From the Editor

With so much emphasis on clinical trials, evidence-based joint decision-making, and comparative-benefit studies when choosing treatment, the growth of the supplement market is a strong comment on the perceived and often real failings of traditional therapies. It also reflects our apparent failure as a profession to educate ourselves and the public about the difference between anecdote-based belief and clinical trial-based confidence, the difference between evidence and innuendo, and, equally important, the limitations of applying population-based clinical trial data to an individual patient.

Which brings me to the discussion of calcium and vitamin D supplementation by Drs. Kilim and Rosen in this issue of the Journal. We know a lot about calcium homeostasis and the role vitamin D plays in regulating circulating calcium levels. Only a small fraction of the calcium in the body circulates (most is in our skeleton), and likely only about 1% is truly exchangeable. But the circulating free calcium level is tightly controlled, as the function of our neuromuscular system, brain, and heart depend on keeping intra- and extracellular calcium levels within precise limits. If necessary, our bodies maintain stable levels of circulating free calcium at the expense of leaching calcium from our bones, placing us at risk of potentially fatal fractures. Thus was born the concept of guaranteeing adequate calcium stores through calcium supplementation.

Control of the free calcium level is not simple. There are several interrelated sensing and modulatory pathways, eg:

• Gut absorption, which is affected by the total gut load of calcium, intestinal integrity, and the specific ingested foodstuffs, and likely by our microbiome
• The parathyroid hormone (PTH) level, which directly or indirectly affects calcium absorption, the calcium-phosphate ratio, and thus, extraskeletal calcium localization and bone calcium content
• Vitamin D, with its many effects after interorgan multistep activation.

Despite this knowledge of calcium metabolism and the intricate cross-talk between the different pathways, I do not believe we truly understand how to determine the amount of dietary and supplemental calcium or vitamin D that is ideal for a given patient. I also do not believe we know with certainty what is the “normal” or ideal 25-hydroxyvitamin D level in that same patient: note the different ranges of normal proposed by different expert working groups.

How do we know when there is insufficient calcium in our diet? The total or free circulating calcium level is far too insensitive and, as noted above, complex homeostatic mechanisms are always trying to maintain an appropriate physiologic calcium level, whatever the intake. Urinary calcium excretion does not necessarily equal the ingested calcium load; there are too many factors influencing renal calcium excretion. Gastrointestinal excretion is also variable and complex. We know when the vitamin D level is functionally much too low, as the PTH level begins to rise; but the “normal” PTH range is wide, and the slope of the relationship between vitamin D and PTH is affected by many factors.

Additionally, accumulating information suggests that vitamin D metabolites significantly affect immune regulation and the onset and expression of a number of organ-specific and systemic autoimmune disorders. Further, the ideal 25-hydroxyvitamin D level for a healthy immune system is not known. Does the body have to compromise something in reconciling the target for a healthy skeleton and the target for a healthy immune system, which may conceivably be different? But importantly, this new knowledge does not imply that vitamin D supplementation will reduce the pain and symptoms from inflammatory arthritis or noninflammatory fibromyalgia.

Despite these many areas of uncertainty, Kilim and Rosen focus on bone health, summarize the wealth of accumulated data, and provide practical management advice we can use in the clinic. But if we struggle so much to know the correct way to manage calcium and vitamin D supplementation in our patients, it is little surprise that most of us struggle even more when asked about using supplements for which the biology is far less understood. As a medical community, we need to uniformly address this lack of understanding wherever it exists. Believing in a supplement or a treatment is not the same as understanding it or having strong evidence about its efficacy and safety.

With so much emphasis on clinical trials, evidence-based joint decision-making, and comparative-benefit studies when choosing treatment, the growth of the supplement market is a strong comment on the perceived and often real failings of traditional therapies. It also reflects our apparent failure as a profession to educate ourselves and the public about the difference between anecdote-based belief and clinical trial-based confidence, the difference between evidence and innuendo, and, equally important, the limitations of applying population-based clinical trial data to an individual patient.

Which brings me to the discussion of calcium and vitamin D supplementation by Drs. Kilim and Rosen in this issue of the Journal. We know a lot about calcium homeostasis and the role vitamin D plays in regulating circulating calcium levels. Only a small fraction of the calcium in the body circulates (most is in our skeleton), and likely only about 1% is truly exchangeable. But the circulating free calcium level is tightly controlled, as the function of our neuromuscular system, brain, and heart depend on keeping intra- and extracellular calcium levels within precise limits. If necessary, our bodies maintain stable levels of circulating free calcium at the expense of leaching calcium from our bones, placing us at risk of potentially fatal fractures. Thus was born the concept of guaranteeing adequate calcium stores through calcium supplementation.

Control of the free calcium level is not simple. There are several interrelated sensing and modulatory pathways, eg:

• Gut absorption, which is affected by the total gut load of calcium, intestinal integrity, and the specific ingested foodstuffs, and likely by our microbiome
• The parathyroid hormone (PTH) level, which directly or indirectly affects calcium absorption, the calcium-phosphate ratio, and thus, extraskeletal calcium localization and bone calcium content
• Vitamin D, with its many effects after interorgan multistep activation.

Despite this knowledge of calcium metabolism and the intricate cross-talk between the different pathways, I do not believe we truly understand how to determine the amount of dietary and supplemental calcium or vitamin D that is ideal for a given patient. I also do not believe we know with certainty what is the “normal” or ideal 25-hydroxyvitamin D level in that same patient: note the different ranges of normal proposed by different expert working groups.

How do we know when there is insufficient calcium in our diet? The total or free circulating calcium level is far too insensitive and, as noted above, complex homeostatic mechanisms are always trying to maintain an appropriate physiologic calcium level, whatever the intake. Urinary calcium excretion does not necessarily equal the ingested calcium load; there are too many factors influencing renal calcium excretion. Gastrointestinal excretion is also variable and complex. We know when the vitamin D level is functionally much too low, as the PTH level begins to rise; but the “normal” PTH range is wide, and the slope of the relationship between vitamin D and PTH is affected by many factors.

Additionally, accumulating information suggests that vitamin D metabolites significantly affect immune regulation and the onset and expression of a number of organ-specific and systemic autoimmune disorders. Further, the ideal 25-hydroxyvitamin D level for a healthy immune system is not known. Does the body have to compromise something in reconciling the target for a healthy skeleton and the target for a healthy immune system, which may conceivably be different? But importantly, this new knowledge does not imply that vitamin D supplementation will reduce the pain and symptoms from inflammatory arthritis or noninflammatory fibromyalgia.

Despite these many areas of uncertainty, Kilim and Rosen focus on bone health, summarize the wealth of accumulated data, and provide practical management advice we can use in the clinic. But if we struggle so much to know the correct way to manage calcium and vitamin D supplementation in our patients, it is little surprise that most of us struggle even more when asked about using supplements for which the biology is far less understood. As a medical community, we need to uniformly address this lack of understanding wherever it exists. Believing in a supplement or a treatment is not the same as understanding it or having strong evidence about its efficacy and safety.

With so much emphasis on clinical trials, evidence-based joint decision-making, and comparative-benefit studies when choosing treatment, the growth of the supplement market is a strong comment on the perceived and often real failings of traditional therapies. It also reflects our apparent failure as a profession to educate ourselves and the public about the difference between anecdote-based belief and clinical trial-based confidence, the difference between evidence and innuendo, and, equally important, the limitations of applying population-based clinical trial data to an individual patient.

Which brings me to the discussion of calcium and vitamin D supplementation by Drs. Kilim and Rosen in this issue of the Journal. We know a lot about calcium homeostasis and the role vitamin D plays in regulating circulating calcium levels. Only a small fraction of the calcium in the body circulates (most is in our skeleton), and likely only about 1% is truly exchangeable. But the circulating free calcium level is tightly controlled, as the function of our neuromuscular system, brain, and heart depend on keeping intra- and extracellular calcium levels within precise limits. If necessary, our bodies maintain stable levels of circulating free calcium at the expense of leaching calcium from our bones, placing us at risk of potentially fatal fractures. Thus was born the concept of guaranteeing adequate calcium stores through calcium supplementation.

Control of the free calcium level is not simple. There are several interrelated sensing and modulatory pathways, eg:

• Gut absorption, which is affected by the total gut load of calcium, intestinal integrity, and the specific ingested foodstuffs, and likely by our microbiome
• The parathyroid hormone (PTH) level, which directly or indirectly affects calcium absorption, the calcium-phosphate ratio, and thus, extraskeletal calcium localization and bone calcium content
• Vitamin D, with its many effects after interorgan multistep activation.

Despite this knowledge of calcium metabolism and the intricate cross-talk between the different pathways, I do not believe we truly understand how to determine the amount of dietary and supplemental calcium or vitamin D that is ideal for a given patient. I also do not believe we know with certainty what is the “normal” or ideal 25-hydroxyvitamin D level in that same patient: note the different ranges of normal proposed by different expert working groups.

How do we know when there is insufficient calcium in our diet? The total or free circulating calcium level is far too insensitive and, as noted above, complex homeostatic mechanisms are always trying to maintain an appropriate physiologic calcium level, whatever the intake. Urinary calcium excretion does not necessarily equal the ingested calcium load; there are too many factors influencing renal calcium excretion. Gastrointestinal excretion is also variable and complex. We know when the vitamin D level is functionally much too low, as the PTH level begins to rise; but the “normal” PTH range is wide, and the slope of the relationship between vitamin D and PTH is affected by many factors.

Additionally, accumulating information suggests that vitamin D metabolites significantly affect immune regulation and the onset and expression of a number of organ-specific and systemic autoimmune disorders. Further, the ideal 25-hydroxyvitamin D level for a healthy immune system is not known. Does the body have to compromise something in reconciling the target for a healthy skeleton and the target for a healthy immune system, which may conceivably be different? But importantly, this new knowledge does not imply that vitamin D supplementation will reduce the pain and symptoms from inflammatory arthritis or noninflammatory fibromyalgia.

Despite these many areas of uncertainty, Kilim and Rosen focus on bone health, summarize the wealth of accumulated data, and provide practical management advice we can use in the clinic. But if we struggle so much to know the correct way to manage calcium and vitamin D supplementation in our patients, it is little surprise that most of us struggle even more when asked about using supplements for which the biology is far less understood. As a medical community, we need to uniformly address this lack of understanding wherever it exists. Believing in a supplement or a treatment is not the same as understanding it or having strong evidence about its efficacy and safety.

Recently, contemporary “culture” has capriciously confounded and confused our national community with a cringeworthy “C” word. Unfortunately, this was followed by only transient public consternation, reflecting the coarsening of our social communication and discourse and the cant of many. But the ripple effects continue.

As a psychiatrist who closely observes the human condition, I contemplated the current confrontational tone in the media, and wondered how corrosive language can confuse and cloud our sensibilities.

Then it occurred to me that there are many commendable clinical “C” words that describe what we psychiatrists do in daily practice. We stay calm while facing crises, and help our patients achieve certainty when stress makes them confused. We compassionately comfort and care for our suffering patients. We strive to engender courage and confidence when fragile patients are confronted with continuous criticism by callous and condescending people. We remain composed when we counsel patients with confrontational and crabby moods and help correct their confusing conflicts. We coordinate their care with courtesy, always aspiring for a cure for their corroded emotional condition.

But then I felt compelled to go further and call on my creativity to consider “C” words that describe severe psychiatric clinical disorders. I came up with the following cogent cascade of common characteristics of serious mental disorders:

• Cerebral pathology
• Circuit disruptions of neural connections
• Chemical imbalance
• Cytokine inflammatory con­flagration
• Cognitive impairment
• Chronic course
• Crippled functioning.

My compulsion continued. I decided to contemplate more “C” words that capture our therapeutic course of action to correct a patient whose cortico-limbic circuitry is being threatened with considerable, even calamitous collapse. My consideration led to clarity, and I came up with the following list of what we psychiatrists conform to in our clinical practice:

• Connect with patients
• Correct diagnosis
• Course-specific intervention
• Choose the appropriate medication
• Combine cognitive-behavioral therapy with medication
• Cognitive assessment at baseline
• Compliance/concordance with treatment
• Continuity of care
• Comorbidities, physical and psychiatric
• Collaborative care with other medical specialists
• Comprehensive treatment plan with other mental health professionals.

A book about dirty words written by a psychoanalyst called the “C” expletive the worst of all cuss words.¹ Its recent emergence in the national media compromised our civility and created a cesspool of contemptible conversations. Let’s transcend the contemptible “C” word of a caustic contemporary “culture” (which had its 15 minutes of infamy), and consider the many coherent and congenial “C” words of psych­iatric practice that bring peace of mind and contentment to those who suffer from psychiatric brain conditions. As for the compulsive or involuntary use of curse words that begin with a “C,” or any other letter, psychiatry has a clinical term for it: coprolalia.

Editor's note: How many C words are there in this editorial? Email answers to [email protected]

Recently, contemporary “culture” has capriciously confounded and confused our national community with a cringeworthy “C” word. Unfortunately, this was followed by only transient public consternation, reflecting the coarsening of our social communication and discourse and the cant of many. But the ripple effects continue.

As a psychiatrist who closely observes the human condition, I contemplated the current confrontational tone in the media, and wondered how corrosive language can confuse and cloud our sensibilities.

Then it occurred to me that there are many commendable clinical “C” words that describe what we psychiatrists do in daily practice. We stay calm while facing crises, and help our patients achieve certainty when stress makes them confused. We compassionately comfort and care for our suffering patients. We strive to engender courage and confidence when fragile patients are confronted with continuous criticism by callous and condescending people. We remain composed when we counsel patients with confrontational and crabby moods and help correct their confusing conflicts. We coordinate their care with courtesy, always aspiring for a cure for their corroded emotional condition.

But then I felt compelled to go further and call on my creativity to consider “C” words that describe severe psychiatric clinical disorders. I came up with the following cogent cascade of common characteristics of serious mental disorders:

• Cerebral pathology
• Circuit disruptions of neural connections
• Chemical imbalance
• Cytokine inflammatory con­flagration
• Cognitive impairment
• Chronic course
• Crippled functioning.

My compulsion continued. I decided to contemplate more “C” words that capture our therapeutic course of action to correct a patient whose cortico-limbic circuitry is being threatened with considerable, even calamitous collapse. My consideration led to clarity, and I came up with the following list of what we psychiatrists conform to in our clinical practice:

• Connect with patients
• Correct diagnosis
• Course-specific intervention
• Choose the appropriate medication
• Combine cognitive-behavioral therapy with medication
• Cognitive assessment at baseline
• Compliance/concordance with treatment
• Continuity of care
• Comorbidities, physical and psychiatric
• Collaborative care with other medical specialists
• Comprehensive treatment plan with other mental health professionals.

A book about dirty words written by a psychoanalyst called the “C” expletive the worst of all cuss words.¹ Its recent emergence in the national media compromised our civility and created a cesspool of contemptible conversations. Let’s transcend the contemptible “C” word of a caustic contemporary “culture” (which had its 15 minutes of infamy), and consider the many coherent and congenial “C” words of psych­iatric practice that bring peace of mind and contentment to those who suffer from psychiatric brain conditions. As for the compulsive or involuntary use of curse words that begin with a “C,” or any other letter, psychiatry has a clinical term for it: coprolalia.

Editor's note: How many C words are there in this editorial? Email answers to [email protected]

Recently, contemporary “culture” has capriciously confounded and confused our national community with a cringeworthy “C” word. Unfortunately, this was followed by only transient public consternation, reflecting the coarsening of our social communication and discourse and the cant of many. But the ripple effects continue.

As a psychiatrist who closely observes the human condition, I contemplated the current confrontational tone in the media, and wondered how corrosive language can confuse and cloud our sensibilities.

Then it occurred to me that there are many commendable clinical “C” words that describe what we psychiatrists do in daily practice. We stay calm while facing crises, and help our patients achieve certainty when stress makes them confused. We compassionately comfort and care for our suffering patients. We strive to engender courage and confidence when fragile patients are confronted with continuous criticism by callous and condescending people. We remain composed when we counsel patients with confrontational and crabby moods and help correct their confusing conflicts. We coordinate their care with courtesy, always aspiring for a cure for their corroded emotional condition.

But then I felt compelled to go further and call on my creativity to consider “C” words that describe severe psychiatric clinical disorders. I came up with the following cogent cascade of common characteristics of serious mental disorders:

• Cerebral pathology
• Circuit disruptions of neural connections
• Chemical imbalance
• Cytokine inflammatory con­flagration
• Cognitive impairment
• Chronic course
• Crippled functioning.

My compulsion continued. I decided to contemplate more “C” words that capture our therapeutic course of action to correct a patient whose cortico-limbic circuitry is being threatened with considerable, even calamitous collapse. My consideration led to clarity, and I came up with the following list of what we psychiatrists conform to in our clinical practice:

• Connect with patients
• Correct diagnosis
• Course-specific intervention
• Choose the appropriate medication
• Combine cognitive-behavioral therapy with medication
• Cognitive assessment at baseline
• Compliance/concordance with treatment
• Continuity of care
• Comorbidities, physical and psychiatric
• Collaborative care with other medical specialists
• Comprehensive treatment plan with other mental health professionals.

A book about dirty words written by a psychoanalyst called the “C” expletive the worst of all cuss words.¹ Its recent emergence in the national media compromised our civility and created a cesspool of contemptible conversations. Let’s transcend the contemptible “C” word of a caustic contemporary “culture” (which had its 15 minutes of infamy), and consider the many coherent and congenial “C” words of psych­iatric practice that bring peace of mind and contentment to those who suffer from psychiatric brain conditions. As for the compulsive or involuntary use of curse words that begin with a “C,” or any other letter, psychiatry has a clinical term for it: coprolalia.

Editor's note: How many C words are there in this editorial? Email answers to [email protected]

Cervical cancer screening represents one of the great public health successes of the 20th Century. Two physician-scientists, George Papanicolaou, MD, PhD (1883–1962), and Harald zur Hausen, MD (1936–), made extraordinary contributions to the evolution of effective cervical cancer screening programs. Dr. Papanicolaou led development of the iconic Pap smear, creating techniques for collecting specimens and using cytologic techniques to identify cervical cancer and its precursors, and Dr. zur Hausen discovered the association of human papillomavirus (HPV) infection with cervical cancer.^1,2

Although it is but a distant memory, in the 1930s cervical and uterine cancer caused more deaths among women than breast, lung, or ovarian cancer. The successful deployment of Pap smear screening resulted in a decrease in cervical cancer rates in developed countries. Cervical cancer deaths remain common in many parts of the world, however. Cervical cancer screening programs can reduce cervical cancer incidence by greater than 80%.³ In the United States between 1973 and 2006, the invasive cervical cancer age-adjusted incidence rates dropped from 10.28 to 3.97 per 100,000 women.⁴

HPV causes cervical cancer

Dr. zur Hausen dedicated his career to identifying viral causes of human cancer. In his Nobel Laureate autobiography, he reported that during his 2-year rotating residency, he loved his obstetrics and gynecology experience, but found it “physically highly demanding” and decided to focus his career in microbiology and immunology.⁵ After proving that herpes simplex virus did not cause cervical cancer he began to explore the role of HPV in the disease process. He first identified HPV types 6 and 11 and showed that these agents caused genital warts. He then used low-stringency hybridization techniques to identify HPV types 16 and 18 in specimens of cervical cancer. Later, he and his colleagues proved that two HPV proteins, E6 and E7, interfere with the function of cell cycle control proteins p53 and retinoblastoma protein, resulting in dysregulated cell growth and cancer.² These findings permitted the development of both HPV vaccines and nucleic acid–based tests to identify high-risk oncogenic HPV (hrHPV) in cells and tissue specimens.

HPV vaccination

Dr. zur Hausen was an energetic and vocal advocate for the development and widescale deployment of HPV vaccines, including vaccination of males and females.⁶ Initially his ideas were rejected by the pharmaceutical industry, but eventually, with advances in virology and vaccine development, multiple companies pursued the development of HPV vaccines, the first cancer prevention vaccines. The best approach to cervical cancer prevention is intensive population-wide HPV vaccination of both boys and girls before exposure to the HPV virus. Beyond its beneficial effect on the incidence of cervical cancer, HPV vaccination also reduces the population incidence of anal, vulvar, and oropharyngeal cancer.⁷ Prevention of oropharyngeal cancer is especially important for men, supporting the recommendation for vaccination of all boys.⁸

Population-wide HPV vaccination will result in a lower prevalence of cervical cancer precursors and reduce the sensitivity of cytology, thereby making primary HPV screening more attractive.⁹ Based on one modelling study, universal HPV vaccination can reduce cervical cancer rates by greater than 50% over current levels, and introduction of primary HPV screening will reduce cervical cancer rates by an additional 20%.¹⁰ In an era of widespread vaccination for HPV, screening for cervical cancer should be intensified for nonvaccinated women.¹⁰

Read about Primary cervical cancer screening with cytology

Primary cervical cancer screening with cytology

Primary screening with cervical cytology alone remains an option supported by many authorities and professional society guidelines.¹¹ Most studies report that HPV testing has greater sensitivity than cervical cytology alone, especially for the detection of adenocarcinoma of the cervix.¹² In one Canadian study, 10,154 women were randomly assigned to HPV or cervical cytology testing. The sensitivity of HPV testing and cervical cytology for detecting cervical intraepithelial neoplasia grade 2 or 3 was 95% and 55%, respectively, with a specificity of 94% and 97%, respectively.¹³ When used together the sensitivity and specificity of cotesting was 100% and 93%, respectively, but resulted in an increased number of colposcopies, which may be costly and add stress for the patient. Many countries are beginning to move away from cervical cancer screening with cytology or cotesting to programs built upon a foundation of primary HPV testing.

Primary cervical cancer screening with HPV testing

The knowledge that hrHPV is a more sensitive test for cervical cancer and its precursors, as well as the relatively lower sensitivity of cytology, is the foundation for transitioning from primary screening with cervical cytology to primary screening with HPV testing. In the Netherlands¹⁴ and Australia^15,16 HPV testing with reflex cytology is the nationwide approach to cervical cancer screening. The basic components of the Dutch primary HPV screening program, as explained by Dr. Lai van Zulyan Mandres, are¹⁴:

1. Samples are collected by a general practitioner and sent to one of 5 central testing facilities for DNA testing for hrHPV.
2. If all previous samples tested negative, the screening occurs at ages 30, 35, 40, 50, and 60 years, a minimum of 5 screens per woman.
3. If there is a history of a previously positive hrHPV, the screening is intensified, with additional specimens collected at ages 45, 55, and 60 years.
4. If the sample is hrHPV negative, the patient continues screening at the standard intervals. No cytology testing is performed.
5. If the sample is hrHPV positive, reflex cytology is performed using the original collected sample. If the cytology shows no intraepithelial lesion or malignancy (NILM), another specimen is obtained for cytology within 6 months. If the second cytology specimen shows atypical squamous cells of undetermined significance (ASCUS) or a more worrisome cytology finding, the patient is sent for colposcopy. If two NILM cytology specimens have been obtained, the patient resumes primary hrHPV screening every 5 years.
6. If the specimen is hrHPV positive and cytology is ASCUS or more worrisome the patient is referred for colposcopy (FIGURE).¹⁴ The Dutch estimate that primary hrHPV screening will reduce the number of cervical cytology specimens by 90% annually.

Australia also has implemented nationwide primary HPV testing for cervical cancer screening. This change was implemented following a 10-year program of universal school-based vaccination of girls and boys, and biennial cytology screening for all women. The Australian screening program initiates hrHPV testing at age 25 years and thereafter every 5 years until age 74. If the hrHPV test is positive, reflex testing for HPV types 16 and 18 are performed on the original specimen along with cervical cytology. Women who test positive for HPV 16 or 18 are immediately referred for colposcopy. If the hrHPV test is positive and reflex testing for HPV 16 and 18 is negative, cervical cytology demonstrating ASCUS, low- or high-grade squamous intraepithelial lesions, or more worrisome results trigger a referral for colposcopy. The Australian program supports testing of self-collected vaginal samples for women who are underscreened or have never been screened.^15,16

Read about Pros and cons of switching approaches

Pros and cons of switching approaches

Deployment of new technology often yields benefits and challenges. A putative benefit of primary HPV screening is a reduction in health care costs without an increase in cervical cancer deaths. Another benefit of primary HPV screening is that it may enable self-collection of specimens for analysis, thereby increasing access to cervical cancer screening for underserved and marginalized populations of women who are not currently participating in cervical cancer screening programs.¹⁷ One challenge is that many women are unaware that hrHPV is the cause of most invasive cervical cancers. The detection of hrHPV in a woman in a long-term relationship who was previously negative for hrHPV may cause the emotions of surprise, fear, anxiety, and anger, thereby stressing the relationship.¹⁸

Another concern is that many women are worried about no longer receiving the familiar “Pap smear” cancer screening test in which they have tremendous faith. When Australia transitioned to primary HPV screening, more than 70,000 women signed a petition to “save women’s lives” by permitting continued access to the cervical cytology testing.¹⁹ Primary HPV testing may result in a transient increase in the number of women referred for colposcopy, potentially overwhelming the capacity of the health care system to deliver this vital service.^20,21 The HPV types that most often cause cervical cancer may vary among countries. For example, in Thailand, HPV 52 and 58 are frequently detected in women with high-grade squamous lesions, and including these subtypes in reflex genotyping may be of regional benefit.²²

Primary cervical cancer screening with HPV testing: When will it be used widely in the United States?

In contrast to the United States, the Netherlands is a small, densely populated country that has a highly integrated health system with centralized laboratory centers, a nationwide electronic health record, and clinicians organized to perform as an integrated team. These features ensure that all lifetime tests results are available in one record, that HPV testing is highly standardized, and that clinicians will follow a prescribed care pathway. The Netherlands’ health system is organized to support the successful transition, in a single step, to primary HPV testing. The United States is the third most populous country in the world, following China and India, with a diverse approach to health care, a highly mobile population, no single interoperable electronic health record, and minimal central control of clinical practice. The United States is not organized to make a “big bang” transition to primary HPV cervical cancer screening. It is likely that the introduction of primary HPV screening will occur first in highly integrated health systems that control the clinical, laboratory, and electronic records of a large population.

The results of the ATHENA study provide a clear clinical algorithm for implementing a primary HPV screening program for cervical cancer in the United States.^23–25 Samples are collected for hrHPV testing at a specified interval, 3 or 5 years, beginning at age 25 years. Women younger than age 25 years should be screened with cytology alone. Detection of hrHPV results in reflex viral typing for HPV 16 and 18. Women with samples positive for HPV 16 and 18 are immediately referred for colposcopy. Samples positive for hrHPV and negative for HPV 16 and 18 have reflex cytology testing performed on the original HPV specimen. If cytology testing reports NILM, repeat cotesting is performed in one year. If cytology testing reports ASCUS or a more concerning result, the woman is referred for colposcopy.

Malcolm Gladwell, in his book The Tipping Point, identified 3 processes that help push an innovative new approach from obscurity into widespread use.²⁶ First, authoritative voices that can catalyze change need to consistently communicate their shared vision for the future. Second, there must be a clear message that galvanizes the many to change their approach. Third, the historical context must be supportive of the change. Over the next decade we are likely to hit a tipping point and transition from cervical cancer screening that relies on cervical cytology to an approach that prioritizes hrHPV testing. When that change will occur in the United States is unclear. But our colleagues in other countries already have transitioned to primary hrHPV testing for cervical cancer screening.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Cervical cancer screening represents one of the great public health successes of the 20th Century. Two physician-scientists, George Papanicolaou, MD, PhD (1883–1962), and Harald zur Hausen, MD (1936–), made extraordinary contributions to the evolution of effective cervical cancer screening programs. Dr. Papanicolaou led development of the iconic Pap smear, creating techniques for collecting specimens and using cytologic techniques to identify cervical cancer and its precursors, and Dr. zur Hausen discovered the association of human papillomavirus (HPV) infection with cervical cancer.^1,2

Although it is but a distant memory, in the 1930s cervical and uterine cancer caused more deaths among women than breast, lung, or ovarian cancer. The successful deployment of Pap smear screening resulted in a decrease in cervical cancer rates in developed countries. Cervical cancer deaths remain common in many parts of the world, however. Cervical cancer screening programs can reduce cervical cancer incidence by greater than 80%.³ In the United States between 1973 and 2006, the invasive cervical cancer age-adjusted incidence rates dropped from 10.28 to 3.97 per 100,000 women.⁴

HPV causes cervical cancer

Dr. zur Hausen dedicated his career to identifying viral causes of human cancer. In his Nobel Laureate autobiography, he reported that during his 2-year rotating residency, he loved his obstetrics and gynecology experience, but found it “physically highly demanding” and decided to focus his career in microbiology and immunology.⁵ After proving that herpes simplex virus did not cause cervical cancer he began to explore the role of HPV in the disease process. He first identified HPV types 6 and 11 and showed that these agents caused genital warts. He then used low-stringency hybridization techniques to identify HPV types 16 and 18 in specimens of cervical cancer. Later, he and his colleagues proved that two HPV proteins, E6 and E7, interfere with the function of cell cycle control proteins p53 and retinoblastoma protein, resulting in dysregulated cell growth and cancer.² These findings permitted the development of both HPV vaccines and nucleic acid–based tests to identify high-risk oncogenic HPV (hrHPV) in cells and tissue specimens.

HPV vaccination

Dr. zur Hausen was an energetic and vocal advocate for the development and widescale deployment of HPV vaccines, including vaccination of males and females.⁶ Initially his ideas were rejected by the pharmaceutical industry, but eventually, with advances in virology and vaccine development, multiple companies pursued the development of HPV vaccines, the first cancer prevention vaccines. The best approach to cervical cancer prevention is intensive population-wide HPV vaccination of both boys and girls before exposure to the HPV virus. Beyond its beneficial effect on the incidence of cervical cancer, HPV vaccination also reduces the population incidence of anal, vulvar, and oropharyngeal cancer.⁷ Prevention of oropharyngeal cancer is especially important for men, supporting the recommendation for vaccination of all boys.⁸

Population-wide HPV vaccination will result in a lower prevalence of cervical cancer precursors and reduce the sensitivity of cytology, thereby making primary HPV screening more attractive.⁹ Based on one modelling study, universal HPV vaccination can reduce cervical cancer rates by greater than 50% over current levels, and introduction of primary HPV screening will reduce cervical cancer rates by an additional 20%.¹⁰ In an era of widespread vaccination for HPV, screening for cervical cancer should be intensified for nonvaccinated women.¹⁰

Read about Primary cervical cancer screening with cytology

Primary cervical cancer screening with cytology

Primary screening with cervical cytology alone remains an option supported by many authorities and professional society guidelines.¹¹ Most studies report that HPV testing has greater sensitivity than cervical cytology alone, especially for the detection of adenocarcinoma of the cervix.¹² In one Canadian study, 10,154 women were randomly assigned to HPV or cervical cytology testing. The sensitivity of HPV testing and cervical cytology for detecting cervical intraepithelial neoplasia grade 2 or 3 was 95% and 55%, respectively, with a specificity of 94% and 97%, respectively.¹³ When used together the sensitivity and specificity of cotesting was 100% and 93%, respectively, but resulted in an increased number of colposcopies, which may be costly and add stress for the patient. Many countries are beginning to move away from cervical cancer screening with cytology or cotesting to programs built upon a foundation of primary HPV testing.

Primary cervical cancer screening with HPV testing

The knowledge that hrHPV is a more sensitive test for cervical cancer and its precursors, as well as the relatively lower sensitivity of cytology, is the foundation for transitioning from primary screening with cervical cytology to primary screening with HPV testing. In the Netherlands¹⁴ and Australia^15,16 HPV testing with reflex cytology is the nationwide approach to cervical cancer screening. The basic components of the Dutch primary HPV screening program, as explained by Dr. Lai van Zulyan Mandres, are¹⁴:

1. Samples are collected by a general practitioner and sent to one of 5 central testing facilities for DNA testing for hrHPV.
2. If all previous samples tested negative, the screening occurs at ages 30, 35, 40, 50, and 60 years, a minimum of 5 screens per woman.
3. If there is a history of a previously positive hrHPV, the screening is intensified, with additional specimens collected at ages 45, 55, and 60 years.
4. If the sample is hrHPV negative, the patient continues screening at the standard intervals. No cytology testing is performed.
5. If the sample is hrHPV positive, reflex cytology is performed using the original collected sample. If the cytology shows no intraepithelial lesion or malignancy (NILM), another specimen is obtained for cytology within 6 months. If the second cytology specimen shows atypical squamous cells of undetermined significance (ASCUS) or a more worrisome cytology finding, the patient is sent for colposcopy. If two NILM cytology specimens have been obtained, the patient resumes primary hrHPV screening every 5 years.
6. If the specimen is hrHPV positive and cytology is ASCUS or more worrisome the patient is referred for colposcopy (FIGURE).¹⁴ The Dutch estimate that primary hrHPV screening will reduce the number of cervical cytology specimens by 90% annually.

Australia also has implemented nationwide primary HPV testing for cervical cancer screening. This change was implemented following a 10-year program of universal school-based vaccination of girls and boys, and biennial cytology screening for all women. The Australian screening program initiates hrHPV testing at age 25 years and thereafter every 5 years until age 74. If the hrHPV test is positive, reflex testing for HPV types 16 and 18 are performed on the original specimen along with cervical cytology. Women who test positive for HPV 16 or 18 are immediately referred for colposcopy. If the hrHPV test is positive and reflex testing for HPV 16 and 18 is negative, cervical cytology demonstrating ASCUS, low- or high-grade squamous intraepithelial lesions, or more worrisome results trigger a referral for colposcopy. The Australian program supports testing of self-collected vaginal samples for women who are underscreened or have never been screened.^15,16

Read about Pros and cons of switching approaches

Pros and cons of switching approaches

Deployment of new technology often yields benefits and challenges. A putative benefit of primary HPV screening is a reduction in health care costs without an increase in cervical cancer deaths. Another benefit of primary HPV screening is that it may enable self-collection of specimens for analysis, thereby increasing access to cervical cancer screening for underserved and marginalized populations of women who are not currently participating in cervical cancer screening programs.¹⁷ One challenge is that many women are unaware that hrHPV is the cause of most invasive cervical cancers. The detection of hrHPV in a woman in a long-term relationship who was previously negative for hrHPV may cause the emotions of surprise, fear, anxiety, and anger, thereby stressing the relationship.¹⁸

Another concern is that many women are worried about no longer receiving the familiar “Pap smear” cancer screening test in which they have tremendous faith. When Australia transitioned to primary HPV screening, more than 70,000 women signed a petition to “save women’s lives” by permitting continued access to the cervical cytology testing.¹⁹ Primary HPV testing may result in a transient increase in the number of women referred for colposcopy, potentially overwhelming the capacity of the health care system to deliver this vital service.^20,21 The HPV types that most often cause cervical cancer may vary among countries. For example, in Thailand, HPV 52 and 58 are frequently detected in women with high-grade squamous lesions, and including these subtypes in reflex genotyping may be of regional benefit.²²

Primary cervical cancer screening with HPV testing: When will it be used widely in the United States?

In contrast to the United States, the Netherlands is a small, densely populated country that has a highly integrated health system with centralized laboratory centers, a nationwide electronic health record, and clinicians organized to perform as an integrated team. These features ensure that all lifetime tests results are available in one record, that HPV testing is highly standardized, and that clinicians will follow a prescribed care pathway. The Netherlands’ health system is organized to support the successful transition, in a single step, to primary HPV testing. The United States is the third most populous country in the world, following China and India, with a diverse approach to health care, a highly mobile population, no single interoperable electronic health record, and minimal central control of clinical practice. The United States is not organized to make a “big bang” transition to primary HPV cervical cancer screening. It is likely that the introduction of primary HPV screening will occur first in highly integrated health systems that control the clinical, laboratory, and electronic records of a large population.

The results of the ATHENA study provide a clear clinical algorithm for implementing a primary HPV screening program for cervical cancer in the United States.^23–25 Samples are collected for hrHPV testing at a specified interval, 3 or 5 years, beginning at age 25 years. Women younger than age 25 years should be screened with cytology alone. Detection of hrHPV results in reflex viral typing for HPV 16 and 18. Women with samples positive for HPV 16 and 18 are immediately referred for colposcopy. Samples positive for hrHPV and negative for HPV 16 and 18 have reflex cytology testing performed on the original HPV specimen. If cytology testing reports NILM, repeat cotesting is performed in one year. If cytology testing reports ASCUS or a more concerning result, the woman is referred for colposcopy.

Malcolm Gladwell, in his book The Tipping Point, identified 3 processes that help push an innovative new approach from obscurity into widespread use.²⁶ First, authoritative voices that can catalyze change need to consistently communicate their shared vision for the future. Second, there must be a clear message that galvanizes the many to change their approach. Third, the historical context must be supportive of the change. Over the next decade we are likely to hit a tipping point and transition from cervical cancer screening that relies on cervical cytology to an approach that prioritizes hrHPV testing. When that change will occur in the United States is unclear. But our colleagues in other countries already have transitioned to primary hrHPV testing for cervical cancer screening.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Cervical cancer screening represents one of the great public health successes of the 20th Century. Two physician-scientists, George Papanicolaou, MD, PhD (1883–1962), and Harald zur Hausen, MD (1936–), made extraordinary contributions to the evolution of effective cervical cancer screening programs. Dr. Papanicolaou led development of the iconic Pap smear, creating techniques for collecting specimens and using cytologic techniques to identify cervical cancer and its precursors, and Dr. zur Hausen discovered the association of human papillomavirus (HPV) infection with cervical cancer.^1,2

Although it is but a distant memory, in the 1930s cervical and uterine cancer caused more deaths among women than breast, lung, or ovarian cancer. The successful deployment of Pap smear screening resulted in a decrease in cervical cancer rates in developed countries. Cervical cancer deaths remain common in many parts of the world, however. Cervical cancer screening programs can reduce cervical cancer incidence by greater than 80%.³ In the United States between 1973 and 2006, the invasive cervical cancer age-adjusted incidence rates dropped from 10.28 to 3.97 per 100,000 women.⁴

HPV causes cervical cancer

Dr. zur Hausen dedicated his career to identifying viral causes of human cancer. In his Nobel Laureate autobiography, he reported that during his 2-year rotating residency, he loved his obstetrics and gynecology experience, but found it “physically highly demanding” and decided to focus his career in microbiology and immunology.⁵ After proving that herpes simplex virus did not cause cervical cancer he began to explore the role of HPV in the disease process. He first identified HPV types 6 and 11 and showed that these agents caused genital warts. He then used low-stringency hybridization techniques to identify HPV types 16 and 18 in specimens of cervical cancer. Later, he and his colleagues proved that two HPV proteins, E6 and E7, interfere with the function of cell cycle control proteins p53 and retinoblastoma protein, resulting in dysregulated cell growth and cancer.² These findings permitted the development of both HPV vaccines and nucleic acid–based tests to identify high-risk oncogenic HPV (hrHPV) in cells and tissue specimens.

HPV vaccination

Dr. zur Hausen was an energetic and vocal advocate for the development and widescale deployment of HPV vaccines, including vaccination of males and females.⁶ Initially his ideas were rejected by the pharmaceutical industry, but eventually, with advances in virology and vaccine development, multiple companies pursued the development of HPV vaccines, the first cancer prevention vaccines. The best approach to cervical cancer prevention is intensive population-wide HPV vaccination of both boys and girls before exposure to the HPV virus. Beyond its beneficial effect on the incidence of cervical cancer, HPV vaccination also reduces the population incidence of anal, vulvar, and oropharyngeal cancer.⁷ Prevention of oropharyngeal cancer is especially important for men, supporting the recommendation for vaccination of all boys.⁸

Population-wide HPV vaccination will result in a lower prevalence of cervical cancer precursors and reduce the sensitivity of cytology, thereby making primary HPV screening more attractive.⁹ Based on one modelling study, universal HPV vaccination can reduce cervical cancer rates by greater than 50% over current levels, and introduction of primary HPV screening will reduce cervical cancer rates by an additional 20%.¹⁰ In an era of widespread vaccination for HPV, screening for cervical cancer should be intensified for nonvaccinated women.¹⁰

Read about Primary cervical cancer screening with cytology

Primary cervical cancer screening with cytology

Primary screening with cervical cytology alone remains an option supported by many authorities and professional society guidelines.¹¹ Most studies report that HPV testing has greater sensitivity than cervical cytology alone, especially for the detection of adenocarcinoma of the cervix.¹² In one Canadian study, 10,154 women were randomly assigned to HPV or cervical cytology testing. The sensitivity of HPV testing and cervical cytology for detecting cervical intraepithelial neoplasia grade 2 or 3 was 95% and 55%, respectively, with a specificity of 94% and 97%, respectively.¹³ When used together the sensitivity and specificity of cotesting was 100% and 93%, respectively, but resulted in an increased number of colposcopies, which may be costly and add stress for the patient. Many countries are beginning to move away from cervical cancer screening with cytology or cotesting to programs built upon a foundation of primary HPV testing.

Primary cervical cancer screening with HPV testing

The knowledge that hrHPV is a more sensitive test for cervical cancer and its precursors, as well as the relatively lower sensitivity of cytology, is the foundation for transitioning from primary screening with cervical cytology to primary screening with HPV testing. In the Netherlands¹⁴ and Australia^15,16 HPV testing with reflex cytology is the nationwide approach to cervical cancer screening. The basic components of the Dutch primary HPV screening program, as explained by Dr. Lai van Zulyan Mandres, are¹⁴:

1. Samples are collected by a general practitioner and sent to one of 5 central testing facilities for DNA testing for hrHPV.
2. If all previous samples tested negative, the screening occurs at ages 30, 35, 40, 50, and 60 years, a minimum of 5 screens per woman.
3. If there is a history of a previously positive hrHPV, the screening is intensified, with additional specimens collected at ages 45, 55, and 60 years.
4. If the sample is hrHPV negative, the patient continues screening at the standard intervals. No cytology testing is performed.
5. If the sample is hrHPV positive, reflex cytology is performed using the original collected sample. If the cytology shows no intraepithelial lesion or malignancy (NILM), another specimen is obtained for cytology within 6 months. If the second cytology specimen shows atypical squamous cells of undetermined significance (ASCUS) or a more worrisome cytology finding, the patient is sent for colposcopy. If two NILM cytology specimens have been obtained, the patient resumes primary hrHPV screening every 5 years.
6. If the specimen is hrHPV positive and cytology is ASCUS or more worrisome the patient is referred for colposcopy (FIGURE).¹⁴ The Dutch estimate that primary hrHPV screening will reduce the number of cervical cytology specimens by 90% annually.

Australia also has implemented nationwide primary HPV testing for cervical cancer screening. This change was implemented following a 10-year program of universal school-based vaccination of girls and boys, and biennial cytology screening for all women. The Australian screening program initiates hrHPV testing at age 25 years and thereafter every 5 years until age 74. If the hrHPV test is positive, reflex testing for HPV types 16 and 18 are performed on the original specimen along with cervical cytology. Women who test positive for HPV 16 or 18 are immediately referred for colposcopy. If the hrHPV test is positive and reflex testing for HPV 16 and 18 is negative, cervical cytology demonstrating ASCUS, low- or high-grade squamous intraepithelial lesions, or more worrisome results trigger a referral for colposcopy. The Australian program supports testing of self-collected vaginal samples for women who are underscreened or have never been screened.^15,16

Read about Pros and cons of switching approaches

Pros and cons of switching approaches

Deployment of new technology often yields benefits and challenges. A putative benefit of primary HPV screening is a reduction in health care costs without an increase in cervical cancer deaths. Another benefit of primary HPV screening is that it may enable self-collection of specimens for analysis, thereby increasing access to cervical cancer screening for underserved and marginalized populations of women who are not currently participating in cervical cancer screening programs.¹⁷ One challenge is that many women are unaware that hrHPV is the cause of most invasive cervical cancers. The detection of hrHPV in a woman in a long-term relationship who was previously negative for hrHPV may cause the emotions of surprise, fear, anxiety, and anger, thereby stressing the relationship.¹⁸

Another concern is that many women are worried about no longer receiving the familiar “Pap smear” cancer screening test in which they have tremendous faith. When Australia transitioned to primary HPV screening, more than 70,000 women signed a petition to “save women’s lives” by permitting continued access to the cervical cytology testing.¹⁹ Primary HPV testing may result in a transient increase in the number of women referred for colposcopy, potentially overwhelming the capacity of the health care system to deliver this vital service.^20,21 The HPV types that most often cause cervical cancer may vary among countries. For example, in Thailand, HPV 52 and 58 are frequently detected in women with high-grade squamous lesions, and including these subtypes in reflex genotyping may be of regional benefit.²²

Primary cervical cancer screening with HPV testing: When will it be used widely in the United States?

In contrast to the United States, the Netherlands is a small, densely populated country that has a highly integrated health system with centralized laboratory centers, a nationwide electronic health record, and clinicians organized to perform as an integrated team. These features ensure that all lifetime tests results are available in one record, that HPV testing is highly standardized, and that clinicians will follow a prescribed care pathway. The Netherlands’ health system is organized to support the successful transition, in a single step, to primary HPV testing. The United States is the third most populous country in the world, following China and India, with a diverse approach to health care, a highly mobile population, no single interoperable electronic health record, and minimal central control of clinical practice. The United States is not organized to make a “big bang” transition to primary HPV cervical cancer screening. It is likely that the introduction of primary HPV screening will occur first in highly integrated health systems that control the clinical, laboratory, and electronic records of a large population.

The results of the ATHENA study provide a clear clinical algorithm for implementing a primary HPV screening program for cervical cancer in the United States.^23–25 Samples are collected for hrHPV testing at a specified interval, 3 or 5 years, beginning at age 25 years. Women younger than age 25 years should be screened with cytology alone. Detection of hrHPV results in reflex viral typing for HPV 16 and 18. Women with samples positive for HPV 16 and 18 are immediately referred for colposcopy. Samples positive for hrHPV and negative for HPV 16 and 18 have reflex cytology testing performed on the original HPV specimen. If cytology testing reports NILM, repeat cotesting is performed in one year. If cytology testing reports ASCUS or a more concerning result, the woman is referred for colposcopy.

Malcolm Gladwell, in his book The Tipping Point, identified 3 processes that help push an innovative new approach from obscurity into widespread use.²⁶ First, authoritative voices that can catalyze change need to consistently communicate their shared vision for the future. Second, there must be a clear message that galvanizes the many to change their approach. Third, the historical context must be supportive of the change. Over the next decade we are likely to hit a tipping point and transition from cervical cancer screening that relies on cervical cytology to an approach that prioritizes hrHPV testing. When that change will occur in the United States is unclear. But our colleagues in other countries already have transitioned to primary hrHPV testing for cervical cancer screening.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

A record-setting 40,000-plus oncology professionals attended this year’s annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. The outstanding education and scientific program, with the theme of Delivering Discoveries: Expanding the Reach of Precision Medicine, was planned and led by ASCO President Dr Bruce Johnson, professor and director of Thoracic Oncology at the Dana Farber Cancer Institute in Boston, and chaired by Sarah Cannon’s Dr David Spigel and Harvard’s Dr Ann Partridge. A recurring finding throughout the meeting was that “less is more” in several key areas of cancer therapy. From small molecules targeting driver mutations across various tumors to the application of immunotherapy in subsets of common cancers, it is clear that more patients are experiencing dramatic results from novel approaches.

A featured plenary session trial was TAILORx, a study of 10,273 women with hormone-receptor–positive, surgically resected breast cancer that had not spread to the lymph nodes, was less than 5 cm, and was not positive for the HER2 gene amplification. This clinical trial was sponsored by the NCI and initiated in 2006. It used the OncotypeDX genetic test to stratify patients into groups of low, intermediate, or high risk for recurrence. The low-risk patients received only hormonal therapy, and the high-risk patients were treated with hormonal therapy plus chemotherapy.

Dr Joseph Sparano, professor of Medicine and Women’s Health at the Albert Einstein College of Medicine in New York, presented the results from the group of 6,700 intermediate risk women who were randomized to receive hormonal therapy alone or in combination with chemotherapy. After 9 years of follow-up, 83.3% of the volunteers, as Dr Sparano appropriately referred to them, who were treated with hormonal therapy were still cancer free, compared with 84.3% of those who also received chemotherapy, demonstrating no statistical benefit for the addition of chemotherapy. Of note, breast cancer experts discussing the trial, including Dr Lisa Carey, professor of Breast Cancer Research at the UNC Lineberger Cancer Institute in Chapel Hill, urged that younger women, under the age of 50, with recurrence scores (RS) toward the higher end of the intermediate risk group (RS, 16-25) should still discuss and consider chemotherapy with their physicians. In summary, all patients fitting the study criteria with low (
These landmark and practice changing results mean that each year about 60,000 women in the United States will be spared the side effects of toxic drugs. These 10,273 study volunteers are true heroes to the women who will be diagnosed with breast cancer in coming years.

In the field of lung cancer, many new trial results using immunotherapy were presented, with the most talked about being single-agent pembrolizumab, a PD1 inhibitor, improving survival over traditional chemotherapy in patients with PD-L1 positive tumors, which comprise the majority of squamous cell and adenocarcinomas of the lung. Also in the plenary, Dr Gilberto Lopes of the Sylvester Cancer Center at the University of Miami, presented these results from the KEYNOTE-042 study. In patients with PD-L1 tumor proportion score (TPS) of >1%, the benefit in overall survival (OS) of pembrolizumab compared with chemotherapy was 16.7 versus 12.1 months, respectively (HR, 0.81). In those patients with a TPS of >20%, the OS benefit was 17.7 versus 1.0 months (HR, 0.77), and in the group with a TPS of >50%, the benefit was 20.0 versus 12.2 months (HR, 0.69). Overall, the quality of life and the occurrence of side effects were substantially better for those patients receiving immunotherapy alone. Other findings presented at the meeting demonstrated the benefit of adding immunotherapy to chemotherapy and of treating with combination immunotherapy (PD-1 and CTLA-4 inhibitors). Many options now exist, much work remains to be done, and accrual to clinical trials is more important than ever.

Another plenary session trial evaluated the benefit of performing a nephrectomy in patients with advanced or metastatic renal cell carcinoma (RCC), a long-held and practiced standard of care. Dr Arnaud Mejean of Paris Descartes University presented findings from the CARMENA trial, which randomized 450 patients with metastatic clear cell RCC to receive cytoreductive nephrectomy followed by sunitinib, or sunitinib alone. The OS results of 18.4 versus 13.9 months, respectively (HR, 0.89) favored sunitinib alone in this noninferiority analysis. Other endpoints lined up in favor of not removing the cancerous kidney, and the presenter and discussants were united in their opinion of the results and the resulting change in doing less surgery in these patients.

In a step away from less therapy, the European Pediatric Soft Tissue Sarcoma Study showed that adding 6 months of low-dose maintenance chemotherapy after standard intensive therapy improves survival in children with high-risk rhabdomyosarcoma. The addition of a vinorelbine and cyclophosphamide low-dose regimen improved 5-year disease-free survival from 69.8% to 77.6% (HR, 0.68) and OS from 73.7% to 86.5% (HR, 0.52) as presented by Dr Gianni Bisogno, University of Padovani, Italy. The maintenance regimen showed no increase in toxicity and actually fewer infections were noted.

In the area of molecular profiling, multiple studies at the meeting demonstrated the importance of assessing cancers for mutations as outstanding results were seen with therapies for NTRK, RET, ROS, and MSI-high driven tumors. In a debate on the role of molecular profiling, I had the opportunity to declare and support our position at Sarah Cannon that all patients with relapsed or metastatic cancers should have this testing performed. It will be through better understanding of the biology of these cancers that we will advance the field for all patients while sometimes finding a target or mutation that will dramatically change the life of a patient.

In keeping with the meeting’s theme, Delivering Discoveries: Expanding the Reach of Precision Medicine, the presentations and the discussions clearly demonstrated that through the use of precision medicine techniques such as prognostic gene assays and molecular profiling, patients can receive the best therapy, even “tailored” therapy, which may often actually be less therapy. It is an exciting time in cancer research, and I have never been more optimistic about the future of cancer treatment for our patients.

A record-setting 40,000-plus oncology professionals attended this year’s annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. The outstanding education and scientific program, with the theme of Delivering Discoveries: Expanding the Reach of Precision Medicine, was planned and led by ASCO President Dr Bruce Johnson, professor and director of Thoracic Oncology at the Dana Farber Cancer Institute in Boston, and chaired by Sarah Cannon’s Dr David Spigel and Harvard’s Dr Ann Partridge. A recurring finding throughout the meeting was that “less is more” in several key areas of cancer therapy. From small molecules targeting driver mutations across various tumors to the application of immunotherapy in subsets of common cancers, it is clear that more patients are experiencing dramatic results from novel approaches.

A featured plenary session trial was TAILORx, a study of 10,273 women with hormone-receptor–positive, surgically resected breast cancer that had not spread to the lymph nodes, was less than 5 cm, and was not positive for the HER2 gene amplification. This clinical trial was sponsored by the NCI and initiated in 2006. It used the OncotypeDX genetic test to stratify patients into groups of low, intermediate, or high risk for recurrence. The low-risk patients received only hormonal therapy, and the high-risk patients were treated with hormonal therapy plus chemotherapy.

Dr Joseph Sparano, professor of Medicine and Women’s Health at the Albert Einstein College of Medicine in New York, presented the results from the group of 6,700 intermediate risk women who were randomized to receive hormonal therapy alone or in combination with chemotherapy. After 9 years of follow-up, 83.3% of the volunteers, as Dr Sparano appropriately referred to them, who were treated with hormonal therapy were still cancer free, compared with 84.3% of those who also received chemotherapy, demonstrating no statistical benefit for the addition of chemotherapy. Of note, breast cancer experts discussing the trial, including Dr Lisa Carey, professor of Breast Cancer Research at the UNC Lineberger Cancer Institute in Chapel Hill, urged that younger women, under the age of 50, with recurrence scores (RS) toward the higher end of the intermediate risk group (RS, 16-25) should still discuss and consider chemotherapy with their physicians. In summary, all patients fitting the study criteria with low (
These landmark and practice changing results mean that each year about 60,000 women in the United States will be spared the side effects of toxic drugs. These 10,273 study volunteers are true heroes to the women who will be diagnosed with breast cancer in coming years.

In the field of lung cancer, many new trial results using immunotherapy were presented, with the most talked about being single-agent pembrolizumab, a PD1 inhibitor, improving survival over traditional chemotherapy in patients with PD-L1 positive tumors, which comprise the majority of squamous cell and adenocarcinomas of the lung. Also in the plenary, Dr Gilberto Lopes of the Sylvester Cancer Center at the University of Miami, presented these results from the KEYNOTE-042 study. In patients with PD-L1 tumor proportion score (TPS) of >1%, the benefit in overall survival (OS) of pembrolizumab compared with chemotherapy was 16.7 versus 12.1 months, respectively (HR, 0.81). In those patients with a TPS of >20%, the OS benefit was 17.7 versus 1.0 months (HR, 0.77), and in the group with a TPS of >50%, the benefit was 20.0 versus 12.2 months (HR, 0.69). Overall, the quality of life and the occurrence of side effects were substantially better for those patients receiving immunotherapy alone. Other findings presented at the meeting demonstrated the benefit of adding immunotherapy to chemotherapy and of treating with combination immunotherapy (PD-1 and CTLA-4 inhibitors). Many options now exist, much work remains to be done, and accrual to clinical trials is more important than ever.

Another plenary session trial evaluated the benefit of performing a nephrectomy in patients with advanced or metastatic renal cell carcinoma (RCC), a long-held and practiced standard of care. Dr Arnaud Mejean of Paris Descartes University presented findings from the CARMENA trial, which randomized 450 patients with metastatic clear cell RCC to receive cytoreductive nephrectomy followed by sunitinib, or sunitinib alone. The OS results of 18.4 versus 13.9 months, respectively (HR, 0.89) favored sunitinib alone in this noninferiority analysis. Other endpoints lined up in favor of not removing the cancerous kidney, and the presenter and discussants were united in their opinion of the results and the resulting change in doing less surgery in these patients.

In a step away from less therapy, the European Pediatric Soft Tissue Sarcoma Study showed that adding 6 months of low-dose maintenance chemotherapy after standard intensive therapy improves survival in children with high-risk rhabdomyosarcoma. The addition of a vinorelbine and cyclophosphamide low-dose regimen improved 5-year disease-free survival from 69.8% to 77.6% (HR, 0.68) and OS from 73.7% to 86.5% (HR, 0.52) as presented by Dr Gianni Bisogno, University of Padovani, Italy. The maintenance regimen showed no increase in toxicity and actually fewer infections were noted.

In the area of molecular profiling, multiple studies at the meeting demonstrated the importance of assessing cancers for mutations as outstanding results were seen with therapies for NTRK, RET, ROS, and MSI-high driven tumors. In a debate on the role of molecular profiling, I had the opportunity to declare and support our position at Sarah Cannon that all patients with relapsed or metastatic cancers should have this testing performed. It will be through better understanding of the biology of these cancers that we will advance the field for all patients while sometimes finding a target or mutation that will dramatically change the life of a patient.

In keeping with the meeting’s theme, Delivering Discoveries: Expanding the Reach of Precision Medicine, the presentations and the discussions clearly demonstrated that through the use of precision medicine techniques such as prognostic gene assays and molecular profiling, patients can receive the best therapy, even “tailored” therapy, which may often actually be less therapy. It is an exciting time in cancer research, and I have never been more optimistic about the future of cancer treatment for our patients.

A record-setting 40,000-plus oncology professionals attended this year’s annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. The outstanding education and scientific program, with the theme of Delivering Discoveries: Expanding the Reach of Precision Medicine, was planned and led by ASCO President Dr Bruce Johnson, professor and director of Thoracic Oncology at the Dana Farber Cancer Institute in Boston, and chaired by Sarah Cannon’s Dr David Spigel and Harvard’s Dr Ann Partridge. A recurring finding throughout the meeting was that “less is more” in several key areas of cancer therapy. From small molecules targeting driver mutations across various tumors to the application of immunotherapy in subsets of common cancers, it is clear that more patients are experiencing dramatic results from novel approaches.

A featured plenary session trial was TAILORx, a study of 10,273 women with hormone-receptor–positive, surgically resected breast cancer that had not spread to the lymph nodes, was less than 5 cm, and was not positive for the HER2 gene amplification. This clinical trial was sponsored by the NCI and initiated in 2006. It used the OncotypeDX genetic test to stratify patients into groups of low, intermediate, or high risk for recurrence. The low-risk patients received only hormonal therapy, and the high-risk patients were treated with hormonal therapy plus chemotherapy.

Dr Joseph Sparano, professor of Medicine and Women’s Health at the Albert Einstein College of Medicine in New York, presented the results from the group of 6,700 intermediate risk women who were randomized to receive hormonal therapy alone or in combination with chemotherapy. After 9 years of follow-up, 83.3% of the volunteers, as Dr Sparano appropriately referred to them, who were treated with hormonal therapy were still cancer free, compared with 84.3% of those who also received chemotherapy, demonstrating no statistical benefit for the addition of chemotherapy. Of note, breast cancer experts discussing the trial, including Dr Lisa Carey, professor of Breast Cancer Research at the UNC Lineberger Cancer Institute in Chapel Hill, urged that younger women, under the age of 50, with recurrence scores (RS) toward the higher end of the intermediate risk group (RS, 16-25) should still discuss and consider chemotherapy with their physicians. In summary, all patients fitting the study criteria with low (
These landmark and practice changing results mean that each year about 60,000 women in the United States will be spared the side effects of toxic drugs. These 10,273 study volunteers are true heroes to the women who will be diagnosed with breast cancer in coming years.

In the field of lung cancer, many new trial results using immunotherapy were presented, with the most talked about being single-agent pembrolizumab, a PD1 inhibitor, improving survival over traditional chemotherapy in patients with PD-L1 positive tumors, which comprise the majority of squamous cell and adenocarcinomas of the lung. Also in the plenary, Dr Gilberto Lopes of the Sylvester Cancer Center at the University of Miami, presented these results from the KEYNOTE-042 study. In patients with PD-L1 tumor proportion score (TPS) of >1%, the benefit in overall survival (OS) of pembrolizumab compared with chemotherapy was 16.7 versus 12.1 months, respectively (HR, 0.81). In those patients with a TPS of >20%, the OS benefit was 17.7 versus 1.0 months (HR, 0.77), and in the group with a TPS of >50%, the benefit was 20.0 versus 12.2 months (HR, 0.69). Overall, the quality of life and the occurrence of side effects were substantially better for those patients receiving immunotherapy alone. Other findings presented at the meeting demonstrated the benefit of adding immunotherapy to chemotherapy and of treating with combination immunotherapy (PD-1 and CTLA-4 inhibitors). Many options now exist, much work remains to be done, and accrual to clinical trials is more important than ever.

Another plenary session trial evaluated the benefit of performing a nephrectomy in patients with advanced or metastatic renal cell carcinoma (RCC), a long-held and practiced standard of care. Dr Arnaud Mejean of Paris Descartes University presented findings from the CARMENA trial, which randomized 450 patients with metastatic clear cell RCC to receive cytoreductive nephrectomy followed by sunitinib, or sunitinib alone. The OS results of 18.4 versus 13.9 months, respectively (HR, 0.89) favored sunitinib alone in this noninferiority analysis. Other endpoints lined up in favor of not removing the cancerous kidney, and the presenter and discussants were united in their opinion of the results and the resulting change in doing less surgery in these patients.

In a step away from less therapy, the European Pediatric Soft Tissue Sarcoma Study showed that adding 6 months of low-dose maintenance chemotherapy after standard intensive therapy improves survival in children with high-risk rhabdomyosarcoma. The addition of a vinorelbine and cyclophosphamide low-dose regimen improved 5-year disease-free survival from 69.8% to 77.6% (HR, 0.68) and OS from 73.7% to 86.5% (HR, 0.52) as presented by Dr Gianni Bisogno, University of Padovani, Italy. The maintenance regimen showed no increase in toxicity and actually fewer infections were noted.

In the area of molecular profiling, multiple studies at the meeting demonstrated the importance of assessing cancers for mutations as outstanding results were seen with therapies for NTRK, RET, ROS, and MSI-high driven tumors. In a debate on the role of molecular profiling, I had the opportunity to declare and support our position at Sarah Cannon that all patients with relapsed or metastatic cancers should have this testing performed. It will be through better understanding of the biology of these cancers that we will advance the field for all patients while sometimes finding a target or mutation that will dramatically change the life of a patient.

In keeping with the meeting’s theme, Delivering Discoveries: Expanding the Reach of Precision Medicine, the presentations and the discussions clearly demonstrated that through the use of precision medicine techniques such as prognostic gene assays and molecular profiling, patients can receive the best therapy, even “tailored” therapy, which may often actually be less therapy. It is an exciting time in cancer research, and I have never been more optimistic about the future of cancer treatment for our patients.

“Before you are a leader, success is all about growing yourself. When you become a leader, success is all about growing others.” – Jack Welch

Serving my colleagues as chairman of the department of hematology and medical oncology at the Cleveland Clinic has been my greatest honor and privilege. I am humbled to lead such compassionate, inquisitive, and accomplished clinician scientists during a time of great change in academic medicine. From the introduction of new therapies to the implementation of new operational processes, my team inspires me to extend my capability beyond what I ever thought possible. I am grateful for the opportunity to grow with them.

Dr. Kalaycio is editor in chief of Hematology News. He chairs the department of hematologic oncology and blood disorders at Cleveland Clinic Taussig Cancer Institute. Contact him at [email protected].

“Before you are a leader, success is all about growing yourself. When you become a leader, success is all about growing others.” – Jack Welch

Serving my colleagues as chairman of the department of hematology and medical oncology at the Cleveland Clinic has been my greatest honor and privilege. I am humbled to lead such compassionate, inquisitive, and accomplished clinician scientists during a time of great change in academic medicine. From the introduction of new therapies to the implementation of new operational processes, my team inspires me to extend my capability beyond what I ever thought possible. I am grateful for the opportunity to grow with them.

Dr. Kalaycio is editor in chief of Hematology News. He chairs the department of hematologic oncology and blood disorders at Cleveland Clinic Taussig Cancer Institute. Contact him at [email protected].

“Before you are a leader, success is all about growing yourself. When you become a leader, success is all about growing others.” – Jack Welch

Serving my colleagues as chairman of the department of hematology and medical oncology at the Cleveland Clinic has been my greatest honor and privilege. I am humbled to lead such compassionate, inquisitive, and accomplished clinician scientists during a time of great change in academic medicine. From the introduction of new therapies to the implementation of new operational processes, my team inspires me to extend my capability beyond what I ever thought possible. I am grateful for the opportunity to grow with them.

Dr. Kalaycio is editor in chief of Hematology News. He chairs the department of hematologic oncology and blood disorders at Cleveland Clinic Taussig Cancer Institute. Contact him at [email protected].

AIDS, the Vietnam War, whatever your preferred scale for measuring horrific events, the numbers from the opioid crisis are as grave or worse. And, once again, it is the young who are dying. How we got to this point is an unbelievable story of corporate greed, government incompetence, regulatory commission overreach, and, unfortunately, physician ignorance.

Every one of us has contributed to this tragedy, and most of us still do. There are some easy first steps surgeons can take, but first let’s review the mistakes made that drove our country into addiction.

BackyardProduction/Thinkstock

In 1995, as their patent on MS Contin was set to expire, Purdue Pharma gained Food and Drug Administration approval for OxyContin (“contin” is pharma talk for continuous). At this time, opioids generally were considered to be dangerous and mainly prescribed for cancer or end-of-life patients. Purdue representatives began an aggressive marketing campaign to break out of this niche. They were aided in this pursuit by the FDA, which wrote in the package insert that iatrogenic addiction was rare and the delayed absorption of OxyContin “is believed to reduce the abuse liability of a drug.” These statements were made without the backing of any clinical trials. But with an on-label statement of reduced addiction risk, representatives could sell OxyContin based on a diminished potential for abuse.

In addition to oncologists, the drug was now marketed to rheumatologists, primary care physicians, and surgeons. OxyContin, therefore, broke through the cancer barrier and became one of the most widely prescribed painkillers in the United States. While generating billions in profits, OxyContin also would become one of the most abused drugs in history.

There were several issues with OxyContin that led to its widespread misuse. The preparation contained up to 160 mg of oxycodone per pill, 16 times more than the strongest Percocet formulary. The tablet also could easily be crushed, overcoming the delayed-release formulation. Because of the FDA insert, sales representatives were free to report an addiction risk of less than 1%, which they did. Widely.

But what science backed this claim? The study referenced was not a study at all. The citation was a one-paragraph, five-sentence letter to the editor published by the New England Journal of Medicine in 1980. In it, the authors briefly described their experience with inpatient opioid therapy. No reference was made to outpatient opioid prescriptions. Still, this letter has been scientifically cited more than 600 times, with a spike starting in 1995, the year OxyContin was released. Even as thousands of Americans were dying each year from opioid use, the “study” continued to be offered as proof of a low risk of addiction. As recently as 2014, the letter was cited in the journal OncoTargets and Therapy to support the statement, “In reality, medical opioid addiction is very rare.”

Maybe if we knew our history we could avoid repeating it. Previously, the drug diacetylmorphine was introduced as a safe, nonaddictive substitute for morphine by Bayer Pharmaceutical in the late 1890s. Diacetylmorphine is better known by its trademarked name, Heroin.

In 1996, the American Pain Society and the American Academy of Pain Medicine formed a committee to issue a joint statement that advocated opioid use for chronic pain and again stating a low risk of addiction. The committee was chaired by J. David Haddox, DDS, MD, a paid speaker (and later executive) for Purdue Pharma. The American Pain Society also launched a campaign to treat pain more aggressively. “Pain is the fifth vital sign” became a far-reaching strategy, which was adopted by the Department of Veterans Affairs and, ultimately, nearly every hospital in the country. The campaign was so successful that, in 2001, the Joint Commission required hospitals to:

• Assess pain in every patient.
• Record the results.
• Provide treatment for the pain.
• Reassess the effectiveness of the treatment.
• Teach staff how to manage pain.

The Joint Commission is not alone in creating opioid-friendly regulations. The Hospital Consumer Assessment of Healthcare Providers and Systems surveys patients after hospital stays. Several of the questions include pain management. One asks the patient whether the hospital staff did “everything they could” to assist with the patient’s pain. The satisfaction scores from these surveys are directly tied to hospital payments.

In 1998, the Federation of State Medical Boards published a statement reassuring doctors that they would not be punished for prescribing even large amounts of opioids if it were in the course of medical treatment. In 2004, the FSMB went further, stating that medical boards should consider “undertreatment of pain” to be a “departure from an acceptable standard of practice,” suggesting that state medical boards should sanction doctors who undertreated pain. According to a report by Catan et al. in the Wall Street Journal, this policy was drawn up with help from Dr. Haddox, who is now a senior executive with Purdue. The FSMB also would later disclose nearly $2 million in funding from opioid manufacturers.

These regulatory groups created widespread legal and financial pressure for doctors to diagnose and quickly treat pain in every patient. But what resources did we have to do this swiftly and effectively? Opioid prescriptions soared. There were 116 million opioid prescriptions issued in 1999; by 2013, it was 207 million. Annually, there are now more opioid prescriptions filled in the United States than there are people. Overdose deaths rose 500% between 1999 and 2016. Last year, there were more than 42,000 opioid-related mortalities in the United States. Like an untended fire, the crisis now spreads unabated.

What about vascular surgeons? Few of us prescribe OxyContin. Surely the 30 Percocets we give out after surgery are safe? In reality, Percocet contains oxycodone, the same opioid found in OxyContin, and therefore, carries a high risk of addiction. Norco, Vicodin, and Lortab all contain the opioid hydrocodone. Some studies have shown a higher risk of addiction with oxycodone, but all opioids carry a significant danger of abuse and dependence. As surgeons, we came into to this crisis with little or no training. This made us susceptible to bad science, bad-faith marketing, and bad ideas from regulatory commissions. Most of us learned how to prescribe postop opioids during the “hidden curriculum” of our third and fourth years of medical school: In other words, the residents taught us. Much like learning sex education on the streets, your mileage may vary. It is no wonder that a 2016 JAMA Internal Medicine news release found that simply having surgery was a risk factor for developing an opioid addiction. Surgeons don’t have an evidence-based plan to treat postoperative pain with opioids. About 6.5% of patients are still taking “postop” opioids 3-6 months after minor surgery; the numbers are about the same for major surgery (5.9%). Therefore, it is unlikely that pain is driving this chronic use.

Richard J. Barth Jr., MD, of Dartmouth-Hitchcock Medical Center in Lebanon, N.H., has studied opioid use following surgery extensively. He found there is a wide variety in surgeons’ opioid-prescribing habits and most of us overprescribe. In one study, 72% of the prescribed pills after surgery were not taken. He recommends the following guideline for opioid prescriptions after inpatient surgical procedures: If the patient took no opioids the day before discharge, no script is needed. For patients taking 1-3 pills the day before discharge, 15 pills are given; and for those taking 4 or more pills, a script for 30 is given.

As vascular surgeons, we must break out of our bubble and address our contributions to this crisis. It is past time to look at our own habits. Overprescribing is dangerous; the excess pills often are found by abusers, sold, or used recreationally by others in the household. Some patients take all of the pills simply because that is what the doctor prescribed; to the patient, he or she is merely following the doctor’s orders, and therefore not engaging in a risky behavior.

As vascular surgeons, there are several steps we can take immediately to reduce our contributions to the opioid epidemic and protect our patients:

• Always use the lowest effective dose of opioids and dramatically reduce the number of pills in your postop scripts. Fewer than 15 pills will cover most surgeries we perform.
• New data show that acetaminophen combined with ibuprofen works better for acute pain than acetaminophen combined with an opioid. Increase your use of nonnarcotic pain medications.
• Counsel your patients on the risk of addiction. If you plan to issue a script with only a few pills or nonnarcotics, let them know why in advance.
• Use caution when prescribing opioids to patients with anxiety or depression. The risk of addiction is much higher in these patients because of the anxiolytic and antidepressant qualities that opioids have.
• Avoid opioids in patients taking benzodiazepines, which can exacerbate the risk of respiratory depression and death.
• Help patients safely dispose of unused opioids.
• Use drug-monitoring programs whenever available.
• Use opioids for acute pain only. We do not have the training to manage long-term use.

Meanwhile, OxyContin still is available and sold exclusively by Purdue Pharma. Before its patent expired, Purdue altered the formulation to make it harder to abuse when crushing the tablets. They then lobbied the FDA to block generic production of the original formula because it was “unsafe.” Though Purdue (under Mundipharma) now markets this original version in South America, Europe, and Asia.

Many lawsuits have been brought against Purdue. Even with such high-profile lawyers as Rudy Giuliani and Eric Holder, Purdue has paid more than $600 million in fines and pleaded guilty to marketing OxyContin with “the intent to defraud or mislead.” Three Purdue executives have pleaded guilty to criminal misdemeanor charges.

In 2015, the FDA approved marketing OxyContin to children as young as age 11 years..

To address their role in the opioid crisis, the Joint Commission issued a statement on April 18, 2016. It was not a master class in self-awareness; the statement claimed that it is a “misconception” that Joint Commission standards pushed doctors to prescribe opioids. Yet, according to a Class Action complaint (Kenova v. JCAHO), in a 2001 monograph published by the Joint Commission (and funded by Purdue Pharma), they wrote “Some clinicians have inaccurate and exaggerated concerns about addiction, tolerance, and risk of death. This attitude prevails despite the fact that there is no evidence that addiction is a significant issue when persons are given opioids for pain control.”

In 2016, the AMA passed a resolution to drop pain as a vital sign. They also urged the Joint Commission to stop requiring hospitals to ask patients about the quality of their pain care. The American College of Surgeons has started an education initiative to help surgeons and patients learn about opioids and surgery (funded by Pacira Pharmaceuticals, makers of EXPAREL, an injectable long-lasting local anesthetic). In a March 2016 statement in the New England Journal of Medicine, Centers for Disease Control and Prevention representatives said of opioids “We know of no other medication routinely used for a nonfatal condition that kills patients so frequently.” As vascular surgeons, we are long overdue for a self-assessment. It is now time to change our practices and habits to help end this national addiction.

Dr. Sheahan is the Claude C. Craighead Jr. Professor and chair, division of vascular and endovascular surgery, Louisiana State University Health Sciences Center, New Orleans.

Resources

1. Hill M et al. Guideline for discharge opioid prescriptions after inpatient general surgical procedures. J Am Coll Surg. In Press.

2. Kenova v. JCAHO Class Action Complaint. United States District Court for the Southern District of West Virginia.

3. Mandell BF. The fifth vital sign: a complex story of politics and patient care. Cleveland Clinic Journal of Medicine 2016 Jun:83:400.

4. Leung PT et al. A 1980 letter on the risk of opioid addiction. New England Journal of Medicine 2017;376:2194-5.

5. www.jointcommission.org/joint_commission_statement_on_pain_management

6. www.cdc.gov/drugoverdose/epidemic/index.html

7. Catan T et al. A pain-drug champion has second thoughts. Wall Street Journal. Dec. 17, 2012 (updated online version).

8. Federation of State Medical Boards news release. www.fsmb.org/globalassets/advocacy/news-releases/2014/rems-grant-press-release-jan2014-final.pdf

9. Chou R et al. American Pain Society – American Academy of Pain Medicine Opioids Guidelines Panel. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain 2009;10:113-130.

10. Van Zee A. The promotion and marketing of OxyContin: Commercial triumph, public health tragedy. Am J Public Health 2009;99:221-7.

11. Keefe, PR. The family that built an empire of pain. The New Yorker. October 30, 2017.

AIDS, the Vietnam War, whatever your preferred scale for measuring horrific events, the numbers from the opioid crisis are as grave or worse. And, once again, it is the young who are dying. How we got to this point is an unbelievable story of corporate greed, government incompetence, regulatory commission overreach, and, unfortunately, physician ignorance.

Every one of us has contributed to this tragedy, and most of us still do. There are some easy first steps surgeons can take, but first let’s review the mistakes made that drove our country into addiction.

BackyardProduction/Thinkstock

In 1995, as their patent on MS Contin was set to expire, Purdue Pharma gained Food and Drug Administration approval for OxyContin (“contin” is pharma talk for continuous). At this time, opioids generally were considered to be dangerous and mainly prescribed for cancer or end-of-life patients. Purdue representatives began an aggressive marketing campaign to break out of this niche. They were aided in this pursuit by the FDA, which wrote in the package insert that iatrogenic addiction was rare and the delayed absorption of OxyContin “is believed to reduce the abuse liability of a drug.” These statements were made without the backing of any clinical trials. But with an on-label statement of reduced addiction risk, representatives could sell OxyContin based on a diminished potential for abuse.

In addition to oncologists, the drug was now marketed to rheumatologists, primary care physicians, and surgeons. OxyContin, therefore, broke through the cancer barrier and became one of the most widely prescribed painkillers in the United States. While generating billions in profits, OxyContin also would become one of the most abused drugs in history.

There were several issues with OxyContin that led to its widespread misuse. The preparation contained up to 160 mg of oxycodone per pill, 16 times more than the strongest Percocet formulary. The tablet also could easily be crushed, overcoming the delayed-release formulation. Because of the FDA insert, sales representatives were free to report an addiction risk of less than 1%, which they did. Widely.

But what science backed this claim? The study referenced was not a study at all. The citation was a one-paragraph, five-sentence letter to the editor published by the New England Journal of Medicine in 1980. In it, the authors briefly described their experience with inpatient opioid therapy. No reference was made to outpatient opioid prescriptions. Still, this letter has been scientifically cited more than 600 times, with a spike starting in 1995, the year OxyContin was released. Even as thousands of Americans were dying each year from opioid use, the “study” continued to be offered as proof of a low risk of addiction. As recently as 2014, the letter was cited in the journal OncoTargets and Therapy to support the statement, “In reality, medical opioid addiction is very rare.”

Maybe if we knew our history we could avoid repeating it. Previously, the drug diacetylmorphine was introduced as a safe, nonaddictive substitute for morphine by Bayer Pharmaceutical in the late 1890s. Diacetylmorphine is better known by its trademarked name, Heroin.

In 1996, the American Pain Society and the American Academy of Pain Medicine formed a committee to issue a joint statement that advocated opioid use for chronic pain and again stating a low risk of addiction. The committee was chaired by J. David Haddox, DDS, MD, a paid speaker (and later executive) for Purdue Pharma. The American Pain Society also launched a campaign to treat pain more aggressively. “Pain is the fifth vital sign” became a far-reaching strategy, which was adopted by the Department of Veterans Affairs and, ultimately, nearly every hospital in the country. The campaign was so successful that, in 2001, the Joint Commission required hospitals to:

• Assess pain in every patient.
• Record the results.
• Provide treatment for the pain.
• Reassess the effectiveness of the treatment.
• Teach staff how to manage pain.

The Joint Commission is not alone in creating opioid-friendly regulations. The Hospital Consumer Assessment of Healthcare Providers and Systems surveys patients after hospital stays. Several of the questions include pain management. One asks the patient whether the hospital staff did “everything they could” to assist with the patient’s pain. The satisfaction scores from these surveys are directly tied to hospital payments.

In 1998, the Federation of State Medical Boards published a statement reassuring doctors that they would not be punished for prescribing even large amounts of opioids if it were in the course of medical treatment. In 2004, the FSMB went further, stating that medical boards should consider “undertreatment of pain” to be a “departure from an acceptable standard of practice,” suggesting that state medical boards should sanction doctors who undertreated pain. According to a report by Catan et al. in the Wall Street Journal, this policy was drawn up with help from Dr. Haddox, who is now a senior executive with Purdue. The FSMB also would later disclose nearly $2 million in funding from opioid manufacturers.

These regulatory groups created widespread legal and financial pressure for doctors to diagnose and quickly treat pain in every patient. But what resources did we have to do this swiftly and effectively? Opioid prescriptions soared. There were 116 million opioid prescriptions issued in 1999; by 2013, it was 207 million. Annually, there are now more opioid prescriptions filled in the United States than there are people. Overdose deaths rose 500% between 1999 and 2016. Last year, there were more than 42,000 opioid-related mortalities in the United States. Like an untended fire, the crisis now spreads unabated.

What about vascular surgeons? Few of us prescribe OxyContin. Surely the 30 Percocets we give out after surgery are safe? In reality, Percocet contains oxycodone, the same opioid found in OxyContin, and therefore, carries a high risk of addiction. Norco, Vicodin, and Lortab all contain the opioid hydrocodone. Some studies have shown a higher risk of addiction with oxycodone, but all opioids carry a significant danger of abuse and dependence. As surgeons, we came into to this crisis with little or no training. This made us susceptible to bad science, bad-faith marketing, and bad ideas from regulatory commissions. Most of us learned how to prescribe postop opioids during the “hidden curriculum” of our third and fourth years of medical school: In other words, the residents taught us. Much like learning sex education on the streets, your mileage may vary. It is no wonder that a 2016 JAMA Internal Medicine news release found that simply having surgery was a risk factor for developing an opioid addiction. Surgeons don’t have an evidence-based plan to treat postoperative pain with opioids. About 6.5% of patients are still taking “postop” opioids 3-6 months after minor surgery; the numbers are about the same for major surgery (5.9%). Therefore, it is unlikely that pain is driving this chronic use.

Richard J. Barth Jr., MD, of Dartmouth-Hitchcock Medical Center in Lebanon, N.H., has studied opioid use following surgery extensively. He found there is a wide variety in surgeons’ opioid-prescribing habits and most of us overprescribe. In one study, 72% of the prescribed pills after surgery were not taken. He recommends the following guideline for opioid prescriptions after inpatient surgical procedures: If the patient took no opioids the day before discharge, no script is needed. For patients taking 1-3 pills the day before discharge, 15 pills are given; and for those taking 4 or more pills, a script for 30 is given.

As vascular surgeons, we must break out of our bubble and address our contributions to this crisis. It is past time to look at our own habits. Overprescribing is dangerous; the excess pills often are found by abusers, sold, or used recreationally by others in the household. Some patients take all of the pills simply because that is what the doctor prescribed; to the patient, he or she is merely following the doctor’s orders, and therefore not engaging in a risky behavior.

As vascular surgeons, there are several steps we can take immediately to reduce our contributions to the opioid epidemic and protect our patients:

• Always use the lowest effective dose of opioids and dramatically reduce the number of pills in your postop scripts. Fewer than 15 pills will cover most surgeries we perform.
• New data show that acetaminophen combined with ibuprofen works better for acute pain than acetaminophen combined with an opioid. Increase your use of nonnarcotic pain medications.
• Counsel your patients on the risk of addiction. If you plan to issue a script with only a few pills or nonnarcotics, let them know why in advance.
• Use caution when prescribing opioids to patients with anxiety or depression. The risk of addiction is much higher in these patients because of the anxiolytic and antidepressant qualities that opioids have.
• Avoid opioids in patients taking benzodiazepines, which can exacerbate the risk of respiratory depression and death.
• Help patients safely dispose of unused opioids.
• Use drug-monitoring programs whenever available.
• Use opioids for acute pain only. We do not have the training to manage long-term use.

Meanwhile, OxyContin still is available and sold exclusively by Purdue Pharma. Before its patent expired, Purdue altered the formulation to make it harder to abuse when crushing the tablets. They then lobbied the FDA to block generic production of the original formula because it was “unsafe.” Though Purdue (under Mundipharma) now markets this original version in South America, Europe, and Asia.

Many lawsuits have been brought against Purdue. Even with such high-profile lawyers as Rudy Giuliani and Eric Holder, Purdue has paid more than $600 million in fines and pleaded guilty to marketing OxyContin with “the intent to defraud or mislead.” Three Purdue executives have pleaded guilty to criminal misdemeanor charges.

In 2015, the FDA approved marketing OxyContin to children as young as age 11 years..

To address their role in the opioid crisis, the Joint Commission issued a statement on April 18, 2016. It was not a master class in self-awareness; the statement claimed that it is a “misconception” that Joint Commission standards pushed doctors to prescribe opioids. Yet, according to a Class Action complaint (Kenova v. JCAHO), in a 2001 monograph published by the Joint Commission (and funded by Purdue Pharma), they wrote “Some clinicians have inaccurate and exaggerated concerns about addiction, tolerance, and risk of death. This attitude prevails despite the fact that there is no evidence that addiction is a significant issue when persons are given opioids for pain control.”

In 2016, the AMA passed a resolution to drop pain as a vital sign. They also urged the Joint Commission to stop requiring hospitals to ask patients about the quality of their pain care. The American College of Surgeons has started an education initiative to help surgeons and patients learn about opioids and surgery (funded by Pacira Pharmaceuticals, makers of EXPAREL, an injectable long-lasting local anesthetic). In a March 2016 statement in the New England Journal of Medicine, Centers for Disease Control and Prevention representatives said of opioids “We know of no other medication routinely used for a nonfatal condition that kills patients so frequently.” As vascular surgeons, we are long overdue for a self-assessment. It is now time to change our practices and habits to help end this national addiction.

Dr. Sheahan is the Claude C. Craighead Jr. Professor and chair, division of vascular and endovascular surgery, Louisiana State University Health Sciences Center, New Orleans.

Resources

1. Hill M et al. Guideline for discharge opioid prescriptions after inpatient general surgical procedures. J Am Coll Surg. In Press.

2. Kenova v. JCAHO Class Action Complaint. United States District Court for the Southern District of West Virginia.

3. Mandell BF. The fifth vital sign: a complex story of politics and patient care. Cleveland Clinic Journal of Medicine 2016 Jun:83:400.

4. Leung PT et al. A 1980 letter on the risk of opioid addiction. New England Journal of Medicine 2017;376:2194-5.

5. www.jointcommission.org/joint_commission_statement_on_pain_management

6. www.cdc.gov/drugoverdose/epidemic/index.html

7. Catan T et al. A pain-drug champion has second thoughts. Wall Street Journal. Dec. 17, 2012 (updated online version).

8. Federation of State Medical Boards news release. www.fsmb.org/globalassets/advocacy/news-releases/2014/rems-grant-press-release-jan2014-final.pdf

9. Chou R et al. American Pain Society – American Academy of Pain Medicine Opioids Guidelines Panel. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain 2009;10:113-130.

10. Van Zee A. The promotion and marketing of OxyContin: Commercial triumph, public health tragedy. Am J Public Health 2009;99:221-7.

11. Keefe, PR. The family that built an empire of pain. The New Yorker. October 30, 2017.

AIDS, the Vietnam War, whatever your preferred scale for measuring horrific events, the numbers from the opioid crisis are as grave or worse. And, once again, it is the young who are dying. How we got to this point is an unbelievable story of corporate greed, government incompetence, regulatory commission overreach, and, unfortunately, physician ignorance.

Every one of us has contributed to this tragedy, and most of us still do. There are some easy first steps surgeons can take, but first let’s review the mistakes made that drove our country into addiction.

BackyardProduction/Thinkstock

In 1995, as their patent on MS Contin was set to expire, Purdue Pharma gained Food and Drug Administration approval for OxyContin (“contin” is pharma talk for continuous). At this time, opioids generally were considered to be dangerous and mainly prescribed for cancer or end-of-life patients. Purdue representatives began an aggressive marketing campaign to break out of this niche. They were aided in this pursuit by the FDA, which wrote in the package insert that iatrogenic addiction was rare and the delayed absorption of OxyContin “is believed to reduce the abuse liability of a drug.” These statements were made without the backing of any clinical trials. But with an on-label statement of reduced addiction risk, representatives could sell OxyContin based on a diminished potential for abuse.

In addition to oncologists, the drug was now marketed to rheumatologists, primary care physicians, and surgeons. OxyContin, therefore, broke through the cancer barrier and became one of the most widely prescribed painkillers in the United States. While generating billions in profits, OxyContin also would become one of the most abused drugs in history.

There were several issues with OxyContin that led to its widespread misuse. The preparation contained up to 160 mg of oxycodone per pill, 16 times more than the strongest Percocet formulary. The tablet also could easily be crushed, overcoming the delayed-release formulation. Because of the FDA insert, sales representatives were free to report an addiction risk of less than 1%, which they did. Widely.

But what science backed this claim? The study referenced was not a study at all. The citation was a one-paragraph, five-sentence letter to the editor published by the New England Journal of Medicine in 1980. In it, the authors briefly described their experience with inpatient opioid therapy. No reference was made to outpatient opioid prescriptions. Still, this letter has been scientifically cited more than 600 times, with a spike starting in 1995, the year OxyContin was released. Even as thousands of Americans were dying each year from opioid use, the “study” continued to be offered as proof of a low risk of addiction. As recently as 2014, the letter was cited in the journal OncoTargets and Therapy to support the statement, “In reality, medical opioid addiction is very rare.”

Maybe if we knew our history we could avoid repeating it. Previously, the drug diacetylmorphine was introduced as a safe, nonaddictive substitute for morphine by Bayer Pharmaceutical in the late 1890s. Diacetylmorphine is better known by its trademarked name, Heroin.

In 1996, the American Pain Society and the American Academy of Pain Medicine formed a committee to issue a joint statement that advocated opioid use for chronic pain and again stating a low risk of addiction. The committee was chaired by J. David Haddox, DDS, MD, a paid speaker (and later executive) for Purdue Pharma. The American Pain Society also launched a campaign to treat pain more aggressively. “Pain is the fifth vital sign” became a far-reaching strategy, which was adopted by the Department of Veterans Affairs and, ultimately, nearly every hospital in the country. The campaign was so successful that, in 2001, the Joint Commission required hospitals to:

• Assess pain in every patient.
• Record the results.
• Provide treatment for the pain.
• Reassess the effectiveness of the treatment.
• Teach staff how to manage pain.

The Joint Commission is not alone in creating opioid-friendly regulations. The Hospital Consumer Assessment of Healthcare Providers and Systems surveys patients after hospital stays. Several of the questions include pain management. One asks the patient whether the hospital staff did “everything they could” to assist with the patient’s pain. The satisfaction scores from these surveys are directly tied to hospital payments.

In 1998, the Federation of State Medical Boards published a statement reassuring doctors that they would not be punished for prescribing even large amounts of opioids if it were in the course of medical treatment. In 2004, the FSMB went further, stating that medical boards should consider “undertreatment of pain” to be a “departure from an acceptable standard of practice,” suggesting that state medical boards should sanction doctors who undertreated pain. According to a report by Catan et al. in the Wall Street Journal, this policy was drawn up with help from Dr. Haddox, who is now a senior executive with Purdue. The FSMB also would later disclose nearly $2 million in funding from opioid manufacturers.

These regulatory groups created widespread legal and financial pressure for doctors to diagnose and quickly treat pain in every patient. But what resources did we have to do this swiftly and effectively? Opioid prescriptions soared. There were 116 million opioid prescriptions issued in 1999; by 2013, it was 207 million. Annually, there are now more opioid prescriptions filled in the United States than there are people. Overdose deaths rose 500% between 1999 and 2016. Last year, there were more than 42,000 opioid-related mortalities in the United States. Like an untended fire, the crisis now spreads unabated.

What about vascular surgeons? Few of us prescribe OxyContin. Surely the 30 Percocets we give out after surgery are safe? In reality, Percocet contains oxycodone, the same opioid found in OxyContin, and therefore, carries a high risk of addiction. Norco, Vicodin, and Lortab all contain the opioid hydrocodone. Some studies have shown a higher risk of addiction with oxycodone, but all opioids carry a significant danger of abuse and dependence. As surgeons, we came into to this crisis with little or no training. This made us susceptible to bad science, bad-faith marketing, and bad ideas from regulatory commissions. Most of us learned how to prescribe postop opioids during the “hidden curriculum” of our third and fourth years of medical school: In other words, the residents taught us. Much like learning sex education on the streets, your mileage may vary. It is no wonder that a 2016 JAMA Internal Medicine news release found that simply having surgery was a risk factor for developing an opioid addiction. Surgeons don’t have an evidence-based plan to treat postoperative pain with opioids. About 6.5% of patients are still taking “postop” opioids 3-6 months after minor surgery; the numbers are about the same for major surgery (5.9%). Therefore, it is unlikely that pain is driving this chronic use.

Richard J. Barth Jr., MD, of Dartmouth-Hitchcock Medical Center in Lebanon, N.H., has studied opioid use following surgery extensively. He found there is a wide variety in surgeons’ opioid-prescribing habits and most of us overprescribe. In one study, 72% of the prescribed pills after surgery were not taken. He recommends the following guideline for opioid prescriptions after inpatient surgical procedures: If the patient took no opioids the day before discharge, no script is needed. For patients taking 1-3 pills the day before discharge, 15 pills are given; and for those taking 4 or more pills, a script for 30 is given.

As vascular surgeons, we must break out of our bubble and address our contributions to this crisis. It is past time to look at our own habits. Overprescribing is dangerous; the excess pills often are found by abusers, sold, or used recreationally by others in the household. Some patients take all of the pills simply because that is what the doctor prescribed; to the patient, he or she is merely following the doctor’s orders, and therefore not engaging in a risky behavior.

As vascular surgeons, there are several steps we can take immediately to reduce our contributions to the opioid epidemic and protect our patients:

• Always use the lowest effective dose of opioids and dramatically reduce the number of pills in your postop scripts. Fewer than 15 pills will cover most surgeries we perform.
• New data show that acetaminophen combined with ibuprofen works better for acute pain than acetaminophen combined with an opioid. Increase your use of nonnarcotic pain medications.
• Counsel your patients on the risk of addiction. If you plan to issue a script with only a few pills or nonnarcotics, let them know why in advance.
• Use caution when prescribing opioids to patients with anxiety or depression. The risk of addiction is much higher in these patients because of the anxiolytic and antidepressant qualities that opioids have.
• Avoid opioids in patients taking benzodiazepines, which can exacerbate the risk of respiratory depression and death.
• Help patients safely dispose of unused opioids.
• Use drug-monitoring programs whenever available.
• Use opioids for acute pain only. We do not have the training to manage long-term use.

Meanwhile, OxyContin still is available and sold exclusively by Purdue Pharma. Before its patent expired, Purdue altered the formulation to make it harder to abuse when crushing the tablets. They then lobbied the FDA to block generic production of the original formula because it was “unsafe.” Though Purdue (under Mundipharma) now markets this original version in South America, Europe, and Asia.

Many lawsuits have been brought against Purdue. Even with such high-profile lawyers as Rudy Giuliani and Eric Holder, Purdue has paid more than $600 million in fines and pleaded guilty to marketing OxyContin with “the intent to defraud or mislead.” Three Purdue executives have pleaded guilty to criminal misdemeanor charges.

In 2015, the FDA approved marketing OxyContin to children as young as age 11 years..

To address their role in the opioid crisis, the Joint Commission issued a statement on April 18, 2016. It was not a master class in self-awareness; the statement claimed that it is a “misconception” that Joint Commission standards pushed doctors to prescribe opioids. Yet, according to a Class Action complaint (Kenova v. JCAHO), in a 2001 monograph published by the Joint Commission (and funded by Purdue Pharma), they wrote “Some clinicians have inaccurate and exaggerated concerns about addiction, tolerance, and risk of death. This attitude prevails despite the fact that there is no evidence that addiction is a significant issue when persons are given opioids for pain control.”

In 2016, the AMA passed a resolution to drop pain as a vital sign. They also urged the Joint Commission to stop requiring hospitals to ask patients about the quality of their pain care. The American College of Surgeons has started an education initiative to help surgeons and patients learn about opioids and surgery (funded by Pacira Pharmaceuticals, makers of EXPAREL, an injectable long-lasting local anesthetic). In a March 2016 statement in the New England Journal of Medicine, Centers for Disease Control and Prevention representatives said of opioids “We know of no other medication routinely used for a nonfatal condition that kills patients so frequently.” As vascular surgeons, we are long overdue for a self-assessment. It is now time to change our practices and habits to help end this national addiction.

Dr. Sheahan is the Claude C. Craighead Jr. Professor and chair, division of vascular and endovascular surgery, Louisiana State University Health Sciences Center, New Orleans.

Resources

1. Hill M et al. Guideline for discharge opioid prescriptions after inpatient general surgical procedures. J Am Coll Surg. In Press.

2. Kenova v. JCAHO Class Action Complaint. United States District Court for the Southern District of West Virginia.

3. Mandell BF. The fifth vital sign: a complex story of politics and patient care. Cleveland Clinic Journal of Medicine 2016 Jun:83:400.

4. Leung PT et al. A 1980 letter on the risk of opioid addiction. New England Journal of Medicine 2017;376:2194-5.

5. www.jointcommission.org/joint_commission_statement_on_pain_management

6. www.cdc.gov/drugoverdose/epidemic/index.html

7. Catan T et al. A pain-drug champion has second thoughts. Wall Street Journal. Dec. 17, 2012 (updated online version).

8. Federation of State Medical Boards news release. www.fsmb.org/globalassets/advocacy/news-releases/2014/rems-grant-press-release-jan2014-final.pdf

9. Chou R et al. American Pain Society – American Academy of Pain Medicine Opioids Guidelines Panel. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain 2009;10:113-130.

10. Van Zee A. The promotion and marketing of OxyContin: Commercial triumph, public health tragedy. Am J Public Health 2009;99:221-7.

11. Keefe, PR. The family that built an empire of pain. The New Yorker. October 30, 2017.

Lerman and Jameson¹ recently called for expanding formal leadership development of physicians and increasing the reach of effective physician leaders. From the perspective of physicians, these are certainly good goals. We should have leaders in white coats who understand the joy of practicing medicine and can rally for our missions, challenges, and passions as doctors, clinical educators, and researchers.

But the rationale for most of their argument seems to stem from the perceived need to train physician leaders to promote the survival of increasingly complex health systems and strategically guide individual institutions. This seems also to be the focus of many health systems as they search for and hire physicians for various system leadership positions. But only in the final sentence of their thoughtful essay do Lerman and Jameson mention “patient and physician satisfaction and improved clinical outcomes,” and then only as a byproduct of achieving “organizational efficiency.”¹

The financial success (ie, survival) of a health system and the emotional well-being and clinical skills of its physicians are clearly interrelated and cannot be completely dichotomized, and I am not implying that Lerman and Jameson have done so. But trying to promote both can create potential for mission malalignment. Achieving an appropriate balance between these two goals, which at a tactical level are not always congruent, is critical. Training leaders in the skills to achieve alignment with the organization’s culture and priorities may make it easier to administer and guide the course of a medical system with apparent physician leadership, but it still may not well represent the human constituents. The recent trend for health systems to establish new committees charged with improving physician wellness is a statement of problem recognition, but whether their existence can accomplish “mission alignment” remains to be seen.

Swensen et al² from the Mayo Clinic have highlighted the need to focus on the needs of the physician, and not primarily on those of the institution, to reduce the epidemic of physician burnout. A physician leader who is wonderfully trained in organizational psychology, communication skills, and performance metrics analysis, but who lacks a deep and authentic understanding of the joys of practicing medicine and delivering care to the sick, of the need to stoke the individual physician’s intellectual curiosity and provide time for reflection to clinicians working in their institutions, is a unidirectional institutional leader, and thus a leader in name alone. We need to be careful about grooming young physician leaders at too early a stage. Having the book knowledge of a physician is not the same as having the heart of one.

We have appropriately morphed away from the academic curriculum vitae as the only ticket to titled organizational leadership. But we need to look closely at our choice of physician leaders and be careful that the physician component of that terminology is not defined by degree alone. Just as the number of first-authored publications and surgical procedures performed should not suffice for selection to leadership positions, nor should participation in leadership courses or the ability to respond as desired in a behavioral interview be viewed as adequate for selection as a leader of physicians. Administrators with a tailored MBA degree, extensive and real job experience in a clinical center, and participation in a seminar on physician behavior can also be successful supervisors and (maybe) leaders in a medical center.

But if we really care about our clinical staff, organizational leadership must include physicians in positions of influence who are true advocates for clinicians and patients, and not primarily caretakers of the health system and enforcers of performance metrics. Although (some of) the latter are absolutely necessary, we need more than that from our physician leaders. We need them to reflect and support our perspective as well as the institution’s needs. We need them to understand and defend the need to maintain the joy of practicing medicine. How can we as physicians really take care of others if there is no one to take care of us?³ 

Note: this discussion is not new. We had a dialogue on this topic in the Journal almost 10 years ago!⁴

Lerman and Jameson¹ recently called for expanding formal leadership development of physicians and increasing the reach of effective physician leaders. From the perspective of physicians, these are certainly good goals. We should have leaders in white coats who understand the joy of practicing medicine and can rally for our missions, challenges, and passions as doctors, clinical educators, and researchers.

But the rationale for most of their argument seems to stem from the perceived need to train physician leaders to promote the survival of increasingly complex health systems and strategically guide individual institutions. This seems also to be the focus of many health systems as they search for and hire physicians for various system leadership positions. But only in the final sentence of their thoughtful essay do Lerman and Jameson mention “patient and physician satisfaction and improved clinical outcomes,” and then only as a byproduct of achieving “organizational efficiency.”¹

The financial success (ie, survival) of a health system and the emotional well-being and clinical skills of its physicians are clearly interrelated and cannot be completely dichotomized, and I am not implying that Lerman and Jameson have done so. But trying to promote both can create potential for mission malalignment. Achieving an appropriate balance between these two goals, which at a tactical level are not always congruent, is critical. Training leaders in the skills to achieve alignment with the organization’s culture and priorities may make it easier to administer and guide the course of a medical system with apparent physician leadership, but it still may not well represent the human constituents. The recent trend for health systems to establish new committees charged with improving physician wellness is a statement of problem recognition, but whether their existence can accomplish “mission alignment” remains to be seen.

Swensen et al² from the Mayo Clinic have highlighted the need to focus on the needs of the physician, and not primarily on those of the institution, to reduce the epidemic of physician burnout. A physician leader who is wonderfully trained in organizational psychology, communication skills, and performance metrics analysis, but who lacks a deep and authentic understanding of the joys of practicing medicine and delivering care to the sick, of the need to stoke the individual physician’s intellectual curiosity and provide time for reflection to clinicians working in their institutions, is a unidirectional institutional leader, and thus a leader in name alone. We need to be careful about grooming young physician leaders at too early a stage. Having the book knowledge of a physician is not the same as having the heart of one.

We have appropriately morphed away from the academic curriculum vitae as the only ticket to titled organizational leadership. But we need to look closely at our choice of physician leaders and be careful that the physician component of that terminology is not defined by degree alone. Just as the number of first-authored publications and surgical procedures performed should not suffice for selection to leadership positions, nor should participation in leadership courses or the ability to respond as desired in a behavioral interview be viewed as adequate for selection as a leader of physicians. Administrators with a tailored MBA degree, extensive and real job experience in a clinical center, and participation in a seminar on physician behavior can also be successful supervisors and (maybe) leaders in a medical center.

But if we really care about our clinical staff, organizational leadership must include physicians in positions of influence who are true advocates for clinicians and patients, and not primarily caretakers of the health system and enforcers of performance metrics. Although (some of) the latter are absolutely necessary, we need more than that from our physician leaders. We need them to reflect and support our perspective as well as the institution’s needs. We need them to understand and defend the need to maintain the joy of practicing medicine. How can we as physicians really take care of others if there is no one to take care of us?³ 

Note: this discussion is not new. We had a dialogue on this topic in the Journal almost 10 years ago!⁴

Lerman and Jameson¹ recently called for expanding formal leadership development of physicians and increasing the reach of effective physician leaders. From the perspective of physicians, these are certainly good goals. We should have leaders in white coats who understand the joy of practicing medicine and can rally for our missions, challenges, and passions as doctors, clinical educators, and researchers.

But the rationale for most of their argument seems to stem from the perceived need to train physician leaders to promote the survival of increasingly complex health systems and strategically guide individual institutions. This seems also to be the focus of many health systems as they search for and hire physicians for various system leadership positions. But only in the final sentence of their thoughtful essay do Lerman and Jameson mention “patient and physician satisfaction and improved clinical outcomes,” and then only as a byproduct of achieving “organizational efficiency.”¹

The financial success (ie, survival) of a health system and the emotional well-being and clinical skills of its physicians are clearly interrelated and cannot be completely dichotomized, and I am not implying that Lerman and Jameson have done so. But trying to promote both can create potential for mission malalignment. Achieving an appropriate balance between these two goals, which at a tactical level are not always congruent, is critical. Training leaders in the skills to achieve alignment with the organization’s culture and priorities may make it easier to administer and guide the course of a medical system with apparent physician leadership, but it still may not well represent the human constituents. The recent trend for health systems to establish new committees charged with improving physician wellness is a statement of problem recognition, but whether their existence can accomplish “mission alignment” remains to be seen.

Swensen et al² from the Mayo Clinic have highlighted the need to focus on the needs of the physician, and not primarily on those of the institution, to reduce the epidemic of physician burnout. A physician leader who is wonderfully trained in organizational psychology, communication skills, and performance metrics analysis, but who lacks a deep and authentic understanding of the joys of practicing medicine and delivering care to the sick, of the need to stoke the individual physician’s intellectual curiosity and provide time for reflection to clinicians working in their institutions, is a unidirectional institutional leader, and thus a leader in name alone. We need to be careful about grooming young physician leaders at too early a stage. Having the book knowledge of a physician is not the same as having the heart of one.

We have appropriately morphed away from the academic curriculum vitae as the only ticket to titled organizational leadership. But we need to look closely at our choice of physician leaders and be careful that the physician component of that terminology is not defined by degree alone. Just as the number of first-authored publications and surgical procedures performed should not suffice for selection to leadership positions, nor should participation in leadership courses or the ability to respond as desired in a behavioral interview be viewed as adequate for selection as a leader of physicians. Administrators with a tailored MBA degree, extensive and real job experience in a clinical center, and participation in a seminar on physician behavior can also be successful supervisors and (maybe) leaders in a medical center.

But if we really care about our clinical staff, organizational leadership must include physicians in positions of influence who are true advocates for clinicians and patients, and not primarily caretakers of the health system and enforcers of performance metrics. Although (some of) the latter are absolutely necessary, we need more than that from our physician leaders. We need them to reflect and support our perspective as well as the institution’s needs. We need them to understand and defend the need to maintain the joy of practicing medicine. How can we as physicians really take care of others if there is no one to take care of us?³ 

Note: this discussion is not new. We had a dialogue on this topic in the Journal almost 10 years ago!⁴