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Denosumab now dominant therapy for osteoporosis linked to cancer
Amid a substantial expansion of therapies in several drug classes for the treatment of osteoporosis, there has been a notable increase in the prescription of denosumab for patients with a cancer-related indication.
In an analysis of claims data from January 2009 to March 2020, the bisphosphonate alendronate represented more than 50% of all prescriptions for bone-directed therapies, but growth in the use of the monoclonal antibody denosumab overall and in cancer-related indications particularly was steady throughout the study period.
“In the malignancy cohort, alendronate and zoledronic acid were each used in approximately 30% of individuals at the onset of the study, but use of both then declined,” Sara Cromer, MD, reported at the annual meeting of the Endocrine Society.
For malignancy-based prescriptions, denosumab surpassed either bisphosphonate by 2013 and then continued to rise.
Denosumab use “reached approximately 50% of all bone-directed medication use in the malignancy cohort” by the end of the study period, said Dr. Cromer, a clinical research fellow in endocrinology at Massachusetts General Hospital, Boston.
The claims data for this analysis was drawn from the Clinformatics Data Mart. The analysis was restricted to individuals aged older than 50 years who received a prescription for a bone-directed therapy. The 15.48 million prescriptions evaluated were drawn from 1.46 million unique individuals. The mean age was 69 years, and 89% of those prescribed a drug were women.
Oncologic indications one of two tracked cohorts
In the context of a large expansion of treatment options in several drug classes for osteoporosis, the objective of this claims analysis was to document trends in treatment choice, according to Dr. Cromer. She and her coinvestigators looked at prescriptions overall as well as in two cohorts defined by ICD codes. One included patients prescribed a prescription by an oncologist. The other included everyone else.
When all prescriptions for bone-directed therapy were evaluated over the study period, alendronate was the most commonly prescribed therapy, and its use increased over time. Prescriptions of zoledronic acid also rose, doubling over the study period, but use was very low in the beginning and it never climbed above 5%.
The proportion of prescriptions written for bisphosphonates other than alendronate and zoledronic acid “declined steadily” over the study period, Dr. Cromer reported.
Denosumab, a monoclonal antibody that targets a step in the process important to maturation of osteoclasts, was approved in 2010. It accounted for 10% of all prescriptions for osteoporosis by 2015 and 15% by 2018. It was still rising through the end of the study period.
In contrast, prescriptions of raloxifene, a selective estrogen receptor modulator, began to decline after 2013. In general, the rates of prescriptions for other agents, including some of the more recently approved drugs, such as teriparatide, abaloparatide, and romosozumab, changed very little over the study period. None of these therapies ever represented more than 2% of prescriptions.
When looking at the cohort of patients who received a bone-directed reason for a noncancer indication, the trends “paralleled those in the all-user analysis,” Dr. Cromer reported.
Denosumab use greater in privately insured
In the malignancy cohort, the decline in the use of bisphosphonates and the rise in the use of denosumab were most pronounced in patients who were privately insured. The increased use of denosumab over the study period “outpaced gains in use of other agents despite guidelines,” said Dr. Cromer, referring to the those issued by the Endocrine Society in 2019 .
In those guidelines, written for management of postmenopausal women at high risk of fractures, bisphosphonates are recommended for initial treatment while denosumab is recommended as an alternative. However, those guidelines do not provide specific recommendations for therapies directed at osteoporosis associated with cancer.
Guidelines for this population exist, including one published by the American Society of Clinical Oncology in 2019.
In the ASCO guidelines, oral bisphosphonates, intravenous bisphosphonates, and subcutaneous denosumab were all identified as “efficacious options,” according to Charles L. Shapiro, MD, director of breast cancer translational research, Mount Sinai Health System, New York.
Specifically, “all three of them work to reduce fractures and improve bone density in women with breast cancer in whom you are trying to prevent or treat osteoporosis,” Dr. Shapiro said in an interview.
There might be relative advantages for one therapy over another in specific subgroups defined by type of cancer or stage of cancer, but trials are not definitive for such outcomes as overall survival. Citing one comparative study associating denosumab with an 18% delay to first skeletal event in women with metastatic breast cancer, Dr. Shapiro observed, “I personally don’t consider an 18% delay [for this outcome] to be that clinically meaningful.”
Although major guidelines from ASCO have not so far favored denosumab over any bisphosphonate in routine care, Dr. Shapiro did not rule out the possibility that future studies will show differences.
Dr. Comer and Dr. Shapiro reported no relevant conflicts of interest.
Amid a substantial expansion of therapies in several drug classes for the treatment of osteoporosis, there has been a notable increase in the prescription of denosumab for patients with a cancer-related indication.
In an analysis of claims data from January 2009 to March 2020, the bisphosphonate alendronate represented more than 50% of all prescriptions for bone-directed therapies, but growth in the use of the monoclonal antibody denosumab overall and in cancer-related indications particularly was steady throughout the study period.
“In the malignancy cohort, alendronate and zoledronic acid were each used in approximately 30% of individuals at the onset of the study, but use of both then declined,” Sara Cromer, MD, reported at the annual meeting of the Endocrine Society.
For malignancy-based prescriptions, denosumab surpassed either bisphosphonate by 2013 and then continued to rise.
Denosumab use “reached approximately 50% of all bone-directed medication use in the malignancy cohort” by the end of the study period, said Dr. Cromer, a clinical research fellow in endocrinology at Massachusetts General Hospital, Boston.
The claims data for this analysis was drawn from the Clinformatics Data Mart. The analysis was restricted to individuals aged older than 50 years who received a prescription for a bone-directed therapy. The 15.48 million prescriptions evaluated were drawn from 1.46 million unique individuals. The mean age was 69 years, and 89% of those prescribed a drug were women.
Oncologic indications one of two tracked cohorts
In the context of a large expansion of treatment options in several drug classes for osteoporosis, the objective of this claims analysis was to document trends in treatment choice, according to Dr. Cromer. She and her coinvestigators looked at prescriptions overall as well as in two cohorts defined by ICD codes. One included patients prescribed a prescription by an oncologist. The other included everyone else.
When all prescriptions for bone-directed therapy were evaluated over the study period, alendronate was the most commonly prescribed therapy, and its use increased over time. Prescriptions of zoledronic acid also rose, doubling over the study period, but use was very low in the beginning and it never climbed above 5%.
The proportion of prescriptions written for bisphosphonates other than alendronate and zoledronic acid “declined steadily” over the study period, Dr. Cromer reported.
Denosumab, a monoclonal antibody that targets a step in the process important to maturation of osteoclasts, was approved in 2010. It accounted for 10% of all prescriptions for osteoporosis by 2015 and 15% by 2018. It was still rising through the end of the study period.
In contrast, prescriptions of raloxifene, a selective estrogen receptor modulator, began to decline after 2013. In general, the rates of prescriptions for other agents, including some of the more recently approved drugs, such as teriparatide, abaloparatide, and romosozumab, changed very little over the study period. None of these therapies ever represented more than 2% of prescriptions.
When looking at the cohort of patients who received a bone-directed reason for a noncancer indication, the trends “paralleled those in the all-user analysis,” Dr. Cromer reported.
Denosumab use greater in privately insured
In the malignancy cohort, the decline in the use of bisphosphonates and the rise in the use of denosumab were most pronounced in patients who were privately insured. The increased use of denosumab over the study period “outpaced gains in use of other agents despite guidelines,” said Dr. Cromer, referring to the those issued by the Endocrine Society in 2019 .
In those guidelines, written for management of postmenopausal women at high risk of fractures, bisphosphonates are recommended for initial treatment while denosumab is recommended as an alternative. However, those guidelines do not provide specific recommendations for therapies directed at osteoporosis associated with cancer.
Guidelines for this population exist, including one published by the American Society of Clinical Oncology in 2019.
In the ASCO guidelines, oral bisphosphonates, intravenous bisphosphonates, and subcutaneous denosumab were all identified as “efficacious options,” according to Charles L. Shapiro, MD, director of breast cancer translational research, Mount Sinai Health System, New York.
Specifically, “all three of them work to reduce fractures and improve bone density in women with breast cancer in whom you are trying to prevent or treat osteoporosis,” Dr. Shapiro said in an interview.
There might be relative advantages for one therapy over another in specific subgroups defined by type of cancer or stage of cancer, but trials are not definitive for such outcomes as overall survival. Citing one comparative study associating denosumab with an 18% delay to first skeletal event in women with metastatic breast cancer, Dr. Shapiro observed, “I personally don’t consider an 18% delay [for this outcome] to be that clinically meaningful.”
Although major guidelines from ASCO have not so far favored denosumab over any bisphosphonate in routine care, Dr. Shapiro did not rule out the possibility that future studies will show differences.
Dr. Comer and Dr. Shapiro reported no relevant conflicts of interest.
Amid a substantial expansion of therapies in several drug classes for the treatment of osteoporosis, there has been a notable increase in the prescription of denosumab for patients with a cancer-related indication.
In an analysis of claims data from January 2009 to March 2020, the bisphosphonate alendronate represented more than 50% of all prescriptions for bone-directed therapies, but growth in the use of the monoclonal antibody denosumab overall and in cancer-related indications particularly was steady throughout the study period.
“In the malignancy cohort, alendronate and zoledronic acid were each used in approximately 30% of individuals at the onset of the study, but use of both then declined,” Sara Cromer, MD, reported at the annual meeting of the Endocrine Society.
For malignancy-based prescriptions, denosumab surpassed either bisphosphonate by 2013 and then continued to rise.
Denosumab use “reached approximately 50% of all bone-directed medication use in the malignancy cohort” by the end of the study period, said Dr. Cromer, a clinical research fellow in endocrinology at Massachusetts General Hospital, Boston.
The claims data for this analysis was drawn from the Clinformatics Data Mart. The analysis was restricted to individuals aged older than 50 years who received a prescription for a bone-directed therapy. The 15.48 million prescriptions evaluated were drawn from 1.46 million unique individuals. The mean age was 69 years, and 89% of those prescribed a drug were women.
Oncologic indications one of two tracked cohorts
In the context of a large expansion of treatment options in several drug classes for osteoporosis, the objective of this claims analysis was to document trends in treatment choice, according to Dr. Cromer. She and her coinvestigators looked at prescriptions overall as well as in two cohorts defined by ICD codes. One included patients prescribed a prescription by an oncologist. The other included everyone else.
When all prescriptions for bone-directed therapy were evaluated over the study period, alendronate was the most commonly prescribed therapy, and its use increased over time. Prescriptions of zoledronic acid also rose, doubling over the study period, but use was very low in the beginning and it never climbed above 5%.
The proportion of prescriptions written for bisphosphonates other than alendronate and zoledronic acid “declined steadily” over the study period, Dr. Cromer reported.
Denosumab, a monoclonal antibody that targets a step in the process important to maturation of osteoclasts, was approved in 2010. It accounted for 10% of all prescriptions for osteoporosis by 2015 and 15% by 2018. It was still rising through the end of the study period.
In contrast, prescriptions of raloxifene, a selective estrogen receptor modulator, began to decline after 2013. In general, the rates of prescriptions for other agents, including some of the more recently approved drugs, such as teriparatide, abaloparatide, and romosozumab, changed very little over the study period. None of these therapies ever represented more than 2% of prescriptions.
When looking at the cohort of patients who received a bone-directed reason for a noncancer indication, the trends “paralleled those in the all-user analysis,” Dr. Cromer reported.
Denosumab use greater in privately insured
In the malignancy cohort, the decline in the use of bisphosphonates and the rise in the use of denosumab were most pronounced in patients who were privately insured. The increased use of denosumab over the study period “outpaced gains in use of other agents despite guidelines,” said Dr. Cromer, referring to the those issued by the Endocrine Society in 2019 .
In those guidelines, written for management of postmenopausal women at high risk of fractures, bisphosphonates are recommended for initial treatment while denosumab is recommended as an alternative. However, those guidelines do not provide specific recommendations for therapies directed at osteoporosis associated with cancer.
Guidelines for this population exist, including one published by the American Society of Clinical Oncology in 2019.
In the ASCO guidelines, oral bisphosphonates, intravenous bisphosphonates, and subcutaneous denosumab were all identified as “efficacious options,” according to Charles L. Shapiro, MD, director of breast cancer translational research, Mount Sinai Health System, New York.
Specifically, “all three of them work to reduce fractures and improve bone density in women with breast cancer in whom you are trying to prevent or treat osteoporosis,” Dr. Shapiro said in an interview.
There might be relative advantages for one therapy over another in specific subgroups defined by type of cancer or stage of cancer, but trials are not definitive for such outcomes as overall survival. Citing one comparative study associating denosumab with an 18% delay to first skeletal event in women with metastatic breast cancer, Dr. Shapiro observed, “I personally don’t consider an 18% delay [for this outcome] to be that clinically meaningful.”
Although major guidelines from ASCO have not so far favored denosumab over any bisphosphonate in routine care, Dr. Shapiro did not rule out the possibility that future studies will show differences.
Dr. Comer and Dr. Shapiro reported no relevant conflicts of interest.
FROM ENDO 2021
Change is hard: Lessons from an EHR conversion
During this “go-live,” 5 hospitals and approximately 300 ambulatory service and physician practice locations made the transition, consolidating over 100 disparate electronic systems and dozens of interfaces into one world-class medical record.
If you’ve ever been part of such an event, you know it is anything but simple. On the contrary, it requires an enormous financial investment along with years of planning, hours of meetings, and months of training. No matter how much preparation goes into it, there are sure to be bumps along the way. It is a traumatic and stressful time for all involved, but the end result is well worth the effort. Still, there are lessons to be learned and wisdom to be gleaned, and this month we’d like to share a few that we found most important. We believe that many of these are useful lessons even to those who will never live through a go-live.
Safety always comes first
Patient safety is a term so often used that it has a tendency to be taken for granted. Health systems build processes and procedures to ensure safety – some even win awards and recognition for their efforts. But the best (and safest) health care institutions build patient safety into their cultures. More than just being taught to use checklists or buzzwords, the staff at these institutions are encouraged to put the welfare of patients first, making all other activities secondary to this pursuit. We had the opportunity to witness the benefits of such a culture during this go-live and were incredibly impressed with the results.
To be successful in an EHR transition of any magnitude, an organization needs to hold patient safety as a core value and provide its employees with the tools to execute on that value. This enables staff to prepare adequately and to identify risks and opportunities before the conversion takes place. Once go-live occurs, staff also must feel empowered to speak up when they identify problem areas that might jeopardize patients’ care. They also must be given a clear escalation path to ensure their voices can be heard. Most importantly, everyone must understand that the electronic health record itself is just one piece of a major operational change.
As workflows are modified to adapt to the new technology, unsafe processes should be called out and fixed quickly. While the EHR may offer the latest in decision support and system integration, no advancement in technology can make up for bad outcomes, nor justify processes that lead to patient harm.
Training is no substitute for good support
It takes a long time to train thousands of employees, especially when that training must occur during the era of social distancing in the midst of a pandemic. Still, even in the best of times, education should be married to hands-on experience in order to have a real impact. Unfortunately, this is extremely challenging.
Trainees forget much of what they’ve learned in the weeks or months between education and go-live, so they must be given immediately accessible support to bridge the gap. This is known as “at-the-elbow” (ATE) support, and as the name implies, it consists of individuals who are familiar with the new system and are always available to end users, answering their questions and helping them navigate. Since health care never sleeps, this support needs to be offered 24/7, and it should also be flexible and plentiful.
There are many areas that will require more support than anticipated to accommodate the number of clinical and other staff who will use the system, so support staff must be nimble and available for redeployment. In addition, ensuring high-quality support is essential. As many ATE experts are hired contractors, their knowledge base and communications skills can vary widely. Accountability is key, and end users should feel empowered to identify gaps in coverage and deficits in knowledge base in the ATE.
As employees become more familiar with the new system, the need for ATE will wane, but there will still be questions that arise for many weeks to months, and new EHR users will also be added all the time. A good after–go-live support system should remain available so clinical and clerical employees can get just-in-time assistance whenever they need it.
Users should be given clear expectations
Clinicians going through an EHR conversion may be frustrated to discover that the data transferred from their old system into the new one is not quite what they expected. While structured elements such as allergies and immunizations may transfer, unstructured patient histories may not come over at all.
There may be gaps in data, or the opposite may even be true: an overabundance of useless information may transfer over, leaving doctors with dozens of meaningless data points to sift through and eliminate to clean up the chart. This can be extremely time-consuming and discouraging and may jeopardize the success of the go-live.
Providers deserve clear expectations prior to conversion. They should be told what will and will not transfer and be informed that there will be extra work required for documentation at the outset. They may also want the option to preemptively reduce patient volumes to accommodate the additional effort involved in preparing charts. No matter what, this will be a heavy lift, and physicians should understand the implications long before go-live to prepare accordingly.
Old habits die hard
One of the most common complaints we’ve heard following EHR conversions is that “things just worked better in the old system.” We always respond with a question: “Were things better, or just different?” The truth may lie somewhere in the middle, but there is no question that muscle memory develops over many years, and change is difficult no matter how much better the new system is. Still, appropriate expectations, access to just-in-time support, and a continual focus on safety will ensure that the long-term benefits of a patient-centered and integrated electronic record will far outweigh the initial challenges of go-live.
Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.
During this “go-live,” 5 hospitals and approximately 300 ambulatory service and physician practice locations made the transition, consolidating over 100 disparate electronic systems and dozens of interfaces into one world-class medical record.
If you’ve ever been part of such an event, you know it is anything but simple. On the contrary, it requires an enormous financial investment along with years of planning, hours of meetings, and months of training. No matter how much preparation goes into it, there are sure to be bumps along the way. It is a traumatic and stressful time for all involved, but the end result is well worth the effort. Still, there are lessons to be learned and wisdom to be gleaned, and this month we’d like to share a few that we found most important. We believe that many of these are useful lessons even to those who will never live through a go-live.
Safety always comes first
Patient safety is a term so often used that it has a tendency to be taken for granted. Health systems build processes and procedures to ensure safety – some even win awards and recognition for their efforts. But the best (and safest) health care institutions build patient safety into their cultures. More than just being taught to use checklists or buzzwords, the staff at these institutions are encouraged to put the welfare of patients first, making all other activities secondary to this pursuit. We had the opportunity to witness the benefits of such a culture during this go-live and were incredibly impressed with the results.
To be successful in an EHR transition of any magnitude, an organization needs to hold patient safety as a core value and provide its employees with the tools to execute on that value. This enables staff to prepare adequately and to identify risks and opportunities before the conversion takes place. Once go-live occurs, staff also must feel empowered to speak up when they identify problem areas that might jeopardize patients’ care. They also must be given a clear escalation path to ensure their voices can be heard. Most importantly, everyone must understand that the electronic health record itself is just one piece of a major operational change.
As workflows are modified to adapt to the new technology, unsafe processes should be called out and fixed quickly. While the EHR may offer the latest in decision support and system integration, no advancement in technology can make up for bad outcomes, nor justify processes that lead to patient harm.
Training is no substitute for good support
It takes a long time to train thousands of employees, especially when that training must occur during the era of social distancing in the midst of a pandemic. Still, even in the best of times, education should be married to hands-on experience in order to have a real impact. Unfortunately, this is extremely challenging.
Trainees forget much of what they’ve learned in the weeks or months between education and go-live, so they must be given immediately accessible support to bridge the gap. This is known as “at-the-elbow” (ATE) support, and as the name implies, it consists of individuals who are familiar with the new system and are always available to end users, answering their questions and helping them navigate. Since health care never sleeps, this support needs to be offered 24/7, and it should also be flexible and plentiful.
There are many areas that will require more support than anticipated to accommodate the number of clinical and other staff who will use the system, so support staff must be nimble and available for redeployment. In addition, ensuring high-quality support is essential. As many ATE experts are hired contractors, their knowledge base and communications skills can vary widely. Accountability is key, and end users should feel empowered to identify gaps in coverage and deficits in knowledge base in the ATE.
As employees become more familiar with the new system, the need for ATE will wane, but there will still be questions that arise for many weeks to months, and new EHR users will also be added all the time. A good after–go-live support system should remain available so clinical and clerical employees can get just-in-time assistance whenever they need it.
Users should be given clear expectations
Clinicians going through an EHR conversion may be frustrated to discover that the data transferred from their old system into the new one is not quite what they expected. While structured elements such as allergies and immunizations may transfer, unstructured patient histories may not come over at all.
There may be gaps in data, or the opposite may even be true: an overabundance of useless information may transfer over, leaving doctors with dozens of meaningless data points to sift through and eliminate to clean up the chart. This can be extremely time-consuming and discouraging and may jeopardize the success of the go-live.
Providers deserve clear expectations prior to conversion. They should be told what will and will not transfer and be informed that there will be extra work required for documentation at the outset. They may also want the option to preemptively reduce patient volumes to accommodate the additional effort involved in preparing charts. No matter what, this will be a heavy lift, and physicians should understand the implications long before go-live to prepare accordingly.
Old habits die hard
One of the most common complaints we’ve heard following EHR conversions is that “things just worked better in the old system.” We always respond with a question: “Were things better, or just different?” The truth may lie somewhere in the middle, but there is no question that muscle memory develops over many years, and change is difficult no matter how much better the new system is. Still, appropriate expectations, access to just-in-time support, and a continual focus on safety will ensure that the long-term benefits of a patient-centered and integrated electronic record will far outweigh the initial challenges of go-live.
Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.
During this “go-live,” 5 hospitals and approximately 300 ambulatory service and physician practice locations made the transition, consolidating over 100 disparate electronic systems and dozens of interfaces into one world-class medical record.
If you’ve ever been part of such an event, you know it is anything but simple. On the contrary, it requires an enormous financial investment along with years of planning, hours of meetings, and months of training. No matter how much preparation goes into it, there are sure to be bumps along the way. It is a traumatic and stressful time for all involved, but the end result is well worth the effort. Still, there are lessons to be learned and wisdom to be gleaned, and this month we’d like to share a few that we found most important. We believe that many of these are useful lessons even to those who will never live through a go-live.
Safety always comes first
Patient safety is a term so often used that it has a tendency to be taken for granted. Health systems build processes and procedures to ensure safety – some even win awards and recognition for their efforts. But the best (and safest) health care institutions build patient safety into their cultures. More than just being taught to use checklists or buzzwords, the staff at these institutions are encouraged to put the welfare of patients first, making all other activities secondary to this pursuit. We had the opportunity to witness the benefits of such a culture during this go-live and were incredibly impressed with the results.
To be successful in an EHR transition of any magnitude, an organization needs to hold patient safety as a core value and provide its employees with the tools to execute on that value. This enables staff to prepare adequately and to identify risks and opportunities before the conversion takes place. Once go-live occurs, staff also must feel empowered to speak up when they identify problem areas that might jeopardize patients’ care. They also must be given a clear escalation path to ensure their voices can be heard. Most importantly, everyone must understand that the electronic health record itself is just one piece of a major operational change.
As workflows are modified to adapt to the new technology, unsafe processes should be called out and fixed quickly. While the EHR may offer the latest in decision support and system integration, no advancement in technology can make up for bad outcomes, nor justify processes that lead to patient harm.
Training is no substitute for good support
It takes a long time to train thousands of employees, especially when that training must occur during the era of social distancing in the midst of a pandemic. Still, even in the best of times, education should be married to hands-on experience in order to have a real impact. Unfortunately, this is extremely challenging.
Trainees forget much of what they’ve learned in the weeks or months between education and go-live, so they must be given immediately accessible support to bridge the gap. This is known as “at-the-elbow” (ATE) support, and as the name implies, it consists of individuals who are familiar with the new system and are always available to end users, answering their questions and helping them navigate. Since health care never sleeps, this support needs to be offered 24/7, and it should also be flexible and plentiful.
There are many areas that will require more support than anticipated to accommodate the number of clinical and other staff who will use the system, so support staff must be nimble and available for redeployment. In addition, ensuring high-quality support is essential. As many ATE experts are hired contractors, their knowledge base and communications skills can vary widely. Accountability is key, and end users should feel empowered to identify gaps in coverage and deficits in knowledge base in the ATE.
As employees become more familiar with the new system, the need for ATE will wane, but there will still be questions that arise for many weeks to months, and new EHR users will also be added all the time. A good after–go-live support system should remain available so clinical and clerical employees can get just-in-time assistance whenever they need it.
Users should be given clear expectations
Clinicians going through an EHR conversion may be frustrated to discover that the data transferred from their old system into the new one is not quite what they expected. While structured elements such as allergies and immunizations may transfer, unstructured patient histories may not come over at all.
There may be gaps in data, or the opposite may even be true: an overabundance of useless information may transfer over, leaving doctors with dozens of meaningless data points to sift through and eliminate to clean up the chart. This can be extremely time-consuming and discouraging and may jeopardize the success of the go-live.
Providers deserve clear expectations prior to conversion. They should be told what will and will not transfer and be informed that there will be extra work required for documentation at the outset. They may also want the option to preemptively reduce patient volumes to accommodate the additional effort involved in preparing charts. No matter what, this will be a heavy lift, and physicians should understand the implications long before go-live to prepare accordingly.
Old habits die hard
One of the most common complaints we’ve heard following EHR conversions is that “things just worked better in the old system.” We always respond with a question: “Were things better, or just different?” The truth may lie somewhere in the middle, but there is no question that muscle memory develops over many years, and change is difficult no matter how much better the new system is. Still, appropriate expectations, access to just-in-time support, and a continual focus on safety will ensure that the long-term benefits of a patient-centered and integrated electronic record will far outweigh the initial challenges of go-live.
Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.
What will neurology look like post pandemic?
Jose Angel Soria-Lopez, MD, has an unusually wide perspective on how neurology patients are responding to the coronavirus pandemic. He treats patients at two San Diego–area clinics, one in a poor neighborhood near the Mexican border and another in an upscale city about 65 miles to the north. While the patient populations are quite different, he’s noticed they’ve share one thing in common lately: An unusually intense focus on their personal health.
“All of a sudden people are really thinking about their health,” Dr. Soria-Lopez said. “There’s a sense that their health is even more important than it used to be.”
But patients are divided on how exactly they want their health care delivered. Some are embracing the convenience of telemedicine, while others want to be seen in person no matter what. Moving forward beyond the pandemic, Dr. Soria-Lopez expects the upswing of interest in health will persist. And he predicts two kinds of neurological care will emerge: “One based on ongoing relationships that rely on physical encounters as a culture, and a second kind of neurology service where other patients – perhaps the younger ones – will switch to convenient, online follow-ups.”
Telemedicine will endure post pandemic
While some don’t foresee such a big divide between in-person and online visits, several of Dr. Soria-Lopez’s colleagues from around the country agreed in interviews that . One neurologist, however, cautioned that telemedicine can worsen disparities in care. And he raised the alarm about another aspect of the pandemic that isn’t going to lift when it’s over: The rise in neurological disorders linked to infection with COVID-19.
Before the pandemic, neurologists said, they rarely if ever treated patients via telemedicine outside of specific settings such as remote stroke care. Over the past year, the use of telemedicine has dramatically increased in neurology as in medicine as a whole. But the levels of adoption differ markedly. Neurologist Andrew N. Wilner, MD, of University of Tennessee Health Science Center, said he has used telemedicine to see a single patient so far. But Johns Hopkins Center for Sleep neurologist Charlene Gamaldo, MD, said her clinic converted to 100% remote visits in March 2020 and remains at that level.
“Where [the rate of telemedicine use] will land will be based on insurance reimbursement and license reciprocation, so it is difficult to predict,” she said. “I imagine that sleep will likely remain a hybrid model if current allowances remain.”
Some patients, especially the older ones, resisted the telemedicine visits at first, Dr. Gamaldo said, and family members had to step in to help. Now, she said, patients prefer them because of their convenience.
Some neurological conditions, of course, can’t be easily evaluated via online video. Dr. Soria-Lopez, who has offices in Chula Vista and Temecula, Calif., prefers that a patient appear in person at first. “It really takes 1-2 physical encounters for there to be some level of trust,” he said, adding that “it’s hard to do the first few visits online unless it’s a very straightforward case with one or two symptoms.”
Neurologists have found that telemedicine is especially useful for med-check visits. Mitzi Joi Williams, MD, an Atlanta-area neurologist and multiple sclerosis specialist, said some patients previously drove 2-3 hours for these visits, which can easily be conducted online. Dr. Williams added that online software can allow her to show MRIs to patients remotely. She simply shares her screen and talks about what the images show.
Physical exams are more difficult online, of course, she said: “You can’t see nuances.” And it can be difficult to not have family members in the room to assist with the patient’s history. But some have joined via conference call and that’s been helpful, she said.
Neurologist Rhonda Voskuhl, MD, of the Brain Research Institute at the University of California, Los Angeles, whose clinic has gone to all-telemedicine visits, said telemedicine will make a huge difference for patients who live in remote areas or have mobility problems. In some cases, patients will actually be able to see their doctors more often, she said.
But she cautioned that it can be challenging to evaluate patients who are having difficulties with walking and sensation, although neurologists could try workarounds such as asking a patient to touch something cold. “We can do some things with coordination like watch patients walk, but walking motor strength is hard to check [via video],” she said. “The best thing to evaluate is cognition. You can talk to them and get a lot of it by asking questions.”
Carlos A. Pérez, MD, a neurologist at the University of Texas Health Science Center at Houston, noted that virtual visits can make it difficult to conduct comprehensive eye evaluations and examine vestibular and neuromuscular components such as weakness. “In multiple sclerosis patients, for example, diagnosing an MS relapse can be particularly difficult, especially when the patients present with mostly visual or sensory problems,” he said.
While he’s a fan of telemedicine overall, Dr. Pérez cautioned that low-income patients may lack computers and access to the Internet. “Access to resources in general seems to vary quite significantly,” he said. “Some patients use their cellphones for virtual visits, and that makes it extremely hard to examine them.”
Neurologist Amit Bar-Or, MD, of the University of Pennsylvania, Philadelphia, noted that in some cases, creativity can make a big difference in helping telemedicine visits to run smoothly. “In examining the cranial nerves, for example, you can get a lot of information. You need to have the person position the camera properly and get close to the camera so you can look at eye movements and facial symmetry.”
Still, he said, “if a patient wants to be seen in person, we should never deny them.”
As for other changes that will linger after the pandemic, San Diego–area neurologist Dr. Soria-Lopez said he expects that waiting rooms will continue to be less populated as patients wait elsewhere to avoid the spread of germs. He predicts there will be more use of “virtual waiting rooms” that allow patients to fill out paperwork remotely and get alerts when medical professionals are ready to see them.
Neurological sequelae from COVID-19
Dr. Pérez, the Houston neurologist, said his colleagues should expect another aspect of the pandemic to persist: an influx of patients with neurological sequelae from COVID-19. As he noted in a 2020 report in Neurology Clinical Practice, coronaviruses have been linked to numerous neurological complications during and after the infectious period. “I have seen a few cases of Guillain-Barré and even postinfectious encephalitis in the clinic [linked to COVID-19],” he said. “Neurologists in general should be aware of the risk for chronic, postinfectious neurologic complications from prior COVID-19 infection.”
And, he said, it’s reasonable for neurologists to add a question to patient histories. It’s a simple yet powerful query: Have you had COVID-19?
Jose Angel Soria-Lopez, MD, has an unusually wide perspective on how neurology patients are responding to the coronavirus pandemic. He treats patients at two San Diego–area clinics, one in a poor neighborhood near the Mexican border and another in an upscale city about 65 miles to the north. While the patient populations are quite different, he’s noticed they’ve share one thing in common lately: An unusually intense focus on their personal health.
“All of a sudden people are really thinking about their health,” Dr. Soria-Lopez said. “There’s a sense that their health is even more important than it used to be.”
But patients are divided on how exactly they want their health care delivered. Some are embracing the convenience of telemedicine, while others want to be seen in person no matter what. Moving forward beyond the pandemic, Dr. Soria-Lopez expects the upswing of interest in health will persist. And he predicts two kinds of neurological care will emerge: “One based on ongoing relationships that rely on physical encounters as a culture, and a second kind of neurology service where other patients – perhaps the younger ones – will switch to convenient, online follow-ups.”
Telemedicine will endure post pandemic
While some don’t foresee such a big divide between in-person and online visits, several of Dr. Soria-Lopez’s colleagues from around the country agreed in interviews that . One neurologist, however, cautioned that telemedicine can worsen disparities in care. And he raised the alarm about another aspect of the pandemic that isn’t going to lift when it’s over: The rise in neurological disorders linked to infection with COVID-19.
Before the pandemic, neurologists said, they rarely if ever treated patients via telemedicine outside of specific settings such as remote stroke care. Over the past year, the use of telemedicine has dramatically increased in neurology as in medicine as a whole. But the levels of adoption differ markedly. Neurologist Andrew N. Wilner, MD, of University of Tennessee Health Science Center, said he has used telemedicine to see a single patient so far. But Johns Hopkins Center for Sleep neurologist Charlene Gamaldo, MD, said her clinic converted to 100% remote visits in March 2020 and remains at that level.
“Where [the rate of telemedicine use] will land will be based on insurance reimbursement and license reciprocation, so it is difficult to predict,” she said. “I imagine that sleep will likely remain a hybrid model if current allowances remain.”
Some patients, especially the older ones, resisted the telemedicine visits at first, Dr. Gamaldo said, and family members had to step in to help. Now, she said, patients prefer them because of their convenience.
Some neurological conditions, of course, can’t be easily evaluated via online video. Dr. Soria-Lopez, who has offices in Chula Vista and Temecula, Calif., prefers that a patient appear in person at first. “It really takes 1-2 physical encounters for there to be some level of trust,” he said, adding that “it’s hard to do the first few visits online unless it’s a very straightforward case with one or two symptoms.”
Neurologists have found that telemedicine is especially useful for med-check visits. Mitzi Joi Williams, MD, an Atlanta-area neurologist and multiple sclerosis specialist, said some patients previously drove 2-3 hours for these visits, which can easily be conducted online. Dr. Williams added that online software can allow her to show MRIs to patients remotely. She simply shares her screen and talks about what the images show.
Physical exams are more difficult online, of course, she said: “You can’t see nuances.” And it can be difficult to not have family members in the room to assist with the patient’s history. But some have joined via conference call and that’s been helpful, she said.
Neurologist Rhonda Voskuhl, MD, of the Brain Research Institute at the University of California, Los Angeles, whose clinic has gone to all-telemedicine visits, said telemedicine will make a huge difference for patients who live in remote areas or have mobility problems. In some cases, patients will actually be able to see their doctors more often, she said.
But she cautioned that it can be challenging to evaluate patients who are having difficulties with walking and sensation, although neurologists could try workarounds such as asking a patient to touch something cold. “We can do some things with coordination like watch patients walk, but walking motor strength is hard to check [via video],” she said. “The best thing to evaluate is cognition. You can talk to them and get a lot of it by asking questions.”
Carlos A. Pérez, MD, a neurologist at the University of Texas Health Science Center at Houston, noted that virtual visits can make it difficult to conduct comprehensive eye evaluations and examine vestibular and neuromuscular components such as weakness. “In multiple sclerosis patients, for example, diagnosing an MS relapse can be particularly difficult, especially when the patients present with mostly visual or sensory problems,” he said.
While he’s a fan of telemedicine overall, Dr. Pérez cautioned that low-income patients may lack computers and access to the Internet. “Access to resources in general seems to vary quite significantly,” he said. “Some patients use their cellphones for virtual visits, and that makes it extremely hard to examine them.”
Neurologist Amit Bar-Or, MD, of the University of Pennsylvania, Philadelphia, noted that in some cases, creativity can make a big difference in helping telemedicine visits to run smoothly. “In examining the cranial nerves, for example, you can get a lot of information. You need to have the person position the camera properly and get close to the camera so you can look at eye movements and facial symmetry.”
Still, he said, “if a patient wants to be seen in person, we should never deny them.”
As for other changes that will linger after the pandemic, San Diego–area neurologist Dr. Soria-Lopez said he expects that waiting rooms will continue to be less populated as patients wait elsewhere to avoid the spread of germs. He predicts there will be more use of “virtual waiting rooms” that allow patients to fill out paperwork remotely and get alerts when medical professionals are ready to see them.
Neurological sequelae from COVID-19
Dr. Pérez, the Houston neurologist, said his colleagues should expect another aspect of the pandemic to persist: an influx of patients with neurological sequelae from COVID-19. As he noted in a 2020 report in Neurology Clinical Practice, coronaviruses have been linked to numerous neurological complications during and after the infectious period. “I have seen a few cases of Guillain-Barré and even postinfectious encephalitis in the clinic [linked to COVID-19],” he said. “Neurologists in general should be aware of the risk for chronic, postinfectious neurologic complications from prior COVID-19 infection.”
And, he said, it’s reasonable for neurologists to add a question to patient histories. It’s a simple yet powerful query: Have you had COVID-19?
Jose Angel Soria-Lopez, MD, has an unusually wide perspective on how neurology patients are responding to the coronavirus pandemic. He treats patients at two San Diego–area clinics, one in a poor neighborhood near the Mexican border and another in an upscale city about 65 miles to the north. While the patient populations are quite different, he’s noticed they’ve share one thing in common lately: An unusually intense focus on their personal health.
“All of a sudden people are really thinking about their health,” Dr. Soria-Lopez said. “There’s a sense that their health is even more important than it used to be.”
But patients are divided on how exactly they want their health care delivered. Some are embracing the convenience of telemedicine, while others want to be seen in person no matter what. Moving forward beyond the pandemic, Dr. Soria-Lopez expects the upswing of interest in health will persist. And he predicts two kinds of neurological care will emerge: “One based on ongoing relationships that rely on physical encounters as a culture, and a second kind of neurology service where other patients – perhaps the younger ones – will switch to convenient, online follow-ups.”
Telemedicine will endure post pandemic
While some don’t foresee such a big divide between in-person and online visits, several of Dr. Soria-Lopez’s colleagues from around the country agreed in interviews that . One neurologist, however, cautioned that telemedicine can worsen disparities in care. And he raised the alarm about another aspect of the pandemic that isn’t going to lift when it’s over: The rise in neurological disorders linked to infection with COVID-19.
Before the pandemic, neurologists said, they rarely if ever treated patients via telemedicine outside of specific settings such as remote stroke care. Over the past year, the use of telemedicine has dramatically increased in neurology as in medicine as a whole. But the levels of adoption differ markedly. Neurologist Andrew N. Wilner, MD, of University of Tennessee Health Science Center, said he has used telemedicine to see a single patient so far. But Johns Hopkins Center for Sleep neurologist Charlene Gamaldo, MD, said her clinic converted to 100% remote visits in March 2020 and remains at that level.
“Where [the rate of telemedicine use] will land will be based on insurance reimbursement and license reciprocation, so it is difficult to predict,” she said. “I imagine that sleep will likely remain a hybrid model if current allowances remain.”
Some patients, especially the older ones, resisted the telemedicine visits at first, Dr. Gamaldo said, and family members had to step in to help. Now, she said, patients prefer them because of their convenience.
Some neurological conditions, of course, can’t be easily evaluated via online video. Dr. Soria-Lopez, who has offices in Chula Vista and Temecula, Calif., prefers that a patient appear in person at first. “It really takes 1-2 physical encounters for there to be some level of trust,” he said, adding that “it’s hard to do the first few visits online unless it’s a very straightforward case with one or two symptoms.”
Neurologists have found that telemedicine is especially useful for med-check visits. Mitzi Joi Williams, MD, an Atlanta-area neurologist and multiple sclerosis specialist, said some patients previously drove 2-3 hours for these visits, which can easily be conducted online. Dr. Williams added that online software can allow her to show MRIs to patients remotely. She simply shares her screen and talks about what the images show.
Physical exams are more difficult online, of course, she said: “You can’t see nuances.” And it can be difficult to not have family members in the room to assist with the patient’s history. But some have joined via conference call and that’s been helpful, she said.
Neurologist Rhonda Voskuhl, MD, of the Brain Research Institute at the University of California, Los Angeles, whose clinic has gone to all-telemedicine visits, said telemedicine will make a huge difference for patients who live in remote areas or have mobility problems. In some cases, patients will actually be able to see their doctors more often, she said.
But she cautioned that it can be challenging to evaluate patients who are having difficulties with walking and sensation, although neurologists could try workarounds such as asking a patient to touch something cold. “We can do some things with coordination like watch patients walk, but walking motor strength is hard to check [via video],” she said. “The best thing to evaluate is cognition. You can talk to them and get a lot of it by asking questions.”
Carlos A. Pérez, MD, a neurologist at the University of Texas Health Science Center at Houston, noted that virtual visits can make it difficult to conduct comprehensive eye evaluations and examine vestibular and neuromuscular components such as weakness. “In multiple sclerosis patients, for example, diagnosing an MS relapse can be particularly difficult, especially when the patients present with mostly visual or sensory problems,” he said.
While he’s a fan of telemedicine overall, Dr. Pérez cautioned that low-income patients may lack computers and access to the Internet. “Access to resources in general seems to vary quite significantly,” he said. “Some patients use their cellphones for virtual visits, and that makes it extremely hard to examine them.”
Neurologist Amit Bar-Or, MD, of the University of Pennsylvania, Philadelphia, noted that in some cases, creativity can make a big difference in helping telemedicine visits to run smoothly. “In examining the cranial nerves, for example, you can get a lot of information. You need to have the person position the camera properly and get close to the camera so you can look at eye movements and facial symmetry.”
Still, he said, “if a patient wants to be seen in person, we should never deny them.”
As for other changes that will linger after the pandemic, San Diego–area neurologist Dr. Soria-Lopez said he expects that waiting rooms will continue to be less populated as patients wait elsewhere to avoid the spread of germs. He predicts there will be more use of “virtual waiting rooms” that allow patients to fill out paperwork remotely and get alerts when medical professionals are ready to see them.
Neurological sequelae from COVID-19
Dr. Pérez, the Houston neurologist, said his colleagues should expect another aspect of the pandemic to persist: an influx of patients with neurological sequelae from COVID-19. As he noted in a 2020 report in Neurology Clinical Practice, coronaviruses have been linked to numerous neurological complications during and after the infectious period. “I have seen a few cases of Guillain-Barré and even postinfectious encephalitis in the clinic [linked to COVID-19],” he said. “Neurologists in general should be aware of the risk for chronic, postinfectious neurologic complications from prior COVID-19 infection.”
And, he said, it’s reasonable for neurologists to add a question to patient histories. It’s a simple yet powerful query: Have you had COVID-19?
Top JAMA editor on leave amid podcast investigation
The American Medical Association’s Joint Oversight Committee announced that Howard Bauchner, MD, is on leave beginning at the end of the day on March 25. Dr. Bauchner is the top editor at JAMA, the journal of the AMA.
“The decision to place the editor-in-chief on administrative leave neither implicates nor exonerates individuals and is standard operating procedure for such investigations,” the committee said in a statement.
More than 2,000 people signed a petition on Change.org calling for an investigation at JAMA over the February podcast episode, called “Structural Racism for Doctors: What Is It?”
Already, Edward H. Livingston, MD, the host of the podcast, has resigned as deputy editor of the journal.
During the podcast, Dr. Livingston, who is White, said, “Structural racism is an unfortunate term. Personally, I think taking racism out of the conversation will help. Many of us are offended by the concept that we are racist.”
The audio of the podcast has been deleted from JAMA’s website. In its place is audio of a statement from Dr. Bauchner. In his statement, which he released in the week prior to his being on leave, he said the comments in the podcast, which also featured Mitch Katz, MD, were “inaccurate, offensive, hurtful, and inconsistent with the standards of JAMA.”
Also deleted was a JAMA tweet promoting the podcast episode. The tweet said: “No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast.”
This story will be updated.
A version of this article first appeared on WedMD.com.
The American Medical Association’s Joint Oversight Committee announced that Howard Bauchner, MD, is on leave beginning at the end of the day on March 25. Dr. Bauchner is the top editor at JAMA, the journal of the AMA.
“The decision to place the editor-in-chief on administrative leave neither implicates nor exonerates individuals and is standard operating procedure for such investigations,” the committee said in a statement.
More than 2,000 people signed a petition on Change.org calling for an investigation at JAMA over the February podcast episode, called “Structural Racism for Doctors: What Is It?”
Already, Edward H. Livingston, MD, the host of the podcast, has resigned as deputy editor of the journal.
During the podcast, Dr. Livingston, who is White, said, “Structural racism is an unfortunate term. Personally, I think taking racism out of the conversation will help. Many of us are offended by the concept that we are racist.”
The audio of the podcast has been deleted from JAMA’s website. In its place is audio of a statement from Dr. Bauchner. In his statement, which he released in the week prior to his being on leave, he said the comments in the podcast, which also featured Mitch Katz, MD, were “inaccurate, offensive, hurtful, and inconsistent with the standards of JAMA.”
Also deleted was a JAMA tweet promoting the podcast episode. The tweet said: “No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast.”
This story will be updated.
A version of this article first appeared on WedMD.com.
The American Medical Association’s Joint Oversight Committee announced that Howard Bauchner, MD, is on leave beginning at the end of the day on March 25. Dr. Bauchner is the top editor at JAMA, the journal of the AMA.
“The decision to place the editor-in-chief on administrative leave neither implicates nor exonerates individuals and is standard operating procedure for such investigations,” the committee said in a statement.
More than 2,000 people signed a petition on Change.org calling for an investigation at JAMA over the February podcast episode, called “Structural Racism for Doctors: What Is It?”
Already, Edward H. Livingston, MD, the host of the podcast, has resigned as deputy editor of the journal.
During the podcast, Dr. Livingston, who is White, said, “Structural racism is an unfortunate term. Personally, I think taking racism out of the conversation will help. Many of us are offended by the concept that we are racist.”
The audio of the podcast has been deleted from JAMA’s website. In its place is audio of a statement from Dr. Bauchner. In his statement, which he released in the week prior to his being on leave, he said the comments in the podcast, which also featured Mitch Katz, MD, were “inaccurate, offensive, hurtful, and inconsistent with the standards of JAMA.”
Also deleted was a JAMA tweet promoting the podcast episode. The tweet said: “No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast.”
This story will be updated.
A version of this article first appeared on WedMD.com.
Could tamoxifen dose be slashed down to 2.5 mg?
Tamoxifen has long been used in breast cancer, both in the adjuvant and preventive setting, but uptake and adherence are notoriously low, mainly because of adverse events.
Using a much lower dose to reduce the incidence of side effects would be a “way forward,” reasoned Swedish researchers. They report that a substantially lower dose of tamoxifen (2.5 mg) may be as effective as the standard dose (20 mg), but reduced by half the incidence of severe vasomotor symptoms, including hot flashes, cold sweats, and night sweats.
The research was published online March 18 in the Journal of Clinical Oncology.
The study involved 1,439 women (aged 40-74 years) who were participating in the Swedish mammography screening program and tested tamoxifen at various doses.
“We performed a dose determination study that we hope will initiate follow-up studies that in turn will influence both adjuvant treatment and prevention of breast cancer,” said lead author Per Hall, MD, PhD, head of the department of medical epidemiology and biostatistics at Karolinska Institutet in Stockholm.
The study measured the effects of the different doses (1, 2.5, 5, 10, and 20 mg) on mammographic breast density.
Dr. Hall emphasized that breast density was used as a proxy for therapy response. “We do not know how that translates to actual clinical effect,” he said in an interview. “This is step one.”
Previous studies have also used breast density changes as a proxy endpoint for tamoxifen therapy response, in both prophylactic and adjuvant settings, the authors note. There is some data to suggest that this does translate to a clinical effect. A recent study showed that tamoxifen at 5 mg/day taken for 3 years reduced the recurrence of breast intraepithelial neoplasia by 50% and contralateral breast cancer by 75%, with a symptom profile similar to placebo (J Clin Oncol. 2019;37:1629-1637).
Lower density, fewer symptoms
In the current study, Dr. Hall and colleagues found that the mammographic breast density (mean overall area) was decreased by 9.6% in the 20 mg tamoxifen group, and similar decreases were seen in the 2.5 and 10 mg dose groups, but not in the placebo and 1 mg dose groups.
These changes were driven primarily by changes observed among premenopausal women where the 20 mg mean decrease was 18.5% (P < .001 for interaction with menopausal status) with decreases of 13.4% in the 2.5 mg group, 19.6% in the 5 mg group, and 17% in the 10 mg group.
The results were quite different in postmenopausal participants, where those who received the 20 mg dose had a density mean decrease of 4%, which was not substantially different to the placebo, 1 mg, 2.5 mg, and 10 mg treatment arms.
The authors point out that the difference in density decrease between premenopausal and postmenopausal women was not dependent on differences in baseline density.
When reviewing adverse events with the various doses, the team found a large decrease in severe vasomotor symptoms with the lower doses of tamoxifen. These adverse events were reported by 34% of women taking 20 mg, 24.4% on 5 mg, 20.5% on 2.5 mg, 18.5% on 1 mg, and 13.7% of women taking placebo. There were no similar trends seen for gynecologic, sexual, or musculoskeletal symptoms.
Future studies should test whether 2.5 mg of tamoxifen reduces the risk of primary breast cancer, Dr. Hall commented.
“We are planning a trial now where women are offered risk assessment when attending mammography screening,” Dr. Hall said. “For those at very high risk, low-dose tamoxifen will be offered.”
The study received support from the Kamprad Foundation, Swedish Research Council, Marit and Hans Rausing’s Initiative Against Breast Cancer, Swedish Cancer Society, and Stockholm County Council.
Dr. Hall reports several relationships with industry, had a pending patent on compositions and methods for prevention of breast cancer with an option to license to Atossa Therapeutics, and has licensed an algorithm for risk prediction based on analyses of mammographic features to iCAD Travel. Several co-authors have also declared relationships with industry.
A version of this article first appeared on Medscape.com.
Tamoxifen has long been used in breast cancer, both in the adjuvant and preventive setting, but uptake and adherence are notoriously low, mainly because of adverse events.
Using a much lower dose to reduce the incidence of side effects would be a “way forward,” reasoned Swedish researchers. They report that a substantially lower dose of tamoxifen (2.5 mg) may be as effective as the standard dose (20 mg), but reduced by half the incidence of severe vasomotor symptoms, including hot flashes, cold sweats, and night sweats.
The research was published online March 18 in the Journal of Clinical Oncology.
The study involved 1,439 women (aged 40-74 years) who were participating in the Swedish mammography screening program and tested tamoxifen at various doses.
“We performed a dose determination study that we hope will initiate follow-up studies that in turn will influence both adjuvant treatment and prevention of breast cancer,” said lead author Per Hall, MD, PhD, head of the department of medical epidemiology and biostatistics at Karolinska Institutet in Stockholm.
The study measured the effects of the different doses (1, 2.5, 5, 10, and 20 mg) on mammographic breast density.
Dr. Hall emphasized that breast density was used as a proxy for therapy response. “We do not know how that translates to actual clinical effect,” he said in an interview. “This is step one.”
Previous studies have also used breast density changes as a proxy endpoint for tamoxifen therapy response, in both prophylactic and adjuvant settings, the authors note. There is some data to suggest that this does translate to a clinical effect. A recent study showed that tamoxifen at 5 mg/day taken for 3 years reduced the recurrence of breast intraepithelial neoplasia by 50% and contralateral breast cancer by 75%, with a symptom profile similar to placebo (J Clin Oncol. 2019;37:1629-1637).
Lower density, fewer symptoms
In the current study, Dr. Hall and colleagues found that the mammographic breast density (mean overall area) was decreased by 9.6% in the 20 mg tamoxifen group, and similar decreases were seen in the 2.5 and 10 mg dose groups, but not in the placebo and 1 mg dose groups.
These changes were driven primarily by changes observed among premenopausal women where the 20 mg mean decrease was 18.5% (P < .001 for interaction with menopausal status) with decreases of 13.4% in the 2.5 mg group, 19.6% in the 5 mg group, and 17% in the 10 mg group.
The results were quite different in postmenopausal participants, where those who received the 20 mg dose had a density mean decrease of 4%, which was not substantially different to the placebo, 1 mg, 2.5 mg, and 10 mg treatment arms.
The authors point out that the difference in density decrease between premenopausal and postmenopausal women was not dependent on differences in baseline density.
When reviewing adverse events with the various doses, the team found a large decrease in severe vasomotor symptoms with the lower doses of tamoxifen. These adverse events were reported by 34% of women taking 20 mg, 24.4% on 5 mg, 20.5% on 2.5 mg, 18.5% on 1 mg, and 13.7% of women taking placebo. There were no similar trends seen for gynecologic, sexual, or musculoskeletal symptoms.
Future studies should test whether 2.5 mg of tamoxifen reduces the risk of primary breast cancer, Dr. Hall commented.
“We are planning a trial now where women are offered risk assessment when attending mammography screening,” Dr. Hall said. “For those at very high risk, low-dose tamoxifen will be offered.”
The study received support from the Kamprad Foundation, Swedish Research Council, Marit and Hans Rausing’s Initiative Against Breast Cancer, Swedish Cancer Society, and Stockholm County Council.
Dr. Hall reports several relationships with industry, had a pending patent on compositions and methods for prevention of breast cancer with an option to license to Atossa Therapeutics, and has licensed an algorithm for risk prediction based on analyses of mammographic features to iCAD Travel. Several co-authors have also declared relationships with industry.
A version of this article first appeared on Medscape.com.
Tamoxifen has long been used in breast cancer, both in the adjuvant and preventive setting, but uptake and adherence are notoriously low, mainly because of adverse events.
Using a much lower dose to reduce the incidence of side effects would be a “way forward,” reasoned Swedish researchers. They report that a substantially lower dose of tamoxifen (2.5 mg) may be as effective as the standard dose (20 mg), but reduced by half the incidence of severe vasomotor symptoms, including hot flashes, cold sweats, and night sweats.
The research was published online March 18 in the Journal of Clinical Oncology.
The study involved 1,439 women (aged 40-74 years) who were participating in the Swedish mammography screening program and tested tamoxifen at various doses.
“We performed a dose determination study that we hope will initiate follow-up studies that in turn will influence both adjuvant treatment and prevention of breast cancer,” said lead author Per Hall, MD, PhD, head of the department of medical epidemiology and biostatistics at Karolinska Institutet in Stockholm.
The study measured the effects of the different doses (1, 2.5, 5, 10, and 20 mg) on mammographic breast density.
Dr. Hall emphasized that breast density was used as a proxy for therapy response. “We do not know how that translates to actual clinical effect,” he said in an interview. “This is step one.”
Previous studies have also used breast density changes as a proxy endpoint for tamoxifen therapy response, in both prophylactic and adjuvant settings, the authors note. There is some data to suggest that this does translate to a clinical effect. A recent study showed that tamoxifen at 5 mg/day taken for 3 years reduced the recurrence of breast intraepithelial neoplasia by 50% and contralateral breast cancer by 75%, with a symptom profile similar to placebo (J Clin Oncol. 2019;37:1629-1637).
Lower density, fewer symptoms
In the current study, Dr. Hall and colleagues found that the mammographic breast density (mean overall area) was decreased by 9.6% in the 20 mg tamoxifen group, and similar decreases were seen in the 2.5 and 10 mg dose groups, but not in the placebo and 1 mg dose groups.
These changes were driven primarily by changes observed among premenopausal women where the 20 mg mean decrease was 18.5% (P < .001 for interaction with menopausal status) with decreases of 13.4% in the 2.5 mg group, 19.6% in the 5 mg group, and 17% in the 10 mg group.
The results were quite different in postmenopausal participants, where those who received the 20 mg dose had a density mean decrease of 4%, which was not substantially different to the placebo, 1 mg, 2.5 mg, and 10 mg treatment arms.
The authors point out that the difference in density decrease between premenopausal and postmenopausal women was not dependent on differences in baseline density.
When reviewing adverse events with the various doses, the team found a large decrease in severe vasomotor symptoms with the lower doses of tamoxifen. These adverse events were reported by 34% of women taking 20 mg, 24.4% on 5 mg, 20.5% on 2.5 mg, 18.5% on 1 mg, and 13.7% of women taking placebo. There were no similar trends seen for gynecologic, sexual, or musculoskeletal symptoms.
Future studies should test whether 2.5 mg of tamoxifen reduces the risk of primary breast cancer, Dr. Hall commented.
“We are planning a trial now where women are offered risk assessment when attending mammography screening,” Dr. Hall said. “For those at very high risk, low-dose tamoxifen will be offered.”
The study received support from the Kamprad Foundation, Swedish Research Council, Marit and Hans Rausing’s Initiative Against Breast Cancer, Swedish Cancer Society, and Stockholm County Council.
Dr. Hall reports several relationships with industry, had a pending patent on compositions and methods for prevention of breast cancer with an option to license to Atossa Therapeutics, and has licensed an algorithm for risk prediction based on analyses of mammographic features to iCAD Travel. Several co-authors have also declared relationships with industry.
A version of this article first appeared on Medscape.com.
Paving the way for diversity in clinical trials
“I’m the first person in my circle of family and friends to participate in a clinical trial.”
Five years ago, Rhonda Long was diagnosed with cholangiocarcinoma, a rare bile duct cancer that’s seen in only about 8,000 Americans each year.
At the time, Mrs. Long, who is Black, said her doctor in Dayton, Ohio, told her she was not a candidate for surgery and suggested palliative care. After seeking a second opinion at Duke University Medical Center, Durham, N.C., where her sister worked, the 51-year-old wife and mother of two had surgery, radiation, and chemotherapy there in North Carolina. When the chemo stopped working after 3 months, her oncologist at Duke referred her to a colleague at Massachusetts General Hospital in Boston, where she was accepted into a clinical trial.
“In 2019, I traveled to Boston from Dayton, Ohio, every 3 weeks for labs and scans, to make sure that the drug wasn’t doing more harm than good, making sure that the drug as developed was maintaining, shrinking, or even eliminating the disease. Physically and financially, it takes a toll on you and loved ones.”
Her medical insurance did not cover the direct expenses from the clinical trial, and she was spending $1,000-$1,500 each trip. Sometimes they drove the 15 hours to Boston, and sometimes they flew on the cheapest flight they could find.
It’s not an unfamiliar story: people traveling, often long distances, to take part in clinical trials they hope will save their lives.
The Lazarex Cancer Foundation of Danville, Calif., helped Mrs. Long do just that.
Marya Shegog, PhD, health equity and diversity coordinator at Lazarex, said that a patient travels an average of 500 miles to participate in a trial.
The financial hurdles often prevent patients from taking part in clinical trials, Dr. Shegog said. “When you are sick, and you have a disease that may be terminal, you start thinking about setting your things in order.”
Many patients have to make a decision.
“Do I bankrupt my family on trying and hoping that this drug works and helps me live longer, or do I start setting things in order so that when I’m gone, they’re okay or at least better than if I wouldn’t have spent all the money traveling back and forth.”
Dr. Shegog, a 17-year cancer survivor, says when she was battling cervical cancer, a clinical trial was never offered or explored.
Lazarex has been helping cancer patients who have run out of options for 15 years. It identifies clinical trial opportunities and reimburses patients for all travel costs. Last year, Lazarex reimbursed more than 1,000 cancer patients. And it has supported more than 6,000 people since opening its doors.
“Lazarex exists to help remove the barriers of people not being able to participate in trials,” Dr. Shegog said. “It’s systemic that the medical system does not treat patients the same and oftentimes does not offer or make aware the opportunities for African Americans to participate.”
But now, thanks in part to COVID-19, new possibilities are taking shape. The pandemic has changed the landscape for trials, forcing many of them to go virtual, which allows patients to schedule telehealth visits and get some services like bloodwork and CT or MRI scans closer to home. Mrs. Long’s trial eventually went virtual.
“It was absolutely fantastic,” she said. “Having the trial locally, it saves us money, it saves wear and tear on my body. Being in the car, being in an airport or in a plane and in a hotel, all of that wears on you physically.”
The move to virtual studies may have lasting effects on research and treatment.
“The current pandemic has forced us to reexamine all of the traditional burdens we place on patients as it relates to receiving cancer treatment,” said Hala Borno, MD, an assistant professor of medicine at the University of California, San Francisco. “Whether they’re coming to our health care facility to see a clinician, for diagnostics such as blood draws and scans, or to receive therapy, this pandemic has challenged us to explore other possibilities that minimize the risk of exposure to SARS-CoV-2. What I find striking is that it has helped us operationalize use of telemedicine and the delivery of care closer to home.”
This is especially encouraging news for minority patients whose participation in trials has for years lagged well behind that of Whites.
But travel is not the only reason. Racial disparities in clinical trials have long been an issue that’s just another part of the implicit bias in health care.
Compared with White people, Black people are largely at higher risk for heart disease, cancer, stroke, diabetes, asthma, and even mental health problems.
And it’s not just African Americans. Asians, Hispanics, Native Americans, and Alaska Natives are all underrepresented in trials at a time when there is growing evidence that drugs may have different effects on different populations.
Dr. Borno is an oncologist who specializes in prostate cancer, a disease that she says shows a “significant disparity,” where Black men are two times more likely to die from advanced prostate cancer, compared with white men. Yet Black men make up just 3% of advanced therapeutic trials.
“A lack of diversity and inclusion in clinical trials is unacceptable,” she said. “If we continue to underrecruit racial/ethnic minorities and older adults to therapeutic clinical trials, we will not be powered to make valid conclusions regarding safety and efficacy in those patient populations. As a result, we can do harm.”
Dr. Borno said that telehealth and telemedicine are not cure-alls, and digital health solutions don’t work for all patients. Approaches, she says, must be tailored to the individual, or disparities could worsen.
In 2020, the Food and Drug Administration approved 53 new drugs. Overall, 32,000 patients took part in these trials. On average, 75% were White, 8% were Black, 6% were Asian, and 11% were Hispanic.
Here’s one stark example of the issue. In 2015, the FDA approved ixazomib (Ninlaro), a promising new drug for multiple myeloma, a blood cancer that affects Black people at disproportionately higher rates than White people. In the United States, one in five people diagnosed with multiple myeloma are Black people. They are more than twice as likely to get the disease as White people. Yet during the clinical trial of 722 participants, only 13 patients, or 1.8%, were Black.
The American Cancer Society estimates that more than 600,000 Americans will die from cancer this year. Historically, Black Americans have the highest death rate and the shortest survival of any racial or ethnic group, stemming largely, it concluded, from centuries of structural racism.
According to Jamie Freedman, MD, head of U.S. medical affairs at Genentech, a global pharmaceutical company, the lack of diversity is often tied to where studies are run.
“Companies tend to choose major academic medical centers where there is a high volume of clinical trial work. When you go to the same tried and true hospitals repeatedly, the pool of patients becomes very homogeneous and tends to be primarily white,” he said. “It’s critical to bring more trials into the community setting by including new sites that can reach underrepresented groups, and Genentech is making significant progress in that area.”
Dr. Freedman believes that, while access is a big hurdle, it doesn’t end there.
“Many patients have a lack of trust in the health care system,” he said. “There are also issues around underserved communities being able to afford quality care, so it’s important to keep time and financial burdens in mind when designing trials to help mitigate barriers such as travel, parking, time off work, and child care.”
Genentech started its diversity and inclusion effort several years ago. Dr. Freeman said that, until more trials become diverse, Black Americans will continue to pay the price. “I think they’re losing their lives in part due to lack of access to these trials. And that is why Genentech and all of us in the health care industry need to change how we design and enroll these studies. We have a long way to go, but I think the steps we’re taking are leading us in the right direction.”
Jennifer Jones-McMeans, PhD, director of global clinical affairs at Abbott Pharmaceuticals, is a clinical research scientist who has designed and led many clinical trials.
She said that Abbott is actively working on solutions.
“We have designed our trials to reduce the barriers to participation and expand access,” she said. “This can be as simple as providing transportation services or home visits for those who are housebound. We’re taking it a step further and providing home health services where someone comes to the home and provides follow-up visits there.”
They also provide interpretation services to address any language barriers.
“We are reaching out to a new set of talented investigators who work closely with underrepresented communities. They are very much wedded and supportive of the communities they treat. By working with doctors within these communities, it expands access to new therapies.”
Spokesperson Keanna Ghazvini said that Pfizer Pharmaceuticals is also committed to increasing minority participation in trials.
“We know that if historically underserved populations are left out of clinical trials, they risk not benefiting from medical breakthroughs down the line,” she said.
The National Institutes of Health’s National Library of Medicine maintains the clinicaltrials.gov database.
There, you can find information on nearly 372,000 publicly and privately supported clinical trials happening in all 50 states and 219 countries. Many are funded by the NIH, but not all of these studies have been evaluated by the U.S. government.
Andrea Denicoff, a nurse consultant at the National Cancer Institute and head of clinical trials operations for the NCI’s National Clinical Trials Network, has been involved in clinical research at the NIH for 35 years.
“It’s really important that our publicly funded trials represent the people of the country,” she said. “There are some cancers that we’re doing a good job in enrolling minorities, and other cancers we need to do a much better job in having a diverse representation in our trials.”
Ms. Denicoff believed opening trials in places where people live is key, but having a diverse clinical trials team is as important.
“We need to reinforce that cancer centers across the country have open doors, and anyone with cancer feels comfortable getting care at that center, and that also includes discussing the option to participate in clinical trials when one might be available. We know from research that when people are invited and asked about trial participation and educated about them, they’ll be much more interested in joining them.”
Ms. Denicoff said that, during the pandemic, the NCI quickly came up with guidance to allow trial sites to send patients their oral study drugs and set up virtual visits. She believes it may help increase future access.
‘Lola Fashoyin-Aje, MD, associate director for science and policy to address disparities in the Oncology Center of Excellence at the FDA, says the agency firmly believes clinical trials should represent the patients who will ultimately get the drug if it’s approved.
But the FDA’s power to require diversity in trials is limited.
“It is important to point out that there are legal constraints which limit’s FDA’s authority to require specific proportional representation in clinical trials by demographic factors,” Dr. Fashoyin-Aje said.
Still, some researchers feel the FDA should play a bigger role. The question is: Should diversity be mandated?
Rhonda Long is now back in Boston to start a new trial, with a new drug that targets her specific mutation. She will be there for 2 months. Once again, Lazarex will help cover some of the cost.
She wants people of color to understand that they are missing out on the promise of new cancer drugs and extended life.
“I feel like there’s not enough emphasis on clinical trials, I don’t believe there’s enough emphasis on second opinions, I don’t think there’s enough emphasis that medicine happens outside our borders, outside of our communities. Clinical trials that don’t have a broad range of participants, how do we know how effective they are if Black and brown people, Asian or Latin American people aren’t represented in the trial?”
And with more trials adopting virtual elements, she said it’s time for minorities to get on board.
Dr. Freedman believed the groundwork is being laid for that to happen. “I don’t think we’ll ever return back to the way we used to do things, where everything has to be done at the clinical trial site. I just don’t think we’re ever going back.”
A version of this article first appeared on WebMD.com.
“I’m the first person in my circle of family and friends to participate in a clinical trial.”
Five years ago, Rhonda Long was diagnosed with cholangiocarcinoma, a rare bile duct cancer that’s seen in only about 8,000 Americans each year.
At the time, Mrs. Long, who is Black, said her doctor in Dayton, Ohio, told her she was not a candidate for surgery and suggested palliative care. After seeking a second opinion at Duke University Medical Center, Durham, N.C., where her sister worked, the 51-year-old wife and mother of two had surgery, radiation, and chemotherapy there in North Carolina. When the chemo stopped working after 3 months, her oncologist at Duke referred her to a colleague at Massachusetts General Hospital in Boston, where she was accepted into a clinical trial.
“In 2019, I traveled to Boston from Dayton, Ohio, every 3 weeks for labs and scans, to make sure that the drug wasn’t doing more harm than good, making sure that the drug as developed was maintaining, shrinking, or even eliminating the disease. Physically and financially, it takes a toll on you and loved ones.”
Her medical insurance did not cover the direct expenses from the clinical trial, and she was spending $1,000-$1,500 each trip. Sometimes they drove the 15 hours to Boston, and sometimes they flew on the cheapest flight they could find.
It’s not an unfamiliar story: people traveling, often long distances, to take part in clinical trials they hope will save their lives.
The Lazarex Cancer Foundation of Danville, Calif., helped Mrs. Long do just that.
Marya Shegog, PhD, health equity and diversity coordinator at Lazarex, said that a patient travels an average of 500 miles to participate in a trial.
The financial hurdles often prevent patients from taking part in clinical trials, Dr. Shegog said. “When you are sick, and you have a disease that may be terminal, you start thinking about setting your things in order.”
Many patients have to make a decision.
“Do I bankrupt my family on trying and hoping that this drug works and helps me live longer, or do I start setting things in order so that when I’m gone, they’re okay or at least better than if I wouldn’t have spent all the money traveling back and forth.”
Dr. Shegog, a 17-year cancer survivor, says when she was battling cervical cancer, a clinical trial was never offered or explored.
Lazarex has been helping cancer patients who have run out of options for 15 years. It identifies clinical trial opportunities and reimburses patients for all travel costs. Last year, Lazarex reimbursed more than 1,000 cancer patients. And it has supported more than 6,000 people since opening its doors.
“Lazarex exists to help remove the barriers of people not being able to participate in trials,” Dr. Shegog said. “It’s systemic that the medical system does not treat patients the same and oftentimes does not offer or make aware the opportunities for African Americans to participate.”
But now, thanks in part to COVID-19, new possibilities are taking shape. The pandemic has changed the landscape for trials, forcing many of them to go virtual, which allows patients to schedule telehealth visits and get some services like bloodwork and CT or MRI scans closer to home. Mrs. Long’s trial eventually went virtual.
“It was absolutely fantastic,” she said. “Having the trial locally, it saves us money, it saves wear and tear on my body. Being in the car, being in an airport or in a plane and in a hotel, all of that wears on you physically.”
The move to virtual studies may have lasting effects on research and treatment.
“The current pandemic has forced us to reexamine all of the traditional burdens we place on patients as it relates to receiving cancer treatment,” said Hala Borno, MD, an assistant professor of medicine at the University of California, San Francisco. “Whether they’re coming to our health care facility to see a clinician, for diagnostics such as blood draws and scans, or to receive therapy, this pandemic has challenged us to explore other possibilities that minimize the risk of exposure to SARS-CoV-2. What I find striking is that it has helped us operationalize use of telemedicine and the delivery of care closer to home.”
This is especially encouraging news for minority patients whose participation in trials has for years lagged well behind that of Whites.
But travel is not the only reason. Racial disparities in clinical trials have long been an issue that’s just another part of the implicit bias in health care.
Compared with White people, Black people are largely at higher risk for heart disease, cancer, stroke, diabetes, asthma, and even mental health problems.
And it’s not just African Americans. Asians, Hispanics, Native Americans, and Alaska Natives are all underrepresented in trials at a time when there is growing evidence that drugs may have different effects on different populations.
Dr. Borno is an oncologist who specializes in prostate cancer, a disease that she says shows a “significant disparity,” where Black men are two times more likely to die from advanced prostate cancer, compared with white men. Yet Black men make up just 3% of advanced therapeutic trials.
“A lack of diversity and inclusion in clinical trials is unacceptable,” she said. “If we continue to underrecruit racial/ethnic minorities and older adults to therapeutic clinical trials, we will not be powered to make valid conclusions regarding safety and efficacy in those patient populations. As a result, we can do harm.”
Dr. Borno said that telehealth and telemedicine are not cure-alls, and digital health solutions don’t work for all patients. Approaches, she says, must be tailored to the individual, or disparities could worsen.
In 2020, the Food and Drug Administration approved 53 new drugs. Overall, 32,000 patients took part in these trials. On average, 75% were White, 8% were Black, 6% were Asian, and 11% were Hispanic.
Here’s one stark example of the issue. In 2015, the FDA approved ixazomib (Ninlaro), a promising new drug for multiple myeloma, a blood cancer that affects Black people at disproportionately higher rates than White people. In the United States, one in five people diagnosed with multiple myeloma are Black people. They are more than twice as likely to get the disease as White people. Yet during the clinical trial of 722 participants, only 13 patients, or 1.8%, were Black.
The American Cancer Society estimates that more than 600,000 Americans will die from cancer this year. Historically, Black Americans have the highest death rate and the shortest survival of any racial or ethnic group, stemming largely, it concluded, from centuries of structural racism.
According to Jamie Freedman, MD, head of U.S. medical affairs at Genentech, a global pharmaceutical company, the lack of diversity is often tied to where studies are run.
“Companies tend to choose major academic medical centers where there is a high volume of clinical trial work. When you go to the same tried and true hospitals repeatedly, the pool of patients becomes very homogeneous and tends to be primarily white,” he said. “It’s critical to bring more trials into the community setting by including new sites that can reach underrepresented groups, and Genentech is making significant progress in that area.”
Dr. Freedman believes that, while access is a big hurdle, it doesn’t end there.
“Many patients have a lack of trust in the health care system,” he said. “There are also issues around underserved communities being able to afford quality care, so it’s important to keep time and financial burdens in mind when designing trials to help mitigate barriers such as travel, parking, time off work, and child care.”
Genentech started its diversity and inclusion effort several years ago. Dr. Freeman said that, until more trials become diverse, Black Americans will continue to pay the price. “I think they’re losing their lives in part due to lack of access to these trials. And that is why Genentech and all of us in the health care industry need to change how we design and enroll these studies. We have a long way to go, but I think the steps we’re taking are leading us in the right direction.”
Jennifer Jones-McMeans, PhD, director of global clinical affairs at Abbott Pharmaceuticals, is a clinical research scientist who has designed and led many clinical trials.
She said that Abbott is actively working on solutions.
“We have designed our trials to reduce the barriers to participation and expand access,” she said. “This can be as simple as providing transportation services or home visits for those who are housebound. We’re taking it a step further and providing home health services where someone comes to the home and provides follow-up visits there.”
They also provide interpretation services to address any language barriers.
“We are reaching out to a new set of talented investigators who work closely with underrepresented communities. They are very much wedded and supportive of the communities they treat. By working with doctors within these communities, it expands access to new therapies.”
Spokesperson Keanna Ghazvini said that Pfizer Pharmaceuticals is also committed to increasing minority participation in trials.
“We know that if historically underserved populations are left out of clinical trials, they risk not benefiting from medical breakthroughs down the line,” she said.
The National Institutes of Health’s National Library of Medicine maintains the clinicaltrials.gov database.
There, you can find information on nearly 372,000 publicly and privately supported clinical trials happening in all 50 states and 219 countries. Many are funded by the NIH, but not all of these studies have been evaluated by the U.S. government.
Andrea Denicoff, a nurse consultant at the National Cancer Institute and head of clinical trials operations for the NCI’s National Clinical Trials Network, has been involved in clinical research at the NIH for 35 years.
“It’s really important that our publicly funded trials represent the people of the country,” she said. “There are some cancers that we’re doing a good job in enrolling minorities, and other cancers we need to do a much better job in having a diverse representation in our trials.”
Ms. Denicoff believed opening trials in places where people live is key, but having a diverse clinical trials team is as important.
“We need to reinforce that cancer centers across the country have open doors, and anyone with cancer feels comfortable getting care at that center, and that also includes discussing the option to participate in clinical trials when one might be available. We know from research that when people are invited and asked about trial participation and educated about them, they’ll be much more interested in joining them.”
Ms. Denicoff said that, during the pandemic, the NCI quickly came up with guidance to allow trial sites to send patients their oral study drugs and set up virtual visits. She believes it may help increase future access.
‘Lola Fashoyin-Aje, MD, associate director for science and policy to address disparities in the Oncology Center of Excellence at the FDA, says the agency firmly believes clinical trials should represent the patients who will ultimately get the drug if it’s approved.
But the FDA’s power to require diversity in trials is limited.
“It is important to point out that there are legal constraints which limit’s FDA’s authority to require specific proportional representation in clinical trials by demographic factors,” Dr. Fashoyin-Aje said.
Still, some researchers feel the FDA should play a bigger role. The question is: Should diversity be mandated?
Rhonda Long is now back in Boston to start a new trial, with a new drug that targets her specific mutation. She will be there for 2 months. Once again, Lazarex will help cover some of the cost.
She wants people of color to understand that they are missing out on the promise of new cancer drugs and extended life.
“I feel like there’s not enough emphasis on clinical trials, I don’t believe there’s enough emphasis on second opinions, I don’t think there’s enough emphasis that medicine happens outside our borders, outside of our communities. Clinical trials that don’t have a broad range of participants, how do we know how effective they are if Black and brown people, Asian or Latin American people aren’t represented in the trial?”
And with more trials adopting virtual elements, she said it’s time for minorities to get on board.
Dr. Freedman believed the groundwork is being laid for that to happen. “I don’t think we’ll ever return back to the way we used to do things, where everything has to be done at the clinical trial site. I just don’t think we’re ever going back.”
A version of this article first appeared on WebMD.com.
“I’m the first person in my circle of family and friends to participate in a clinical trial.”
Five years ago, Rhonda Long was diagnosed with cholangiocarcinoma, a rare bile duct cancer that’s seen in only about 8,000 Americans each year.
At the time, Mrs. Long, who is Black, said her doctor in Dayton, Ohio, told her she was not a candidate for surgery and suggested palliative care. After seeking a second opinion at Duke University Medical Center, Durham, N.C., where her sister worked, the 51-year-old wife and mother of two had surgery, radiation, and chemotherapy there in North Carolina. When the chemo stopped working after 3 months, her oncologist at Duke referred her to a colleague at Massachusetts General Hospital in Boston, where she was accepted into a clinical trial.
“In 2019, I traveled to Boston from Dayton, Ohio, every 3 weeks for labs and scans, to make sure that the drug wasn’t doing more harm than good, making sure that the drug as developed was maintaining, shrinking, or even eliminating the disease. Physically and financially, it takes a toll on you and loved ones.”
Her medical insurance did not cover the direct expenses from the clinical trial, and she was spending $1,000-$1,500 each trip. Sometimes they drove the 15 hours to Boston, and sometimes they flew on the cheapest flight they could find.
It’s not an unfamiliar story: people traveling, often long distances, to take part in clinical trials they hope will save their lives.
The Lazarex Cancer Foundation of Danville, Calif., helped Mrs. Long do just that.
Marya Shegog, PhD, health equity and diversity coordinator at Lazarex, said that a patient travels an average of 500 miles to participate in a trial.
The financial hurdles often prevent patients from taking part in clinical trials, Dr. Shegog said. “When you are sick, and you have a disease that may be terminal, you start thinking about setting your things in order.”
Many patients have to make a decision.
“Do I bankrupt my family on trying and hoping that this drug works and helps me live longer, or do I start setting things in order so that when I’m gone, they’re okay or at least better than if I wouldn’t have spent all the money traveling back and forth.”
Dr. Shegog, a 17-year cancer survivor, says when she was battling cervical cancer, a clinical trial was never offered or explored.
Lazarex has been helping cancer patients who have run out of options for 15 years. It identifies clinical trial opportunities and reimburses patients for all travel costs. Last year, Lazarex reimbursed more than 1,000 cancer patients. And it has supported more than 6,000 people since opening its doors.
“Lazarex exists to help remove the barriers of people not being able to participate in trials,” Dr. Shegog said. “It’s systemic that the medical system does not treat patients the same and oftentimes does not offer or make aware the opportunities for African Americans to participate.”
But now, thanks in part to COVID-19, new possibilities are taking shape. The pandemic has changed the landscape for trials, forcing many of them to go virtual, which allows patients to schedule telehealth visits and get some services like bloodwork and CT or MRI scans closer to home. Mrs. Long’s trial eventually went virtual.
“It was absolutely fantastic,” she said. “Having the trial locally, it saves us money, it saves wear and tear on my body. Being in the car, being in an airport or in a plane and in a hotel, all of that wears on you physically.”
The move to virtual studies may have lasting effects on research and treatment.
“The current pandemic has forced us to reexamine all of the traditional burdens we place on patients as it relates to receiving cancer treatment,” said Hala Borno, MD, an assistant professor of medicine at the University of California, San Francisco. “Whether they’re coming to our health care facility to see a clinician, for diagnostics such as blood draws and scans, or to receive therapy, this pandemic has challenged us to explore other possibilities that minimize the risk of exposure to SARS-CoV-2. What I find striking is that it has helped us operationalize use of telemedicine and the delivery of care closer to home.”
This is especially encouraging news for minority patients whose participation in trials has for years lagged well behind that of Whites.
But travel is not the only reason. Racial disparities in clinical trials have long been an issue that’s just another part of the implicit bias in health care.
Compared with White people, Black people are largely at higher risk for heart disease, cancer, stroke, diabetes, asthma, and even mental health problems.
And it’s not just African Americans. Asians, Hispanics, Native Americans, and Alaska Natives are all underrepresented in trials at a time when there is growing evidence that drugs may have different effects on different populations.
Dr. Borno is an oncologist who specializes in prostate cancer, a disease that she says shows a “significant disparity,” where Black men are two times more likely to die from advanced prostate cancer, compared with white men. Yet Black men make up just 3% of advanced therapeutic trials.
“A lack of diversity and inclusion in clinical trials is unacceptable,” she said. “If we continue to underrecruit racial/ethnic minorities and older adults to therapeutic clinical trials, we will not be powered to make valid conclusions regarding safety and efficacy in those patient populations. As a result, we can do harm.”
Dr. Borno said that telehealth and telemedicine are not cure-alls, and digital health solutions don’t work for all patients. Approaches, she says, must be tailored to the individual, or disparities could worsen.
In 2020, the Food and Drug Administration approved 53 new drugs. Overall, 32,000 patients took part in these trials. On average, 75% were White, 8% were Black, 6% were Asian, and 11% were Hispanic.
Here’s one stark example of the issue. In 2015, the FDA approved ixazomib (Ninlaro), a promising new drug for multiple myeloma, a blood cancer that affects Black people at disproportionately higher rates than White people. In the United States, one in five people diagnosed with multiple myeloma are Black people. They are more than twice as likely to get the disease as White people. Yet during the clinical trial of 722 participants, only 13 patients, or 1.8%, were Black.
The American Cancer Society estimates that more than 600,000 Americans will die from cancer this year. Historically, Black Americans have the highest death rate and the shortest survival of any racial or ethnic group, stemming largely, it concluded, from centuries of structural racism.
According to Jamie Freedman, MD, head of U.S. medical affairs at Genentech, a global pharmaceutical company, the lack of diversity is often tied to where studies are run.
“Companies tend to choose major academic medical centers where there is a high volume of clinical trial work. When you go to the same tried and true hospitals repeatedly, the pool of patients becomes very homogeneous and tends to be primarily white,” he said. “It’s critical to bring more trials into the community setting by including new sites that can reach underrepresented groups, and Genentech is making significant progress in that area.”
Dr. Freedman believes that, while access is a big hurdle, it doesn’t end there.
“Many patients have a lack of trust in the health care system,” he said. “There are also issues around underserved communities being able to afford quality care, so it’s important to keep time and financial burdens in mind when designing trials to help mitigate barriers such as travel, parking, time off work, and child care.”
Genentech started its diversity and inclusion effort several years ago. Dr. Freeman said that, until more trials become diverse, Black Americans will continue to pay the price. “I think they’re losing their lives in part due to lack of access to these trials. And that is why Genentech and all of us in the health care industry need to change how we design and enroll these studies. We have a long way to go, but I think the steps we’re taking are leading us in the right direction.”
Jennifer Jones-McMeans, PhD, director of global clinical affairs at Abbott Pharmaceuticals, is a clinical research scientist who has designed and led many clinical trials.
She said that Abbott is actively working on solutions.
“We have designed our trials to reduce the barriers to participation and expand access,” she said. “This can be as simple as providing transportation services or home visits for those who are housebound. We’re taking it a step further and providing home health services where someone comes to the home and provides follow-up visits there.”
They also provide interpretation services to address any language barriers.
“We are reaching out to a new set of talented investigators who work closely with underrepresented communities. They are very much wedded and supportive of the communities they treat. By working with doctors within these communities, it expands access to new therapies.”
Spokesperson Keanna Ghazvini said that Pfizer Pharmaceuticals is also committed to increasing minority participation in trials.
“We know that if historically underserved populations are left out of clinical trials, they risk not benefiting from medical breakthroughs down the line,” she said.
The National Institutes of Health’s National Library of Medicine maintains the clinicaltrials.gov database.
There, you can find information on nearly 372,000 publicly and privately supported clinical trials happening in all 50 states and 219 countries. Many are funded by the NIH, but not all of these studies have been evaluated by the U.S. government.
Andrea Denicoff, a nurse consultant at the National Cancer Institute and head of clinical trials operations for the NCI’s National Clinical Trials Network, has been involved in clinical research at the NIH for 35 years.
“It’s really important that our publicly funded trials represent the people of the country,” she said. “There are some cancers that we’re doing a good job in enrolling minorities, and other cancers we need to do a much better job in having a diverse representation in our trials.”
Ms. Denicoff believed opening trials in places where people live is key, but having a diverse clinical trials team is as important.
“We need to reinforce that cancer centers across the country have open doors, and anyone with cancer feels comfortable getting care at that center, and that also includes discussing the option to participate in clinical trials when one might be available. We know from research that when people are invited and asked about trial participation and educated about them, they’ll be much more interested in joining them.”
Ms. Denicoff said that, during the pandemic, the NCI quickly came up with guidance to allow trial sites to send patients their oral study drugs and set up virtual visits. She believes it may help increase future access.
‘Lola Fashoyin-Aje, MD, associate director for science and policy to address disparities in the Oncology Center of Excellence at the FDA, says the agency firmly believes clinical trials should represent the patients who will ultimately get the drug if it’s approved.
But the FDA’s power to require diversity in trials is limited.
“It is important to point out that there are legal constraints which limit’s FDA’s authority to require specific proportional representation in clinical trials by demographic factors,” Dr. Fashoyin-Aje said.
Still, some researchers feel the FDA should play a bigger role. The question is: Should diversity be mandated?
Rhonda Long is now back in Boston to start a new trial, with a new drug that targets her specific mutation. She will be there for 2 months. Once again, Lazarex will help cover some of the cost.
She wants people of color to understand that they are missing out on the promise of new cancer drugs and extended life.
“I feel like there’s not enough emphasis on clinical trials, I don’t believe there’s enough emphasis on second opinions, I don’t think there’s enough emphasis that medicine happens outside our borders, outside of our communities. Clinical trials that don’t have a broad range of participants, how do we know how effective they are if Black and brown people, Asian or Latin American people aren’t represented in the trial?”
And with more trials adopting virtual elements, she said it’s time for minorities to get on board.
Dr. Freedman believed the groundwork is being laid for that to happen. “I don’t think we’ll ever return back to the way we used to do things, where everything has to be done at the clinical trial site. I just don’t think we’re ever going back.”
A version of this article first appeared on WebMD.com.
Dapagliflozin may cut risk of HF hospitalization in patients with type 2 diabetes
Background: Dapagliflozin is a selective inhibitor of sodium-glucose transporter 2 (SGLT2) in the kidney; the drug blocks glucose reabsorption in the proximal tubule. It is taken once daily by mouth. An initial study sponsored by AstraZeneca was published January 2019 in the New England Journal of Medicine – “Dapagliflozin and cardiovascular outcomes in type 2 diabetes.” Until recently there was not an FDA-approved indication for the drug.
Study design: Randomized, double-blind, placebo-controlled trial.
Setting: 882 clinical sites in 33 countries.
Synopsis: The study randomized approximately 17,000 patients to receive either dapagliflozin or placebo in addition to any other diabetes treatments prescribed by their physician. This study demonstrated its primary safety outcome, which was that patients on dapagliflozin did not have any more major adverse cardiac events (MACE), compared with placebo. There were two primary efficacy outcomes. First, there was no change in MACE with dapagliflozin, compared with placebo. Second, and pertinent to this drug’s approval, was that dapagliflozin reduced risk of hospitalization for heart failure (HF) from 5.8% to 4.9%, compared to placebo; this includes both HF with both preserved and reduced ejection fractions.
Bottom line: Dapagliflozin now has an FDA-approved indication to reduce hospitalizations for HF in patients with type 2 diabetes. Based on this study, the number needed to treat with dapagliflozin is 111 patients to prevent one hospitalization for HF.
Citation: Farxiga approved in the US to reduce the risk of hospitalization for heart failure in patients with type-2 diabetes. AstraZeneca Press Release, 2019 Oct 21.
Dr. Como is a hospitalist and clinical instructor of medicine at the University of Utah, Salt Lake City.
Background: Dapagliflozin is a selective inhibitor of sodium-glucose transporter 2 (SGLT2) in the kidney; the drug blocks glucose reabsorption in the proximal tubule. It is taken once daily by mouth. An initial study sponsored by AstraZeneca was published January 2019 in the New England Journal of Medicine – “Dapagliflozin and cardiovascular outcomes in type 2 diabetes.” Until recently there was not an FDA-approved indication for the drug.
Study design: Randomized, double-blind, placebo-controlled trial.
Setting: 882 clinical sites in 33 countries.
Synopsis: The study randomized approximately 17,000 patients to receive either dapagliflozin or placebo in addition to any other diabetes treatments prescribed by their physician. This study demonstrated its primary safety outcome, which was that patients on dapagliflozin did not have any more major adverse cardiac events (MACE), compared with placebo. There were two primary efficacy outcomes. First, there was no change in MACE with dapagliflozin, compared with placebo. Second, and pertinent to this drug’s approval, was that dapagliflozin reduced risk of hospitalization for heart failure (HF) from 5.8% to 4.9%, compared to placebo; this includes both HF with both preserved and reduced ejection fractions.
Bottom line: Dapagliflozin now has an FDA-approved indication to reduce hospitalizations for HF in patients with type 2 diabetes. Based on this study, the number needed to treat with dapagliflozin is 111 patients to prevent one hospitalization for HF.
Citation: Farxiga approved in the US to reduce the risk of hospitalization for heart failure in patients with type-2 diabetes. AstraZeneca Press Release, 2019 Oct 21.
Dr. Como is a hospitalist and clinical instructor of medicine at the University of Utah, Salt Lake City.
Background: Dapagliflozin is a selective inhibitor of sodium-glucose transporter 2 (SGLT2) in the kidney; the drug blocks glucose reabsorption in the proximal tubule. It is taken once daily by mouth. An initial study sponsored by AstraZeneca was published January 2019 in the New England Journal of Medicine – “Dapagliflozin and cardiovascular outcomes in type 2 diabetes.” Until recently there was not an FDA-approved indication for the drug.
Study design: Randomized, double-blind, placebo-controlled trial.
Setting: 882 clinical sites in 33 countries.
Synopsis: The study randomized approximately 17,000 patients to receive either dapagliflozin or placebo in addition to any other diabetes treatments prescribed by their physician. This study demonstrated its primary safety outcome, which was that patients on dapagliflozin did not have any more major adverse cardiac events (MACE), compared with placebo. There were two primary efficacy outcomes. First, there was no change in MACE with dapagliflozin, compared with placebo. Second, and pertinent to this drug’s approval, was that dapagliflozin reduced risk of hospitalization for heart failure (HF) from 5.8% to 4.9%, compared to placebo; this includes both HF with both preserved and reduced ejection fractions.
Bottom line: Dapagliflozin now has an FDA-approved indication to reduce hospitalizations for HF in patients with type 2 diabetes. Based on this study, the number needed to treat with dapagliflozin is 111 patients to prevent one hospitalization for HF.
Citation: Farxiga approved in the US to reduce the risk of hospitalization for heart failure in patients with type-2 diabetes. AstraZeneca Press Release, 2019 Oct 21.
Dr. Como is a hospitalist and clinical instructor of medicine at the University of Utah, Salt Lake City.
FDA warning letters target OTC cannabidiol product claims for pain relief
The Food and Drug Administration has warned two manufacturers about illegal marketing of drugs containing cannabidiol (CBD) for over-the-counter use without an approved new drug application, for using substandard manufacturing processes, and for failure to comply with current good manufacturing practices. These warnings add to 51 previous warning letters issued by the FDA since 2015 to other manufacturers of products containing CBD who were violating the Federal Food, Drug, and Cosmetic Act.
In a news release, the agency explained that its two most recent letters, sent to Honest Globe Inc. on March 15 and BioLyte Laboratories LLC on March 18, were issued because CBD has “known pharmacologic effects on humans, with demonstrated risks, it cannot be legally marketed as an inactive ingredient in OTC drug products that are not reviewed and approved by the FDA.” They also describe the companies’ failures to comply with current good manufacturing practices.
“The FDA continues to alert the public to potential safety and efficacy concerns with unapproved CBD products sold online and in stores across the country,” FDA Principal Deputy Commissioner Amy P. Abernethy, MD, PhD, said in the release. “It’s important that consumers understand that the FDA has only approved one drug containing CBD as an ingredient [Epidiolex]. These other, unapproved, CBD products may have dangerous health impacts and side effects. We remain focused on exploring potential pathways for CBD products to be lawfully marketed while also educating the public about these outstanding questions of CBD’s safety. Meanwhile, we will continue to monitor and take action, as needed, against companies that unlawfully market their products – prioritizing those that pose a risk to public health.”
The specific products from Santa Ana, Calif.–based Honest Globe that the FDA called unapproved new drugs and misbranded under the Federal Food, Drug, and Cosmetic Act included Elixicure Original Pain Relief and Elixicure Lavender Pain Relief, both of which were described as containing CBD. Products from Grand Rapids, Mich.–based BioLyte Laboratories LLC that the FDA similarly cited for violations included Silver Gel, Silver Gel with Aloe, Silver Liquid Supplement, Therapeutic Pain Gel, Pain Relief Cream, and Magnesium Oil Spray.
The agency has asked the two companies to respond to its letters within 15 working days, “stating how they will address these violations or providing their reasoning and supporting information as to why they believe these products are not in violation of the law. Failure to adequately address the violations promptly may result in legal action, including product seizure and/or injunction.”
The Food and Drug Administration has warned two manufacturers about illegal marketing of drugs containing cannabidiol (CBD) for over-the-counter use without an approved new drug application, for using substandard manufacturing processes, and for failure to comply with current good manufacturing practices. These warnings add to 51 previous warning letters issued by the FDA since 2015 to other manufacturers of products containing CBD who were violating the Federal Food, Drug, and Cosmetic Act.
In a news release, the agency explained that its two most recent letters, sent to Honest Globe Inc. on March 15 and BioLyte Laboratories LLC on March 18, were issued because CBD has “known pharmacologic effects on humans, with demonstrated risks, it cannot be legally marketed as an inactive ingredient in OTC drug products that are not reviewed and approved by the FDA.” They also describe the companies’ failures to comply with current good manufacturing practices.
“The FDA continues to alert the public to potential safety and efficacy concerns with unapproved CBD products sold online and in stores across the country,” FDA Principal Deputy Commissioner Amy P. Abernethy, MD, PhD, said in the release. “It’s important that consumers understand that the FDA has only approved one drug containing CBD as an ingredient [Epidiolex]. These other, unapproved, CBD products may have dangerous health impacts and side effects. We remain focused on exploring potential pathways for CBD products to be lawfully marketed while also educating the public about these outstanding questions of CBD’s safety. Meanwhile, we will continue to monitor and take action, as needed, against companies that unlawfully market their products – prioritizing those that pose a risk to public health.”
The specific products from Santa Ana, Calif.–based Honest Globe that the FDA called unapproved new drugs and misbranded under the Federal Food, Drug, and Cosmetic Act included Elixicure Original Pain Relief and Elixicure Lavender Pain Relief, both of which were described as containing CBD. Products from Grand Rapids, Mich.–based BioLyte Laboratories LLC that the FDA similarly cited for violations included Silver Gel, Silver Gel with Aloe, Silver Liquid Supplement, Therapeutic Pain Gel, Pain Relief Cream, and Magnesium Oil Spray.
The agency has asked the two companies to respond to its letters within 15 working days, “stating how they will address these violations or providing their reasoning and supporting information as to why they believe these products are not in violation of the law. Failure to adequately address the violations promptly may result in legal action, including product seizure and/or injunction.”
The Food and Drug Administration has warned two manufacturers about illegal marketing of drugs containing cannabidiol (CBD) for over-the-counter use without an approved new drug application, for using substandard manufacturing processes, and for failure to comply with current good manufacturing practices. These warnings add to 51 previous warning letters issued by the FDA since 2015 to other manufacturers of products containing CBD who were violating the Federal Food, Drug, and Cosmetic Act.
In a news release, the agency explained that its two most recent letters, sent to Honest Globe Inc. on March 15 and BioLyte Laboratories LLC on March 18, were issued because CBD has “known pharmacologic effects on humans, with demonstrated risks, it cannot be legally marketed as an inactive ingredient in OTC drug products that are not reviewed and approved by the FDA.” They also describe the companies’ failures to comply with current good manufacturing practices.
“The FDA continues to alert the public to potential safety and efficacy concerns with unapproved CBD products sold online and in stores across the country,” FDA Principal Deputy Commissioner Amy P. Abernethy, MD, PhD, said in the release. “It’s important that consumers understand that the FDA has only approved one drug containing CBD as an ingredient [Epidiolex]. These other, unapproved, CBD products may have dangerous health impacts and side effects. We remain focused on exploring potential pathways for CBD products to be lawfully marketed while also educating the public about these outstanding questions of CBD’s safety. Meanwhile, we will continue to monitor and take action, as needed, against companies that unlawfully market their products – prioritizing those that pose a risk to public health.”
The specific products from Santa Ana, Calif.–based Honest Globe that the FDA called unapproved new drugs and misbranded under the Federal Food, Drug, and Cosmetic Act included Elixicure Original Pain Relief and Elixicure Lavender Pain Relief, both of which were described as containing CBD. Products from Grand Rapids, Mich.–based BioLyte Laboratories LLC that the FDA similarly cited for violations included Silver Gel, Silver Gel with Aloe, Silver Liquid Supplement, Therapeutic Pain Gel, Pain Relief Cream, and Magnesium Oil Spray.
The agency has asked the two companies to respond to its letters within 15 working days, “stating how they will address these violations or providing their reasoning and supporting information as to why they believe these products are not in violation of the law. Failure to adequately address the violations promptly may result in legal action, including product seizure and/or injunction.”
Low concordance between troponin assays for ACS
Clinicians should be aware that the discordance between high-sensitivity cardiac troponin (hs-cTn) assays is significant enough that management recommendations may change, for example, for a patient assessed for suspected acute coronary syndrome (ACS) in one hospital and transferred to another that uses a different assay, according to a team of international researchers.
When hs-cTn concentrations were measured using the three Food and Drug Administration–approved assays, only 37.4% (384 of 1,027 samples) of blood samples were classified into the same analytical benchmark category.
“We didn’t expect such low concordance, to be honest, but I have to stress that this first assessment used just one-time blood testing and serial testing is what is more commonly recommended now,” said Júlia Karády, MD, from Massachusetts General Hospital and Harvard Medical School, both in Boston.
To see if concordance improved with serial testing, the researchers looked at the 242 patients for whom serial samples were available and saw concordance of management recommendations across assays rise to 74.8%.
“We tested the 0/2-hour algorithm and found that the overall agreement almost doubled, so I think that a very important message from our study is that serial testing improves the agreement between the assays in terms of clinical management and patient stratification,” said Dr. Karády.
Dr. Karády and colleagues published their findings in the Journal of the American College of Cardiology.
The researchers tested three assays referred to clinically as high-sensitivity assays: Elecsys 2010 platform (Roche Diagnostics); ARCHITECT i2000SR (Abbott Diagnostics); and hsVista (Siemens Diagnostics). All three have received FDA approval, starting with Elecsys in 2017.
The proportion of patients with similar management recommendations differed between the assays for both “rule-out” (87.2%, 73.1%, and 78.5% for Roche, Abbott, and Siemens, respectively) and “observe” (9.5%, 24%, and 17.8%; both P < .001). For the purposes of “rule-in,” no difference was noted (3.3%, 2.9%, and 3.7%).
“It’s important to note that this was a highly selected population of patients with an intermediate likelihood for ACS, not an all-comer population. This group comprises about 20% of the [emergency department] population and actually is the group we struggle with the most, which is hardest to diagnose because it excludes the very low– and very high–risk patients,” said Dr. Karády.
The patients included in this study all had suspected ACS and were enrolled in the ROMICAT-I and II trials.
Among 1,027 samples from 624 patients (mean age, 52.8 years; 39.4% women), samples were classified as below the limit of detection (LOD) in 56.3%, 10.4%, and 41.2% (P < .001) by Roche, Abbott, and Siemens, respectively.
The proportion of sample with a troponin measurement between LOD to the 99th percentile also differed significantly between the assays at 36.5%, 83.5%, and 52.6%, respectively (P < .001).
Only the proportion classified greater than 99th percentile did not differ (7.2%, 6.0%, and 6.2%; P = .114).
When the researchers looked at sex-specific difference, no differences were seen in rule-in numbers for men, but significant differences were seen for women.
“One possible explanation for this could be differences in the representation of men and women in the various reference populations used to develop the 99th percentile values for these assays,” suggested Dr. Karády.
They estimate around 30%-40% of U.S. centers are currently using high-sensitivity troponin assays and this number is “rapidly rising.”
The diagnostic algorithms developed for use with high-sensitivity assays, such as the 0/2-h algorithm, acknowledge differences in performance characteristics and recommend that assay-specific cut points be used for clinical decision-making rather than relying on generally applicable thresholds.
Joseph S. Alpert, MD, University of Arizona, Tucson, and coauthors of an accompanying editorial said the take-home message here is caveat emptor.
“First, ‘let the buyer (i.e., the clinician) beware’ when patients are transferred from one hospital to another, where different hs-cTn assays may be used,” they wrote. This is particularly true in women and in those with troponin levels in the “observe (gray zone)” clinical management recommendation.
Dr. Karády has received grant support from the Fulbright Visiting Researcher Grant and the Rosztoczy Foundation. One of the coauthors of the editorial comment consults or has consulted for most of the major diagnostic companies, including the manufacturers of the three assays tested in this study. Dr. Alpert disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Clinicians should be aware that the discordance between high-sensitivity cardiac troponin (hs-cTn) assays is significant enough that management recommendations may change, for example, for a patient assessed for suspected acute coronary syndrome (ACS) in one hospital and transferred to another that uses a different assay, according to a team of international researchers.
When hs-cTn concentrations were measured using the three Food and Drug Administration–approved assays, only 37.4% (384 of 1,027 samples) of blood samples were classified into the same analytical benchmark category.
“We didn’t expect such low concordance, to be honest, but I have to stress that this first assessment used just one-time blood testing and serial testing is what is more commonly recommended now,” said Júlia Karády, MD, from Massachusetts General Hospital and Harvard Medical School, both in Boston.
To see if concordance improved with serial testing, the researchers looked at the 242 patients for whom serial samples were available and saw concordance of management recommendations across assays rise to 74.8%.
“We tested the 0/2-hour algorithm and found that the overall agreement almost doubled, so I think that a very important message from our study is that serial testing improves the agreement between the assays in terms of clinical management and patient stratification,” said Dr. Karády.
Dr. Karády and colleagues published their findings in the Journal of the American College of Cardiology.
The researchers tested three assays referred to clinically as high-sensitivity assays: Elecsys 2010 platform (Roche Diagnostics); ARCHITECT i2000SR (Abbott Diagnostics); and hsVista (Siemens Diagnostics). All three have received FDA approval, starting with Elecsys in 2017.
The proportion of patients with similar management recommendations differed between the assays for both “rule-out” (87.2%, 73.1%, and 78.5% for Roche, Abbott, and Siemens, respectively) and “observe” (9.5%, 24%, and 17.8%; both P < .001). For the purposes of “rule-in,” no difference was noted (3.3%, 2.9%, and 3.7%).
“It’s important to note that this was a highly selected population of patients with an intermediate likelihood for ACS, not an all-comer population. This group comprises about 20% of the [emergency department] population and actually is the group we struggle with the most, which is hardest to diagnose because it excludes the very low– and very high–risk patients,” said Dr. Karády.
The patients included in this study all had suspected ACS and were enrolled in the ROMICAT-I and II trials.
Among 1,027 samples from 624 patients (mean age, 52.8 years; 39.4% women), samples were classified as below the limit of detection (LOD) in 56.3%, 10.4%, and 41.2% (P < .001) by Roche, Abbott, and Siemens, respectively.
The proportion of sample with a troponin measurement between LOD to the 99th percentile also differed significantly between the assays at 36.5%, 83.5%, and 52.6%, respectively (P < .001).
Only the proportion classified greater than 99th percentile did not differ (7.2%, 6.0%, and 6.2%; P = .114).
When the researchers looked at sex-specific difference, no differences were seen in rule-in numbers for men, but significant differences were seen for women.
“One possible explanation for this could be differences in the representation of men and women in the various reference populations used to develop the 99th percentile values for these assays,” suggested Dr. Karády.
They estimate around 30%-40% of U.S. centers are currently using high-sensitivity troponin assays and this number is “rapidly rising.”
The diagnostic algorithms developed for use with high-sensitivity assays, such as the 0/2-h algorithm, acknowledge differences in performance characteristics and recommend that assay-specific cut points be used for clinical decision-making rather than relying on generally applicable thresholds.
Joseph S. Alpert, MD, University of Arizona, Tucson, and coauthors of an accompanying editorial said the take-home message here is caveat emptor.
“First, ‘let the buyer (i.e., the clinician) beware’ when patients are transferred from one hospital to another, where different hs-cTn assays may be used,” they wrote. This is particularly true in women and in those with troponin levels in the “observe (gray zone)” clinical management recommendation.
Dr. Karády has received grant support from the Fulbright Visiting Researcher Grant and the Rosztoczy Foundation. One of the coauthors of the editorial comment consults or has consulted for most of the major diagnostic companies, including the manufacturers of the three assays tested in this study. Dr. Alpert disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Clinicians should be aware that the discordance between high-sensitivity cardiac troponin (hs-cTn) assays is significant enough that management recommendations may change, for example, for a patient assessed for suspected acute coronary syndrome (ACS) in one hospital and transferred to another that uses a different assay, according to a team of international researchers.
When hs-cTn concentrations were measured using the three Food and Drug Administration–approved assays, only 37.4% (384 of 1,027 samples) of blood samples were classified into the same analytical benchmark category.
“We didn’t expect such low concordance, to be honest, but I have to stress that this first assessment used just one-time blood testing and serial testing is what is more commonly recommended now,” said Júlia Karády, MD, from Massachusetts General Hospital and Harvard Medical School, both in Boston.
To see if concordance improved with serial testing, the researchers looked at the 242 patients for whom serial samples were available and saw concordance of management recommendations across assays rise to 74.8%.
“We tested the 0/2-hour algorithm and found that the overall agreement almost doubled, so I think that a very important message from our study is that serial testing improves the agreement between the assays in terms of clinical management and patient stratification,” said Dr. Karády.
Dr. Karády and colleagues published their findings in the Journal of the American College of Cardiology.
The researchers tested three assays referred to clinically as high-sensitivity assays: Elecsys 2010 platform (Roche Diagnostics); ARCHITECT i2000SR (Abbott Diagnostics); and hsVista (Siemens Diagnostics). All three have received FDA approval, starting with Elecsys in 2017.
The proportion of patients with similar management recommendations differed between the assays for both “rule-out” (87.2%, 73.1%, and 78.5% for Roche, Abbott, and Siemens, respectively) and “observe” (9.5%, 24%, and 17.8%; both P < .001). For the purposes of “rule-in,” no difference was noted (3.3%, 2.9%, and 3.7%).
“It’s important to note that this was a highly selected population of patients with an intermediate likelihood for ACS, not an all-comer population. This group comprises about 20% of the [emergency department] population and actually is the group we struggle with the most, which is hardest to diagnose because it excludes the very low– and very high–risk patients,” said Dr. Karády.
The patients included in this study all had suspected ACS and were enrolled in the ROMICAT-I and II trials.
Among 1,027 samples from 624 patients (mean age, 52.8 years; 39.4% women), samples were classified as below the limit of detection (LOD) in 56.3%, 10.4%, and 41.2% (P < .001) by Roche, Abbott, and Siemens, respectively.
The proportion of sample with a troponin measurement between LOD to the 99th percentile also differed significantly between the assays at 36.5%, 83.5%, and 52.6%, respectively (P < .001).
Only the proportion classified greater than 99th percentile did not differ (7.2%, 6.0%, and 6.2%; P = .114).
When the researchers looked at sex-specific difference, no differences were seen in rule-in numbers for men, but significant differences were seen for women.
“One possible explanation for this could be differences in the representation of men and women in the various reference populations used to develop the 99th percentile values for these assays,” suggested Dr. Karády.
They estimate around 30%-40% of U.S. centers are currently using high-sensitivity troponin assays and this number is “rapidly rising.”
The diagnostic algorithms developed for use with high-sensitivity assays, such as the 0/2-h algorithm, acknowledge differences in performance characteristics and recommend that assay-specific cut points be used for clinical decision-making rather than relying on generally applicable thresholds.
Joseph S. Alpert, MD, University of Arizona, Tucson, and coauthors of an accompanying editorial said the take-home message here is caveat emptor.
“First, ‘let the buyer (i.e., the clinician) beware’ when patients are transferred from one hospital to another, where different hs-cTn assays may be used,” they wrote. This is particularly true in women and in those with troponin levels in the “observe (gray zone)” clinical management recommendation.
Dr. Karády has received grant support from the Fulbright Visiting Researcher Grant and the Rosztoczy Foundation. One of the coauthors of the editorial comment consults or has consulted for most of the major diagnostic companies, including the manufacturers of the three assays tested in this study. Dr. Alpert disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Artifactual hypoglycemia: When there’s a problem in the tube
If you are looking for zebras you might consider adrenal insufficiency, which could cause both hyperkalemia and hypoglycemia, but this would make no sense in someone asymptomatic.
This pattern is one I have seen commonly when I am on call, and I am contacted about abnormal labs. The lab reported no hemolysis seen, but this is the typical pattern seen with hemolytic specimens and/or specimens that have been held a long time before they are analyzed.
Lippi and colleagues reported on the clinically significant increase in potassium in samples that visually appeared not to be hemolyzed.1 Hemolyzed specimens can also drop glucose values, but not as profoundly as raising potassium values. When left unprocessed, glycolysis occurs in the white blood cells of a blood sample and may consume 5%-7% of the sample’s glucose content per hour.2
Khaled and colleagues looked at the drop in glucose levels in samples over time based on what anticoagulants were used.3 They found that, at 3 hours, glucose measurements were decreased by 28.4 mg/dL when sodium citrate is used, 58 mg/dL when EDTA was used, 15.4 mg/dL when fluoride oxalate was used, and 60.2 mg/dL when no anticoagulant is used.
Low blood sugars caused by elevated WBCs in blood samples has been well described.4 It has been described with moderate and very high WBC counts, as well as with the leukocytosis seen with polycythemia vera.5 The term “leukocyte larceny” has been used to describe high WBC counts that can not only utilize glucose, but also oxygen.
Saccheti and colleagues described a patient with a WBC greater than 500,000 who had repeatedly low oxygen levels on blood gases, that did not correlate with the normal oxygen saturations measured by pulse oximetry.6 This same issue has been seen in patients with extreme thrombocytosis.7Pearl: When labs don’t make sense clinically, always look at the possibility that there may be a problem in the tube and not in the person. Especially think of this when blood samples may have been held for a long time before they are run, such as with visiting nurse visits and blood draws at shelters and nursing homes.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].
References
1. Lippi G et al. Clin Chem Lab Med. 2006;44(3):311-6.
2. Mikesh LM and Bruns DE. Clin Chem. 2008 May;54(5):930-2.
3. Khaled S et al. Al-Mukhtar Journal of Sciences. 2018;33(2):100-6.
4. Goodenow TJ and Malarkey WB. JAMA. 1977;237(18):1961-2.
5. R Arem et al. Arch Intern Med. 1982 Nov;142(12):2199-201.
6. Sacchetti A et al. J Emerg Med. 1990;8:567–569.
7. A Mehta et al. Eur Respir J. 2008 Feb;31(2):469-72.
If you are looking for zebras you might consider adrenal insufficiency, which could cause both hyperkalemia and hypoglycemia, but this would make no sense in someone asymptomatic.
This pattern is one I have seen commonly when I am on call, and I am contacted about abnormal labs. The lab reported no hemolysis seen, but this is the typical pattern seen with hemolytic specimens and/or specimens that have been held a long time before they are analyzed.
Lippi and colleagues reported on the clinically significant increase in potassium in samples that visually appeared not to be hemolyzed.1 Hemolyzed specimens can also drop glucose values, but not as profoundly as raising potassium values. When left unprocessed, glycolysis occurs in the white blood cells of a blood sample and may consume 5%-7% of the sample’s glucose content per hour.2
Khaled and colleagues looked at the drop in glucose levels in samples over time based on what anticoagulants were used.3 They found that, at 3 hours, glucose measurements were decreased by 28.4 mg/dL when sodium citrate is used, 58 mg/dL when EDTA was used, 15.4 mg/dL when fluoride oxalate was used, and 60.2 mg/dL when no anticoagulant is used.
Low blood sugars caused by elevated WBCs in blood samples has been well described.4 It has been described with moderate and very high WBC counts, as well as with the leukocytosis seen with polycythemia vera.5 The term “leukocyte larceny” has been used to describe high WBC counts that can not only utilize glucose, but also oxygen.
Saccheti and colleagues described a patient with a WBC greater than 500,000 who had repeatedly low oxygen levels on blood gases, that did not correlate with the normal oxygen saturations measured by pulse oximetry.6 This same issue has been seen in patients with extreme thrombocytosis.7Pearl: When labs don’t make sense clinically, always look at the possibility that there may be a problem in the tube and not in the person. Especially think of this when blood samples may have been held for a long time before they are run, such as with visiting nurse visits and blood draws at shelters and nursing homes.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].
References
1. Lippi G et al. Clin Chem Lab Med. 2006;44(3):311-6.
2. Mikesh LM and Bruns DE. Clin Chem. 2008 May;54(5):930-2.
3. Khaled S et al. Al-Mukhtar Journal of Sciences. 2018;33(2):100-6.
4. Goodenow TJ and Malarkey WB. JAMA. 1977;237(18):1961-2.
5. R Arem et al. Arch Intern Med. 1982 Nov;142(12):2199-201.
6. Sacchetti A et al. J Emerg Med. 1990;8:567–569.
7. A Mehta et al. Eur Respir J. 2008 Feb;31(2):469-72.
If you are looking for zebras you might consider adrenal insufficiency, which could cause both hyperkalemia and hypoglycemia, but this would make no sense in someone asymptomatic.
This pattern is one I have seen commonly when I am on call, and I am contacted about abnormal labs. The lab reported no hemolysis seen, but this is the typical pattern seen with hemolytic specimens and/or specimens that have been held a long time before they are analyzed.
Lippi and colleagues reported on the clinically significant increase in potassium in samples that visually appeared not to be hemolyzed.1 Hemolyzed specimens can also drop glucose values, but not as profoundly as raising potassium values. When left unprocessed, glycolysis occurs in the white blood cells of a blood sample and may consume 5%-7% of the sample’s glucose content per hour.2
Khaled and colleagues looked at the drop in glucose levels in samples over time based on what anticoagulants were used.3 They found that, at 3 hours, glucose measurements were decreased by 28.4 mg/dL when sodium citrate is used, 58 mg/dL when EDTA was used, 15.4 mg/dL when fluoride oxalate was used, and 60.2 mg/dL when no anticoagulant is used.
Low blood sugars caused by elevated WBCs in blood samples has been well described.4 It has been described with moderate and very high WBC counts, as well as with the leukocytosis seen with polycythemia vera.5 The term “leukocyte larceny” has been used to describe high WBC counts that can not only utilize glucose, but also oxygen.
Saccheti and colleagues described a patient with a WBC greater than 500,000 who had repeatedly low oxygen levels on blood gases, that did not correlate with the normal oxygen saturations measured by pulse oximetry.6 This same issue has been seen in patients with extreme thrombocytosis.7Pearl: When labs don’t make sense clinically, always look at the possibility that there may be a problem in the tube and not in the person. Especially think of this when blood samples may have been held for a long time before they are run, such as with visiting nurse visits and blood draws at shelters and nursing homes.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].
References
1. Lippi G et al. Clin Chem Lab Med. 2006;44(3):311-6.
2. Mikesh LM and Bruns DE. Clin Chem. 2008 May;54(5):930-2.
3. Khaled S et al. Al-Mukhtar Journal of Sciences. 2018;33(2):100-6.
4. Goodenow TJ and Malarkey WB. JAMA. 1977;237(18):1961-2.
5. R Arem et al. Arch Intern Med. 1982 Nov;142(12):2199-201.
6. Sacchetti A et al. J Emerg Med. 1990;8:567–569.
7. A Mehta et al. Eur Respir J. 2008 Feb;31(2):469-72.