newly learned information and difficulty modifying his behavior according to feedback. Mr. S is weaned from high doses of the FGA and is stabilized on 2 antiepileptic agents, sertraline, and low-dose olanzapine. A rehabilitation plan is developed, and Mr. S remains out of the hospital.

A team-based approach

Psychiatric clinicians need to recognize the subtle as well as overt cognitive deficits present in patients with many of the illnesses that we treat on a daily basis. In this era of performance- and value-based care, it is important to understand the common neuropsychological tests available to assist in providing patient-centered care tailored to specific cognitive deficits. Including a neuropsychologist is essential to implementing a team-based approach.

Continue to: Bottom Line

Neuropsychological testing can help pinpoint key cognitive deficits that interfere with the potential for optimal patient outcomes. Psychiatric clinicians need to be knowledgeable about the common tests used and how to incorporate the results into their diagnosis and treatment plans.

Related Resources

• The American Academy of Clinical Neuropsychology. www.theaacn.org.
• Schwarz L. Answers to 7 questions about using neuropsychological testing in your practice. Current Psychiatry. 2014;13(3):33-39.

Drug Brand Names

Lithium • Eskalith, Lithobid
Olanzapine • Zyprexa
Sertraline • Zoloft

We have all treated a patient for whom you know you had the diagnosis correct, the medication regimen was working, and the patient adhered to treatment, but something was still “off.” There was something cognitively that wasn’t right, and you had identified subtle (and some overt) errors in the standard psychiatric cognitive assessment that didn’t seem amenable to psychotropic medications. Perhaps what was needed was neuropsychological testing, one of the most useful but underutilized resources available to help fine-tune diagnosis and treatment. Finding a neuropsychologist who is sensitive to the unique needs of patients with psychiatric disorders, and knowing what and how to communicate the clinical picture and need for the referral, can be challenging due to the limited availability, time, and cost of a full battery of standardized tests.

This article describes the purpose of neuropsychological testing, why it is an important part of psychiatry, and how to make the best use of it.

What is neuropsychological testing?

Neuropsychological testing is a comprehensive evaluation designed to assess cognitive functioning, such as attention, language, learning, memory, and visuospatial and executive functioning. Neuropsychology has its own vocabulary and lexicon that are important for psychiatric clinicians to understand. Some terms, such as aphasia, working memory, and dementia, are familiar to many clinicians. However, others, such as information processing speed, performance validity testing, and semantic memory, might not be. Common neuropsychological terms are defined in Table 1.

The neuropsychologist’s role

A neuropsychologist is a psychologist with advanced training in brain-behavior relationships who can help determine if cognitive problems are related to neurologic, medical, or psychiatric factors. A neuro­psychological evaluation can identify the etiology of a patient’s cognitive difficulties, such as stroke, poorly controlled diabetes, or mental health symptoms, to help guide treatment. It can be difficult to determine if a patient who is experiencing significant cognitive, functional, or behavioral changes has an underlying cognitive disorder (eg, dementia or major neurocognitive disorder) or something else, such as a psychiatric condition. Indeed, many psychiatric conditions, including schizophrenia, bipolar disorder, posttraumatic stress disorder (PTSD), and major depressive disorder (MDD), can present with significant cognitive difficulties. Thus, when patients report an increase in forgetfulness or changes in their ability to care for themselves, neuropsychological testing can help determine the cause.

How to refer to a neuropsychologist

Developing a referral network with a neuro­psychologist should be a component of establishing a psychiatric practice. A neuropsychologist can help identify deficits that may interfere with the patient’s ability to adhere to a treatment plan, monitor medications, or actively participate in treatment and therapy. When making a referral for neuropsychological testing, it is important to be clear about the specific concerns so the neuropsychologist knows how to best evaluate the patient. A psychiatric clinician does not order specific neuropsychological tests, but thoroughly describes the problem so the neuropsychologist can determine the appropriate tests after interviewing the patient. For example, if a patient reports memory problems, it is essential to give the neuropsychologist specific clinical data so he/she can determine if the symptoms are due to a neurodegenerative or psychiatric condition. Then, after interviewing the patient (and, possibly, a family member), the neuropsychologist can construct a battery of tests to best answer the question.

Which neuropsychological tests are available?

There is a large battery of neuropsychological tests that require a licensed psychologist to administer and interpret.¹ Those commonly used in research and practice to differentiate neurologically-based cognitive deficits associated with psychiatric disorders include the Wechsler Adult Intelligence Scale-4th edition (WAIS-IV) for assessing intelligence, the California Verbal Learning Test-Third Edition (CVLT-3) for verbal memory and learning, the Brief Visuospatial Memory Test-Revised for visual memory, the Wisconsin Card Sorting Test (WCST) for executive functions, and the Ruff 2&7 Selective Attention Test for sustained attention.² These and other commonly used tests are described in Table 2.¹

Neuropsychological testing vs psychological testing

The neuropsychologist will use psychometric properties (such as the validity and reliability of the test) and available normative data to pick the most appropriate tests. To date, there are no specific tests that clearly delineate psychiatric from nonpsychiatric etiologies, although the Screen for Cognitive Impairment in Psychiatry (SCIP)³ was developed in 2013 to explore cognitive abilities in the functional psychoses; it is beginning to be used in other studies.^4,5 The neuropsychologist will consider the patient’s current concerns, the onset and progression of these concerns, and the pattern in testing behavior to help determine if psychiatric conditions are the most likely etiology.

Continue to: In addition to cognitive tests...

In addition to cognitive tests, the neuropsychologist might also administer psychological tests. These might include commonly used screening tools such as the Patient Health Questionnaire-9 (PHQ-9)⁶ or Geriatric Depression Scale (GDS),⁷ or more comprehensive objective personality measures, such as the Minnesota Multiphasic Personality Inventory-2-Restructured Format (MMPI-2-RF)⁸ or Personality Assessment Inventory (PAI).⁹ These tests, along with a thorough clinical history, can help identify if a psychiatric condition is present. In addition, for the more extensive tests such as the MMPI-2-RF or PAI, there are certain neuropsychological profiles that are consistent with a psychiatric etiology for cognitive difficulties. These profiles are formulated based on specific test scores in combination with complex patient variables.

Understanding the report

While there will be stylistic differences in reports depending on the neuropsychologist’s setting, referral source, and personal preferences, most will include discussion of why the patient was referred for evaluation and a description of the onset and progression of the problem.¹⁰ Reports often also include pertinent medical and psychiatric history, substance use history, and family medical history. A section on social history is important to help establish premorbid functioning, and might include information about prenatal/birth complications, developmental milestones, educational history, and occupational history. Information about current psychosocial support or stressors, including marital status or current/past legal issues, can be helpful. In addition to this history, there is often a section on behavioral observations, especially if anything stood out or might have affected the validity of the data.

There are also objective measures of validity that the neuropsychologist might administer to evaluate whether the results are valid. Issues of validity are monitored through the evaluation, and are used to determine if the results are consistent with known neurologic patterns. If the results are deemed not valid, then low scores cannot be reliably interpreted as evidence of impairment. This is akin to an arm moving during an X-ray, thereby blurring the results. If valid, the results of objective testing are include in the neuropsychologist’s report; this can range from providing raw scores, standard scores, and/or percentiles to a general description of how the patient did on testing.

The section that is usually of most interest to psychiatric clinicians is the summary, which explains the results, might offer a diagnosis, and discusses possible etiologies. This might be where the neuropsychologist discusses if the findings are due to a neurologic or psychiatric condition. From this comes the neuropsychologist’s recommendations. When a psychiatric condition is determined to be the underlying etiology, the neuropsychologist might recommend psychotherapy or some other psychiatric treatment.

Why is neuropsychological testing important?

Schizophrenia, MDD, bipolar disorder, and PTSD produce significant neurobiologic changes that often result in deterioration of a patient’s global cognitive function. Increased emphasis and attention in psychiatric research have yielded more clues to the neurobiology of cognition. However, even though many psychiatric clinicians are trained in cognitive assessments, such as the “clock test,” “serial sevens,” “numbers forward and backward,” “proverb,” and “word recall,” and common scenarios to evaluate judgment and insight, such as “mailing a letter” and “smoke in a movie theatre,” most of these components are not completed during a standard psychiatric evaluation. Because the time allotted to completing a psychiatric evaluation continues to be shortened, it is sometimes difficult to complete the “6 bullets” required by the Centers for Medicare & Medicaid Services as part of the mental status exam (Table 3¹¹).

Continue to: To date, the best evidence...

To date, the best evidence for neuropsychological deficits exists for patients with schizophrenia, bipolar disorder, MDD, and PTSD.^12,13 The Box^2,14-24 describes the findings of studies of neuropsychological deficits in patients with schizophrenia and bipolar disorder.

Box

Continue to: Neuropsychological testing

The following 2 cases illustrate the pivotal role of neuropsychological testing in formulating an accurate differential diagnosis, and facilitating improved outcomes.

Case 1

A veteran with PTSD and memory complaints

Mr. J, age 70, is a married man who spent his career in the military, including combat service in the Vietnam War. His service in Vietnam included an event in which he couldn’t save platoon members from an ambush and death in a firefight, after which he developed PTSD. He retired after 25 years of service.

Mr. J’s psychiatrist refers him to a neuropsychologist for complaints of memory difficulties, including a fear that he’s developing Alzheimer’s disease (AD). Because of the concern for AD, he undergoes tests of learning and memory, such as the CVLT-3, the Brief Visuospatial Memory Test-Revised, and the Logical Memory subtest from the Wechsler Memory Scale–4th Edition. Other tests include a measure of confrontation naming, verbal fluency (phonemic and semantic fluency), construction, attention, processing speed, and problem solving. In addition, a measure of psychiatric and emotional functioning is also administered (the MMPI-2-RF).

The results determined that Mr. J’s subjective experience of recall deficits is better explained by anxiety resulting from the cumulative impact of day-to-day emotional stress in the setting of chronic PTSD.²⁵ Mr. J was experiencing cognitive sequelae from a complicated emotional dynamic, comprised of situational stress, amplified by coping difficulties that were rooted in older posttraumatic symptoms. These emotions, and the cognitive load they generated, interfered with the normal processes of attention and organization necessary for the encoding of information to be remembered.²⁶ He described being visibly angered by the clutter in his home (the result of multiple people living there, including a young grandchild), having his efforts to get things done interrupted by the needs of others, and a perceived loss of control gradually generalized to even mundane circumstances, as often occurs with traumatic responses. In short, he was chronically overwhelmed and not experiencing the beginnings of dementia.

For Mr. J, neuropsychological testing helped define the focus and course of therapy. If he had been diagnosed with a major neurocognitive disorder, therapy might have taken a more acceptance and grief-based approach, to help him adjust to a chronic, potentially life-limiting condition. Because this diagnosis was ruled out, and his cognitive complaints were determined to be secondary to a core diagnosis of PTSD, therapy instead focused on treating PTSD.

Continue to: Case 2

A 55-year-old with bipolar I disorder

Mr. S, age 55, is taken to the emergency department (ED) because of his complaints of a severe headache. While undergoing brain MRI, Mr. S becomes highly agitated and aggressive to the radiology staff and is transferred to the psychiatric inpatient unit. He has a history of bipolar disorder that was treated with lithium approximately 20 years ago. Due to continued agitation, he is transferred to the state hospital and prescribed multiple medications, including an unspecified first-generation antipsychotic (FGA) that results in drooling and causes him to stoop and shuffle.

Mr. S’s wife contacts a community psychiatrist after becoming frustrated by her inability to communicate with the staff at the state hospital. During a 1-hour consult, she reveals that Mr. S was a competitive speedboat racer and had suffered numerous concussions due to accidents; at least 3 of these concussions that occurred when he was in his 20s and 30s had included a loss of consciousness. Mr. S had always been treated in the ED, and never required hospitalization. He had a previous marriage, was estranged from his ex-wife and 3 children, and has a history of alcohol abuse.

The MRI taken in the ED reveals numerous patches of scar tissue throughout the cortex, most notably in the striatum areas. The psychiatrist suspects that Mr. S’s agitation and irritation were related to focal seizure activity. He encourages Mr. S’s wife to speak with the attending psychiatrist at the state hospital and ask for him to be discharged home under her care.

Eventually, Mr. S is referred for a neurologic consult and neuropsychological testing. The testing included measures of attention and working, learning and memory, and executive functioning. The results reveal numerous deficits that Mr. S had been able to compensate for when he was younger, including problems with recall of newly learned information and difficulty modifying his behavior according to feedback. Mr. S is weaned from high doses of the FGA and is stabilized on 2 antiepileptic agents, sertraline, and low-dose olanzapine. A rehabilitation plan is developed, and Mr. S remains out of the hospital.

A team-based approach

Psychiatric clinicians need to recognize the subtle as well as overt cognitive deficits present in patients with many of the illnesses that we treat on a daily basis. In this era of performance- and value-based care, it is important to understand the common neuropsychological tests available to assist in providing patient-centered care tailored to specific cognitive deficits. Including a neuropsychologist is essential to implementing a team-based approach.

Continue to: Bottom Line

Neuropsychological testing can help pinpoint key cognitive deficits that interfere with the potential for optimal patient outcomes. Psychiatric clinicians need to be knowledgeable about the common tests used and how to incorporate the results into their diagnosis and treatment plans.

Related Resources

• The American Academy of Clinical Neuropsychology. www.theaacn.org.
• Schwarz L. Answers to 7 questions about using neuropsychological testing in your practice. Current Psychiatry. 2014;13(3):33-39.

Drug Brand Names

Lithium • Eskalith, Lithobid
Olanzapine • Zyprexa
Sertraline • Zoloft

Although evidence suggests that bipolar disorder (BD) and borderline personality disorder (BPD) are distinct entities, their differential diagnosis is often challenging as a result of considerable overlap of phenotypical features. Moreover, BD and BPD frequently co-occur, which makes it even more difficult to differentiate these 2 conditions. Strategies for improving diagnostic accuracy are critical to optimizing patients’ clinical outcomes and long-term prognosis. Misdiagnosing these 2 conditions can be particularly deleterious, and failure to recognize their co-occurrence can result in additional burden to typically complex and severe clinical presentations.

This article describes key aspects of the differential diagnosis between BD and BPD, emphasizing core features and major dissimilarities between these 2 conditions, and discusses the implications of misdiagnosis. The goal is to highlight the clinical and psychopathological aspects of BD and BPD to help clinicians properly distinguish these 2 disorders.

Psychopathological and sociodemographic correlates

Bipolar disorder is a chronic and severe mental illness that is classified based on clusters of symptoms—manic, hypomanic, and depressive.¹ It is among the 10 leading causes of disability worldwide, with significant morbidity arising from acute affective episodes and subacute states.² Data suggest the lifetime prevalence of BPD is 2.1%, and subthreshold forms may affect an additional 2.4% of the US population.³ The onset of symptoms typically occurs during late adolescence or early adulthood, and mood lability and cyclothymic temperament are the most common prodromal features.⁴

In contrast, personality disorders, such as BPD, are characteristically pervasive and maladaptive patterns of emotional responses that usually deviate from an individual’s stage of development and cultural background.¹ These disorders tend to cause significant impairment, particularly in personal, occupational, and social domains. Environmental factors, such as early childhood trauma, seem to play an important role in the genesis of personality disorders, which may be particularly relevant in BPD, a disorder characterized by marked impulsivity and a pattern of instability in personal relationships, self-image, and affect.^1,5,6 Similarly to BD, BPD is also chronic and highly disabling.

According to the National Survey on Alcohol and Related Conditions (NESARC), approximately 15% of US adults were found to have at least one type of personality disorder, and 6% met criteria for a cluster B personality disorder (antisocial, borderline, narcissistic, and histrionic).⁷ The lifetime prevalence of BPD is nearly 2%, with higher estimates observed in psychiatric settings.^7,8

As a result of the phenotypical resemblance between BD and BPD (Figure), the differential diagnosis is often difficult. Recent studies suggest that co-occurrence of BD and BPD is common, with rates of comorbid BPD as high as 29% in BD I and 24% in BD II.^8,9 On the other hand, nearly 20% of individuals with BPD seem to have comorbid BD.^8,9 Several studies suggest that comorbid personality disorders represent a negative prognostic factor in the course of mood disorders, and the presence of BPD in patients with BD seems to be associated with more severe clinical presentations, greater treatment complexity, a higher number of depressive episodes, poor inter-episode functioning, and higher rates of other comorbidities, such as substance use disorders (SUDs).^8-11 The effect of BD on the course of BPD is unclear and fairly unexplored, although it has been suggested that better control of mood symptoms may lead to more stable psychosocial functioning in BPD.⁹

Whether BD and BPD are part of the same spectrum is a matter for debate.^12-14 Multidimensional approaches have been proposed to better characterize these disorders in at-risk populations, based on structured interviews, self-administered and clinician-rated clinical scales (Table 1), neuroimaging studies, biological markers, and machine-learning models.^15,16 Compelling evidence suggests that BD and BPD have distinct underlying neurobiological and psychopathological mechanisms^12,13; however, the differential diagnosis still relies on phenotypical features, since the search for biological markers has not yet identified specific biomarkers that can be used in clinical practice.

Continue to: Core features of BPD...

Core features of BPD, such as mood lability, impulsivity, and risk-taking behaviors, are also part of the diagnostic criteria for BD (Table 2).¹ Similarly, depressive symptoms prevail in the course of BD.^17,18 This adds complexity to the differential because “depressivity” is also part of the diagnostic criteria for BPD.¹ Therefore, comprehensive psychiatric assessments and longitudinal observations are critical to diagnostic accuracy and treatment planning. Further characterization of symptoms, such as onset patterns, clinical course, phenomenology of symptoms (eg, timing, frequency, duration, triggers), and personality traits, will provide information to properly distinguish these 2 syndromes when, for example, it is unclear if the “mood swings” and impulsivity are part of a mood or a personality disorder (Table 3).

Clinical features: A closer look

Borderline personality disorder. Affect dysregulation, emotional instability, impoverished and unstable self-image, and chronic feelings of emptiness are core features of BPD.^1,5,19 These characteristics, when combined with a fear of abandonment or rejection, a compromised ability to recognize the feelings and needs of others, and extremes of idealization-devaluation, tend to culminate in problematic and chaotic relationships.^6,19 Individuals with BPD may become suspicious or paranoid under stressful situations. Under these circumstances, individuals with BPD may also experience depersonalization and other dissociative symptoms.^6,20 The mood lability and emotional instability observed in patients with BPD usually are in response to environmental factors, and although generally intense and out of proportion, they tend to be ephemeral and short-lived, typically lasting a few hours.^1,5 The anxiety and depressive symptoms reported by patients with BPD frequently are associated with feelings of “falling apart” or “losing control,” pessimism, shame, and low self-esteem. Coping strategies tend to be poorly developed and/or maladaptive, and individuals with BPD usually display a hostile and antagonistic demeanor and engage in suicidal or non­suicidal self-injury (NSSI) behaviors as means to alleviate overwhelming emotional distress. Impulsivity, disinhibition, poor tolerance to frustration, and risk-taking behaviors are also characteristic of BPD.^1,5 As a result, BPD is usually associated with significant impairment in functioning, multiple hospitalizations, and high rates of comorbid mood disorders, posttraumatic stress disorder (PTSD), SUDs, and death by suicide.

Bipolar disorder. Conversely, the fluctuations in mood and affect observed in patients with BD are usually episodic rather than pervasive, and tend to last longer (typically days to weeks) compared with the transient mood shifts observed in patients with BPD.^4,17,18 The impulsivity, psychomotor agitation, and increased goal-directed activity reported by patients with BD are usually seen in the context of an acute affective episode, and are far less common during periods of stability or euthymic affect.^4,17,18 Grandiosity and inflated self-esteem—hallmarks of a manic or hypomanic state—seem to oppose the unstable self-image observed in BPD, although indecisiveness and low self-worth may be observed in individuals with BD during depressive episodes. Antidepressant-induced mania or hypomania, atypical depressive episodes, and disruptions in sleep and circadian rhythms may be predictors of BD.^4,21 Furthermore, although psychosocial stressors may be associated with acute affective episodes in early stages of bipolar illness, over time minimal stressors are necessary to ignite new affective episodes.^22,23 Although BD is associated with high rates of suicide, suicide attempts are usually seen in the context of an acute depressive episode, and NSSI behaviors are less common among patients with BD.²⁴

Lastly, other biographical data, such as a history of early life trauma, comorbidity, and a family history of psychiatric illnesses, can be particularly helpful in establishing the differential diagnosis between BD and BPD.²⁵ For instance, evidence suggests that the heritability of BD may be as high as 70%, which usually translates into an extensive family history of bipolar and related disorders.²⁶ In addition, studies suggest a high co-occurrence of anxiety disorders, attention-deficit/hyperactivity disorder, and SUDs in patients with BD, whereas PTSD, SUDs, and eating disorders tend to be highly comorbid with BPD.²⁷ Childhood adversity (ie, a history of physical, sexual, or emotional abuse, or neglect) seems to be pivotal in the genesis of BPD and may predispose these individuals to psychotic and dissociative symptoms, particularly those with a history of sexual abuse, while playing a more secondary role in BD.^28-31

Implications of misdiagnosis

In the view of the limitations of the existing models, multidimensional approaches are necessary to improve diagnostic accuracy. Presently, the differential diagnosis of BD and BPD continues to rely on clinical findings and syndromic classifications. Misdiagnosing BD and BPD has adverse therapeutic and prognostic implications.³² For instance, while psychotropic medications and neuromodulatory therapies (eg, electroconvulsive therapy, repetitive transcranial magnetic stimulation) are considered first-line treatments for patients with BD, psychosocial interventions tend to be adjunctive treatments in BD.³³ Conversely, although pharmacotherapy might be helpful for patients with BPD, psychosocial and behavioral interventions are the mainstay treatment for this disorder, with the strongest evidence supporting cognitive-behavioral therapy, dialectical behavioral therapy, mentalization-based therapy, and transference-focused therapy.^34-36 Thus, misdiagnosing BD as BPD with comorbid depression may result in the use of antidepressants, which can be detrimental in BD. Antidepressant treatment of BD, particularly as monotherapy, has been associated with manic or hypomanic switch, mixed states, and frequent cycling.²¹ Moreover, delays in diagnosis and proper treatment of BD may result in protracted mood symptoms, prolonged affective episodes, higher rates of disability, functional impairment, and overall worse clinical outcomes.²⁴ In addition, because behavioral and psychosocial interventions are usually adjunctive therapies rather than first-line interventions for patients with BD, misdiagnosing BPD as BD may ultimately prevent these individuals from receiving proper treatment, likely resulting in more severe functional impairment, multiple hospitalizations, self-inflicted injuries, and suicide attempts, since psychotropic medications are not particularly effective for improving self-efficacy and coping strategies, nor for correcting cognitive distortions, particularly in self-image, and pathological personality traits, all of which are critical aspects of BPD treatment.

Continue to: Several factors might...

Several factors might make clinicians reluctant to diagnose BPD, or bias them to diagnose BD more frequently. These include a lack of familiarity with the diagnostic criteria for BPD, the phenotypical resemblance between BP and BPD, or even concerns about the stigma and negative implications that are associated with a BPD diagnosis.^32,37,38

Whereas BD is currently perceived as a condition with a strong biological basis, there are considerable misconceptions regarding BPD and its nature.^4-6,22,26 As a consequence, individuals with BPD tend to be perceived as “difficult-to-treat,” “uncooperative,” or “attention-seeking.” These misconceptions may result in poor clinician-patient relationships, unmet clinical and psychiatric needs, and frustration for both clinicians and patients.³⁷

Through advances in biological psychiatry, precision medicine may someday be a part of psychiatric practice. Biological “signatures” may eventually help clinicians in diagnosing and treating psychiatric disorders. Presently, however, rigorous history-taking and comprehensive clinical assessments are still the most powerful tools a clinician can use to accomplish these goals. Finally, destigmatizing psychiatric disorders and educating patients and clinicians are also critical to improving clinical outcomes and promoting mental health in a compassionate and empathetic fashion.

Bottom Line

Despite the phenotypical resemblance between bipolar disorder (BP) and borderline personality disorder (BPD), the 2 are independent conditions with distinct neurobiological and psychopathological underpinnings. Clinicians can use a rigorous assessment of pathological personality traits and characterization of symptoms, such as onset patterns, clinical course, and phenomenology, to properly distinguish between BP and BPD.

Related Resources

• Fiedorowicz JG, Black DW. Borderline, bipolar, or both? Frame your diagnosis on the patient history. Current Psychiatry. 2010; 9(1):21-24,29-32.
• Zimmerman M. Improving the recognition of borderline personality disorder. Current Psychiatry. 2017;16(10):13-19.
• National Institute of Mental Health. Overview on bipolar disorder. www.nimh.nih.gov/health/publications/bipolar-disorder/index.shtml. Revised October 2018.
• National Institute of Mental Health. Overview on borderline personality disorder. www.nimh.nih.gov/health/publications/borderline-personality-disorder-fact-sheet/index.shtml.

Although evidence suggests that bipolar disorder (BD) and borderline personality disorder (BPD) are distinct entities, their differential diagnosis is often challenging as a result of considerable overlap of phenotypical features. Moreover, BD and BPD frequently co-occur, which makes it even more difficult to differentiate these 2 conditions. Strategies for improving diagnostic accuracy are critical to optimizing patients’ clinical outcomes and long-term prognosis. Misdiagnosing these 2 conditions can be particularly deleterious, and failure to recognize their co-occurrence can result in additional burden to typically complex and severe clinical presentations.

This article describes key aspects of the differential diagnosis between BD and BPD, emphasizing core features and major dissimilarities between these 2 conditions, and discusses the implications of misdiagnosis. The goal is to highlight the clinical and psychopathological aspects of BD and BPD to help clinicians properly distinguish these 2 disorders.

Psychopathological and sociodemographic correlates

Bipolar disorder is a chronic and severe mental illness that is classified based on clusters of symptoms—manic, hypomanic, and depressive.¹ It is among the 10 leading causes of disability worldwide, with significant morbidity arising from acute affective episodes and subacute states.² Data suggest the lifetime prevalence of BPD is 2.1%, and subthreshold forms may affect an additional 2.4% of the US population.³ The onset of symptoms typically occurs during late adolescence or early adulthood, and mood lability and cyclothymic temperament are the most common prodromal features.⁴

In contrast, personality disorders, such as BPD, are characteristically pervasive and maladaptive patterns of emotional responses that usually deviate from an individual’s stage of development and cultural background.¹ These disorders tend to cause significant impairment, particularly in personal, occupational, and social domains. Environmental factors, such as early childhood trauma, seem to play an important role in the genesis of personality disorders, which may be particularly relevant in BPD, a disorder characterized by marked impulsivity and a pattern of instability in personal relationships, self-image, and affect.^1,5,6 Similarly to BD, BPD is also chronic and highly disabling.

According to the National Survey on Alcohol and Related Conditions (NESARC), approximately 15% of US adults were found to have at least one type of personality disorder, and 6% met criteria for a cluster B personality disorder (antisocial, borderline, narcissistic, and histrionic).⁷ The lifetime prevalence of BPD is nearly 2%, with higher estimates observed in psychiatric settings.^7,8

As a result of the phenotypical resemblance between BD and BPD (Figure), the differential diagnosis is often difficult. Recent studies suggest that co-occurrence of BD and BPD is common, with rates of comorbid BPD as high as 29% in BD I and 24% in BD II.^8,9 On the other hand, nearly 20% of individuals with BPD seem to have comorbid BD.^8,9 Several studies suggest that comorbid personality disorders represent a negative prognostic factor in the course of mood disorders, and the presence of BPD in patients with BD seems to be associated with more severe clinical presentations, greater treatment complexity, a higher number of depressive episodes, poor inter-episode functioning, and higher rates of other comorbidities, such as substance use disorders (SUDs).^8-11 The effect of BD on the course of BPD is unclear and fairly unexplored, although it has been suggested that better control of mood symptoms may lead to more stable psychosocial functioning in BPD.⁹

Whether BD and BPD are part of the same spectrum is a matter for debate.^12-14 Multidimensional approaches have been proposed to better characterize these disorders in at-risk populations, based on structured interviews, self-administered and clinician-rated clinical scales (Table 1), neuroimaging studies, biological markers, and machine-learning models.^15,16 Compelling evidence suggests that BD and BPD have distinct underlying neurobiological and psychopathological mechanisms^12,13; however, the differential diagnosis still relies on phenotypical features, since the search for biological markers has not yet identified specific biomarkers that can be used in clinical practice.

Continue to: Core features of BPD...

Core features of BPD, such as mood lability, impulsivity, and risk-taking behaviors, are also part of the diagnostic criteria for BD (Table 2).¹ Similarly, depressive symptoms prevail in the course of BD.^17,18 This adds complexity to the differential because “depressivity” is also part of the diagnostic criteria for BPD.¹ Therefore, comprehensive psychiatric assessments and longitudinal observations are critical to diagnostic accuracy and treatment planning. Further characterization of symptoms, such as onset patterns, clinical course, phenomenology of symptoms (eg, timing, frequency, duration, triggers), and personality traits, will provide information to properly distinguish these 2 syndromes when, for example, it is unclear if the “mood swings” and impulsivity are part of a mood or a personality disorder (Table 3).

Clinical features: A closer look

Borderline personality disorder. Affect dysregulation, emotional instability, impoverished and unstable self-image, and chronic feelings of emptiness are core features of BPD.^1,5,19 These characteristics, when combined with a fear of abandonment or rejection, a compromised ability to recognize the feelings and needs of others, and extremes of idealization-devaluation, tend to culminate in problematic and chaotic relationships.^6,19 Individuals with BPD may become suspicious or paranoid under stressful situations. Under these circumstances, individuals with BPD may also experience depersonalization and other dissociative symptoms.^6,20 The mood lability and emotional instability observed in patients with BPD usually are in response to environmental factors, and although generally intense and out of proportion, they tend to be ephemeral and short-lived, typically lasting a few hours.^1,5 The anxiety and depressive symptoms reported by patients with BPD frequently are associated with feelings of “falling apart” or “losing control,” pessimism, shame, and low self-esteem. Coping strategies tend to be poorly developed and/or maladaptive, and individuals with BPD usually display a hostile and antagonistic demeanor and engage in suicidal or non­suicidal self-injury (NSSI) behaviors as means to alleviate overwhelming emotional distress. Impulsivity, disinhibition, poor tolerance to frustration, and risk-taking behaviors are also characteristic of BPD.^1,5 As a result, BPD is usually associated with significant impairment in functioning, multiple hospitalizations, and high rates of comorbid mood disorders, posttraumatic stress disorder (PTSD), SUDs, and death by suicide.

Bipolar disorder. Conversely, the fluctuations in mood and affect observed in patients with BD are usually episodic rather than pervasive, and tend to last longer (typically days to weeks) compared with the transient mood shifts observed in patients with BPD.^4,17,18 The impulsivity, psychomotor agitation, and increased goal-directed activity reported by patients with BD are usually seen in the context of an acute affective episode, and are far less common during periods of stability or euthymic affect.^4,17,18 Grandiosity and inflated self-esteem—hallmarks of a manic or hypomanic state—seem to oppose the unstable self-image observed in BPD, although indecisiveness and low self-worth may be observed in individuals with BD during depressive episodes. Antidepressant-induced mania or hypomania, atypical depressive episodes, and disruptions in sleep and circadian rhythms may be predictors of BD.^4,21 Furthermore, although psychosocial stressors may be associated with acute affective episodes in early stages of bipolar illness, over time minimal stressors are necessary to ignite new affective episodes.^22,23 Although BD is associated with high rates of suicide, suicide attempts are usually seen in the context of an acute depressive episode, and NSSI behaviors are less common among patients with BD.²⁴

Lastly, other biographical data, such as a history of early life trauma, comorbidity, and a family history of psychiatric illnesses, can be particularly helpful in establishing the differential diagnosis between BD and BPD.²⁵ For instance, evidence suggests that the heritability of BD may be as high as 70%, which usually translates into an extensive family history of bipolar and related disorders.²⁶ In addition, studies suggest a high co-occurrence of anxiety disorders, attention-deficit/hyperactivity disorder, and SUDs in patients with BD, whereas PTSD, SUDs, and eating disorders tend to be highly comorbid with BPD.²⁷ Childhood adversity (ie, a history of physical, sexual, or emotional abuse, or neglect) seems to be pivotal in the genesis of BPD and may predispose these individuals to psychotic and dissociative symptoms, particularly those with a history of sexual abuse, while playing a more secondary role in BD.^28-31

Implications of misdiagnosis

In the view of the limitations of the existing models, multidimensional approaches are necessary to improve diagnostic accuracy. Presently, the differential diagnosis of BD and BPD continues to rely on clinical findings and syndromic classifications. Misdiagnosing BD and BPD has adverse therapeutic and prognostic implications.³² For instance, while psychotropic medications and neuromodulatory therapies (eg, electroconvulsive therapy, repetitive transcranial magnetic stimulation) are considered first-line treatments for patients with BD, psychosocial interventions tend to be adjunctive treatments in BD.³³ Conversely, although pharmacotherapy might be helpful for patients with BPD, psychosocial and behavioral interventions are the mainstay treatment for this disorder, with the strongest evidence supporting cognitive-behavioral therapy, dialectical behavioral therapy, mentalization-based therapy, and transference-focused therapy.^34-36 Thus, misdiagnosing BD as BPD with comorbid depression may result in the use of antidepressants, which can be detrimental in BD. Antidepressant treatment of BD, particularly as monotherapy, has been associated with manic or hypomanic switch, mixed states, and frequent cycling.²¹ Moreover, delays in diagnosis and proper treatment of BD may result in protracted mood symptoms, prolonged affective episodes, higher rates of disability, functional impairment, and overall worse clinical outcomes.²⁴ In addition, because behavioral and psychosocial interventions are usually adjunctive therapies rather than first-line interventions for patients with BD, misdiagnosing BPD as BD may ultimately prevent these individuals from receiving proper treatment, likely resulting in more severe functional impairment, multiple hospitalizations, self-inflicted injuries, and suicide attempts, since psychotropic medications are not particularly effective for improving self-efficacy and coping strategies, nor for correcting cognitive distortions, particularly in self-image, and pathological personality traits, all of which are critical aspects of BPD treatment.

Continue to: Several factors might...

Several factors might make clinicians reluctant to diagnose BPD, or bias them to diagnose BD more frequently. These include a lack of familiarity with the diagnostic criteria for BPD, the phenotypical resemblance between BP and BPD, or even concerns about the stigma and negative implications that are associated with a BPD diagnosis.^32,37,38

Whereas BD is currently perceived as a condition with a strong biological basis, there are considerable misconceptions regarding BPD and its nature.^4-6,22,26 As a consequence, individuals with BPD tend to be perceived as “difficult-to-treat,” “uncooperative,” or “attention-seeking.” These misconceptions may result in poor clinician-patient relationships, unmet clinical and psychiatric needs, and frustration for both clinicians and patients.³⁷

Through advances in biological psychiatry, precision medicine may someday be a part of psychiatric practice. Biological “signatures” may eventually help clinicians in diagnosing and treating psychiatric disorders. Presently, however, rigorous history-taking and comprehensive clinical assessments are still the most powerful tools a clinician can use to accomplish these goals. Finally, destigmatizing psychiatric disorders and educating patients and clinicians are also critical to improving clinical outcomes and promoting mental health in a compassionate and empathetic fashion.

Bottom Line

Despite the phenotypical resemblance between bipolar disorder (BP) and borderline personality disorder (BPD), the 2 are independent conditions with distinct neurobiological and psychopathological underpinnings. Clinicians can use a rigorous assessment of pathological personality traits and characterization of symptoms, such as onset patterns, clinical course, and phenomenology, to properly distinguish between BP and BPD.

Related Resources

• Fiedorowicz JG, Black DW. Borderline, bipolar, or both? Frame your diagnosis on the patient history. Current Psychiatry. 2010; 9(1):21-24,29-32.
• Zimmerman M. Improving the recognition of borderline personality disorder. Current Psychiatry. 2017;16(10):13-19.
• National Institute of Mental Health. Overview on bipolar disorder. www.nimh.nih.gov/health/publications/bipolar-disorder/index.shtml. Revised October 2018.
• National Institute of Mental Health. Overview on borderline personality disorder. www.nimh.nih.gov/health/publications/borderline-personality-disorder-fact-sheet/index.shtml.

Although evidence suggests that bipolar disorder (BD) and borderline personality disorder (BPD) are distinct entities, their differential diagnosis is often challenging as a result of considerable overlap of phenotypical features. Moreover, BD and BPD frequently co-occur, which makes it even more difficult to differentiate these 2 conditions. Strategies for improving diagnostic accuracy are critical to optimizing patients’ clinical outcomes and long-term prognosis. Misdiagnosing these 2 conditions can be particularly deleterious, and failure to recognize their co-occurrence can result in additional burden to typically complex and severe clinical presentations.

This article describes key aspects of the differential diagnosis between BD and BPD, emphasizing core features and major dissimilarities between these 2 conditions, and discusses the implications of misdiagnosis. The goal is to highlight the clinical and psychopathological aspects of BD and BPD to help clinicians properly distinguish these 2 disorders.

Psychopathological and sociodemographic correlates

Bipolar disorder is a chronic and severe mental illness that is classified based on clusters of symptoms—manic, hypomanic, and depressive.¹ It is among the 10 leading causes of disability worldwide, with significant morbidity arising from acute affective episodes and subacute states.² Data suggest the lifetime prevalence of BPD is 2.1%, and subthreshold forms may affect an additional 2.4% of the US population.³ The onset of symptoms typically occurs during late adolescence or early adulthood, and mood lability and cyclothymic temperament are the most common prodromal features.⁴

In contrast, personality disorders, such as BPD, are characteristically pervasive and maladaptive patterns of emotional responses that usually deviate from an individual’s stage of development and cultural background.¹ These disorders tend to cause significant impairment, particularly in personal, occupational, and social domains. Environmental factors, such as early childhood trauma, seem to play an important role in the genesis of personality disorders, which may be particularly relevant in BPD, a disorder characterized by marked impulsivity and a pattern of instability in personal relationships, self-image, and affect.^1,5,6 Similarly to BD, BPD is also chronic and highly disabling.

According to the National Survey on Alcohol and Related Conditions (NESARC), approximately 15% of US adults were found to have at least one type of personality disorder, and 6% met criteria for a cluster B personality disorder (antisocial, borderline, narcissistic, and histrionic).⁷ The lifetime prevalence of BPD is nearly 2%, with higher estimates observed in psychiatric settings.^7,8

As a result of the phenotypical resemblance between BD and BPD (Figure), the differential diagnosis is often difficult. Recent studies suggest that co-occurrence of BD and BPD is common, with rates of comorbid BPD as high as 29% in BD I and 24% in BD II.^8,9 On the other hand, nearly 20% of individuals with BPD seem to have comorbid BD.^8,9 Several studies suggest that comorbid personality disorders represent a negative prognostic factor in the course of mood disorders, and the presence of BPD in patients with BD seems to be associated with more severe clinical presentations, greater treatment complexity, a higher number of depressive episodes, poor inter-episode functioning, and higher rates of other comorbidities, such as substance use disorders (SUDs).^8-11 The effect of BD on the course of BPD is unclear and fairly unexplored, although it has been suggested that better control of mood symptoms may lead to more stable psychosocial functioning in BPD.⁹

Whether BD and BPD are part of the same spectrum is a matter for debate.^12-14 Multidimensional approaches have been proposed to better characterize these disorders in at-risk populations, based on structured interviews, self-administered and clinician-rated clinical scales (Table 1), neuroimaging studies, biological markers, and machine-learning models.^15,16 Compelling evidence suggests that BD and BPD have distinct underlying neurobiological and psychopathological mechanisms^12,13; however, the differential diagnosis still relies on phenotypical features, since the search for biological markers has not yet identified specific biomarkers that can be used in clinical practice.

Continue to: Core features of BPD...

Core features of BPD, such as mood lability, impulsivity, and risk-taking behaviors, are also part of the diagnostic criteria for BD (Table 2).¹ Similarly, depressive symptoms prevail in the course of BD.^17,18 This adds complexity to the differential because “depressivity” is also part of the diagnostic criteria for BPD.¹ Therefore, comprehensive psychiatric assessments and longitudinal observations are critical to diagnostic accuracy and treatment planning. Further characterization of symptoms, such as onset patterns, clinical course, phenomenology of symptoms (eg, timing, frequency, duration, triggers), and personality traits, will provide information to properly distinguish these 2 syndromes when, for example, it is unclear if the “mood swings” and impulsivity are part of a mood or a personality disorder (Table 3).

Clinical features: A closer look

Borderline personality disorder. Affect dysregulation, emotional instability, impoverished and unstable self-image, and chronic feelings of emptiness are core features of BPD.^1,5,19 These characteristics, when combined with a fear of abandonment or rejection, a compromised ability to recognize the feelings and needs of others, and extremes of idealization-devaluation, tend to culminate in problematic and chaotic relationships.^6,19 Individuals with BPD may become suspicious or paranoid under stressful situations. Under these circumstances, individuals with BPD may also experience depersonalization and other dissociative symptoms.^6,20 The mood lability and emotional instability observed in patients with BPD usually are in response to environmental factors, and although generally intense and out of proportion, they tend to be ephemeral and short-lived, typically lasting a few hours.^1,5 The anxiety and depressive symptoms reported by patients with BPD frequently are associated with feelings of “falling apart” or “losing control,” pessimism, shame, and low self-esteem. Coping strategies tend to be poorly developed and/or maladaptive, and individuals with BPD usually display a hostile and antagonistic demeanor and engage in suicidal or non­suicidal self-injury (NSSI) behaviors as means to alleviate overwhelming emotional distress. Impulsivity, disinhibition, poor tolerance to frustration, and risk-taking behaviors are also characteristic of BPD.^1,5 As a result, BPD is usually associated with significant impairment in functioning, multiple hospitalizations, and high rates of comorbid mood disorders, posttraumatic stress disorder (PTSD), SUDs, and death by suicide.

Bipolar disorder. Conversely, the fluctuations in mood and affect observed in patients with BD are usually episodic rather than pervasive, and tend to last longer (typically days to weeks) compared with the transient mood shifts observed in patients with BPD.^4,17,18 The impulsivity, psychomotor agitation, and increased goal-directed activity reported by patients with BD are usually seen in the context of an acute affective episode, and are far less common during periods of stability or euthymic affect.^4,17,18 Grandiosity and inflated self-esteem—hallmarks of a manic or hypomanic state—seem to oppose the unstable self-image observed in BPD, although indecisiveness and low self-worth may be observed in individuals with BD during depressive episodes. Antidepressant-induced mania or hypomania, atypical depressive episodes, and disruptions in sleep and circadian rhythms may be predictors of BD.^4,21 Furthermore, although psychosocial stressors may be associated with acute affective episodes in early stages of bipolar illness, over time minimal stressors are necessary to ignite new affective episodes.^22,23 Although BD is associated with high rates of suicide, suicide attempts are usually seen in the context of an acute depressive episode, and NSSI behaviors are less common among patients with BD.²⁴

Lastly, other biographical data, such as a history of early life trauma, comorbidity, and a family history of psychiatric illnesses, can be particularly helpful in establishing the differential diagnosis between BD and BPD.²⁵ For instance, evidence suggests that the heritability of BD may be as high as 70%, which usually translates into an extensive family history of bipolar and related disorders.²⁶ In addition, studies suggest a high co-occurrence of anxiety disorders, attention-deficit/hyperactivity disorder, and SUDs in patients with BD, whereas PTSD, SUDs, and eating disorders tend to be highly comorbid with BPD.²⁷ Childhood adversity (ie, a history of physical, sexual, or emotional abuse, or neglect) seems to be pivotal in the genesis of BPD and may predispose these individuals to psychotic and dissociative symptoms, particularly those with a history of sexual abuse, while playing a more secondary role in BD.^28-31

Implications of misdiagnosis

In the view of the limitations of the existing models, multidimensional approaches are necessary to improve diagnostic accuracy. Presently, the differential diagnosis of BD and BPD continues to rely on clinical findings and syndromic classifications. Misdiagnosing BD and BPD has adverse therapeutic and prognostic implications.³² For instance, while psychotropic medications and neuromodulatory therapies (eg, electroconvulsive therapy, repetitive transcranial magnetic stimulation) are considered first-line treatments for patients with BD, psychosocial interventions tend to be adjunctive treatments in BD.³³ Conversely, although pharmacotherapy might be helpful for patients with BPD, psychosocial and behavioral interventions are the mainstay treatment for this disorder, with the strongest evidence supporting cognitive-behavioral therapy, dialectical behavioral therapy, mentalization-based therapy, and transference-focused therapy.^34-36 Thus, misdiagnosing BD as BPD with comorbid depression may result in the use of antidepressants, which can be detrimental in BD. Antidepressant treatment of BD, particularly as monotherapy, has been associated with manic or hypomanic switch, mixed states, and frequent cycling.²¹ Moreover, delays in diagnosis and proper treatment of BD may result in protracted mood symptoms, prolonged affective episodes, higher rates of disability, functional impairment, and overall worse clinical outcomes.²⁴ In addition, because behavioral and psychosocial interventions are usually adjunctive therapies rather than first-line interventions for patients with BD, misdiagnosing BPD as BD may ultimately prevent these individuals from receiving proper treatment, likely resulting in more severe functional impairment, multiple hospitalizations, self-inflicted injuries, and suicide attempts, since psychotropic medications are not particularly effective for improving self-efficacy and coping strategies, nor for correcting cognitive distortions, particularly in self-image, and pathological personality traits, all of which are critical aspects of BPD treatment.

Continue to: Several factors might...

Several factors might make clinicians reluctant to diagnose BPD, or bias them to diagnose BD more frequently. These include a lack of familiarity with the diagnostic criteria for BPD, the phenotypical resemblance between BP and BPD, or even concerns about the stigma and negative implications that are associated with a BPD diagnosis.^32,37,38

Whereas BD is currently perceived as a condition with a strong biological basis, there are considerable misconceptions regarding BPD and its nature.^4-6,22,26 As a consequence, individuals with BPD tend to be perceived as “difficult-to-treat,” “uncooperative,” or “attention-seeking.” These misconceptions may result in poor clinician-patient relationships, unmet clinical and psychiatric needs, and frustration for both clinicians and patients.³⁷

Through advances in biological psychiatry, precision medicine may someday be a part of psychiatric practice. Biological “signatures” may eventually help clinicians in diagnosing and treating psychiatric disorders. Presently, however, rigorous history-taking and comprehensive clinical assessments are still the most powerful tools a clinician can use to accomplish these goals. Finally, destigmatizing psychiatric disorders and educating patients and clinicians are also critical to improving clinical outcomes and promoting mental health in a compassionate and empathetic fashion.

Bottom Line

Despite the phenotypical resemblance between bipolar disorder (BP) and borderline personality disorder (BPD), the 2 are independent conditions with distinct neurobiological and psychopathological underpinnings. Clinicians can use a rigorous assessment of pathological personality traits and characterization of symptoms, such as onset patterns, clinical course, and phenomenology, to properly distinguish between BP and BPD.

Related Resources

• Fiedorowicz JG, Black DW. Borderline, bipolar, or both? Frame your diagnosis on the patient history. Current Psychiatry. 2010; 9(1):21-24,29-32.
• Zimmerman M. Improving the recognition of borderline personality disorder. Current Psychiatry. 2017;16(10):13-19.
• National Institute of Mental Health. Overview on bipolar disorder. www.nimh.nih.gov/health/publications/bipolar-disorder/index.shtml. Revised October 2018.
• National Institute of Mental Health. Overview on borderline personality disorder. www.nimh.nih.gov/health/publications/borderline-personality-disorder-fact-sheet/index.shtml.

At some point during their career, many mental health professionals will lose a patient to suicide, but few will be prepared for the experience and its aftermath. As I described in Part 1 of this article (Current Psychiatry. October 2019, p. 14-16,19-22,30-32), a suicide loss is often associated with multiple personal and professional issues, including legal and ethical concerns, confidentiality constraints that may impede discussing and processing the loss, colleagues’ blaming/unsupportive reactions, stigma around both suicide and professional vulnerability, and potential effects on one’s clinical work. In Part 2, I explore the opportunities for personal and professional growth that can paradoxically result from a suicide loss, guidelines for appropriate postventions and procedures that should take place after such losses, and how to best support a colleague who has lost a patient to suicide.

A chance for growth

Traumatic experiences such as a suicide loss can paradoxically present a multitude of opportunities for new growth and profound personal transformation.¹ Such transformation is primarily fostered by social support in the aftermath of the trauma.²

Virtually all of the models of the clinician’s suicide grief trajectory I described in Part 1 not only assume the eventual resolution of the distressing reactions accompanying the original loss, but also suggest that mastery of these reactions can be a catalyst for both personal and professional growth. Clearly, not everyone who experiences such a loss will experience subsequent growth; there are many reports of clinicians leaving the field³ or becoming “burned out” after this occurs. Yet most clinicians who have described this loss in the literature and in discussion groups (including those I’ve conducted) have reported more positive eventual outcomes. It is difficult to establish whether this is due to a cohort effect—clinicians who are most likely to write about their experiences, be interviewed for research studies, and/or to seek out and participate in discussion/support groups may be more prone to find benefits in this experience, either by virtue of their nature or through the subsequent process of sharing these experiences in a supportive atmosphere.

The literature on patient suicide loss, as well as anecdotal reports, confirms that clinicians who experience optimal support are able to identify many retrospective benefits of their experience.^4-6 Clinicians generally report that they are better able to identify potential risk and protective factors for suicide, and are more knowledgeable about optimal interventions with individuals who are suicidal. They also describe an increased sensitivity towards patients who are suicidal and those bereaved by suicide. In addition, clinicians report a reduction in therapeutic grandiosity/omnipotence, and more realistic appraisals and expectations in relation to their clinical competence. In their effort to understand the “whys” of their patient’s suicide, they are likely to retrospectively identify errors in treatment, “missed cues,” or things they might subsequently do differently,⁷ and to learn from these mistakes. Optimally, clinicians become more aware of their own therapeutic limitations, both in the short- and the long-term, and can use this knowledge to better determine how they will continue their clinical work. They also become much more aware of the issues involved in the aftermath of a patient suicide, including perceived gaps in the clinical and institutional systems that could optimally offer support to families and clinicians.

In addition to the positive changes related to knowledge and clinical skills, many clinicians also note deeper personal changes subsequent to their patient’s suicide, consistent with the literature on posttraumatic growth.¹ Munson⁸ explored internal changes in clinicians following a patient suicide and found that in the aftermath, clinicians experienced both posttraumatic growth and compassion fatigue. He also found that the amount of time that elapsed since the patient’s suicide predicted posttraumatic growth, and the seemingly counterintuitive result that the number of years of clinical experience prior to the suicide was negatively correlated with posttraumatic growth.

Huhra et al⁴ described some of the existential issues that a clinician is likely to confront following a patient suicide. A clinician’s attempt to find a way to meaningfully understand the circumstances around this loss often prompts reflection on mortality, freedom, choice and personal autonomy, and the scope and limits of one’s responsibility toward others. The suicide challenges one’s previous conceptions and expectations around these professional issues, and the clinician must construct new paradigms that serve to integrate these new experiences and perspectives in a coherent way.

One of the most notable sequelae of this (and to other traumatic) experience is a subsequent desire to make use of the learning inherent in these experiences and to “give back.” Once they feel that they have resolved their own grief process, many clinicians express the desire to support others with similar experiences. Even when their experiences have been quite distressing, many clinicians are able to view the suicide as an opportunity to learn about ongoing limitations in the systems of support, and to work toward changing these in a way that ensures that future clinician-survivors will have more supportive experiences. Many view these new perspectives, and their consequent ability to be more helpful, as “unexpected gifts.” They often express gratitude toward the people and resources that have allowed them to make these transformations. Jones⁵ noted “the tragedy of patient suicide can also be an opportunity for us as therapists to grow in our skills at assessing and intervening in a suicidal crisis, to broaden and deepen the support we give and receive, to grow in our appreciation of the precious gift that life is, and to help each other live it more fully.”

Continue to: Guidelines for postvention

Guidelines for postvention

When a patient suicide occurs in the context of an agency setting, Grad⁹ recommends prompt responses on 4 levels:

• administrative
• institutional
• educational
• emotional.

Numerous authors^5,10-21 have developed suggestions, guidelines, and detailed postvention protocols to help agencies and clinicians in various mental health settings navigate the often-complicated sequelae to a patient’s suicide. The Table highlights a few of these. Most emphasize that information about suicide loss, including both its statistical likelihood and its potential aftermath, should integrated into clinicians’ general education and training. They also suggest that suicide postvention policies and protocols be in place from the outset, and that such information be incorporated into institutional policy and procedure manuals. In addition, they stress that legal, institutional, and administrative needs be balanced with the emotional needs of affected clinicians and staff, as well as those of the surviving family.

Institutional and administrative procedures

The following are some of the recommended procedures that should take place following a suicide loss. The postvention protocols listed in the Table provide more detailed recommendations.

Legal/ethical. It is essential to consult with a legal representative/risk management specialist associated with the affected agency (ideally, one with specific expertise in suicide litigation.). It is also crucial to clarify who holds privilege after a patient’s death (varies by state), what may and may not be shared under the restrictions of confidentiality and Health Insurance Portability and Accountability Act (HIPAA) laws, and to clarify procedures for chart completion and review. It is also important to clarify the specific information to be shared both within and outside of the agency, and how to address the needs of current patients in the agency settings.

Case review. The optimal purpose of the case review (also known as a psychological autopsy) is to facilitate learning, identify gaps in agency procedures and training, improve pre- and postvention procedures, and help clinicians cope with the loss.²² Again, the legal and administrative needs of the agency need to be balanced with the attention to the emotional impact on the treating clinician.¹⁷ Ellis and Patel¹⁸ recommend delaying this procedure until the treating clinician is no longer in the “shock” phase of the loss, and is able to think and process events more objectively.

Continue to: Family contact

Family contact. Most authors have recommended that clinicians and/or agencies reach out to surviving families. Although some legal representatives will advise against this, experts in the field of suicide litigation have noted that compassionate family contact reduces liability and facilitates healing for both parties. In a personal communication (May 2008), Eric Harris, of the American Psychological Association Trust, recommended “compassion over caution” when considering these issues. Again, it is important to clarify who holds privilege after a patient’s death in determining when and with whom the patient’s confidential information may be shared. When confidentiality may be broken, clinical judgment should be used to determine how best to present the information to grieving family members.

Even if surviving family members do not hold privilege, there are many things that clinicians can do to be helpful.²³ Inevitably, families will want any information that will help them make sense of the loss, and general psychoeducation about mental illness and suicide can be helpful in this regard. In addition, providing information about “Survivors After Suicide” support groups, reading materials, etc., can be helpful. Both support groups and survivor-related bibliographies are available on the web sites of the American Association of Suicidology (www.suicidology.org) and The American Foundation for Suicide Prevention (www.afsp.org).

In addition, clinicians should ask the family if it would be helpful if they were to attend the funeral/memorial services, and how to introduce themselves if asked by other attendees.

Patients in clinics/hospitals. When a patient suicide occurs in a clinic or hospital setting, it is likely to impact other patients in that setting to the extent that they have heard, about the event, even from outside sources.According to Hodgkinson,²⁴ in addition to being overwhelmed with intense feelings about the suicide loss (particularly if they had known the patient), affected patients are likely to be at increased risk for suicidal behaviors. This is consistent with the considerable literature on suicide contagion.

Thus, it is important to clarify information to be shared with patients; however, avoid describing details of the method, because this can foster contagion and “copycat” suicides. In addition, Kaye and Soreff²² noted that these patients may now be concerned about the staff’s ability to be helpful to them, because they were unable to help the deceased. In light of this, take extra care to attend to the impact of the suicide on current patients, and to monitor both pre-existing and new suicidality.

Continue to: Helping affected clinicians

Suggestions for optimally supporting affected clinicians include:

• clear communication about the nature of upcoming administrative procedures (including chart and institutional reviews)
• consultation from supervisors and/or colleagues that is supportive and reassuring, rather than blaming
• opportunities for the clinician to talk openly about the experience of the loss, either individually or in group settings, without fear of judgment or censure
• recognition that the loss is likely to impact clinical work, support in monitoring this impact, and the provision of medical leaves and/or modified caseloads (ie, fewer high-risk patients) as necessary.

Box 1

Both researchers and clinician-survivors in my practice and support groups have noted that speaking with other clinicians who have experienced suicide loss can be particularly reassuring and validating. If none are available on staff, the listserve and online support groups of the American Association of Suicidology’s Clinician Survivor Task Force may be helpful (Box 1⁷). In addition, the film “Collateral Damages: The Impact of Patient Suicide on the Physician” features physicians describing their experience of losing a patient to suicide (Box 2).

Box 2

Schultz¹⁴ offered suggestions for staff in supervisory positions, noting that they may bear at least some clinical and legal responsibility for the treatments that they supervise. She encouraged supervisors to take an active stance in advocating for trainees, to encourage colleagues to express their support, and to discourage rumors and other stigmatizing reactions. Schultz also urges supervisors to¹⁴:

• allow extra time for the clinician to engage in the normative exploration of the “whys” that are unique to suicide survivors
• use education about suicide to help the clinician gain a more realistic perspective on their relative culpability
• become aware of and provide education about normative grief reactions following a suicide.

Continue to: Because a suicide loss...

Because a suicide loss is likely to affect a clinician’s subsequent clinical activity, Schultz encourages supervisors to help clinicians monitor this impact on their work.¹⁴

A supportive environment is key

Losing a patient to suicide is a complicated, potentially traumatic process that many mental health clinicians will face. Yet with comprehensive and supportive postvention policies in place, clinicians who are impacted are more likely to experience healing and posttraumatic growth in both personal and professional domains.

Bottom Line

Although often traumatic, losing a patient to suicide presents clinicians with an opportunity for personal and professional growth. Following established postvention protocols can help ensure that legal, institutional, and administrative needs are balanced with the emotional needs of affected clinicians and staff, as well as those of the surviving family.

Related Resources

• American Association of Suicidology Clinician Survivor Task Force. www.cliniciansurvivor.org.
• Dotinga R. Coping when a patient commits suicide. July 21, 2017. www.mdedge.com/psychiatry/article/142975/depression/coping-when-patient-commits-suicide.
• Gutin N. Losing a patent to suicide: What we know. Part 1. 2019;18(10):14-16,19-22,30-32.

At some point during their career, many mental health professionals will lose a patient to suicide, but few will be prepared for the experience and its aftermath. As I described in Part 1 of this article (Current Psychiatry. October 2019, p. 14-16,19-22,30-32), a suicide loss is often associated with multiple personal and professional issues, including legal and ethical concerns, confidentiality constraints that may impede discussing and processing the loss, colleagues’ blaming/unsupportive reactions, stigma around both suicide and professional vulnerability, and potential effects on one’s clinical work. In Part 2, I explore the opportunities for personal and professional growth that can paradoxically result from a suicide loss, guidelines for appropriate postventions and procedures that should take place after such losses, and how to best support a colleague who has lost a patient to suicide.

A chance for growth

Traumatic experiences such as a suicide loss can paradoxically present a multitude of opportunities for new growth and profound personal transformation.¹ Such transformation is primarily fostered by social support in the aftermath of the trauma.²

Virtually all of the models of the clinician’s suicide grief trajectory I described in Part 1 not only assume the eventual resolution of the distressing reactions accompanying the original loss, but also suggest that mastery of these reactions can be a catalyst for both personal and professional growth. Clearly, not everyone who experiences such a loss will experience subsequent growth; there are many reports of clinicians leaving the field³ or becoming “burned out” after this occurs. Yet most clinicians who have described this loss in the literature and in discussion groups (including those I’ve conducted) have reported more positive eventual outcomes. It is difficult to establish whether this is due to a cohort effect—clinicians who are most likely to write about their experiences, be interviewed for research studies, and/or to seek out and participate in discussion/support groups may be more prone to find benefits in this experience, either by virtue of their nature or through the subsequent process of sharing these experiences in a supportive atmosphere.

The literature on patient suicide loss, as well as anecdotal reports, confirms that clinicians who experience optimal support are able to identify many retrospective benefits of their experience.^4-6 Clinicians generally report that they are better able to identify potential risk and protective factors for suicide, and are more knowledgeable about optimal interventions with individuals who are suicidal. They also describe an increased sensitivity towards patients who are suicidal and those bereaved by suicide. In addition, clinicians report a reduction in therapeutic grandiosity/omnipotence, and more realistic appraisals and expectations in relation to their clinical competence. In their effort to understand the “whys” of their patient’s suicide, they are likely to retrospectively identify errors in treatment, “missed cues,” or things they might subsequently do differently,⁷ and to learn from these mistakes. Optimally, clinicians become more aware of their own therapeutic limitations, both in the short- and the long-term, and can use this knowledge to better determine how they will continue their clinical work. They also become much more aware of the issues involved in the aftermath of a patient suicide, including perceived gaps in the clinical and institutional systems that could optimally offer support to families and clinicians.

In addition to the positive changes related to knowledge and clinical skills, many clinicians also note deeper personal changes subsequent to their patient’s suicide, consistent with the literature on posttraumatic growth.¹ Munson⁸ explored internal changes in clinicians following a patient suicide and found that in the aftermath, clinicians experienced both posttraumatic growth and compassion fatigue. He also found that the amount of time that elapsed since the patient’s suicide predicted posttraumatic growth, and the seemingly counterintuitive result that the number of years of clinical experience prior to the suicide was negatively correlated with posttraumatic growth.

Huhra et al⁴ described some of the existential issues that a clinician is likely to confront following a patient suicide. A clinician’s attempt to find a way to meaningfully understand the circumstances around this loss often prompts reflection on mortality, freedom, choice and personal autonomy, and the scope and limits of one’s responsibility toward others. The suicide challenges one’s previous conceptions and expectations around these professional issues, and the clinician must construct new paradigms that serve to integrate these new experiences and perspectives in a coherent way.

One of the most notable sequelae of this (and to other traumatic) experience is a subsequent desire to make use of the learning inherent in these experiences and to “give back.” Once they feel that they have resolved their own grief process, many clinicians express the desire to support others with similar experiences. Even when their experiences have been quite distressing, many clinicians are able to view the suicide as an opportunity to learn about ongoing limitations in the systems of support, and to work toward changing these in a way that ensures that future clinician-survivors will have more supportive experiences. Many view these new perspectives, and their consequent ability to be more helpful, as “unexpected gifts.” They often express gratitude toward the people and resources that have allowed them to make these transformations. Jones⁵ noted “the tragedy of patient suicide can also be an opportunity for us as therapists to grow in our skills at assessing and intervening in a suicidal crisis, to broaden and deepen the support we give and receive, to grow in our appreciation of the precious gift that life is, and to help each other live it more fully.”

Continue to: Guidelines for postvention

Guidelines for postvention

When a patient suicide occurs in the context of an agency setting, Grad⁹ recommends prompt responses on 4 levels:

• administrative
• institutional
• educational
• emotional.

Numerous authors^5,10-21 have developed suggestions, guidelines, and detailed postvention protocols to help agencies and clinicians in various mental health settings navigate the often-complicated sequelae to a patient’s suicide. The Table highlights a few of these. Most emphasize that information about suicide loss, including both its statistical likelihood and its potential aftermath, should integrated into clinicians’ general education and training. They also suggest that suicide postvention policies and protocols be in place from the outset, and that such information be incorporated into institutional policy and procedure manuals. In addition, they stress that legal, institutional, and administrative needs be balanced with the emotional needs of affected clinicians and staff, as well as those of the surviving family.

Institutional and administrative procedures

The following are some of the recommended procedures that should take place following a suicide loss. The postvention protocols listed in the Table provide more detailed recommendations.

Legal/ethical. It is essential to consult with a legal representative/risk management specialist associated with the affected agency (ideally, one with specific expertise in suicide litigation.). It is also crucial to clarify who holds privilege after a patient’s death (varies by state), what may and may not be shared under the restrictions of confidentiality and Health Insurance Portability and Accountability Act (HIPAA) laws, and to clarify procedures for chart completion and review. It is also important to clarify the specific information to be shared both within and outside of the agency, and how to address the needs of current patients in the agency settings.

Case review. The optimal purpose of the case review (also known as a psychological autopsy) is to facilitate learning, identify gaps in agency procedures and training, improve pre- and postvention procedures, and help clinicians cope with the loss.²² Again, the legal and administrative needs of the agency need to be balanced with the attention to the emotional impact on the treating clinician.¹⁷ Ellis and Patel¹⁸ recommend delaying this procedure until the treating clinician is no longer in the “shock” phase of the loss, and is able to think and process events more objectively.

Continue to: Family contact

Family contact. Most authors have recommended that clinicians and/or agencies reach out to surviving families. Although some legal representatives will advise against this, experts in the field of suicide litigation have noted that compassionate family contact reduces liability and facilitates healing for both parties. In a personal communication (May 2008), Eric Harris, of the American Psychological Association Trust, recommended “compassion over caution” when considering these issues. Again, it is important to clarify who holds privilege after a patient’s death in determining when and with whom the patient’s confidential information may be shared. When confidentiality may be broken, clinical judgment should be used to determine how best to present the information to grieving family members.

Even if surviving family members do not hold privilege, there are many things that clinicians can do to be helpful.²³ Inevitably, families will want any information that will help them make sense of the loss, and general psychoeducation about mental illness and suicide can be helpful in this regard. In addition, providing information about “Survivors After Suicide” support groups, reading materials, etc., can be helpful. Both support groups and survivor-related bibliographies are available on the web sites of the American Association of Suicidology (www.suicidology.org) and The American Foundation for Suicide Prevention (www.afsp.org).

In addition, clinicians should ask the family if it would be helpful if they were to attend the funeral/memorial services, and how to introduce themselves if asked by other attendees.

Patients in clinics/hospitals. When a patient suicide occurs in a clinic or hospital setting, it is likely to impact other patients in that setting to the extent that they have heard, about the event, even from outside sources.According to Hodgkinson,²⁴ in addition to being overwhelmed with intense feelings about the suicide loss (particularly if they had known the patient), affected patients are likely to be at increased risk for suicidal behaviors. This is consistent with the considerable literature on suicide contagion.

Thus, it is important to clarify information to be shared with patients; however, avoid describing details of the method, because this can foster contagion and “copycat” suicides. In addition, Kaye and Soreff²² noted that these patients may now be concerned about the staff’s ability to be helpful to them, because they were unable to help the deceased. In light of this, take extra care to attend to the impact of the suicide on current patients, and to monitor both pre-existing and new suicidality.

Continue to: Helping affected clinicians

Suggestions for optimally supporting affected clinicians include:

• clear communication about the nature of upcoming administrative procedures (including chart and institutional reviews)
• consultation from supervisors and/or colleagues that is supportive and reassuring, rather than blaming
• opportunities for the clinician to talk openly about the experience of the loss, either individually or in group settings, without fear of judgment or censure
• recognition that the loss is likely to impact clinical work, support in monitoring this impact, and the provision of medical leaves and/or modified caseloads (ie, fewer high-risk patients) as necessary.

Box 1

Both researchers and clinician-survivors in my practice and support groups have noted that speaking with other clinicians who have experienced suicide loss can be particularly reassuring and validating. If none are available on staff, the listserve and online support groups of the American Association of Suicidology’s Clinician Survivor Task Force may be helpful (Box 1⁷). In addition, the film “Collateral Damages: The Impact of Patient Suicide on the Physician” features physicians describing their experience of losing a patient to suicide (Box 2).

Box 2

Schultz¹⁴ offered suggestions for staff in supervisory positions, noting that they may bear at least some clinical and legal responsibility for the treatments that they supervise. She encouraged supervisors to take an active stance in advocating for trainees, to encourage colleagues to express their support, and to discourage rumors and other stigmatizing reactions. Schultz also urges supervisors to¹⁴:

• allow extra time for the clinician to engage in the normative exploration of the “whys” that are unique to suicide survivors
• use education about suicide to help the clinician gain a more realistic perspective on their relative culpability
• become aware of and provide education about normative grief reactions following a suicide.

Continue to: Because a suicide loss...

Because a suicide loss is likely to affect a clinician’s subsequent clinical activity, Schultz encourages supervisors to help clinicians monitor this impact on their work.¹⁴

A supportive environment is key

Losing a patient to suicide is a complicated, potentially traumatic process that many mental health clinicians will face. Yet with comprehensive and supportive postvention policies in place, clinicians who are impacted are more likely to experience healing and posttraumatic growth in both personal and professional domains.

Bottom Line

Although often traumatic, losing a patient to suicide presents clinicians with an opportunity for personal and professional growth. Following established postvention protocols can help ensure that legal, institutional, and administrative needs are balanced with the emotional needs of affected clinicians and staff, as well as those of the surviving family.

Related Resources

• American Association of Suicidology Clinician Survivor Task Force. www.cliniciansurvivor.org.
• Dotinga R. Coping when a patient commits suicide. July 21, 2017. www.mdedge.com/psychiatry/article/142975/depression/coping-when-patient-commits-suicide.
• Gutin N. Losing a patent to suicide: What we know. Part 1. 2019;18(10):14-16,19-22,30-32.

At some point during their career, many mental health professionals will lose a patient to suicide, but few will be prepared for the experience and its aftermath. As I described in Part 1 of this article (Current Psychiatry. October 2019, p. 14-16,19-22,30-32), a suicide loss is often associated with multiple personal and professional issues, including legal and ethical concerns, confidentiality constraints that may impede discussing and processing the loss, colleagues’ blaming/unsupportive reactions, stigma around both suicide and professional vulnerability, and potential effects on one’s clinical work. In Part 2, I explore the opportunities for personal and professional growth that can paradoxically result from a suicide loss, guidelines for appropriate postventions and procedures that should take place after such losses, and how to best support a colleague who has lost a patient to suicide.

A chance for growth

Traumatic experiences such as a suicide loss can paradoxically present a multitude of opportunities for new growth and profound personal transformation.¹ Such transformation is primarily fostered by social support in the aftermath of the trauma.²

Virtually all of the models of the clinician’s suicide grief trajectory I described in Part 1 not only assume the eventual resolution of the distressing reactions accompanying the original loss, but also suggest that mastery of these reactions can be a catalyst for both personal and professional growth. Clearly, not everyone who experiences such a loss will experience subsequent growth; there are many reports of clinicians leaving the field³ or becoming “burned out” after this occurs. Yet most clinicians who have described this loss in the literature and in discussion groups (including those I’ve conducted) have reported more positive eventual outcomes. It is difficult to establish whether this is due to a cohort effect—clinicians who are most likely to write about their experiences, be interviewed for research studies, and/or to seek out and participate in discussion/support groups may be more prone to find benefits in this experience, either by virtue of their nature or through the subsequent process of sharing these experiences in a supportive atmosphere.

The literature on patient suicide loss, as well as anecdotal reports, confirms that clinicians who experience optimal support are able to identify many retrospective benefits of their experience.^4-6 Clinicians generally report that they are better able to identify potential risk and protective factors for suicide, and are more knowledgeable about optimal interventions with individuals who are suicidal. They also describe an increased sensitivity towards patients who are suicidal and those bereaved by suicide. In addition, clinicians report a reduction in therapeutic grandiosity/omnipotence, and more realistic appraisals and expectations in relation to their clinical competence. In their effort to understand the “whys” of their patient’s suicide, they are likely to retrospectively identify errors in treatment, “missed cues,” or things they might subsequently do differently,⁷ and to learn from these mistakes. Optimally, clinicians become more aware of their own therapeutic limitations, both in the short- and the long-term, and can use this knowledge to better determine how they will continue their clinical work. They also become much more aware of the issues involved in the aftermath of a patient suicide, including perceived gaps in the clinical and institutional systems that could optimally offer support to families and clinicians.

In addition to the positive changes related to knowledge and clinical skills, many clinicians also note deeper personal changes subsequent to their patient’s suicide, consistent with the literature on posttraumatic growth.¹ Munson⁸ explored internal changes in clinicians following a patient suicide and found that in the aftermath, clinicians experienced both posttraumatic growth and compassion fatigue. He also found that the amount of time that elapsed since the patient’s suicide predicted posttraumatic growth, and the seemingly counterintuitive result that the number of years of clinical experience prior to the suicide was negatively correlated with posttraumatic growth.

Huhra et al⁴ described some of the existential issues that a clinician is likely to confront following a patient suicide. A clinician’s attempt to find a way to meaningfully understand the circumstances around this loss often prompts reflection on mortality, freedom, choice and personal autonomy, and the scope and limits of one’s responsibility toward others. The suicide challenges one’s previous conceptions and expectations around these professional issues, and the clinician must construct new paradigms that serve to integrate these new experiences and perspectives in a coherent way.

One of the most notable sequelae of this (and to other traumatic) experience is a subsequent desire to make use of the learning inherent in these experiences and to “give back.” Once they feel that they have resolved their own grief process, many clinicians express the desire to support others with similar experiences. Even when their experiences have been quite distressing, many clinicians are able to view the suicide as an opportunity to learn about ongoing limitations in the systems of support, and to work toward changing these in a way that ensures that future clinician-survivors will have more supportive experiences. Many view these new perspectives, and their consequent ability to be more helpful, as “unexpected gifts.” They often express gratitude toward the people and resources that have allowed them to make these transformations. Jones⁵ noted “the tragedy of patient suicide can also be an opportunity for us as therapists to grow in our skills at assessing and intervening in a suicidal crisis, to broaden and deepen the support we give and receive, to grow in our appreciation of the precious gift that life is, and to help each other live it more fully.”

Continue to: Guidelines for postvention

Guidelines for postvention

When a patient suicide occurs in the context of an agency setting, Grad⁹ recommends prompt responses on 4 levels:

• administrative
• institutional
• educational
• emotional.

Numerous authors^5,10-21 have developed suggestions, guidelines, and detailed postvention protocols to help agencies and clinicians in various mental health settings navigate the often-complicated sequelae to a patient’s suicide. The Table highlights a few of these. Most emphasize that information about suicide loss, including both its statistical likelihood and its potential aftermath, should integrated into clinicians’ general education and training. They also suggest that suicide postvention policies and protocols be in place from the outset, and that such information be incorporated into institutional policy and procedure manuals. In addition, they stress that legal, institutional, and administrative needs be balanced with the emotional needs of affected clinicians and staff, as well as those of the surviving family.

Institutional and administrative procedures

The following are some of the recommended procedures that should take place following a suicide loss. The postvention protocols listed in the Table provide more detailed recommendations.

Legal/ethical. It is essential to consult with a legal representative/risk management specialist associated with the affected agency (ideally, one with specific expertise in suicide litigation.). It is also crucial to clarify who holds privilege after a patient’s death (varies by state), what may and may not be shared under the restrictions of confidentiality and Health Insurance Portability and Accountability Act (HIPAA) laws, and to clarify procedures for chart completion and review. It is also important to clarify the specific information to be shared both within and outside of the agency, and how to address the needs of current patients in the agency settings.

Case review. The optimal purpose of the case review (also known as a psychological autopsy) is to facilitate learning, identify gaps in agency procedures and training, improve pre- and postvention procedures, and help clinicians cope with the loss.²² Again, the legal and administrative needs of the agency need to be balanced with the attention to the emotional impact on the treating clinician.¹⁷ Ellis and Patel¹⁸ recommend delaying this procedure until the treating clinician is no longer in the “shock” phase of the loss, and is able to think and process events more objectively.

Continue to: Family contact

Family contact. Most authors have recommended that clinicians and/or agencies reach out to surviving families. Although some legal representatives will advise against this, experts in the field of suicide litigation have noted that compassionate family contact reduces liability and facilitates healing for both parties. In a personal communication (May 2008), Eric Harris, of the American Psychological Association Trust, recommended “compassion over caution” when considering these issues. Again, it is important to clarify who holds privilege after a patient’s death in determining when and with whom the patient’s confidential information may be shared. When confidentiality may be broken, clinical judgment should be used to determine how best to present the information to grieving family members.

Even if surviving family members do not hold privilege, there are many things that clinicians can do to be helpful.²³ Inevitably, families will want any information that will help them make sense of the loss, and general psychoeducation about mental illness and suicide can be helpful in this regard. In addition, providing information about “Survivors After Suicide” support groups, reading materials, etc., can be helpful. Both support groups and survivor-related bibliographies are available on the web sites of the American Association of Suicidology (www.suicidology.org) and The American Foundation for Suicide Prevention (www.afsp.org).

In addition, clinicians should ask the family if it would be helpful if they were to attend the funeral/memorial services, and how to introduce themselves if asked by other attendees.

Patients in clinics/hospitals. When a patient suicide occurs in a clinic or hospital setting, it is likely to impact other patients in that setting to the extent that they have heard, about the event, even from outside sources.According to Hodgkinson,²⁴ in addition to being overwhelmed with intense feelings about the suicide loss (particularly if they had known the patient), affected patients are likely to be at increased risk for suicidal behaviors. This is consistent with the considerable literature on suicide contagion.

Thus, it is important to clarify information to be shared with patients; however, avoid describing details of the method, because this can foster contagion and “copycat” suicides. In addition, Kaye and Soreff²² noted that these patients may now be concerned about the staff’s ability to be helpful to them, because they were unable to help the deceased. In light of this, take extra care to attend to the impact of the suicide on current patients, and to monitor both pre-existing and new suicidality.

Continue to: Helping affected clinicians

Suggestions for optimally supporting affected clinicians include:

• clear communication about the nature of upcoming administrative procedures (including chart and institutional reviews)
• consultation from supervisors and/or colleagues that is supportive and reassuring, rather than blaming
• opportunities for the clinician to talk openly about the experience of the loss, either individually or in group settings, without fear of judgment or censure
• recognition that the loss is likely to impact clinical work, support in monitoring this impact, and the provision of medical leaves and/or modified caseloads (ie, fewer high-risk patients) as necessary.

Box 1

Both researchers and clinician-survivors in my practice and support groups have noted that speaking with other clinicians who have experienced suicide loss can be particularly reassuring and validating. If none are available on staff, the listserve and online support groups of the American Association of Suicidology’s Clinician Survivor Task Force may be helpful (Box 1⁷). In addition, the film “Collateral Damages: The Impact of Patient Suicide on the Physician” features physicians describing their experience of losing a patient to suicide (Box 2).

Box 2

Schultz¹⁴ offered suggestions for staff in supervisory positions, noting that they may bear at least some clinical and legal responsibility for the treatments that they supervise. She encouraged supervisors to take an active stance in advocating for trainees, to encourage colleagues to express their support, and to discourage rumors and other stigmatizing reactions. Schultz also urges supervisors to¹⁴:

• allow extra time for the clinician to engage in the normative exploration of the “whys” that are unique to suicide survivors
• use education about suicide to help the clinician gain a more realistic perspective on their relative culpability
• become aware of and provide education about normative grief reactions following a suicide.

Continue to: Because a suicide loss...

Because a suicide loss is likely to affect a clinician’s subsequent clinical activity, Schultz encourages supervisors to help clinicians monitor this impact on their work.¹⁴

A supportive environment is key

Losing a patient to suicide is a complicated, potentially traumatic process that many mental health clinicians will face. Yet with comprehensive and supportive postvention policies in place, clinicians who are impacted are more likely to experience healing and posttraumatic growth in both personal and professional domains.

Bottom Line

Although often traumatic, losing a patient to suicide presents clinicians with an opportunity for personal and professional growth. Following established postvention protocols can help ensure that legal, institutional, and administrative needs are balanced with the emotional needs of affected clinicians and staff, as well as those of the surviving family.

Related Resources

• American Association of Suicidology Clinician Survivor Task Force. www.cliniciansurvivor.org.
• Dotinga R. Coping when a patient commits suicide. July 21, 2017. www.mdedge.com/psychiatry/article/142975/depression/coping-when-patient-commits-suicide.
• Gutin N. Losing a patent to suicide: What we know. Part 1. 2019;18(10):14-16,19-22,30-32.

Members of the American Academy of Dermatology have voted to remove a board member for launching an organization that offered board certification to physician assistants (PAs).

Of 6,467 votes cast, 97% favored removal of Scott M. Dinehart, MD, from his position on the American Academy of Dermatology/Association board of directors, which met the two-thirds threshold required for board removal. The vote follows a unanimous decision by the AAD/A board to present AAD members with a resolution to dismiss Dr. Dinehart for his involvement with the American Board of Dermatology Physician Assistants (ABDPA), an organization that planned to offer board certification to PAs who work with dermatologists. Dr. Dinehart’s association with the group violated his fiduciary duties to the AAD/A and represented a conflict of interest, according to the AAD/A board.

In an interview with Dermatology News, Dr. Dinehart said it was an honor and privilege to serve on the board, and that he was disappointed by those who chose to rescind his election. Most people who study the issue will realize the recent events were precipitated by a turf battle between dermatologists and dermatology PAs, he added.

“I want to emphasize my record of service to dermatology not only in Arkansas but also across the United States and internationally,” Dr. Dinehart said in the interview. “I have always been committed to doing what is best for patients and our specialty and will continue to do so. In addition to providing direct patient care, I am a tireless educator, willing to teach all health professionals whether they are medical students, physician assistants, residents, family doctors, or other physician specialists. I appreciate the opportunity I have had to serve you and look forward to continuing to express my vision for excellence in dermatology as I move forward in my career.”

In a statement to members, AAD/A Secretary Treasurer Marta Van Beek, MD, said the issue has been a difficult matter for the AAD/A to address, but that the voting results clearly represent the will of members.

“I want to thank the members for their thoughtful participation in the process and their continued engagement with the AAD/A as we return our focus to the important work that we are undertaking on behalf of our specialty and our patients,” Dr. Van Beek, professor of dermatology, University of Iowa, Iowa City, said in the statement.

The ABDPA was formed legally at the end of September and announced its official launch on Oct. 7. The new organization immediately drew criticism from dermatologists and triggered an online petition that denounced the group and called for Dr Dinehart’s removal from the AAD/A board. The petition, started by an anonymous dermatologist, states Dr. Dinehart’s concurrent relationships with the AAD and the ABDPA represent a major conflict of interest. As of Oct. 31, the petition had collected 4,200 signatures.

AAD President George J. Hruza, MD, said that Dr. Dinehart’s action to incorporate and organize the for-profit entity ABDPA LLC was in direct contradiction to the AAD’s Truth in Advertising and Professional Disclosure policy that states that practitioners should not advertise that they are board certified unless they are certified by an American Board of Medical Specialties or American Osteopathic Association medical board. The for-profit venture would enable PAs to advertise themselves as board certified, Dr. Hruza said in a previous interview with Dermatology News. He added that the group was “set up to potentially mislead patients into thinking that physician assistants with this certification would have training and experience equivalent to an ABD-certified dermatologist.

In a letter to AAD members, Dr. Dinehart however, said the ABDPA was intended to improve patient care by establishing certain educational, training, and professional standards for the growing number of PAs in dermatology. That mission was not in conflict with AAD’s values, but rather, the ABDPA would have furthered AAD’s purpose “to promote the highest standards in allied health professionals and services as they relate to dermatology,” according to Dr. Dinehart. He called the removal vote a drastic measure and contended that his actions did not justify dismissal from the AAD/A board.

After learning of the board’s concerns, Dr. Dinehart discontinued his relationship with the ABDPA and ended its operations.

Members voted on Dr. Dinehart’s position from Oct. 21 to Oct. 29. The seat vacated by the recall election will be filled through the AAD/A’s annual election, which opens Saturday, March 21, 2020, according to the AAD/A. The successful candidate will be selected to start their term immediately and fill the vacated seat until the close of the 2022 AAD/A Annual Meeting.

[email protected]

Members of the American Academy of Dermatology have voted to remove a board member for launching an organization that offered board certification to physician assistants (PAs).

Of 6,467 votes cast, 97% favored removal of Scott M. Dinehart, MD, from his position on the American Academy of Dermatology/Association board of directors, which met the two-thirds threshold required for board removal. The vote follows a unanimous decision by the AAD/A board to present AAD members with a resolution to dismiss Dr. Dinehart for his involvement with the American Board of Dermatology Physician Assistants (ABDPA), an organization that planned to offer board certification to PAs who work with dermatologists. Dr. Dinehart’s association with the group violated his fiduciary duties to the AAD/A and represented a conflict of interest, according to the AAD/A board.

In an interview with Dermatology News, Dr. Dinehart said it was an honor and privilege to serve on the board, and that he was disappointed by those who chose to rescind his election. Most people who study the issue will realize the recent events were precipitated by a turf battle between dermatologists and dermatology PAs, he added.

“I want to emphasize my record of service to dermatology not only in Arkansas but also across the United States and internationally,” Dr. Dinehart said in the interview. “I have always been committed to doing what is best for patients and our specialty and will continue to do so. In addition to providing direct patient care, I am a tireless educator, willing to teach all health professionals whether they are medical students, physician assistants, residents, family doctors, or other physician specialists. I appreciate the opportunity I have had to serve you and look forward to continuing to express my vision for excellence in dermatology as I move forward in my career.”

In a statement to members, AAD/A Secretary Treasurer Marta Van Beek, MD, said the issue has been a difficult matter for the AAD/A to address, but that the voting results clearly represent the will of members.

“I want to thank the members for their thoughtful participation in the process and their continued engagement with the AAD/A as we return our focus to the important work that we are undertaking on behalf of our specialty and our patients,” Dr. Van Beek, professor of dermatology, University of Iowa, Iowa City, said in the statement.

The ABDPA was formed legally at the end of September and announced its official launch on Oct. 7. The new organization immediately drew criticism from dermatologists and triggered an online petition that denounced the group and called for Dr Dinehart’s removal from the AAD/A board. The petition, started by an anonymous dermatologist, states Dr. Dinehart’s concurrent relationships with the AAD and the ABDPA represent a major conflict of interest. As of Oct. 31, the petition had collected 4,200 signatures.

AAD President George J. Hruza, MD, said that Dr. Dinehart’s action to incorporate and organize the for-profit entity ABDPA LLC was in direct contradiction to the AAD’s Truth in Advertising and Professional Disclosure policy that states that practitioners should not advertise that they are board certified unless they are certified by an American Board of Medical Specialties or American Osteopathic Association medical board. The for-profit venture would enable PAs to advertise themselves as board certified, Dr. Hruza said in a previous interview with Dermatology News. He added that the group was “set up to potentially mislead patients into thinking that physician assistants with this certification would have training and experience equivalent to an ABD-certified dermatologist.

In a letter to AAD members, Dr. Dinehart however, said the ABDPA was intended to improve patient care by establishing certain educational, training, and professional standards for the growing number of PAs in dermatology. That mission was not in conflict with AAD’s values, but rather, the ABDPA would have furthered AAD’s purpose “to promote the highest standards in allied health professionals and services as they relate to dermatology,” according to Dr. Dinehart. He called the removal vote a drastic measure and contended that his actions did not justify dismissal from the AAD/A board.

After learning of the board’s concerns, Dr. Dinehart discontinued his relationship with the ABDPA and ended its operations.

Members voted on Dr. Dinehart’s position from Oct. 21 to Oct. 29. The seat vacated by the recall election will be filled through the AAD/A’s annual election, which opens Saturday, March 21, 2020, according to the AAD/A. The successful candidate will be selected to start their term immediately and fill the vacated seat until the close of the 2022 AAD/A Annual Meeting.

[email protected]

Members of the American Academy of Dermatology have voted to remove a board member for launching an organization that offered board certification to physician assistants (PAs).

Of 6,467 votes cast, 97% favored removal of Scott M. Dinehart, MD, from his position on the American Academy of Dermatology/Association board of directors, which met the two-thirds threshold required for board removal. The vote follows a unanimous decision by the AAD/A board to present AAD members with a resolution to dismiss Dr. Dinehart for his involvement with the American Board of Dermatology Physician Assistants (ABDPA), an organization that planned to offer board certification to PAs who work with dermatologists. Dr. Dinehart’s association with the group violated his fiduciary duties to the AAD/A and represented a conflict of interest, according to the AAD/A board.

In an interview with Dermatology News, Dr. Dinehart said it was an honor and privilege to serve on the board, and that he was disappointed by those who chose to rescind his election. Most people who study the issue will realize the recent events were precipitated by a turf battle between dermatologists and dermatology PAs, he added.

“I want to emphasize my record of service to dermatology not only in Arkansas but also across the United States and internationally,” Dr. Dinehart said in the interview. “I have always been committed to doing what is best for patients and our specialty and will continue to do so. In addition to providing direct patient care, I am a tireless educator, willing to teach all health professionals whether they are medical students, physician assistants, residents, family doctors, or other physician specialists. I appreciate the opportunity I have had to serve you and look forward to continuing to express my vision for excellence in dermatology as I move forward in my career.”

In a statement to members, AAD/A Secretary Treasurer Marta Van Beek, MD, said the issue has been a difficult matter for the AAD/A to address, but that the voting results clearly represent the will of members.

“I want to thank the members for their thoughtful participation in the process and their continued engagement with the AAD/A as we return our focus to the important work that we are undertaking on behalf of our specialty and our patients,” Dr. Van Beek, professor of dermatology, University of Iowa, Iowa City, said in the statement.

The ABDPA was formed legally at the end of September and announced its official launch on Oct. 7. The new organization immediately drew criticism from dermatologists and triggered an online petition that denounced the group and called for Dr Dinehart’s removal from the AAD/A board. The petition, started by an anonymous dermatologist, states Dr. Dinehart’s concurrent relationships with the AAD and the ABDPA represent a major conflict of interest. As of Oct. 31, the petition had collected 4,200 signatures.

AAD President George J. Hruza, MD, said that Dr. Dinehart’s action to incorporate and organize the for-profit entity ABDPA LLC was in direct contradiction to the AAD’s Truth in Advertising and Professional Disclosure policy that states that practitioners should not advertise that they are board certified unless they are certified by an American Board of Medical Specialties or American Osteopathic Association medical board. The for-profit venture would enable PAs to advertise themselves as board certified, Dr. Hruza said in a previous interview with Dermatology News. He added that the group was “set up to potentially mislead patients into thinking that physician assistants with this certification would have training and experience equivalent to an ABD-certified dermatologist.

In a letter to AAD members, Dr. Dinehart however, said the ABDPA was intended to improve patient care by establishing certain educational, training, and professional standards for the growing number of PAs in dermatology. That mission was not in conflict with AAD’s values, but rather, the ABDPA would have furthered AAD’s purpose “to promote the highest standards in allied health professionals and services as they relate to dermatology,” according to Dr. Dinehart. He called the removal vote a drastic measure and contended that his actions did not justify dismissal from the AAD/A board.

After learning of the board’s concerns, Dr. Dinehart discontinued his relationship with the ABDPA and ended its operations.

Members voted on Dr. Dinehart’s position from Oct. 21 to Oct. 29. The seat vacated by the recall election will be filled through the AAD/A’s annual election, which opens Saturday, March 21, 2020, according to the AAD/A. The successful candidate will be selected to start their term immediately and fill the vacated seat until the close of the 2022 AAD/A Annual Meeting.

[email protected]

Reinforcing previous findings, a new study has determined that the next-generation corrector elexacaftor, in combination with tezacaftor and ivacaftor, can effectively treat patients with Phe508del-minimal function genotypes who did not respond to previous cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimens.

“These results provide evidence that elexacaftor-tezacaftor-ivacaftor can modulate a single Phe508del allele in people with cystic fibrosis, thus addressing the underlying cause of disease in the large majority of patients,” wrote Peter G. Middleton, PhD, of the University of Sydney (Australia) and his coauthors. The study was published in the New England Journal of Medicine.

To further determine if the elexacaftor-tezacaftor-ivacaftor regimen was effective and safe, the researchers launched a randomized, placebo-controlled phase 3 trial of 403 cystic fibrosis patients age 12 or older who had a single Phe508del allele. Patients in the combination group (n = 200) received 200 mg of elexacaftor once daily, 100 mg of tezacaftor once daily, and 150 mg of ivacaftor every 12 hours for 24 weeks. Patients in the other group (n = 203) received matched placebos.

At 14 weeks, patients in the combination group had a change in percentage of predicted forced expiratory volume in 1 second (FEV₁) that was 13.8 points higher than the placebo group (95% confidence interval, 12.1-15.4, P less than .001). At 24 weeks, the combination group had a predicted FEV₁ difference that was 14.3 percentage points higher (95% confidence interval, 12.7-15.8, P less than .001). The rate of pulmonary exacerbations was 63% lower (rate ratio 0.37; 95% CI, 0.25-0.55, P less than .001) and sweat chloride concentration was 41.8 mmol/L lower (95% CI, –44.4 to –39.3, P less than .001) in the combination group through 24 weeks.

At least one adverse event occurred in 93.1% of patients in the combination group and 96% of patients in the placebo group. Serious adverse events occurred in 28 patients (13.9%) in the combination group and 42 patients (20.9%) in the placebo group. There were no deaths in either group.

The study was funded by Vertex Pharmaceuticals. The authors had disclosures, including receiving personal fees and grants from various pharmaceutical companies and being on the advisory board, owning stock, or being an employee of Vertex Pharmaceuticals.

SOURCE: Middleton PG et al. 2019 Oct 31. N Engl J Med. doi: 10.1056/NEJMoa1908639.

Reinforcing previous findings, a new study has determined that the next-generation corrector elexacaftor, in combination with tezacaftor and ivacaftor, can effectively treat patients with Phe508del-minimal function genotypes who did not respond to previous cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimens.

“These results provide evidence that elexacaftor-tezacaftor-ivacaftor can modulate a single Phe508del allele in people with cystic fibrosis, thus addressing the underlying cause of disease in the large majority of patients,” wrote Peter G. Middleton, PhD, of the University of Sydney (Australia) and his coauthors. The study was published in the New England Journal of Medicine.

To further determine if the elexacaftor-tezacaftor-ivacaftor regimen was effective and safe, the researchers launched a randomized, placebo-controlled phase 3 trial of 403 cystic fibrosis patients age 12 or older who had a single Phe508del allele. Patients in the combination group (n = 200) received 200 mg of elexacaftor once daily, 100 mg of tezacaftor once daily, and 150 mg of ivacaftor every 12 hours for 24 weeks. Patients in the other group (n = 203) received matched placebos.

At 14 weeks, patients in the combination group had a change in percentage of predicted forced expiratory volume in 1 second (FEV₁) that was 13.8 points higher than the placebo group (95% confidence interval, 12.1-15.4, P less than .001). At 24 weeks, the combination group had a predicted FEV₁ difference that was 14.3 percentage points higher (95% confidence interval, 12.7-15.8, P less than .001). The rate of pulmonary exacerbations was 63% lower (rate ratio 0.37; 95% CI, 0.25-0.55, P less than .001) and sweat chloride concentration was 41.8 mmol/L lower (95% CI, –44.4 to –39.3, P less than .001) in the combination group through 24 weeks.

At least one adverse event occurred in 93.1% of patients in the combination group and 96% of patients in the placebo group. Serious adverse events occurred in 28 patients (13.9%) in the combination group and 42 patients (20.9%) in the placebo group. There were no deaths in either group.

The study was funded by Vertex Pharmaceuticals. The authors had disclosures, including receiving personal fees and grants from various pharmaceutical companies and being on the advisory board, owning stock, or being an employee of Vertex Pharmaceuticals.

SOURCE: Middleton PG et al. 2019 Oct 31. N Engl J Med. doi: 10.1056/NEJMoa1908639.

Reinforcing previous findings, a new study has determined that the next-generation corrector elexacaftor, in combination with tezacaftor and ivacaftor, can effectively treat patients with Phe508del-minimal function genotypes who did not respond to previous cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimens.

“These results provide evidence that elexacaftor-tezacaftor-ivacaftor can modulate a single Phe508del allele in people with cystic fibrosis, thus addressing the underlying cause of disease in the large majority of patients,” wrote Peter G. Middleton, PhD, of the University of Sydney (Australia) and his coauthors. The study was published in the New England Journal of Medicine.

To further determine if the elexacaftor-tezacaftor-ivacaftor regimen was effective and safe, the researchers launched a randomized, placebo-controlled phase 3 trial of 403 cystic fibrosis patients age 12 or older who had a single Phe508del allele. Patients in the combination group (n = 200) received 200 mg of elexacaftor once daily, 100 mg of tezacaftor once daily, and 150 mg of ivacaftor every 12 hours for 24 weeks. Patients in the other group (n = 203) received matched placebos.

At 14 weeks, patients in the combination group had a change in percentage of predicted forced expiratory volume in 1 second (FEV₁) that was 13.8 points higher than the placebo group (95% confidence interval, 12.1-15.4, P less than .001). At 24 weeks, the combination group had a predicted FEV₁ difference that was 14.3 percentage points higher (95% confidence interval, 12.7-15.8, P less than .001). The rate of pulmonary exacerbations was 63% lower (rate ratio 0.37; 95% CI, 0.25-0.55, P less than .001) and sweat chloride concentration was 41.8 mmol/L lower (95% CI, –44.4 to –39.3, P less than .001) in the combination group through 24 weeks.

At least one adverse event occurred in 93.1% of patients in the combination group and 96% of patients in the placebo group. Serious adverse events occurred in 28 patients (13.9%) in the combination group and 42 patients (20.9%) in the placebo group. There were no deaths in either group.

The study was funded by Vertex Pharmaceuticals. The authors had disclosures, including receiving personal fees and grants from various pharmaceutical companies and being on the advisory board, owning stock, or being an employee of Vertex Pharmaceuticals.

SOURCE: Middleton PG et al. 2019 Oct 31. N Engl J Med. doi: 10.1056/NEJMoa1908639.

NATIONAL HARBOR, MD. – Paying for value over volume is being seen as a key part of driving down the cost of prescription drugs. But setting up value-based contracts can be a challenge.

Gregory Twachtman/MDedge News

“In Utah, we thought we would be an appropriate laboratory to try and figure out, ‘Is there a way that we can do this different?’ ” Diana Brixner, PhD, of the University of Utah, Salt Lake City, said at the annual meeting of the Academy of Managed Care Pharmacy. “How can we be creative and have alternatives to high-deductible plans in Utah through value-based–type programs?”

The state considered three different options, she noted. The first option was value-based drug coverage, which pays for only those drugs that are deemed valuable by an independent source. Uptake on these types of contracts has been slow, Dr. Brixner noted, particularly as patient advocates have argued that some drugs may not be cost effective but are still the best choice for certain patients. In those cases, value-based drug coverage has the potential to hinder access.

“There are certainly still different areas and issues that need to be worked out, but in concept, this could potentially help the solution of getting more affordable care to patients,” Dr. Brixner said.

The second option is outcomes-based contracting, which involves working with manufacturers to determine appropriate disease states with vetted outcomes measures and building pharmacy contracts around them.

“We are very optimistic about the potential for outcomes-based contracting as well,” Dr. Brixner said.

CVS has looked into zero copays for preventive medicines, Dr. Brixner said. She added that studies have shown the potential for millions in savings from these kinds of arrangements.

But there are concerns with all of these designs. Drug manufacturers, for instance, have concerns about getting accurate data to determine the payment parameters. Another concern from the manufacturer side is the inability to discuss information about off-label drug use that could be important to negotiating a value-based contract.

For payers, a key concern is making sure there are measurable outcomes, as well as appropriate risk sharing.

In the end, different conditions lend themselves to different types of value-based contracting, Dr. Brixner said. For example, multiple sclerosis is better suited to a value-based drug coverage contract, while rheumatoid arthritis fits better in an outcomes-based contracting design.

Gregory Twachtman/MDedge News

Kenneth Schaecher, MD, associate chief medical officer of the University of Utah Health Plan, highlighted some of the challenges of value-based care from a payer perspective, including determining outcomes to use in contracts.

“One of the challenges that we get is trying to decide what is a measure that is important to both the health plans and the patients and the providers,” he said. “If the measure is not reflective of an outcome relative to those, it is going to be very hard to impact it” through a value-based contract. He noted that patient-reported outcomes do not work well in value-based contracts.

The timeliness of the data can also present a challenge, especially when factoring in member turnover from health plans.

But there are examples of success, he noted. Dr. Schaecher highlighted a few examples, including an outcomes-based contract between Cigna and Merck for Januvia and Janumet, which included higher discounts for improvements in hemoglobin A_1c across the insured population. Additional discounts were offered if adherence improved. And if both outcomes and adherence improved, Cigna would move the drugs to formulary tiers with lower copays.

[email protected]

NATIONAL HARBOR, MD. – Paying for value over volume is being seen as a key part of driving down the cost of prescription drugs. But setting up value-based contracts can be a challenge.

Gregory Twachtman/MDedge News

“In Utah, we thought we would be an appropriate laboratory to try and figure out, ‘Is there a way that we can do this different?’ ” Diana Brixner, PhD, of the University of Utah, Salt Lake City, said at the annual meeting of the Academy of Managed Care Pharmacy. “How can we be creative and have alternatives to high-deductible plans in Utah through value-based–type programs?”

The state considered three different options, she noted. The first option was value-based drug coverage, which pays for only those drugs that are deemed valuable by an independent source. Uptake on these types of contracts has been slow, Dr. Brixner noted, particularly as patient advocates have argued that some drugs may not be cost effective but are still the best choice for certain patients. In those cases, value-based drug coverage has the potential to hinder access.

“There are certainly still different areas and issues that need to be worked out, but in concept, this could potentially help the solution of getting more affordable care to patients,” Dr. Brixner said.

The second option is outcomes-based contracting, which involves working with manufacturers to determine appropriate disease states with vetted outcomes measures and building pharmacy contracts around them.

“We are very optimistic about the potential for outcomes-based contracting as well,” Dr. Brixner said.

CVS has looked into zero copays for preventive medicines, Dr. Brixner said. She added that studies have shown the potential for millions in savings from these kinds of arrangements.

But there are concerns with all of these designs. Drug manufacturers, for instance, have concerns about getting accurate data to determine the payment parameters. Another concern from the manufacturer side is the inability to discuss information about off-label drug use that could be important to negotiating a value-based contract.

For payers, a key concern is making sure there are measurable outcomes, as well as appropriate risk sharing.

In the end, different conditions lend themselves to different types of value-based contracting, Dr. Brixner said. For example, multiple sclerosis is better suited to a value-based drug coverage contract, while rheumatoid arthritis fits better in an outcomes-based contracting design.

Gregory Twachtman/MDedge News

Kenneth Schaecher, MD, associate chief medical officer of the University of Utah Health Plan, highlighted some of the challenges of value-based care from a payer perspective, including determining outcomes to use in contracts.

“One of the challenges that we get is trying to decide what is a measure that is important to both the health plans and the patients and the providers,” he said. “If the measure is not reflective of an outcome relative to those, it is going to be very hard to impact it” through a value-based contract. He noted that patient-reported outcomes do not work well in value-based contracts.

The timeliness of the data can also present a challenge, especially when factoring in member turnover from health plans.

But there are examples of success, he noted. Dr. Schaecher highlighted a few examples, including an outcomes-based contract between Cigna and Merck for Januvia and Janumet, which included higher discounts for improvements in hemoglobin A_1c across the insured population. Additional discounts were offered if adherence improved. And if both outcomes and adherence improved, Cigna would move the drugs to formulary tiers with lower copays.

[email protected]

NATIONAL HARBOR, MD. – Paying for value over volume is being seen as a key part of driving down the cost of prescription drugs. But setting up value-based contracts can be a challenge.

Gregory Twachtman/MDedge News

“In Utah, we thought we would be an appropriate laboratory to try and figure out, ‘Is there a way that we can do this different?’ ” Diana Brixner, PhD, of the University of Utah, Salt Lake City, said at the annual meeting of the Academy of Managed Care Pharmacy. “How can we be creative and have alternatives to high-deductible plans in Utah through value-based–type programs?”

The state considered three different options, she noted. The first option was value-based drug coverage, which pays for only those drugs that are deemed valuable by an independent source. Uptake on these types of contracts has been slow, Dr. Brixner noted, particularly as patient advocates have argued that some drugs may not be cost effective but are still the best choice for certain patients. In those cases, value-based drug coverage has the potential to hinder access.

“There are certainly still different areas and issues that need to be worked out, but in concept, this could potentially help the solution of getting more affordable care to patients,” Dr. Brixner said.

The second option is outcomes-based contracting, which involves working with manufacturers to determine appropriate disease states with vetted outcomes measures and building pharmacy contracts around them.

“We are very optimistic about the potential for outcomes-based contracting as well,” Dr. Brixner said.

CVS has looked into zero copays for preventive medicines, Dr. Brixner said. She added that studies have shown the potential for millions in savings from these kinds of arrangements.

But there are concerns with all of these designs. Drug manufacturers, for instance, have concerns about getting accurate data to determine the payment parameters. Another concern from the manufacturer side is the inability to discuss information about off-label drug use that could be important to negotiating a value-based contract.

For payers, a key concern is making sure there are measurable outcomes, as well as appropriate risk sharing.

In the end, different conditions lend themselves to different types of value-based contracting, Dr. Brixner said. For example, multiple sclerosis is better suited to a value-based drug coverage contract, while rheumatoid arthritis fits better in an outcomes-based contracting design.

Gregory Twachtman/MDedge News

Kenneth Schaecher, MD, associate chief medical officer of the University of Utah Health Plan, highlighted some of the challenges of value-based care from a payer perspective, including determining outcomes to use in contracts.

“One of the challenges that we get is trying to decide what is a measure that is important to both the health plans and the patients and the providers,” he said. “If the measure is not reflective of an outcome relative to those, it is going to be very hard to impact it” through a value-based contract. He noted that patient-reported outcomes do not work well in value-based contracts.

The timeliness of the data can also present a challenge, especially when factoring in member turnover from health plans.

But there are examples of success, he noted. Dr. Schaecher highlighted a few examples, including an outcomes-based contract between Cigna and Merck for Januvia and Janumet, which included higher discounts for improvements in hemoglobin A_1c across the insured population. Additional discounts were offered if adherence improved. And if both outcomes and adherence improved, Cigna would move the drugs to formulary tiers with lower copays.

[email protected]

NATIONAL HARBOR, MD. – Nebulous pricing associated with prior authorization continues to be a major pain point for health care professionals, but this may become a thing of the past – thanks to a technology called real-time pharmacy benefit.

Real-time pharmacy benefits (RTPB) is software or a software component that allows practicing clinicians to look up a patient’s out-of-pocket costs for a specific drug, regardless of the patient’s health insurance coverage. Users can see the costs, copayment, and deductible for branded and generic, as well as compare insurance costs versus cash pricing.

Lindsey Colbert, RN, program manager for care team efficiency at HealthPartners, and Leann McDowell, PharmD, supervisor, pharmacy utilization management at HealthPartners, investigated how integrating RTPB software into their existing platforms and operations could help address pricing nuances and their associated burden on patients and health care professionals. They presented the results of their pilot test and post–pilot test expansion at the annual meeting of the Academy of Managed Care Pharmacy.

“Historically, clinicians were told not to quote prices, because having numerous insurance plans made it difficult to know what was going to be covered,” Ms. Colbert said. “Now, with real-time benefits, clinicians have pricing information readily available to them.”

HealthPartners pilot-tested RTPB at two locations before expanding to additional sites. They found that integrating real-time pharmacy benefits information improved the user experience and added cost savings for patients while improving workflow efficiency.

Health care professionals were more like to use RTPB for inquiries when the perceived patient cost was $50 or more – a price many clinicians perceive to be too expensive for many patients.

Before RTPB implementation, participating health care professionals reported waiting at least 45 minutes to get pricing on drugs requiring prior authorization. Integrating the RTPB software shaved the wait time down to 4 minutes – allowing them to quote drug prices to patients at the point of service.

Despite the benefits, everyone is not on board with RTPB.

Health care professionals already feel burdened by the information requirements of their electronic health records systems. They “count the number of computer clicks they have to make, so getting them to make an additional click to use RTPB requires another buy-in,” Ms. Colbert said.

While participating health care professionals were asked to run every prescription through RTPB, they reported using the software only when they knew a patient would either perceive cost as a potential barrier, or if they knew a drug would be expensive.

Investigators said they plan to continue working with clinicians to make RTPB integration more user-friendly by eventually eliminating the additional computer click required to run the program. They also plan to monitor the progress of the National Council for Prescription Drug Programs – developer of RTPB – regarding its adaptation of its new standard.

NATIONAL HARBOR, MD. – Nebulous pricing associated with prior authorization continues to be a major pain point for health care professionals, but this may become a thing of the past – thanks to a technology called real-time pharmacy benefit.

Real-time pharmacy benefits (RTPB) is software or a software component that allows practicing clinicians to look up a patient’s out-of-pocket costs for a specific drug, regardless of the patient’s health insurance coverage. Users can see the costs, copayment, and deductible for branded and generic, as well as compare insurance costs versus cash pricing.

Lindsey Colbert, RN, program manager for care team efficiency at HealthPartners, and Leann McDowell, PharmD, supervisor, pharmacy utilization management at HealthPartners, investigated how integrating RTPB software into their existing platforms and operations could help address pricing nuances and their associated burden on patients and health care professionals. They presented the results of their pilot test and post–pilot test expansion at the annual meeting of the Academy of Managed Care Pharmacy.

“Historically, clinicians were told not to quote prices, because having numerous insurance plans made it difficult to know what was going to be covered,” Ms. Colbert said. “Now, with real-time benefits, clinicians have pricing information readily available to them.”

HealthPartners pilot-tested RTPB at two locations before expanding to additional sites. They found that integrating real-time pharmacy benefits information improved the user experience and added cost savings for patients while improving workflow efficiency.

Health care professionals were more like to use RTPB for inquiries when the perceived patient cost was $50 or more – a price many clinicians perceive to be too expensive for many patients.

Before RTPB implementation, participating health care professionals reported waiting at least 45 minutes to get pricing on drugs requiring prior authorization. Integrating the RTPB software shaved the wait time down to 4 minutes – allowing them to quote drug prices to patients at the point of service.

Despite the benefits, everyone is not on board with RTPB.

Health care professionals already feel burdened by the information requirements of their electronic health records systems. They “count the number of computer clicks they have to make, so getting them to make an additional click to use RTPB requires another buy-in,” Ms. Colbert said.

While participating health care professionals were asked to run every prescription through RTPB, they reported using the software only when they knew a patient would either perceive cost as a potential barrier, or if they knew a drug would be expensive.

Investigators said they plan to continue working with clinicians to make RTPB integration more user-friendly by eventually eliminating the additional computer click required to run the program. They also plan to monitor the progress of the National Council for Prescription Drug Programs – developer of RTPB – regarding its adaptation of its new standard.

NATIONAL HARBOR, MD. – Nebulous pricing associated with prior authorization continues to be a major pain point for health care professionals, but this may become a thing of the past – thanks to a technology called real-time pharmacy benefit.

Real-time pharmacy benefits (RTPB) is software or a software component that allows practicing clinicians to look up a patient’s out-of-pocket costs for a specific drug, regardless of the patient’s health insurance coverage. Users can see the costs, copayment, and deductible for branded and generic, as well as compare insurance costs versus cash pricing.

Lindsey Colbert, RN, program manager for care team efficiency at HealthPartners, and Leann McDowell, PharmD, supervisor, pharmacy utilization management at HealthPartners, investigated how integrating RTPB software into their existing platforms and operations could help address pricing nuances and their associated burden on patients and health care professionals. They presented the results of their pilot test and post–pilot test expansion at the annual meeting of the Academy of Managed Care Pharmacy.

“Historically, clinicians were told not to quote prices, because having numerous insurance plans made it difficult to know what was going to be covered,” Ms. Colbert said. “Now, with real-time benefits, clinicians have pricing information readily available to them.”

HealthPartners pilot-tested RTPB at two locations before expanding to additional sites. They found that integrating real-time pharmacy benefits information improved the user experience and added cost savings for patients while improving workflow efficiency.

Health care professionals were more like to use RTPB for inquiries when the perceived patient cost was $50 or more – a price many clinicians perceive to be too expensive for many patients.

Before RTPB implementation, participating health care professionals reported waiting at least 45 minutes to get pricing on drugs requiring prior authorization. Integrating the RTPB software shaved the wait time down to 4 minutes – allowing them to quote drug prices to patients at the point of service.

Despite the benefits, everyone is not on board with RTPB.

Health care professionals already feel burdened by the information requirements of their electronic health records systems. They “count the number of computer clicks they have to make, so getting them to make an additional click to use RTPB requires another buy-in,” Ms. Colbert said.

While participating health care professionals were asked to run every prescription through RTPB, they reported using the software only when they knew a patient would either perceive cost as a potential barrier, or if they knew a drug would be expensive.

Investigators said they plan to continue working with clinicians to make RTPB integration more user-friendly by eventually eliminating the additional computer click required to run the program. They also plan to monitor the progress of the National Council for Prescription Drug Programs – developer of RTPB – regarding its adaptation of its new standard.

BARCELONA – Programmed death-ligand 1 (PD-L1) status in patients with advanced triple negative or HER2-positive breast cancer appears to identify distinct disease entities with varying likelihood of benefit from immune checkpoint inhibition, according to Giampaolo Bianchini, MD.

This observation, which contrasts with findings in other solid tumors and expands the road map to improved outcomes with immunotherapy for metastatic breast cancer, is based in part on new findings presented at the European Society for Medical Oncology Congress.

Among additional lessons from those findings: PD-L1 assays are not easily interchangeable, and studies with a “one size fits all” approach should be avoided, Dr. Bianchini, head of the Breast Cancer Group – Medical Oncology and clinical translational and immunotherapy research at Ospedale San Raffaele, Milan, said at the congress.
 

IMPassion130 and PD-L1 assays

In the phase 3 IMpassion130 trial assessing nanoparticle, albumin-bound (nab)-paclitaxel chemotherapy + either the anti-PD-L1 monoclonal antibody atezolizumab or placebo for the first-line treatment of metastatic triple-negative breast cancer (mTNBC), investigators used, and validated, the VENTANA PD-L1 SP142 assay to evaluate PD-L1 expression in immune cells (IC). PD-L1 positivity was defined using a 1% cutoff, meaning that PD-L1-stained IC encompassed at least 1% of the tumor area.

The trial demonstrated significantly improved progression-free survival (PFS) in the atezolizumab arm, both in the intention-to-treat (ITT) analysis (7.2 vs. 5.5 months in the placebo arm; hazard ratio, 0.80), and the PD-L1-positive subgroup (7.5 vs. 5.0 months; HR, 0.62), and the results were published in November 2018 (N Engl J Med. 2018; 379:2108-21).

“IMpassion130 is the first phase 3 trial demonstrating clinical benefit of cancer immunotherapy in patients with PD-L1-positive, metastatic triple-negative breast cancer,” Hope S. Rugo, MD, said at the congress. “The combination of atezolizumab and nab-paclitaxel is now approved in the United States and Europe for this indication.”

Subgroup analyses indicated that PFS and OS benefit with atezolizumab + nab-paclitaxel vs. nab-paclitaxel alone was greater in double-positive patients (those with SP142 positivity and either SP263 or 22C3 positivity) than in patients who were SP263-positive/SP142-negative or 22C3-positive/SP142-negative.

Dr. Rugo and her colleagues also found that the benefits with atezolizumab + nab-paclitaxel in PD-L1-positive patients were apparent regardless of the source of tissue for testing (breast or distant metastases).

They concluded that the findings of the assays are not equivalent; 22C3 and SP263 identified more patients as PD-L1 positive, and SP142-positivity was encompassed in positive tests for both.

“The clinical benefit in the 22C3-positive and the SP263-positive subgroups appear to be driven by the SP142-positive subgroup, and [SP142] identifies patients with the longest median progression-free and overall survival from the addition of atezolizumab to nab-paclitaxel,” she said “The SP142 assay with an IC cutoff of 1% or greater is the approved diagnostic test used to identify patients with metastatic triple-negative breast cancer who are most likely to benefit from the addition of the checkpoint inhibitor atezolizumab to nab-paclitaxel.”

As for whether the SP142 should be the assay of choice in other settings in which it hasn’t been validated, Dr. Rugo said it is advisable to use the assay that has been validated in a positive trial.

“That’s what we would generally do ... however, recognizing that some countries are not using SP142, and some sites may not have access, certainly you encompass that population in the patients whose tumors are positive by both other assays,” she said. “The risk is that you might overtreat, and the cost of treatment is greater.”

Excess toxicity is also a concern in that situation, she said, adding that “hopefully in the future we’ll be able to figure out ways to have even more patients benefit from the addition of immunotherapy so that won’t be an issue.”

“What this data shows is that you can feel secure that you are encompassing the patient population identified by the parent trial to benefit from the addition of atezolizumab by using either of the other two assays; you’re only missing 1% – so that’s very reasonable,” she said. “The risk is that you’re overtreating; it’s quite likely that there’s a population there that isn’t benefiting as much, but that’s a balance.”

The findings from IMPassion130 with regard to OS in the unselected population that included PD-L1-negative patients (18.7 vs. 21.0 months with vs. without atezolizumab; HR, 0.86) underscore the fact that “one size does not fit all” when it comes to immunotherapy benefit, Dr. Bianchini said.

This is further demonstrated by the post hoc analysis comparing IHC assays, he said, explaining that 63% of IMPassion130 patients who were considered PD-L1-negative based on the SP142 “actually scored as PD-L1-positive by the other tests.

“So the very clinically important question is if there is any evidence from the data that [the PD-L1-negative group] benefits in a significant way from the addition of atezolizumab,” he said. “I don’t see evidence for a clinical benefit, I see evidence to look for new biomarkers to identify a potential population who will benefit.”

The “absence of evidence is not evidence of absence,” he stressed, noting that it may be possible – with the right biomarkers – to identify PD-L1-negative patients who would benefit.

What the findings do show, however, is support for the FDA decision to approve the SP142 assay with an IC cutoff of 1% as a companion diagnostic tool, and that PD-L1 is ideally assessed using samples from both the primary and metastatic site, as the IMPassion130 data “do not inform whether PD-L1 assessment in primary and metastatic sites is equally informative,” he said.

In addition, Dr. Bianchini said the findings suggest that more information is needed about using different cutoffs for SP263 and 22C3, and he cautioned against “directly translating these finding to other disease settings or immune combinations.

“Defining new biomarkers to identify who within the PD-L1-negative group might benefit from this combination remains an unmet need,” he said. “For sure, I don’t see a space for the other tests to define this population,” he added.

KEYNOTE-119, KATE2, and future directions

Both the randomized, open-label, phase 3 KEYNOTE-119 study of the checkpoint inhibitor pembrolizumab vs. single-agent chemotherapy for mTNBC, and the phase 2 KATE2 trial of the antibody-drug conjugate trastuzumab emtansine (T-DM1) + either atezolizumab or placebo in previously treated HER2-positive breast cancer patients, failed to meet their respective primary study endpoints.

But the news isn’t all bad, Dr. Bianchini said.

For example, in KEYNOTE-119, second- or third-line pembrolizumab monotherapy did not significantly improve OS vs. chemotherapy for mTNBC, but the pembrolizumab treatment effect increased as PD-L1 enrichment increased, he explained.

Pembrolizumab showed promising antitumor activity and manageable safety in mTNBC in prior trials, and was therefore further assessed in the KEYNOTE-119 study of 601 patients with centrally confirmed TNBC, 1-2 prior systemic treatments for mTNBC, progression on the latest therapy, and a prior anthracycline or taxane, Javier Cortés, MD, PhD, of Instituto Oncológico, Madrid, reported at the congress.

Sharon Worcester/MDedge News

Pembrolizumab was given at a dose of 200 mg every 3 weeks, and chemotherapy was physician’s choice of capecitabine, eribulin, gemcitabine, or vinorelbine.

At a median follow-up of 9.9 months in the pembrolizumab group and 10.9 months in the chemotherapy group, OS did not differ significantly between the groups; this was true overall, in patients with a CPS of 10 or greater, and in those with a CPS of 1 or greater.

In all-comers, the HR for OS was 0.97, compared with 0.78 in patients with CPS of 10 or greater, and 0.86 in those with CPS of 1 or greater, Dr. Cortés said.

“One of the most interesting exploratory analyses was OS in those patients with CPS of 20 or higher,” he said, noting that median OS in that group was 14.9 vs.12.5 months with pembrolizumab vs. with chemotherapy (HR, 0.58).

Pembrolizumab did not improve overall PFS, but again, the rates improved with higher CPS. Duration of response, however, was longer with pembrolizumab vs. chemotherapy (12.2 vs. 8.3 months overall; 12.2 vs. 6.5 months for CPS of 1 or greater; and not reached vs. 7.1 months for CPS of 10 or greater).

Grade 3-5 AEs occurred in 35% vs. 49% of patients in the pembrolizumab vs. chemotherapy groups, with nine deaths occurring in each, Dr. Cortés said, adding that treatment-related AEs occurred in 14% (with one death) and 36% (with two deaths), respectively, and grade 3-4 immune-mediated AEs and infusion reactions occurred in 3.2% vs. 1.0% (no deaths), respectively.

In the double-blind, signal-seeking KATE2 trial, as reported in 2018 at the San Antonio Breast Cancer Symposium, no overall PFS improvement was seen with atezolizumab + T-DM1 (median of 8.2 vs. 6.8 months; HR, 0.82; 12-month PFS 38% vs. 34%), but again, a possible benefit was seen in PD-L1-positive patients (8.5 vs. 4.1 months; HR, 0.60).

KATE2 included 202 patients with advanced HER2-positive breast cancer that progressed after treatment with T-DM1 and a taxane. They were randomized 2:1 to receive intravenous T-DM1 at a dose of 3.6 mg/kg plus atezolizumab (1,200 mg) or placebo every 3 weeks until loss of clinical benefit or intolerable toxicity.

The “overall survival and final safety results” show that at a median follow-up of 19.0 months in the atezolizumab arm and 18.2 months in the placebo arm, with 52 OS events reported, median OS was not reached in either arm and 1-year survival was similar in the two groups (89.1% and 89.0%), Leisha A. Emens, MD, PhD, professor of medicine in hematology/oncology and co-leader of the Hillman Cancer Immunology and Immunotherapy Program at Hillman Cancer Center, University of Pittsburgh Medical Center (UPMC) reported at the congress.

“And when you look at duration of response, you see an increase not just in the number ... but the quality of the response,” he said, noting that for PFS, as well, a trend toward superiority is seen “that is consistent with all the other endpoints.”

“So overall, the application of incrementally restrictive cut-off of CPS lends weight to the exploratory analysis showing better survival from pembrolizumab in tumors with CPS more than 20,” Dr. Bianchini said, noting that the “real question,” however, is whether the finding “is worth clinical implementation.

“We know a lot about the primary tumor and immune infiltration. We’ve learned ... that if you wait and look ahead at immune infiltration in the advanced stage, you find that the tumor becomes smart,” he said, explaining that tumor/immune co-evolution leads to increased immuno-editing and immune subversion and it becomes “much harder to just hit the tumor with PD-L1, because this is not the only mechanism of immune escape.”

A review of several studies shows that in similar populations defined by biomarkers, response rates in patients treated with checkpoint inhibitors decrease in the second- and third-line setting vs. the first-line setting, he said.

For example, pembrolizumab response rates in the first-line and second-line or greater setting in cohort B of the KEYNOTE-086 study were 21.4% and 5.7%, respectively, compared with 12.3% in the second- to third-line setting in KEYNOTE-119, he said.

Another consideration is whether monotherapy or combination therapy is preferable, and the data suggest that regardless of how PD-L1-positivity is defined (by CPS cutoff of 1 vs. 20, for example), most patients treated with monotherapy progress within the first 3 months, he said.

“I don’t see that this is a safe approach for the majority of these patients. So without better biomarkers, combinations should always be preferred, at least to avoid early progression,” Dr. Bianchini said, adding that the open question, then, is: “If we set the new standard in the first-line as the combination of nab-paclitaxel and atezolizumab for PD-L1-positive patients defined by the VENTANA [SP142 assay], should we continue with immune checkpoint [inhibition] using different combinations?”

“Of course, at the time the trial was designed, the results of IMpassion were not available, but it’s very important, because [the findings] add to the evidence that immunotherapy is extremely relevant for some patients,” he said.

KATE2 further demonstrated the importance of PD-L1 status, he said, adding that due to its limitations, including small sample size and short follow-up, longer follow-up is needed to better evaluate duration of response and PFS.

“Despite the trial limitations, the qualitative effect seen in all clinical endpoints – overall response rate, progression-free survival, overall survival – in PD-L1-positive tumors defined by SP142 ... provided strong and robust signals supporting the investigation of immune checkpoint inhibitors in HER-positive breast cancer,” he said, noting that “many trials are ongoing in the early setting and the advanced setting.”

In addition to the lessons of these trials with respect to the interchangeability of PD-L1 IHC assays and the value of PD-L1 assessment for identifying the likelihood of benefit from immune checkpoint inhibitors, the findings highlight the possibility that PD-L1-negative tumors require different immunotherapy approaches or alternative therapeutic strategies, and underscore that the benefit of immunotherapy in PD-L1-positive patients is still restricted to a minority.

“So new studies and approaches with immuno-oncology are needed, and we need more effective biomarkers, because we need to have precision oncology applied – we need to go in that direction,” he concluded.

Dr. Bianchini reported consultancy/honorarium and or advisory board activity associated with Roche, MSD, AstraZeneca, Pfizer, Chugai, EISAI, Lilly, Novartis, Amgen, Sanofi, Neopharm, and Genomic Health. The IMPassion30 trial was funded by F. Hoffmann-La Roche Ltd.; Dr. Rugo reported research grants, other funding, and or travel/accommodation/expenses from Pfizer, Novartis, Eli Lilly, Merck, OBI, EISAI, Plexxikon, Genentech/Roche, MacroGenics, PUMA, Mylan, Immunomedics, Daiichi Sankyo, and Celltrion. KEYNOTE-119 was funded by Merck Sharp & Dohme Corp.; Dr. Cortés and Dr. Emens reported numerous funding relationships but none with F. Hoffman-La Roche. KATE2 was funded by F. Hoffmann-La Roche.
 

Sources: IMPassion130; ESMO Abstract LBA20; KEYNOTE-119: ESMO Abstract LBA21; KATE2: ESMO Abstract 305O.

BARCELONA – Programmed death-ligand 1 (PD-L1) status in patients with advanced triple negative or HER2-positive breast cancer appears to identify distinct disease entities with varying likelihood of benefit from immune checkpoint inhibition, according to Giampaolo Bianchini, MD.

This observation, which contrasts with findings in other solid tumors and expands the road map to improved outcomes with immunotherapy for metastatic breast cancer, is based in part on new findings presented at the European Society for Medical Oncology Congress.

Among additional lessons from those findings: PD-L1 assays are not easily interchangeable, and studies with a “one size fits all” approach should be avoided, Dr. Bianchini, head of the Breast Cancer Group – Medical Oncology and clinical translational and immunotherapy research at Ospedale San Raffaele, Milan, said at the congress.
 

IMPassion130 and PD-L1 assays

In the phase 3 IMpassion130 trial assessing nanoparticle, albumin-bound (nab)-paclitaxel chemotherapy + either the anti-PD-L1 monoclonal antibody atezolizumab or placebo for the first-line treatment of metastatic triple-negative breast cancer (mTNBC), investigators used, and validated, the VENTANA PD-L1 SP142 assay to evaluate PD-L1 expression in immune cells (IC). PD-L1 positivity was defined using a 1% cutoff, meaning that PD-L1-stained IC encompassed at least 1% of the tumor area.

The trial demonstrated significantly improved progression-free survival (PFS) in the atezolizumab arm, both in the intention-to-treat (ITT) analysis (7.2 vs. 5.5 months in the placebo arm; hazard ratio, 0.80), and the PD-L1-positive subgroup (7.5 vs. 5.0 months; HR, 0.62), and the results were published in November 2018 (N Engl J Med. 2018; 379:2108-21).

“IMpassion130 is the first phase 3 trial demonstrating clinical benefit of cancer immunotherapy in patients with PD-L1-positive, metastatic triple-negative breast cancer,” Hope S. Rugo, MD, said at the congress. “The combination of atezolizumab and nab-paclitaxel is now approved in the United States and Europe for this indication.”

Subgroup analyses indicated that PFS and OS benefit with atezolizumab + nab-paclitaxel vs. nab-paclitaxel alone was greater in double-positive patients (those with SP142 positivity and either SP263 or 22C3 positivity) than in patients who were SP263-positive/SP142-negative or 22C3-positive/SP142-negative.

Dr. Rugo and her colleagues also found that the benefits with atezolizumab + nab-paclitaxel in PD-L1-positive patients were apparent regardless of the source of tissue for testing (breast or distant metastases).

They concluded that the findings of the assays are not equivalent; 22C3 and SP263 identified more patients as PD-L1 positive, and SP142-positivity was encompassed in positive tests for both.

“The clinical benefit in the 22C3-positive and the SP263-positive subgroups appear to be driven by the SP142-positive subgroup, and [SP142] identifies patients with the longest median progression-free and overall survival from the addition of atezolizumab to nab-paclitaxel,” she said “The SP142 assay with an IC cutoff of 1% or greater is the approved diagnostic test used to identify patients with metastatic triple-negative breast cancer who are most likely to benefit from the addition of the checkpoint inhibitor atezolizumab to nab-paclitaxel.”

As for whether the SP142 should be the assay of choice in other settings in which it hasn’t been validated, Dr. Rugo said it is advisable to use the assay that has been validated in a positive trial.

“That’s what we would generally do ... however, recognizing that some countries are not using SP142, and some sites may not have access, certainly you encompass that population in the patients whose tumors are positive by both other assays,” she said. “The risk is that you might overtreat, and the cost of treatment is greater.”

Excess toxicity is also a concern in that situation, she said, adding that “hopefully in the future we’ll be able to figure out ways to have even more patients benefit from the addition of immunotherapy so that won’t be an issue.”

“What this data shows is that you can feel secure that you are encompassing the patient population identified by the parent trial to benefit from the addition of atezolizumab by using either of the other two assays; you’re only missing 1% – so that’s very reasonable,” she said. “The risk is that you’re overtreating; it’s quite likely that there’s a population there that isn’t benefiting as much, but that’s a balance.”

The findings from IMPassion130 with regard to OS in the unselected population that included PD-L1-negative patients (18.7 vs. 21.0 months with vs. without atezolizumab; HR, 0.86) underscore the fact that “one size does not fit all” when it comes to immunotherapy benefit, Dr. Bianchini said.

This is further demonstrated by the post hoc analysis comparing IHC assays, he said, explaining that 63% of IMPassion130 patients who were considered PD-L1-negative based on the SP142 “actually scored as PD-L1-positive by the other tests.

“So the very clinically important question is if there is any evidence from the data that [the PD-L1-negative group] benefits in a significant way from the addition of atezolizumab,” he said. “I don’t see evidence for a clinical benefit, I see evidence to look for new biomarkers to identify a potential population who will benefit.”

The “absence of evidence is not evidence of absence,” he stressed, noting that it may be possible – with the right biomarkers – to identify PD-L1-negative patients who would benefit.

What the findings do show, however, is support for the FDA decision to approve the SP142 assay with an IC cutoff of 1% as a companion diagnostic tool, and that PD-L1 is ideally assessed using samples from both the primary and metastatic site, as the IMPassion130 data “do not inform whether PD-L1 assessment in primary and metastatic sites is equally informative,” he said.

In addition, Dr. Bianchini said the findings suggest that more information is needed about using different cutoffs for SP263 and 22C3, and he cautioned against “directly translating these finding to other disease settings or immune combinations.

“Defining new biomarkers to identify who within the PD-L1-negative group might benefit from this combination remains an unmet need,” he said. “For sure, I don’t see a space for the other tests to define this population,” he added.

KEYNOTE-119, KATE2, and future directions

Both the randomized, open-label, phase 3 KEYNOTE-119 study of the checkpoint inhibitor pembrolizumab vs. single-agent chemotherapy for mTNBC, and the phase 2 KATE2 trial of the antibody-drug conjugate trastuzumab emtansine (T-DM1) + either atezolizumab or placebo in previously treated HER2-positive breast cancer patients, failed to meet their respective primary study endpoints.

But the news isn’t all bad, Dr. Bianchini said.

For example, in KEYNOTE-119, second- or third-line pembrolizumab monotherapy did not significantly improve OS vs. chemotherapy for mTNBC, but the pembrolizumab treatment effect increased as PD-L1 enrichment increased, he explained.

Pembrolizumab showed promising antitumor activity and manageable safety in mTNBC in prior trials, and was therefore further assessed in the KEYNOTE-119 study of 601 patients with centrally confirmed TNBC, 1-2 prior systemic treatments for mTNBC, progression on the latest therapy, and a prior anthracycline or taxane, Javier Cortés, MD, PhD, of Instituto Oncológico, Madrid, reported at the congress.

Sharon Worcester/MDedge News

Pembrolizumab was given at a dose of 200 mg every 3 weeks, and chemotherapy was physician’s choice of capecitabine, eribulin, gemcitabine, or vinorelbine.

At a median follow-up of 9.9 months in the pembrolizumab group and 10.9 months in the chemotherapy group, OS did not differ significantly between the groups; this was true overall, in patients with a CPS of 10 or greater, and in those with a CPS of 1 or greater.

In all-comers, the HR for OS was 0.97, compared with 0.78 in patients with CPS of 10 or greater, and 0.86 in those with CPS of 1 or greater, Dr. Cortés said.

“One of the most interesting exploratory analyses was OS in those patients with CPS of 20 or higher,” he said, noting that median OS in that group was 14.9 vs.12.5 months with pembrolizumab vs. with chemotherapy (HR, 0.58).

Pembrolizumab did not improve overall PFS, but again, the rates improved with higher CPS. Duration of response, however, was longer with pembrolizumab vs. chemotherapy (12.2 vs. 8.3 months overall; 12.2 vs. 6.5 months for CPS of 1 or greater; and not reached vs. 7.1 months for CPS of 10 or greater).

Grade 3-5 AEs occurred in 35% vs. 49% of patients in the pembrolizumab vs. chemotherapy groups, with nine deaths occurring in each, Dr. Cortés said, adding that treatment-related AEs occurred in 14% (with one death) and 36% (with two deaths), respectively, and grade 3-4 immune-mediated AEs and infusion reactions occurred in 3.2% vs. 1.0% (no deaths), respectively.

In the double-blind, signal-seeking KATE2 trial, as reported in 2018 at the San Antonio Breast Cancer Symposium, no overall PFS improvement was seen with atezolizumab + T-DM1 (median of 8.2 vs. 6.8 months; HR, 0.82; 12-month PFS 38% vs. 34%), but again, a possible benefit was seen in PD-L1-positive patients (8.5 vs. 4.1 months; HR, 0.60).

KATE2 included 202 patients with advanced HER2-positive breast cancer that progressed after treatment with T-DM1 and a taxane. They were randomized 2:1 to receive intravenous T-DM1 at a dose of 3.6 mg/kg plus atezolizumab (1,200 mg) or placebo every 3 weeks until loss of clinical benefit or intolerable toxicity.

The “overall survival and final safety results” show that at a median follow-up of 19.0 months in the atezolizumab arm and 18.2 months in the placebo arm, with 52 OS events reported, median OS was not reached in either arm and 1-year survival was similar in the two groups (89.1% and 89.0%), Leisha A. Emens, MD, PhD, professor of medicine in hematology/oncology and co-leader of the Hillman Cancer Immunology and Immunotherapy Program at Hillman Cancer Center, University of Pittsburgh Medical Center (UPMC) reported at the congress.

“And when you look at duration of response, you see an increase not just in the number ... but the quality of the response,” he said, noting that for PFS, as well, a trend toward superiority is seen “that is consistent with all the other endpoints.”

“So overall, the application of incrementally restrictive cut-off of CPS lends weight to the exploratory analysis showing better survival from pembrolizumab in tumors with CPS more than 20,” Dr. Bianchini said, noting that the “real question,” however, is whether the finding “is worth clinical implementation.

“We know a lot about the primary tumor and immune infiltration. We’ve learned ... that if you wait and look ahead at immune infiltration in the advanced stage, you find that the tumor becomes smart,” he said, explaining that tumor/immune co-evolution leads to increased immuno-editing and immune subversion and it becomes “much harder to just hit the tumor with PD-L1, because this is not the only mechanism of immune escape.”

A review of several studies shows that in similar populations defined by biomarkers, response rates in patients treated with checkpoint inhibitors decrease in the second- and third-line setting vs. the first-line setting, he said.

For example, pembrolizumab response rates in the first-line and second-line or greater setting in cohort B of the KEYNOTE-086 study were 21.4% and 5.7%, respectively, compared with 12.3% in the second- to third-line setting in KEYNOTE-119, he said.

Another consideration is whether monotherapy or combination therapy is preferable, and the data suggest that regardless of how PD-L1-positivity is defined (by CPS cutoff of 1 vs. 20, for example), most patients treated with monotherapy progress within the first 3 months, he said.

“I don’t see that this is a safe approach for the majority of these patients. So without better biomarkers, combinations should always be preferred, at least to avoid early progression,” Dr. Bianchini said, adding that the open question, then, is: “If we set the new standard in the first-line as the combination of nab-paclitaxel and atezolizumab for PD-L1-positive patients defined by the VENTANA [SP142 assay], should we continue with immune checkpoint [inhibition] using different combinations?”

“Of course, at the time the trial was designed, the results of IMpassion were not available, but it’s very important, because [the findings] add to the evidence that immunotherapy is extremely relevant for some patients,” he said.

KATE2 further demonstrated the importance of PD-L1 status, he said, adding that due to its limitations, including small sample size and short follow-up, longer follow-up is needed to better evaluate duration of response and PFS.

“Despite the trial limitations, the qualitative effect seen in all clinical endpoints – overall response rate, progression-free survival, overall survival – in PD-L1-positive tumors defined by SP142 ... provided strong and robust signals supporting the investigation of immune checkpoint inhibitors in HER-positive breast cancer,” he said, noting that “many trials are ongoing in the early setting and the advanced setting.”

In addition to the lessons of these trials with respect to the interchangeability of PD-L1 IHC assays and the value of PD-L1 assessment for identifying the likelihood of benefit from immune checkpoint inhibitors, the findings highlight the possibility that PD-L1-negative tumors require different immunotherapy approaches or alternative therapeutic strategies, and underscore that the benefit of immunotherapy in PD-L1-positive patients is still restricted to a minority.

“So new studies and approaches with immuno-oncology are needed, and we need more effective biomarkers, because we need to have precision oncology applied – we need to go in that direction,” he concluded.

Dr. Bianchini reported consultancy/honorarium and or advisory board activity associated with Roche, MSD, AstraZeneca, Pfizer, Chugai, EISAI, Lilly, Novartis, Amgen, Sanofi, Neopharm, and Genomic Health. The IMPassion30 trial was funded by F. Hoffmann-La Roche Ltd.; Dr. Rugo reported research grants, other funding, and or travel/accommodation/expenses from Pfizer, Novartis, Eli Lilly, Merck, OBI, EISAI, Plexxikon, Genentech/Roche, MacroGenics, PUMA, Mylan, Immunomedics, Daiichi Sankyo, and Celltrion. KEYNOTE-119 was funded by Merck Sharp & Dohme Corp.; Dr. Cortés and Dr. Emens reported numerous funding relationships but none with F. Hoffman-La Roche. KATE2 was funded by F. Hoffmann-La Roche.
 

Sources: IMPassion130; ESMO Abstract LBA20; KEYNOTE-119: ESMO Abstract LBA21; KATE2: ESMO Abstract 305O.

BARCELONA – Programmed death-ligand 1 (PD-L1) status in patients with advanced triple negative or HER2-positive breast cancer appears to identify distinct disease entities with varying likelihood of benefit from immune checkpoint inhibition, according to Giampaolo Bianchini, MD.

This observation, which contrasts with findings in other solid tumors and expands the road map to improved outcomes with immunotherapy for metastatic breast cancer, is based in part on new findings presented at the European Society for Medical Oncology Congress.

Among additional lessons from those findings: PD-L1 assays are not easily interchangeable, and studies with a “one size fits all” approach should be avoided, Dr. Bianchini, head of the Breast Cancer Group – Medical Oncology and clinical translational and immunotherapy research at Ospedale San Raffaele, Milan, said at the congress.
 

IMPassion130 and PD-L1 assays

In the phase 3 IMpassion130 trial assessing nanoparticle, albumin-bound (nab)-paclitaxel chemotherapy + either the anti-PD-L1 monoclonal antibody atezolizumab or placebo for the first-line treatment of metastatic triple-negative breast cancer (mTNBC), investigators used, and validated, the VENTANA PD-L1 SP142 assay to evaluate PD-L1 expression in immune cells (IC). PD-L1 positivity was defined using a 1% cutoff, meaning that PD-L1-stained IC encompassed at least 1% of the tumor area.

The trial demonstrated significantly improved progression-free survival (PFS) in the atezolizumab arm, both in the intention-to-treat (ITT) analysis (7.2 vs. 5.5 months in the placebo arm; hazard ratio, 0.80), and the PD-L1-positive subgroup (7.5 vs. 5.0 months; HR, 0.62), and the results were published in November 2018 (N Engl J Med. 2018; 379:2108-21).

“IMpassion130 is the first phase 3 trial demonstrating clinical benefit of cancer immunotherapy in patients with PD-L1-positive, metastatic triple-negative breast cancer,” Hope S. Rugo, MD, said at the congress. “The combination of atezolizumab and nab-paclitaxel is now approved in the United States and Europe for this indication.”

Subgroup analyses indicated that PFS and OS benefit with atezolizumab + nab-paclitaxel vs. nab-paclitaxel alone was greater in double-positive patients (those with SP142 positivity and either SP263 or 22C3 positivity) than in patients who were SP263-positive/SP142-negative or 22C3-positive/SP142-negative.

Dr. Rugo and her colleagues also found that the benefits with atezolizumab + nab-paclitaxel in PD-L1-positive patients were apparent regardless of the source of tissue for testing (breast or distant metastases).

They concluded that the findings of the assays are not equivalent; 22C3 and SP263 identified more patients as PD-L1 positive, and SP142-positivity was encompassed in positive tests for both.

“The clinical benefit in the 22C3-positive and the SP263-positive subgroups appear to be driven by the SP142-positive subgroup, and [SP142] identifies patients with the longest median progression-free and overall survival from the addition of atezolizumab to nab-paclitaxel,” she said “The SP142 assay with an IC cutoff of 1% or greater is the approved diagnostic test used to identify patients with metastatic triple-negative breast cancer who are most likely to benefit from the addition of the checkpoint inhibitor atezolizumab to nab-paclitaxel.”

As for whether the SP142 should be the assay of choice in other settings in which it hasn’t been validated, Dr. Rugo said it is advisable to use the assay that has been validated in a positive trial.

“That’s what we would generally do ... however, recognizing that some countries are not using SP142, and some sites may not have access, certainly you encompass that population in the patients whose tumors are positive by both other assays,” she said. “The risk is that you might overtreat, and the cost of treatment is greater.”

Excess toxicity is also a concern in that situation, she said, adding that “hopefully in the future we’ll be able to figure out ways to have even more patients benefit from the addition of immunotherapy so that won’t be an issue.”

“What this data shows is that you can feel secure that you are encompassing the patient population identified by the parent trial to benefit from the addition of atezolizumab by using either of the other two assays; you’re only missing 1% – so that’s very reasonable,” she said. “The risk is that you’re overtreating; it’s quite likely that there’s a population there that isn’t benefiting as much, but that’s a balance.”

The findings from IMPassion130 with regard to OS in the unselected population that included PD-L1-negative patients (18.7 vs. 21.0 months with vs. without atezolizumab; HR, 0.86) underscore the fact that “one size does not fit all” when it comes to immunotherapy benefit, Dr. Bianchini said.

This is further demonstrated by the post hoc analysis comparing IHC assays, he said, explaining that 63% of IMPassion130 patients who were considered PD-L1-negative based on the SP142 “actually scored as PD-L1-positive by the other tests.

“So the very clinically important question is if there is any evidence from the data that [the PD-L1-negative group] benefits in a significant way from the addition of atezolizumab,” he said. “I don’t see evidence for a clinical benefit, I see evidence to look for new biomarkers to identify a potential population who will benefit.”

The “absence of evidence is not evidence of absence,” he stressed, noting that it may be possible – with the right biomarkers – to identify PD-L1-negative patients who would benefit.

What the findings do show, however, is support for the FDA decision to approve the SP142 assay with an IC cutoff of 1% as a companion diagnostic tool, and that PD-L1 is ideally assessed using samples from both the primary and metastatic site, as the IMPassion130 data “do not inform whether PD-L1 assessment in primary and metastatic sites is equally informative,” he said.

In addition, Dr. Bianchini said the findings suggest that more information is needed about using different cutoffs for SP263 and 22C3, and he cautioned against “directly translating these finding to other disease settings or immune combinations.

“Defining new biomarkers to identify who within the PD-L1-negative group might benefit from this combination remains an unmet need,” he said. “For sure, I don’t see a space for the other tests to define this population,” he added.

KEYNOTE-119, KATE2, and future directions

Both the randomized, open-label, phase 3 KEYNOTE-119 study of the checkpoint inhibitor pembrolizumab vs. single-agent chemotherapy for mTNBC, and the phase 2 KATE2 trial of the antibody-drug conjugate trastuzumab emtansine (T-DM1) + either atezolizumab or placebo in previously treated HER2-positive breast cancer patients, failed to meet their respective primary study endpoints.

But the news isn’t all bad, Dr. Bianchini said.

For example, in KEYNOTE-119, second- or third-line pembrolizumab monotherapy did not significantly improve OS vs. chemotherapy for mTNBC, but the pembrolizumab treatment effect increased as PD-L1 enrichment increased, he explained.

Pembrolizumab showed promising antitumor activity and manageable safety in mTNBC in prior trials, and was therefore further assessed in the KEYNOTE-119 study of 601 patients with centrally confirmed TNBC, 1-2 prior systemic treatments for mTNBC, progression on the latest therapy, and a prior anthracycline or taxane, Javier Cortés, MD, PhD, of Instituto Oncológico, Madrid, reported at the congress.

Sharon Worcester/MDedge News

Pembrolizumab was given at a dose of 200 mg every 3 weeks, and chemotherapy was physician’s choice of capecitabine, eribulin, gemcitabine, or vinorelbine.

At a median follow-up of 9.9 months in the pembrolizumab group and 10.9 months in the chemotherapy group, OS did not differ significantly between the groups; this was true overall, in patients with a CPS of 10 or greater, and in those with a CPS of 1 or greater.

In all-comers, the HR for OS was 0.97, compared with 0.78 in patients with CPS of 10 or greater, and 0.86 in those with CPS of 1 or greater, Dr. Cortés said.

“One of the most interesting exploratory analyses was OS in those patients with CPS of 20 or higher,” he said, noting that median OS in that group was 14.9 vs.12.5 months with pembrolizumab vs. with chemotherapy (HR, 0.58).

Pembrolizumab did not improve overall PFS, but again, the rates improved with higher CPS. Duration of response, however, was longer with pembrolizumab vs. chemotherapy (12.2 vs. 8.3 months overall; 12.2 vs. 6.5 months for CPS of 1 or greater; and not reached vs. 7.1 months for CPS of 10 or greater).

Grade 3-5 AEs occurred in 35% vs. 49% of patients in the pembrolizumab vs. chemotherapy groups, with nine deaths occurring in each, Dr. Cortés said, adding that treatment-related AEs occurred in 14% (with one death) and 36% (with two deaths), respectively, and grade 3-4 immune-mediated AEs and infusion reactions occurred in 3.2% vs. 1.0% (no deaths), respectively.

In the double-blind, signal-seeking KATE2 trial, as reported in 2018 at the San Antonio Breast Cancer Symposium, no overall PFS improvement was seen with atezolizumab + T-DM1 (median of 8.2 vs. 6.8 months; HR, 0.82; 12-month PFS 38% vs. 34%), but again, a possible benefit was seen in PD-L1-positive patients (8.5 vs. 4.1 months; HR, 0.60).

KATE2 included 202 patients with advanced HER2-positive breast cancer that progressed after treatment with T-DM1 and a taxane. They were randomized 2:1 to receive intravenous T-DM1 at a dose of 3.6 mg/kg plus atezolizumab (1,200 mg) or placebo every 3 weeks until loss of clinical benefit or intolerable toxicity.

The “overall survival and final safety results” show that at a median follow-up of 19.0 months in the atezolizumab arm and 18.2 months in the placebo arm, with 52 OS events reported, median OS was not reached in either arm and 1-year survival was similar in the two groups (89.1% and 89.0%), Leisha A. Emens, MD, PhD, professor of medicine in hematology/oncology and co-leader of the Hillman Cancer Immunology and Immunotherapy Program at Hillman Cancer Center, University of Pittsburgh Medical Center (UPMC) reported at the congress.

“And when you look at duration of response, you see an increase not just in the number ... but the quality of the response,” he said, noting that for PFS, as well, a trend toward superiority is seen “that is consistent with all the other endpoints.”

“So overall, the application of incrementally restrictive cut-off of CPS lends weight to the exploratory analysis showing better survival from pembrolizumab in tumors with CPS more than 20,” Dr. Bianchini said, noting that the “real question,” however, is whether the finding “is worth clinical implementation.

“We know a lot about the primary tumor and immune infiltration. We’ve learned ... that if you wait and look ahead at immune infiltration in the advanced stage, you find that the tumor becomes smart,” he said, explaining that tumor/immune co-evolution leads to increased immuno-editing and immune subversion and it becomes “much harder to just hit the tumor with PD-L1, because this is not the only mechanism of immune escape.”

A review of several studies shows that in similar populations defined by biomarkers, response rates in patients treated with checkpoint inhibitors decrease in the second- and third-line setting vs. the first-line setting, he said.

For example, pembrolizumab response rates in the first-line and second-line or greater setting in cohort B of the KEYNOTE-086 study were 21.4% and 5.7%, respectively, compared with 12.3% in the second- to third-line setting in KEYNOTE-119, he said.

Another consideration is whether monotherapy or combination therapy is preferable, and the data suggest that regardless of how PD-L1-positivity is defined (by CPS cutoff of 1 vs. 20, for example), most patients treated with monotherapy progress within the first 3 months, he said.

“I don’t see that this is a safe approach for the majority of these patients. So without better biomarkers, combinations should always be preferred, at least to avoid early progression,” Dr. Bianchini said, adding that the open question, then, is: “If we set the new standard in the first-line as the combination of nab-paclitaxel and atezolizumab for PD-L1-positive patients defined by the VENTANA [SP142 assay], should we continue with immune checkpoint [inhibition] using different combinations?”

“Of course, at the time the trial was designed, the results of IMpassion were not available, but it’s very important, because [the findings] add to the evidence that immunotherapy is extremely relevant for some patients,” he said.

KATE2 further demonstrated the importance of PD-L1 status, he said, adding that due to its limitations, including small sample size and short follow-up, longer follow-up is needed to better evaluate duration of response and PFS.

“Despite the trial limitations, the qualitative effect seen in all clinical endpoints – overall response rate, progression-free survival, overall survival – in PD-L1-positive tumors defined by SP142 ... provided strong and robust signals supporting the investigation of immune checkpoint inhibitors in HER-positive breast cancer,” he said, noting that “many trials are ongoing in the early setting and the advanced setting.”

In addition to the lessons of these trials with respect to the interchangeability of PD-L1 IHC assays and the value of PD-L1 assessment for identifying the likelihood of benefit from immune checkpoint inhibitors, the findings highlight the possibility that PD-L1-negative tumors require different immunotherapy approaches or alternative therapeutic strategies, and underscore that the benefit of immunotherapy in PD-L1-positive patients is still restricted to a minority.

“So new studies and approaches with immuno-oncology are needed, and we need more effective biomarkers, because we need to have precision oncology applied – we need to go in that direction,” he concluded.

Dr. Bianchini reported consultancy/honorarium and or advisory board activity associated with Roche, MSD, AstraZeneca, Pfizer, Chugai, EISAI, Lilly, Novartis, Amgen, Sanofi, Neopharm, and Genomic Health. The IMPassion30 trial was funded by F. Hoffmann-La Roche Ltd.; Dr. Rugo reported research grants, other funding, and or travel/accommodation/expenses from Pfizer, Novartis, Eli Lilly, Merck, OBI, EISAI, Plexxikon, Genentech/Roche, MacroGenics, PUMA, Mylan, Immunomedics, Daiichi Sankyo, and Celltrion. KEYNOTE-119 was funded by Merck Sharp & Dohme Corp.; Dr. Cortés and Dr. Emens reported numerous funding relationships but none with F. Hoffman-La Roche. KATE2 was funded by F. Hoffmann-La Roche.
 

Sources: IMPassion130; ESMO Abstract LBA20; KEYNOTE-119: ESMO Abstract LBA21; KATE2: ESMO Abstract 305O.

Genital lichen simplex chronicus

Lichen simplex chronicus (LSC) is an inflammatory skin condition that develops secondary to persistent rubbing or scratching of skin. Although LSC can occur anywhere on the body, genital LSC develops in association with genital itch, with the itch often described as intense and unrelenting. The itching sensation leads to scratching and rubbing of the area, which can provide temporary symptomatic relief.^1,2 However, this action of rubbing and scratching stimulates local cutaneous nerves, inducing an even more intense itch sensation. This process, identified as the ‘itch-scratch cycle,’ plays a prominent role in all cases of LSC.¹

On physical examination LSC appears as poorly defined, pink to red plaques with accentuated skin markings on bilateral labia majora. Less commonly, it can present as asymmetrical or unilateral plaques.³ LSC can extend onto labia minora, mons pubis, and medial thighs. However, the vagina is spared.¹ Excoriations, marked by their geometric, angular appearance, often can be appreciated overlying plaques of LSC. Additionally, crusting, scale, broken hairs, hyperpigmentation, and scarring may be seen in LSC.²

In this case, white discharge was noted on vaginal examination, which was suspicious for vaginal candidiasis. Wet mount examination revealed multiple candida hyphae and spores (FIGURE 2), confirming vaginal candidiasis. This vulvovaginal fungal infection caused persistent vulvar pruritus, with subsequent development of LSC due to prolonged scratching. The patient was treated with both oral fluconazole and topical mometasone ointment, for vaginal candidiasis and vulvar LSC, respectively. Mometasone ointment is categorized as a class II (high potency) topical steroid. However, it is worth noting that mometasone cream is categorized as a class IV (medium potency) topical steroid.
 

FIGURE 2 Wet mount of vaginal discharge, revealing candida hyphae and spores

Treatment

Successful treatment of LSC requires addressing 4 elements, including recognizing and treating the underlying etiology, restoring barrier function, reducing inflammation, and interrupting the itch-scratch cycle.³

Identifying the underlying etiology. Knowing the etiology of vulvar pruritus is a key step in resolution of the condition because LSC is driven by repetitive rubbing and scratching behaviors in response to the itch. The differential diagnosis for vulvar pruritus is broad. Evaluation and workup should be tailored to suit each unique patient presentation. A review of past medical history and full-body skin examination can identify a contributing inflammatory skin disease, such as atopic dermatitis, psoriasis, lichen planus, lichen sclerosus, or autoimmune vesiculobullous disease (pemphigus).^1,2 Careful review of products applied in the genital area can reveal an underlying irritant or allergic contact dermatitis. Scented soap or detergent commonly cause vulvar dermatitis.¹ A speculum examination may suggest inflammatory vaginitis or atrophic vaginitis (genitourinary syndrome of menopause); run off of vaginal discharge onto the vulvar skin can result in vulvar pruritus. Vaginal wet mount can diagnose vulvovaginal candidiasis, trichomonas infection, and bacterial vaginitis.¹ A skin scraping with mineral oil or potassium hydroxide can suggest scabies infestation or cutaneous dermatophyte infection, respectively.² Treatment of vulvar pruritus should be initiated based on diagnosis.

Restoring barrier function. The repetitive scratching and rubbing behaviors disrupt the cutaneous barrier layer and lead to stimulation of the local nerves. This creates more itch and further traumatization to the barrier. Barrier function can be restored through soaking the area, with sitz baths or damp towels. Following 20- to 30-minute soaks, a lubricant, such as petroleum jelly, should be applied to the area.³

Reducing inflammation. To reduce inflammation, topical steroids should be applied to areas of LSC.³ In severe cases, high potency topical steroids should be prescribed. Examples of high potency topical steroids include:

• clobetasol propionate 0.05%
• betamethasone dipropionate 0.05%
• halobetasol propionate 0.05%.

Ointment is the choice vehicle because it is both more potent and associated with decreased stinging sensation. High potency steroid ointment should be applied twice daily for at least 2 to 4 weeks. The transition to lower potency topical steroids, such as triamcinolone acetonide 0.1% ointment, can be made as the LSC improves.²

Interrupting the itch-scratch cycle. As noted above, persistent rubbing and scratching generates increased itch sensation. Thus, breaking the itch-scratch cycle is essential. Nighttime scratching can be improved with hydroxyzine. The effective dosage ranges between 25 and 75 mg and should be titrated up slowly every 5 to 7 days. Sedation is a major adverse effect of hydroxyzine, limiting the treatment of daytime itching. Selective serotonin reuptake inhibitors (SSRIs), such as citalopram, also have been found to be effective. Over the counter, nonsedation antihistamines have not been found to be useful in breaking the itch-scratch cycle. The clinical course of LSC is chronic (as the name implies), waxing and waning, and sometimes can be challenging to treat—some patients require years-long continued follow-up and treatment.³
 

Genital lichen simplex chronicus

Lichen simplex chronicus (LSC) is an inflammatory skin condition that develops secondary to persistent rubbing or scratching of skin. Although LSC can occur anywhere on the body, genital LSC develops in association with genital itch, with the itch often described as intense and unrelenting. The itching sensation leads to scratching and rubbing of the area, which can provide temporary symptomatic relief.^1,2 However, this action of rubbing and scratching stimulates local cutaneous nerves, inducing an even more intense itch sensation. This process, identified as the ‘itch-scratch cycle,’ plays a prominent role in all cases of LSC.¹

On physical examination LSC appears as poorly defined, pink to red plaques with accentuated skin markings on bilateral labia majora. Less commonly, it can present as asymmetrical or unilateral plaques.³ LSC can extend onto labia minora, mons pubis, and medial thighs. However, the vagina is spared.¹ Excoriations, marked by their geometric, angular appearance, often can be appreciated overlying plaques of LSC. Additionally, crusting, scale, broken hairs, hyperpigmentation, and scarring may be seen in LSC.²

In this case, white discharge was noted on vaginal examination, which was suspicious for vaginal candidiasis. Wet mount examination revealed multiple candida hyphae and spores (FIGURE 2), confirming vaginal candidiasis. This vulvovaginal fungal infection caused persistent vulvar pruritus, with subsequent development of LSC due to prolonged scratching. The patient was treated with both oral fluconazole and topical mometasone ointment, for vaginal candidiasis and vulvar LSC, respectively. Mometasone ointment is categorized as a class II (high potency) topical steroid. However, it is worth noting that mometasone cream is categorized as a class IV (medium potency) topical steroid.
 

FIGURE 2 Wet mount of vaginal discharge, revealing candida hyphae and spores

Treatment

Successful treatment of LSC requires addressing 4 elements, including recognizing and treating the underlying etiology, restoring barrier function, reducing inflammation, and interrupting the itch-scratch cycle.³

Identifying the underlying etiology. Knowing the etiology of vulvar pruritus is a key step in resolution of the condition because LSC is driven by repetitive rubbing and scratching behaviors in response to the itch. The differential diagnosis for vulvar pruritus is broad. Evaluation and workup should be tailored to suit each unique patient presentation. A review of past medical history and full-body skin examination can identify a contributing inflammatory skin disease, such as atopic dermatitis, psoriasis, lichen planus, lichen sclerosus, or autoimmune vesiculobullous disease (pemphigus).^1,2 Careful review of products applied in the genital area can reveal an underlying irritant or allergic contact dermatitis. Scented soap or detergent commonly cause vulvar dermatitis.¹ A speculum examination may suggest inflammatory vaginitis or atrophic vaginitis (genitourinary syndrome of menopause); run off of vaginal discharge onto the vulvar skin can result in vulvar pruritus. Vaginal wet mount can diagnose vulvovaginal candidiasis, trichomonas infection, and bacterial vaginitis.¹ A skin scraping with mineral oil or potassium hydroxide can suggest scabies infestation or cutaneous dermatophyte infection, respectively.² Treatment of vulvar pruritus should be initiated based on diagnosis.

Restoring barrier function. The repetitive scratching and rubbing behaviors disrupt the cutaneous barrier layer and lead to stimulation of the local nerves. This creates more itch and further traumatization to the barrier. Barrier function can be restored through soaking the area, with sitz baths or damp towels. Following 20- to 30-minute soaks, a lubricant, such as petroleum jelly, should be applied to the area.³

Reducing inflammation. To reduce inflammation, topical steroids should be applied to areas of LSC.³ In severe cases, high potency topical steroids should be prescribed. Examples of high potency topical steroids include:

• clobetasol propionate 0.05%
• betamethasone dipropionate 0.05%
• halobetasol propionate 0.05%.

Ointment is the choice vehicle because it is both more potent and associated with decreased stinging sensation. High potency steroid ointment should be applied twice daily for at least 2 to 4 weeks. The transition to lower potency topical steroids, such as triamcinolone acetonide 0.1% ointment, can be made as the LSC improves.²

Interrupting the itch-scratch cycle. As noted above, persistent rubbing and scratching generates increased itch sensation. Thus, breaking the itch-scratch cycle is essential. Nighttime scratching can be improved with hydroxyzine. The effective dosage ranges between 25 and 75 mg and should be titrated up slowly every 5 to 7 days. Sedation is a major adverse effect of hydroxyzine, limiting the treatment of daytime itching. Selective serotonin reuptake inhibitors (SSRIs), such as citalopram, also have been found to be effective. Over the counter, nonsedation antihistamines have not been found to be useful in breaking the itch-scratch cycle. The clinical course of LSC is chronic (as the name implies), waxing and waning, and sometimes can be challenging to treat—some patients require years-long continued follow-up and treatment.³
 

Genital lichen simplex chronicus

Lichen simplex chronicus (LSC) is an inflammatory skin condition that develops secondary to persistent rubbing or scratching of skin. Although LSC can occur anywhere on the body, genital LSC develops in association with genital itch, with the itch often described as intense and unrelenting. The itching sensation leads to scratching and rubbing of the area, which can provide temporary symptomatic relief.^1,2 However, this action of rubbing and scratching stimulates local cutaneous nerves, inducing an even more intense itch sensation. This process, identified as the ‘itch-scratch cycle,’ plays a prominent role in all cases of LSC.¹

On physical examination LSC appears as poorly defined, pink to red plaques with accentuated skin markings on bilateral labia majora. Less commonly, it can present as asymmetrical or unilateral plaques.³ LSC can extend onto labia minora, mons pubis, and medial thighs. However, the vagina is spared.¹ Excoriations, marked by their geometric, angular appearance, often can be appreciated overlying plaques of LSC. Additionally, crusting, scale, broken hairs, hyperpigmentation, and scarring may be seen in LSC.²

In this case, white discharge was noted on vaginal examination, which was suspicious for vaginal candidiasis. Wet mount examination revealed multiple candida hyphae and spores (FIGURE 2), confirming vaginal candidiasis. This vulvovaginal fungal infection caused persistent vulvar pruritus, with subsequent development of LSC due to prolonged scratching. The patient was treated with both oral fluconazole and topical mometasone ointment, for vaginal candidiasis and vulvar LSC, respectively. Mometasone ointment is categorized as a class II (high potency) topical steroid. However, it is worth noting that mometasone cream is categorized as a class IV (medium potency) topical steroid.
 

FIGURE 2 Wet mount of vaginal discharge, revealing candida hyphae and spores

Treatment

Successful treatment of LSC requires addressing 4 elements, including recognizing and treating the underlying etiology, restoring barrier function, reducing inflammation, and interrupting the itch-scratch cycle.³

Identifying the underlying etiology. Knowing the etiology of vulvar pruritus is a key step in resolution of the condition because LSC is driven by repetitive rubbing and scratching behaviors in response to the itch. The differential diagnosis for vulvar pruritus is broad. Evaluation and workup should be tailored to suit each unique patient presentation. A review of past medical history and full-body skin examination can identify a contributing inflammatory skin disease, such as atopic dermatitis, psoriasis, lichen planus, lichen sclerosus, or autoimmune vesiculobullous disease (pemphigus).^1,2 Careful review of products applied in the genital area can reveal an underlying irritant or allergic contact dermatitis. Scented soap or detergent commonly cause vulvar dermatitis.¹ A speculum examination may suggest inflammatory vaginitis or atrophic vaginitis (genitourinary syndrome of menopause); run off of vaginal discharge onto the vulvar skin can result in vulvar pruritus. Vaginal wet mount can diagnose vulvovaginal candidiasis, trichomonas infection, and bacterial vaginitis.¹ A skin scraping with mineral oil or potassium hydroxide can suggest scabies infestation or cutaneous dermatophyte infection, respectively.² Treatment of vulvar pruritus should be initiated based on diagnosis.

Restoring barrier function. The repetitive scratching and rubbing behaviors disrupt the cutaneous barrier layer and lead to stimulation of the local nerves. This creates more itch and further traumatization to the barrier. Barrier function can be restored through soaking the area, with sitz baths or damp towels. Following 20- to 30-minute soaks, a lubricant, such as petroleum jelly, should be applied to the area.³

Reducing inflammation. To reduce inflammation, topical steroids should be applied to areas of LSC.³ In severe cases, high potency topical steroids should be prescribed. Examples of high potency topical steroids include:

• clobetasol propionate 0.05%
• betamethasone dipropionate 0.05%
• halobetasol propionate 0.05%.

Ointment is the choice vehicle because it is both more potent and associated with decreased stinging sensation. High potency steroid ointment should be applied twice daily for at least 2 to 4 weeks. The transition to lower potency topical steroids, such as triamcinolone acetonide 0.1% ointment, can be made as the LSC improves.²

Interrupting the itch-scratch cycle. As noted above, persistent rubbing and scratching generates increased itch sensation. Thus, breaking the itch-scratch cycle is essential. Nighttime scratching can be improved with hydroxyzine. The effective dosage ranges between 25 and 75 mg and should be titrated up slowly every 5 to 7 days. Sedation is a major adverse effect of hydroxyzine, limiting the treatment of daytime itching. Selective serotonin reuptake inhibitors (SSRIs), such as citalopram, also have been found to be effective. Over the counter, nonsedation antihistamines have not been found to be useful in breaking the itch-scratch cycle. The clinical course of LSC is chronic (as the name implies), waxing and waning, and sometimes can be challenging to treat—some patients require years-long continued follow-up and treatment.³
 

Mohs micrographic surgery (MMS) has been met with controversy since its inception in the 1930s. Current debate centers on the types of tumors treated with MMS, increasing utilization, third-party payer reimbursement, the Appropriate Use Criteria (AUC), and subspecialty certification.

Controversies in Applications

Controversy surrounding treatment with MMS for certain tumor types is abundant, in large part due to a lack of well-designed studies. Perhaps most notably, the surgical management of melanoma has been hotly contested for decades.¹ An increasing number of Mohs surgeons advocate the use of MMS for treatment of melanoma. Advocates reason that tumor margins may be ill-defined, necessitating histologic examination of the margin for tumor clearance. In a study by Zitelli et al,² 5-year survival and metastatic rates for 535 patients with melanomas treated by MMS with frozen sections were the same or better when compared to historical controls treated with conventional wide local excision. Melanoma-associated antigen recognized by T cells (MART-1) immunostaining may offer improved diagnostic accuracy.³ Others believe that staged excision with permanent sections processed vertically, en face, or horizontally (“slow Mohs”) is more accurate and efficacious for the treatment of melanoma.¹ Advocates of this approach maintain that when compared to MMS with frozen sections, staged excision with permanent sections enables more accurate interpretation of residual melanoma and atypical junctional melanocytic hyperplasia as well as circumvents difficulty in interpreting freeze artifact.⁴

Although Merkel cell carcinoma has traditionally been treated with wide local excision, MMS with or without adjuvant radiotherapy has gained traction as a treatment option. Advocates for treatment by MMS hold that Merkel cell carcinoma is a contiguous tumor with a high rate of residual tumor persistence, making histologic margin control an ideal characteristic of treatment. However, in the absence of large randomized controlled studies comparing MMS to wide local excision, controversy surrounds the most appropriate surgical approach.¹ In a retrospective study of 86 patients by O’Connor et al,⁵ MMS was demonstrated to compare favorably to standard surgical excision. Standard surgical excision was associated with a 31.7% (13/41) local persistence rate and 48.8% (20/41) regional metastasis rate compared to 8.3% (1/12) and 33.3% (4/12) for MMS, respectively.⁵

Controversies in Increasing Utilization

The incidence of skin cancers has increased in recent years. As a result, it is reasonable to expect the rates of MMS to increase. Nonetheless, there is escalating concern among groups of third-party payers, the public, and physicians that MMS is being overused.⁶ Growth of the body of evidence supporting the appropriateness of MMS remains essential. Such studies continue to support reasons for increased MMS usage, demonstrating the stability of the percentage of skin cancers treated with MMS in the setting of increasing skin cancer incidence, the procedure’s superior efficacy for appropriately chosen cases, its expanding application to melanoma and other tumors, and an emphasis of MMS in residency training programs.^6-9

A current hot topic of controversy focuses on the wide variation among Mohs surgeons in the mean number of stages used to resect a tumor. Overuse among outliers has been proposed to stem from lack of technical expertise or from abuse of the current fee-for-service payment model, which bases compensation on the number of stages performed. A study by Krishnan et al¹⁰ determined that the mean number of stages per tumor in the studied population (all physicians [N=2305] receiving Medicare payments for MMS from January 2012 to December 2014) was 1.74, with a range of 1.09 to 4.11. Persistently high outliers were more likely to perform MMS in a solo practice, with an odds ratio of 2.35.¹⁰ In response to the wide variation in mean stages used to resect a skin cancer and its implications on increased financial burden and surgery to individual patients, intervention has been proposed. Notably, it has been demonstrated that mailing out individual reports of practice patterns to high-outlier physicians resulted in a reduction in mean stages per tumor as well as an associated cost savings when compared to outlier physicians who did not receive these reports.¹¹

Controversies in Reimbursement

Mohs micrographic surgery also has been in the spotlight for debate regarding reimbursement. The procedure has been targeted partly in response to its substantial contribution to total Medicare reimbursements paid out. In 2013, primary MMS billing codes constituted nearly 19% of total reimbursements to dermatologists and approximately 0.5% of total reimbursements to all physicians participating in Medicare.¹² Mohs micrographic surgery codes have correspondingly received frequent review by the Relative Value Scale Update Committee and remained on a list of potentially misvalued services according to the Centers for Medicare & Medicaid Services for years.¹³ Due to continued scrutiny and review, especially by the Relative Value Scale Update Committee and Centers for Medicare & Medicaid Services, reimbursement to perform MMS and reconstructive surgery has gone down by more than 20% in the last 15 years.¹⁴ Public perception mirrors third-party payer concerns for overcompensation. An article title in the New York Times theatrically postures “Patients’ Costs Skyrocket, Specialists’ Incomes Soar.” The article recounts an MMS patient’s “outrage at charges” associated with treatment of her “minor medical problem” and the simultaneous “sharp climb” in dermatologist income over the last 2 decades.¹⁵

However, studies continue to demonstrate the cost-effectiveness of MMS. A study by Ravitskiy et al¹⁶ demonstrates the cost-effectiveness of MMS, regardless of place of service or type of tumor. Of 406 tumors studied, MMS was the least expensive surgical procedure evaluated ($805 per tumor) when compared to standard surgical excision with permanent margins ($1026 per tumor), standard surgical excision with frozen margins ($1200 per tumor), and ambulatory surgery center standard surgical excision ($2507 per tumor). Furthermore, adjusted for inflation, the cost of MMS was lower in 2009 vs 1998.¹⁶ Similar results have been consistently demonstrated.¹⁷

Controversies in the AUC

To provide clinicians, policy makers, and insurers guidance for utilization of MMS in the setting of concerns for overutilization, overcompensation, and inappropriate application, the MMS AUC were established in 2012. The guidelines were developed by a process integrating evidence-based medicine, clinical experience, and expert opinion and is applicable to 270 clinical scenarios.¹⁸

A unique set of debate accompanies the guidelines. Namely, controversy has surrounded the classification of most primary superficial basal cell carcinomas as appropriate for treatment by MMS. These tumors have comparable cure rates when treated by MMS or curettage and cryosurgery, are often multifocal and require more Mohs stages than other basal cell carcinoma subtypes, and largely lack data on recurrence and invasion.¹⁹ The guidelines also have been scrutinized for including only studies from the United States.²⁰ Furthermore, the report is largely based on expert opinion rather than evidence.

Some Mohs surgeons have concerns that the guidelines will minimize clinical judgment. Nonetheless, deviations from the AUC practiced by Mohs surgeons have been reported where clinical judgment supplants guideline criteria. The most commonly cited reasons for performing MMS on tumors classified as uncertain or inappropriate, according to one study by Ruiz et al,²¹ included performing multiple MMSs on the same day, tumor location on the lower legs, and incorporation into an adjacent wound. Reported discrepancies in the AUC further emphasize the importance of clinical judgment and call into question the need for future revision of the criteria.²² For example, a primary squamous cell carcinoma in situ greater than or equal to 2 cm located on the trunk and extremities (excluding pretibial surfaces, hands, feet, nail units, and ankles) in a healthy patient is categorized as appropriate, while a recurrent but otherwise identical squamous cell carcinoma in situ is categorized as uncertain. These counterintuitive criteria are unsupported by existing studies.

Controversies in Subspecialty Certification

Recently, debate also has surfaced regarding subspecialty certification. Over the last decade, proponents of subspecialty certification have argued that board certification would bring consistency and decrease divisiveness among dermatologists; help to prevent exclusion of Mohs surgeons from insurance networks and teaching opportunities at the Veterans Administration; and demonstrate competence to patients, the media, and payers. Those in opposition contest that practices may be restricted by insurers using lack of certification to eliminate dermatologists from their networks, economic credentialing may be applied to dermatologists such that those without the subspecialty certification may not be deemed qualified to manage skin cancer, major limitations may be set determining which dermatologists can sit for the certification examination, and subspecialty certification could create disenfranchisement of many dermatologists. A 2017 American Academy of Dermatology member survey demonstrated ambivalence regarding subcertification, with 51% of respondents pro-subcertification and 48% anti-subcertification.²³

Nonetheless, after years of debate the American Board of Dermatology proposed subspecialty certification in Micrographic Dermatologic Surgery, which was approved by the American Board of Medical Specialties on October 26, 2018. The first certification examination will likely take place in 2 years, and a maintenance of certification examination will be required every 10 years.²⁴

Final Thoughts

Further investigation is needed to elucidate and optimize solutions to many of the current controversies associated with MMS.

Mohs micrographic surgery (MMS) has been met with controversy since its inception in the 1930s. Current debate centers on the types of tumors treated with MMS, increasing utilization, third-party payer reimbursement, the Appropriate Use Criteria (AUC), and subspecialty certification.

Controversies in Applications

Controversy surrounding treatment with MMS for certain tumor types is abundant, in large part due to a lack of well-designed studies. Perhaps most notably, the surgical management of melanoma has been hotly contested for decades.¹ An increasing number of Mohs surgeons advocate the use of MMS for treatment of melanoma. Advocates reason that tumor margins may be ill-defined, necessitating histologic examination of the margin for tumor clearance. In a study by Zitelli et al,² 5-year survival and metastatic rates for 535 patients with melanomas treated by MMS with frozen sections were the same or better when compared to historical controls treated with conventional wide local excision. Melanoma-associated antigen recognized by T cells (MART-1) immunostaining may offer improved diagnostic accuracy.³ Others believe that staged excision with permanent sections processed vertically, en face, or horizontally (“slow Mohs”) is more accurate and efficacious for the treatment of melanoma.¹ Advocates of this approach maintain that when compared to MMS with frozen sections, staged excision with permanent sections enables more accurate interpretation of residual melanoma and atypical junctional melanocytic hyperplasia as well as circumvents difficulty in interpreting freeze artifact.⁴

Although Merkel cell carcinoma has traditionally been treated with wide local excision, MMS with or without adjuvant radiotherapy has gained traction as a treatment option. Advocates for treatment by MMS hold that Merkel cell carcinoma is a contiguous tumor with a high rate of residual tumor persistence, making histologic margin control an ideal characteristic of treatment. However, in the absence of large randomized controlled studies comparing MMS to wide local excision, controversy surrounds the most appropriate surgical approach.¹ In a retrospective study of 86 patients by O’Connor et al,⁵ MMS was demonstrated to compare favorably to standard surgical excision. Standard surgical excision was associated with a 31.7% (13/41) local persistence rate and 48.8% (20/41) regional metastasis rate compared to 8.3% (1/12) and 33.3% (4/12) for MMS, respectively.⁵

Controversies in Increasing Utilization

The incidence of skin cancers has increased in recent years. As a result, it is reasonable to expect the rates of MMS to increase. Nonetheless, there is escalating concern among groups of third-party payers, the public, and physicians that MMS is being overused.⁶ Growth of the body of evidence supporting the appropriateness of MMS remains essential. Such studies continue to support reasons for increased MMS usage, demonstrating the stability of the percentage of skin cancers treated with MMS in the setting of increasing skin cancer incidence, the procedure’s superior efficacy for appropriately chosen cases, its expanding application to melanoma and other tumors, and an emphasis of MMS in residency training programs.^6-9

A current hot topic of controversy focuses on the wide variation among Mohs surgeons in the mean number of stages used to resect a tumor. Overuse among outliers has been proposed to stem from lack of technical expertise or from abuse of the current fee-for-service payment model, which bases compensation on the number of stages performed. A study by Krishnan et al¹⁰ determined that the mean number of stages per tumor in the studied population (all physicians [N=2305] receiving Medicare payments for MMS from January 2012 to December 2014) was 1.74, with a range of 1.09 to 4.11. Persistently high outliers were more likely to perform MMS in a solo practice, with an odds ratio of 2.35.¹⁰ In response to the wide variation in mean stages used to resect a skin cancer and its implications on increased financial burden and surgery to individual patients, intervention has been proposed. Notably, it has been demonstrated that mailing out individual reports of practice patterns to high-outlier physicians resulted in a reduction in mean stages per tumor as well as an associated cost savings when compared to outlier physicians who did not receive these reports.¹¹

Controversies in Reimbursement

Mohs micrographic surgery also has been in the spotlight for debate regarding reimbursement. The procedure has been targeted partly in response to its substantial contribution to total Medicare reimbursements paid out. In 2013, primary MMS billing codes constituted nearly 19% of total reimbursements to dermatologists and approximately 0.5% of total reimbursements to all physicians participating in Medicare.¹² Mohs micrographic surgery codes have correspondingly received frequent review by the Relative Value Scale Update Committee and remained on a list of potentially misvalued services according to the Centers for Medicare & Medicaid Services for years.¹³ Due to continued scrutiny and review, especially by the Relative Value Scale Update Committee and Centers for Medicare & Medicaid Services, reimbursement to perform MMS and reconstructive surgery has gone down by more than 20% in the last 15 years.¹⁴ Public perception mirrors third-party payer concerns for overcompensation. An article title in the New York Times theatrically postures “Patients’ Costs Skyrocket, Specialists’ Incomes Soar.” The article recounts an MMS patient’s “outrage at charges” associated with treatment of her “minor medical problem” and the simultaneous “sharp climb” in dermatologist income over the last 2 decades.¹⁵

However, studies continue to demonstrate the cost-effectiveness of MMS. A study by Ravitskiy et al¹⁶ demonstrates the cost-effectiveness of MMS, regardless of place of service or type of tumor. Of 406 tumors studied, MMS was the least expensive surgical procedure evaluated ($805 per tumor) when compared to standard surgical excision with permanent margins ($1026 per tumor), standard surgical excision with frozen margins ($1200 per tumor), and ambulatory surgery center standard surgical excision ($2507 per tumor). Furthermore, adjusted for inflation, the cost of MMS was lower in 2009 vs 1998.¹⁶ Similar results have been consistently demonstrated.¹⁷

Controversies in the AUC

To provide clinicians, policy makers, and insurers guidance for utilization of MMS in the setting of concerns for overutilization, overcompensation, and inappropriate application, the MMS AUC were established in 2012. The guidelines were developed by a process integrating evidence-based medicine, clinical experience, and expert opinion and is applicable to 270 clinical scenarios.¹⁸

A unique set of debate accompanies the guidelines. Namely, controversy has surrounded the classification of most primary superficial basal cell carcinomas as appropriate for treatment by MMS. These tumors have comparable cure rates when treated by MMS or curettage and cryosurgery, are often multifocal and require more Mohs stages than other basal cell carcinoma subtypes, and largely lack data on recurrence and invasion.¹⁹ The guidelines also have been scrutinized for including only studies from the United States.²⁰ Furthermore, the report is largely based on expert opinion rather than evidence.

Some Mohs surgeons have concerns that the guidelines will minimize clinical judgment. Nonetheless, deviations from the AUC practiced by Mohs surgeons have been reported where clinical judgment supplants guideline criteria. The most commonly cited reasons for performing MMS on tumors classified as uncertain or inappropriate, according to one study by Ruiz et al,²¹ included performing multiple MMSs on the same day, tumor location on the lower legs, and incorporation into an adjacent wound. Reported discrepancies in the AUC further emphasize the importance of clinical judgment and call into question the need for future revision of the criteria.²² For example, a primary squamous cell carcinoma in situ greater than or equal to 2 cm located on the trunk and extremities (excluding pretibial surfaces, hands, feet, nail units, and ankles) in a healthy patient is categorized as appropriate, while a recurrent but otherwise identical squamous cell carcinoma in situ is categorized as uncertain. These counterintuitive criteria are unsupported by existing studies.

Controversies in Subspecialty Certification

Recently, debate also has surfaced regarding subspecialty certification. Over the last decade, proponents of subspecialty certification have argued that board certification would bring consistency and decrease divisiveness among dermatologists; help to prevent exclusion of Mohs surgeons from insurance networks and teaching opportunities at the Veterans Administration; and demonstrate competence to patients, the media, and payers. Those in opposition contest that practices may be restricted by insurers using lack of certification to eliminate dermatologists from their networks, economic credentialing may be applied to dermatologists such that those without the subspecialty certification may not be deemed qualified to manage skin cancer, major limitations may be set determining which dermatologists can sit for the certification examination, and subspecialty certification could create disenfranchisement of many dermatologists. A 2017 American Academy of Dermatology member survey demonstrated ambivalence regarding subcertification, with 51% of respondents pro-subcertification and 48% anti-subcertification.²³

Nonetheless, after years of debate the American Board of Dermatology proposed subspecialty certification in Micrographic Dermatologic Surgery, which was approved by the American Board of Medical Specialties on October 26, 2018. The first certification examination will likely take place in 2 years, and a maintenance of certification examination will be required every 10 years.²⁴

Final Thoughts

Further investigation is needed to elucidate and optimize solutions to many of the current controversies associated with MMS.

Mohs micrographic surgery (MMS) has been met with controversy since its inception in the 1930s. Current debate centers on the types of tumors treated with MMS, increasing utilization, third-party payer reimbursement, the Appropriate Use Criteria (AUC), and subspecialty certification.

Controversies in Applications

Controversy surrounding treatment with MMS for certain tumor types is abundant, in large part due to a lack of well-designed studies. Perhaps most notably, the surgical management of melanoma has been hotly contested for decades.¹ An increasing number of Mohs surgeons advocate the use of MMS for treatment of melanoma. Advocates reason that tumor margins may be ill-defined, necessitating histologic examination of the margin for tumor clearance. In a study by Zitelli et al,² 5-year survival and metastatic rates for 535 patients with melanomas treated by MMS with frozen sections were the same or better when compared to historical controls treated with conventional wide local excision. Melanoma-associated antigen recognized by T cells (MART-1) immunostaining may offer improved diagnostic accuracy.³ Others believe that staged excision with permanent sections processed vertically, en face, or horizontally (“slow Mohs”) is more accurate and efficacious for the treatment of melanoma.¹ Advocates of this approach maintain that when compared to MMS with frozen sections, staged excision with permanent sections enables more accurate interpretation of residual melanoma and atypical junctional melanocytic hyperplasia as well as circumvents difficulty in interpreting freeze artifact.⁴

Although Merkel cell carcinoma has traditionally been treated with wide local excision, MMS with or without adjuvant radiotherapy has gained traction as a treatment option. Advocates for treatment by MMS hold that Merkel cell carcinoma is a contiguous tumor with a high rate of residual tumor persistence, making histologic margin control an ideal characteristic of treatment. However, in the absence of large randomized controlled studies comparing MMS to wide local excision, controversy surrounds the most appropriate surgical approach.¹ In a retrospective study of 86 patients by O’Connor et al,⁵ MMS was demonstrated to compare favorably to standard surgical excision. Standard surgical excision was associated with a 31.7% (13/41) local persistence rate and 48.8% (20/41) regional metastasis rate compared to 8.3% (1/12) and 33.3% (4/12) for MMS, respectively.⁵

Controversies in Increasing Utilization

The incidence of skin cancers has increased in recent years. As a result, it is reasonable to expect the rates of MMS to increase. Nonetheless, there is escalating concern among groups of third-party payers, the public, and physicians that MMS is being overused.⁶ Growth of the body of evidence supporting the appropriateness of MMS remains essential. Such studies continue to support reasons for increased MMS usage, demonstrating the stability of the percentage of skin cancers treated with MMS in the setting of increasing skin cancer incidence, the procedure’s superior efficacy for appropriately chosen cases, its expanding application to melanoma and other tumors, and an emphasis of MMS in residency training programs.^6-9

A current hot topic of controversy focuses on the wide variation among Mohs surgeons in the mean number of stages used to resect a tumor. Overuse among outliers has been proposed to stem from lack of technical expertise or from abuse of the current fee-for-service payment model, which bases compensation on the number of stages performed. A study by Krishnan et al¹⁰ determined that the mean number of stages per tumor in the studied population (all physicians [N=2305] receiving Medicare payments for MMS from January 2012 to December 2014) was 1.74, with a range of 1.09 to 4.11. Persistently high outliers were more likely to perform MMS in a solo practice, with an odds ratio of 2.35.¹⁰ In response to the wide variation in mean stages used to resect a skin cancer and its implications on increased financial burden and surgery to individual patients, intervention has been proposed. Notably, it has been demonstrated that mailing out individual reports of practice patterns to high-outlier physicians resulted in a reduction in mean stages per tumor as well as an associated cost savings when compared to outlier physicians who did not receive these reports.¹¹

Controversies in Reimbursement

Mohs micrographic surgery also has been in the spotlight for debate regarding reimbursement. The procedure has been targeted partly in response to its substantial contribution to total Medicare reimbursements paid out. In 2013, primary MMS billing codes constituted nearly 19% of total reimbursements to dermatologists and approximately 0.5% of total reimbursements to all physicians participating in Medicare.¹² Mohs micrographic surgery codes have correspondingly received frequent review by the Relative Value Scale Update Committee and remained on a list of potentially misvalued services according to the Centers for Medicare & Medicaid Services for years.¹³ Due to continued scrutiny and review, especially by the Relative Value Scale Update Committee and Centers for Medicare & Medicaid Services, reimbursement to perform MMS and reconstructive surgery has gone down by more than 20% in the last 15 years.¹⁴ Public perception mirrors third-party payer concerns for overcompensation. An article title in the New York Times theatrically postures “Patients’ Costs Skyrocket, Specialists’ Incomes Soar.” The article recounts an MMS patient’s “outrage at charges” associated with treatment of her “minor medical problem” and the simultaneous “sharp climb” in dermatologist income over the last 2 decades.¹⁵

However, studies continue to demonstrate the cost-effectiveness of MMS. A study by Ravitskiy et al¹⁶ demonstrates the cost-effectiveness of MMS, regardless of place of service or type of tumor. Of 406 tumors studied, MMS was the least expensive surgical procedure evaluated ($805 per tumor) when compared to standard surgical excision with permanent margins ($1026 per tumor), standard surgical excision with frozen margins ($1200 per tumor), and ambulatory surgery center standard surgical excision ($2507 per tumor). Furthermore, adjusted for inflation, the cost of MMS was lower in 2009 vs 1998.¹⁶ Similar results have been consistently demonstrated.¹⁷

Controversies in the AUC

To provide clinicians, policy makers, and insurers guidance for utilization of MMS in the setting of concerns for overutilization, overcompensation, and inappropriate application, the MMS AUC were established in 2012. The guidelines were developed by a process integrating evidence-based medicine, clinical experience, and expert opinion and is applicable to 270 clinical scenarios.¹⁸

A unique set of debate accompanies the guidelines. Namely, controversy has surrounded the classification of most primary superficial basal cell carcinomas as appropriate for treatment by MMS. These tumors have comparable cure rates when treated by MMS or curettage and cryosurgery, are often multifocal and require more Mohs stages than other basal cell carcinoma subtypes, and largely lack data on recurrence and invasion.¹⁹ The guidelines also have been scrutinized for including only studies from the United States.²⁰ Furthermore, the report is largely based on expert opinion rather than evidence.

Some Mohs surgeons have concerns that the guidelines will minimize clinical judgment. Nonetheless, deviations from the AUC practiced by Mohs surgeons have been reported where clinical judgment supplants guideline criteria. The most commonly cited reasons for performing MMS on tumors classified as uncertain or inappropriate, according to one study by Ruiz et al,²¹ included performing multiple MMSs on the same day, tumor location on the lower legs, and incorporation into an adjacent wound. Reported discrepancies in the AUC further emphasize the importance of clinical judgment and call into question the need for future revision of the criteria.²² For example, a primary squamous cell carcinoma in situ greater than or equal to 2 cm located on the trunk and extremities (excluding pretibial surfaces, hands, feet, nail units, and ankles) in a healthy patient is categorized as appropriate, while a recurrent but otherwise identical squamous cell carcinoma in situ is categorized as uncertain. These counterintuitive criteria are unsupported by existing studies.

Controversies in Subspecialty Certification

Recently, debate also has surfaced regarding subspecialty certification. Over the last decade, proponents of subspecialty certification have argued that board certification would bring consistency and decrease divisiveness among dermatologists; help to prevent exclusion of Mohs surgeons from insurance networks and teaching opportunities at the Veterans Administration; and demonstrate competence to patients, the media, and payers. Those in opposition contest that practices may be restricted by insurers using lack of certification to eliminate dermatologists from their networks, economic credentialing may be applied to dermatologists such that those without the subspecialty certification may not be deemed qualified to manage skin cancer, major limitations may be set determining which dermatologists can sit for the certification examination, and subspecialty certification could create disenfranchisement of many dermatologists. A 2017 American Academy of Dermatology member survey demonstrated ambivalence regarding subcertification, with 51% of respondents pro-subcertification and 48% anti-subcertification.²³

Nonetheless, after years of debate the American Board of Dermatology proposed subspecialty certification in Micrographic Dermatologic Surgery, which was approved by the American Board of Medical Specialties on October 26, 2018. The first certification examination will likely take place in 2 years, and a maintenance of certification examination will be required every 10 years.²⁴

Final Thoughts

Further investigation is needed to elucidate and optimize solutions to many of the current controversies associated with MMS.