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New Drug Approvals Are the Wrong Metric for Cancer Policy
How should we define success in cancer policy — what should the endpoint be?
It’s debatable. Is it fewer cancer deaths? Perhaps improved access to therapies or a reduction in disparities?
One thing I know with certainty: The number of new cancer drugs approved by the US Food and Drug Administration (FDA) is not and should not be our primary endpoint in and of itself.
I’ll go a step further: It is not even a surrogate marker for success.
Unfortunately, a new drug approval does not necessarily mean improved patient outcomes. In fact, the majority of cancer drugs approved these days improve neither survival nor quality of life. Our previous work has shown better mortality outcomes in other high-income countries that have not approved or do not fund several cancer drugs that the FDA has approved.
Even if a drug has a meaningful benefit, at an average cost of more than $250,000 per year, if a new drug cannot reach patients because of access or cost issues, it’s meaningless.
However, regulators and media celebrate the number (and speed) of drug approvals every year as if it were a marker of success in and of itself. But approving more drugs should not be the goal; improving outcomes should. The FDA’s current approach is akin to a university celebrating its graduation rate by lowering the requirements to pass.
When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine ‘ending cancer as we know it’ is premature and even embarrassing.
This is exactly what the FDA has been doing with our regulatory standards for drug approval. They have gradually lowered the requirements for approval from two randomized trials to one randomized trial, then further to one randomized trial with a surrogate endpoint. In many instances, they have gone even further, demanding merely single-arm trials. They’ve also gone from requiring overall survival benefits to celebrating nondetrimental effects on overall survival. It’s no wonder that we approve more drugs today than we did in the past — the bar for approval is pretty low nowadays.
In 2019, our lab found an interesting phenomenon: The number of approvals based on surrogate endpoints has been increasing while the number of accelerated approvals has been decreasing. This made no sense at first, because you’d think surrogate-based approvals and accelerated approvals would be collinear. However, we realized that the recent approvals based on surrogate endpoints were regular approvals instead of accelerated approvals, which explained the phenomenon. Not only is the FDA approving more drugs on the basis of lower levels of evidence, but the agency is also offering regular instead of accelerated approval, thereby removing the safety net of a confirmatory trial.
Nearly everybody sees this as a cause for celebration. Pharma celebrates record profits, regulators celebrate record numbers of drug approvals, insurance companies celebrate because they can pass these costs on as insurance premiums and make even more money, and physicians and patients celebrate access to the shiniest, sexiest new cancer drug.
Everybody is happy in this system. The only problem is that patient outcomes don’t improve, resources are taken away from other priorities, and society suffers a net harm.
When you contrast this celebration with the reality on the ground, the difference is stark and sobering. In our clinics, patients lack access to even old chemotherapeutic drugs that are already generic and cheap but make a meaningful difference in patient outcomes. Citing a current lack of incentives, several generic cancer drug manufacturers have stopped making these drugs; the US supply now relies heavily on importing them from emerging economies such as India. When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine “ending cancer as we know it” is premature and even embarrassing.
5-Fluorouracil, methotrexate, and the platinums are backbones of cancer treatment. Cisplatin and carboplatin are not drugs we use with the hope of improving survival by a couple of months; these drugs are the difference between life and death for patients with testicular and ovarian cancers. In a survey of 948 global oncologists, these were considered among the most essential cancer drugs by oncologists in high-income and low- and middle-income countries alike. Although oncologists in low- and middle-income countries sometimes argue that even these cheap generic drugs may be unaffordable to their patients, they usually remain available; access is a function of both availability and affordability. However, the shortage situation in the US is unique in that availability — rather than affordability — is impacting access.
Our profit-over-patients policy has landed us in a terrible paradox.
Generic drugs are cheap, and any industrialized country can manufacture them. This is why so few companies actually do so; the profit margins are low and companies have little incentive to produce them, despite their benefit. Meanwhile, the FDA is approving and offering access to new shiny molecules that cost more than $15,000 per month yet offer less than a month of progression-free survival benefit and no overall survival benefit (see margetuximab in breast cancer). We have a literal fatal attraction to everything new and shiny.
This is a clear misalignment of priorities in US cancer drug policy. Our profit-over-patients policy has landed us in a terrible paradox: If a drug is cheap and meaningful, it won’t be available, but if it is marginal and expensive, we will do everything to ensure patients can get it. It’s no wonder that patients on Medicaid are disproportionately affected by these drug shortages. Unless all patients have easy access to cisplatin, carboplatin, and 5-fluorouracil, it is frankly embarrassing to celebrate the number of new cancer drugs approved each year.
We all have a responsibility in this — policymakers and lawmakers, regulators and payers, manufacturers and distributors, the American Society of Clinical Oncology and other oncology societies, and physicians and patients. This is where our advocacy work should focus. The primary endpoint of our cancer policy should not be how many new treatments we can approve or how many expensive drugs a rich person with the best insurance can get at a leading cancer center. The true measure of our civilization is how it treats its most vulnerable members.
Dr. Gyawali has disclosed the following relevant financial relationship: Received consulting fees from Vivio Health.
Dr. Gyawali is an associate professor in the Departments of Oncology and Public Health Sciences and a scientist in the Division of Cancer Care and Epidemiology at Queen’s University in Kingston, Ontario, Canada, and is also affiliated faculty at the Program on Regulation, Therapeutics, and Law in the Department of Medicine at Brigham and Women’s Hospital in Boston. His clinical and research interests revolve around cancer policy, global oncology, evidence-based oncology, financial toxicities of cancer treatment, clinical trial methods, and supportive care. He tweets at @oncology_bg.
A version of this article appeared on Medscape.com.
How should we define success in cancer policy — what should the endpoint be?
It’s debatable. Is it fewer cancer deaths? Perhaps improved access to therapies or a reduction in disparities?
One thing I know with certainty: The number of new cancer drugs approved by the US Food and Drug Administration (FDA) is not and should not be our primary endpoint in and of itself.
I’ll go a step further: It is not even a surrogate marker for success.
Unfortunately, a new drug approval does not necessarily mean improved patient outcomes. In fact, the majority of cancer drugs approved these days improve neither survival nor quality of life. Our previous work has shown better mortality outcomes in other high-income countries that have not approved or do not fund several cancer drugs that the FDA has approved.
Even if a drug has a meaningful benefit, at an average cost of more than $250,000 per year, if a new drug cannot reach patients because of access or cost issues, it’s meaningless.
However, regulators and media celebrate the number (and speed) of drug approvals every year as if it were a marker of success in and of itself. But approving more drugs should not be the goal; improving outcomes should. The FDA’s current approach is akin to a university celebrating its graduation rate by lowering the requirements to pass.
When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine ‘ending cancer as we know it’ is premature and even embarrassing.
This is exactly what the FDA has been doing with our regulatory standards for drug approval. They have gradually lowered the requirements for approval from two randomized trials to one randomized trial, then further to one randomized trial with a surrogate endpoint. In many instances, they have gone even further, demanding merely single-arm trials. They’ve also gone from requiring overall survival benefits to celebrating nondetrimental effects on overall survival. It’s no wonder that we approve more drugs today than we did in the past — the bar for approval is pretty low nowadays.
In 2019, our lab found an interesting phenomenon: The number of approvals based on surrogate endpoints has been increasing while the number of accelerated approvals has been decreasing. This made no sense at first, because you’d think surrogate-based approvals and accelerated approvals would be collinear. However, we realized that the recent approvals based on surrogate endpoints were regular approvals instead of accelerated approvals, which explained the phenomenon. Not only is the FDA approving more drugs on the basis of lower levels of evidence, but the agency is also offering regular instead of accelerated approval, thereby removing the safety net of a confirmatory trial.
Nearly everybody sees this as a cause for celebration. Pharma celebrates record profits, regulators celebrate record numbers of drug approvals, insurance companies celebrate because they can pass these costs on as insurance premiums and make even more money, and physicians and patients celebrate access to the shiniest, sexiest new cancer drug.
Everybody is happy in this system. The only problem is that patient outcomes don’t improve, resources are taken away from other priorities, and society suffers a net harm.
When you contrast this celebration with the reality on the ground, the difference is stark and sobering. In our clinics, patients lack access to even old chemotherapeutic drugs that are already generic and cheap but make a meaningful difference in patient outcomes. Citing a current lack of incentives, several generic cancer drug manufacturers have stopped making these drugs; the US supply now relies heavily on importing them from emerging economies such as India. When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine “ending cancer as we know it” is premature and even embarrassing.
5-Fluorouracil, methotrexate, and the platinums are backbones of cancer treatment. Cisplatin and carboplatin are not drugs we use with the hope of improving survival by a couple of months; these drugs are the difference between life and death for patients with testicular and ovarian cancers. In a survey of 948 global oncologists, these were considered among the most essential cancer drugs by oncologists in high-income and low- and middle-income countries alike. Although oncologists in low- and middle-income countries sometimes argue that even these cheap generic drugs may be unaffordable to their patients, they usually remain available; access is a function of both availability and affordability. However, the shortage situation in the US is unique in that availability — rather than affordability — is impacting access.
Our profit-over-patients policy has landed us in a terrible paradox.
Generic drugs are cheap, and any industrialized country can manufacture them. This is why so few companies actually do so; the profit margins are low and companies have little incentive to produce them, despite their benefit. Meanwhile, the FDA is approving and offering access to new shiny molecules that cost more than $15,000 per month yet offer less than a month of progression-free survival benefit and no overall survival benefit (see margetuximab in breast cancer). We have a literal fatal attraction to everything new and shiny.
This is a clear misalignment of priorities in US cancer drug policy. Our profit-over-patients policy has landed us in a terrible paradox: If a drug is cheap and meaningful, it won’t be available, but if it is marginal and expensive, we will do everything to ensure patients can get it. It’s no wonder that patients on Medicaid are disproportionately affected by these drug shortages. Unless all patients have easy access to cisplatin, carboplatin, and 5-fluorouracil, it is frankly embarrassing to celebrate the number of new cancer drugs approved each year.
We all have a responsibility in this — policymakers and lawmakers, regulators and payers, manufacturers and distributors, the American Society of Clinical Oncology and other oncology societies, and physicians and patients. This is where our advocacy work should focus. The primary endpoint of our cancer policy should not be how many new treatments we can approve or how many expensive drugs a rich person with the best insurance can get at a leading cancer center. The true measure of our civilization is how it treats its most vulnerable members.
Dr. Gyawali has disclosed the following relevant financial relationship: Received consulting fees from Vivio Health.
Dr. Gyawali is an associate professor in the Departments of Oncology and Public Health Sciences and a scientist in the Division of Cancer Care and Epidemiology at Queen’s University in Kingston, Ontario, Canada, and is also affiliated faculty at the Program on Regulation, Therapeutics, and Law in the Department of Medicine at Brigham and Women’s Hospital in Boston. His clinical and research interests revolve around cancer policy, global oncology, evidence-based oncology, financial toxicities of cancer treatment, clinical trial methods, and supportive care. He tweets at @oncology_bg.
A version of this article appeared on Medscape.com.
How should we define success in cancer policy — what should the endpoint be?
It’s debatable. Is it fewer cancer deaths? Perhaps improved access to therapies or a reduction in disparities?
One thing I know with certainty: The number of new cancer drugs approved by the US Food and Drug Administration (FDA) is not and should not be our primary endpoint in and of itself.
I’ll go a step further: It is not even a surrogate marker for success.
Unfortunately, a new drug approval does not necessarily mean improved patient outcomes. In fact, the majority of cancer drugs approved these days improve neither survival nor quality of life. Our previous work has shown better mortality outcomes in other high-income countries that have not approved or do not fund several cancer drugs that the FDA has approved.
Even if a drug has a meaningful benefit, at an average cost of more than $250,000 per year, if a new drug cannot reach patients because of access or cost issues, it’s meaningless.
However, regulators and media celebrate the number (and speed) of drug approvals every year as if it were a marker of success in and of itself. But approving more drugs should not be the goal; improving outcomes should. The FDA’s current approach is akin to a university celebrating its graduation rate by lowering the requirements to pass.
When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine ‘ending cancer as we know it’ is premature and even embarrassing.
This is exactly what the FDA has been doing with our regulatory standards for drug approval. They have gradually lowered the requirements for approval from two randomized trials to one randomized trial, then further to one randomized trial with a surrogate endpoint. In many instances, they have gone even further, demanding merely single-arm trials. They’ve also gone from requiring overall survival benefits to celebrating nondetrimental effects on overall survival. It’s no wonder that we approve more drugs today than we did in the past — the bar for approval is pretty low nowadays.
In 2019, our lab found an interesting phenomenon: The number of approvals based on surrogate endpoints has been increasing while the number of accelerated approvals has been decreasing. This made no sense at first, because you’d think surrogate-based approvals and accelerated approvals would be collinear. However, we realized that the recent approvals based on surrogate endpoints were regular approvals instead of accelerated approvals, which explained the phenomenon. Not only is the FDA approving more drugs on the basis of lower levels of evidence, but the agency is also offering regular instead of accelerated approval, thereby removing the safety net of a confirmatory trial.
Nearly everybody sees this as a cause for celebration. Pharma celebrates record profits, regulators celebrate record numbers of drug approvals, insurance companies celebrate because they can pass these costs on as insurance premiums and make even more money, and physicians and patients celebrate access to the shiniest, sexiest new cancer drug.
Everybody is happy in this system. The only problem is that patient outcomes don’t improve, resources are taken away from other priorities, and society suffers a net harm.
When you contrast this celebration with the reality on the ground, the difference is stark and sobering. In our clinics, patients lack access to even old chemotherapeutic drugs that are already generic and cheap but make a meaningful difference in patient outcomes. Citing a current lack of incentives, several generic cancer drug manufacturers have stopped making these drugs; the US supply now relies heavily on importing them from emerging economies such as India. When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine “ending cancer as we know it” is premature and even embarrassing.
5-Fluorouracil, methotrexate, and the platinums are backbones of cancer treatment. Cisplatin and carboplatin are not drugs we use with the hope of improving survival by a couple of months; these drugs are the difference between life and death for patients with testicular and ovarian cancers. In a survey of 948 global oncologists, these were considered among the most essential cancer drugs by oncologists in high-income and low- and middle-income countries alike. Although oncologists in low- and middle-income countries sometimes argue that even these cheap generic drugs may be unaffordable to their patients, they usually remain available; access is a function of both availability and affordability. However, the shortage situation in the US is unique in that availability — rather than affordability — is impacting access.
Our profit-over-patients policy has landed us in a terrible paradox.
Generic drugs are cheap, and any industrialized country can manufacture them. This is why so few companies actually do so; the profit margins are low and companies have little incentive to produce them, despite their benefit. Meanwhile, the FDA is approving and offering access to new shiny molecules that cost more than $15,000 per month yet offer less than a month of progression-free survival benefit and no overall survival benefit (see margetuximab in breast cancer). We have a literal fatal attraction to everything new and shiny.
This is a clear misalignment of priorities in US cancer drug policy. Our profit-over-patients policy has landed us in a terrible paradox: If a drug is cheap and meaningful, it won’t be available, but if it is marginal and expensive, we will do everything to ensure patients can get it. It’s no wonder that patients on Medicaid are disproportionately affected by these drug shortages. Unless all patients have easy access to cisplatin, carboplatin, and 5-fluorouracil, it is frankly embarrassing to celebrate the number of new cancer drugs approved each year.
We all have a responsibility in this — policymakers and lawmakers, regulators and payers, manufacturers and distributors, the American Society of Clinical Oncology and other oncology societies, and physicians and patients. This is where our advocacy work should focus. The primary endpoint of our cancer policy should not be how many new treatments we can approve or how many expensive drugs a rich person with the best insurance can get at a leading cancer center. The true measure of our civilization is how it treats its most vulnerable members.
Dr. Gyawali has disclosed the following relevant financial relationship: Received consulting fees from Vivio Health.
Dr. Gyawali is an associate professor in the Departments of Oncology and Public Health Sciences and a scientist in the Division of Cancer Care and Epidemiology at Queen’s University in Kingston, Ontario, Canada, and is also affiliated faculty at the Program on Regulation, Therapeutics, and Law in the Department of Medicine at Brigham and Women’s Hospital in Boston. His clinical and research interests revolve around cancer policy, global oncology, evidence-based oncology, financial toxicities of cancer treatment, clinical trial methods, and supportive care. He tweets at @oncology_bg.
A version of this article appeared on Medscape.com.
We Must Learn About Abortion as Primary Care Doctors
“No greater opportunity, responsibility, or obligation can fall to the lot of a human being than to become a physician. In the care of the suffering, [the physician] needs technical skill, scientific knowledge, and human understanding.”1 Internal medicine physicians have risen to this challenge for centuries. Today, it is time for us to use these skills to care for patients who need access to reproductive care — particularly medication abortion. Nationally accredited internal medicine training programs have not been required to provide abortion education, and this may evolve in the future.
However, considering the difficulty in people receiving contraception, the failure rate of contraception, the known risks from pregnancy, the increasing difficulty in accessing abortion, and the recent advocating to protect access to reproductive care by leadership of internal medicine and internal medicine subspecialty societies, we advocate that abortion must become a part of our education and practice.2
Most abortions are performed during the first trimester and can be managed with medications that are very safe.3 In fact, legal medication abortion is so safe that pregnancy in the United States has fourteen times the mortality risk as does legal medication abortion.4 Inability to access an abortion has widely documented negative health effects for women and their children.5,6
Within this context, it is important for internal medicine physicians to understand that the ability to access an abortion is the ability to access a life-saving procedure and there is no medical justification for restricting such a prescription any more than restricting any other standard medical therapy. Furthermore, the recent widespread criminalization of abortion gives new urgency to expanding the pool of physicians who understand this and are trained, able, and willing to prescribe medication abortion.
We understand that reproductive health care may not now be a component of clinical practice for some, but given the heterogeneity of internal medicine, we believe that some knowledge about medical abortion is an essential competency of foundational medical knowledge.7 The heterogeneity of practice in internal medicine lends itself to different levels of knowledge that should be embraced. Because of poor access to abortion, both ambulatory and hospital-based physicians will increasingly be required to care for patients who need abortion for medical or other reasons.
We advocate that all physicians — including those with internal medicine training — should understand counseling about choices and options (including an unbiased discussion of the options to continue or terminate the pregnancy), the safety of medication abortion in contrast to the risks from pregnancy, and where to refer someone seeking an abortion. In addition to this information, primary care physicians with a special interest in women’s health must have basic knowledge about mifepristone and misoprostol and how they work, the benefits and risks of these, and what the pregnant person seeking an abortion will experience.8
Lastly, physicians who wish to provide medication abortion — including in primary care, hospital medicine, and subspecialty care — should receive training and ongoing professional development. Such professional development should include counseling, indications, contraindications, medication regimens, navigating required documentation and reporting, and anticipating possible side effects and complications.
A major challenge to internal medicine and other primary care physicians, subspecialists, and hospitalists addressing abortion is the inadequate training in and knowledge about providing this care. However, the entire spectrum of medical education (undergraduate, graduate, and continuing education) should evolve to address this lack.
Integrating this education into medical conferences and journals is a meaningful start, possibly in partnership with medical societies that have been teaching these skills for decades. Partnering with other specialties can also help us stay current on the local legal landscape and engage in collaborative advocacy.
Specifically, some resources for training can be found at:
- www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2014/11/abortion-training-and-education
- https://prochoice.org/providers/continuing-medical-education/
- www.reproductiveaccess.org/medicationabortion/
Some may have concerns that managing the possible complications of medication abortion is a reason for internal medicine to not be involved in abortion care. However, medication abortions are safe and effective for pregnancy termination and internal medicine physicians can refer patients with complications to peers in gynecology, family medicine, and emergency medicine should complications arise.8 We have managed countless other conditions this way, including most recently during the pandemic.
We live in a country with increasing barriers to care – now with laws in many states that prevent basic health care for women. Internal medicine doctors increasingly may see patients who need care urgently, particularly those who practice in states that neighbor those that prevent this access. We are calling for all who practice internal medicine to educate themselves, optimizing their skills within the full scope of medical practice to provide possibly lifesaving care and thereby address increased needs for medical services.
We must continue to advocate for our patients. The COVID-19 pandemic has reinforced the fact that internal medicine–trained physicians are able to care for conditions that are new and, as a profession, we are capable of rapidly switching practices and learning new modalities of care. It is time for us to extend this competency to care for patients who constitute half the population and are at risk: women.
Dr. Barrett is an internal medicine hospitalist based in Albuquerque, New Mexico; she completed a medical justice in advocacy fellowship in 2022. Dr. Radhakrishnan is an internal medicine physician educator who completed an equity matters fellowship in 2022 and is based in Scottsdale, Arizona. Neither reports conflicts of interest.
References
1. Harrison’s Principles of Internal Medicine, 20e. Jameson J et al., eds. McGraw Hill; 2018. Accessed Sept. 27, 2023.
2. Serchen J et al. Reproductive Health Policy in the United States: An American College of Physicians Policy Brief. Ann Intern Med.2023;176:364-6. epub 28 Feb. 2023.
3. Jatlaoui TC et al. Abortion Surveillance — United States, 2016. MMWR Surveill Summ 2019;68(No. SS-11):1-41.
4. Raymond EG and Grimes DA. The comparative safety of legal induced abortion and childbirth in the United States. Obstet Gynecol. 2012;119(2 Pt 1):215-9.
5. Ralph LJ et al. Self-reported Physical Health of Women Who Did and Did Not Terminate Pregnancy After Seeking Abortion Services: A Cohort Study. Ann Intern Med.2019;171:238-47. epub 11 June 2019.
6. Gerdts C et al. Side effects, physical health consequences, and mortality associated with abortion and birth after an unwanted pregnancy. Women’s Health Issues 2016;26:55-59.
7. Nobel K et al. Patient-reported experience with discussion of all options during pregnancy options counseling in the US south. Contraception. 2022;106:68-74.
8. Liu N and Ray JG. Short-Term Adverse Outcomes After Mifepristone–Misoprostol Versus Procedural Induced Abortion: A Population-Based Propensity-Weighted Study. Ann Intern Med.2023;176:145-53. epub 3 January 2023.
“No greater opportunity, responsibility, or obligation can fall to the lot of a human being than to become a physician. In the care of the suffering, [the physician] needs technical skill, scientific knowledge, and human understanding.”1 Internal medicine physicians have risen to this challenge for centuries. Today, it is time for us to use these skills to care for patients who need access to reproductive care — particularly medication abortion. Nationally accredited internal medicine training programs have not been required to provide abortion education, and this may evolve in the future.
However, considering the difficulty in people receiving contraception, the failure rate of contraception, the known risks from pregnancy, the increasing difficulty in accessing abortion, and the recent advocating to protect access to reproductive care by leadership of internal medicine and internal medicine subspecialty societies, we advocate that abortion must become a part of our education and practice.2
Most abortions are performed during the first trimester and can be managed with medications that are very safe.3 In fact, legal medication abortion is so safe that pregnancy in the United States has fourteen times the mortality risk as does legal medication abortion.4 Inability to access an abortion has widely documented negative health effects for women and their children.5,6
Within this context, it is important for internal medicine physicians to understand that the ability to access an abortion is the ability to access a life-saving procedure and there is no medical justification for restricting such a prescription any more than restricting any other standard medical therapy. Furthermore, the recent widespread criminalization of abortion gives new urgency to expanding the pool of physicians who understand this and are trained, able, and willing to prescribe medication abortion.
We understand that reproductive health care may not now be a component of clinical practice for some, but given the heterogeneity of internal medicine, we believe that some knowledge about medical abortion is an essential competency of foundational medical knowledge.7 The heterogeneity of practice in internal medicine lends itself to different levels of knowledge that should be embraced. Because of poor access to abortion, both ambulatory and hospital-based physicians will increasingly be required to care for patients who need abortion for medical or other reasons.
We advocate that all physicians — including those with internal medicine training — should understand counseling about choices and options (including an unbiased discussion of the options to continue or terminate the pregnancy), the safety of medication abortion in contrast to the risks from pregnancy, and where to refer someone seeking an abortion. In addition to this information, primary care physicians with a special interest in women’s health must have basic knowledge about mifepristone and misoprostol and how they work, the benefits and risks of these, and what the pregnant person seeking an abortion will experience.8
Lastly, physicians who wish to provide medication abortion — including in primary care, hospital medicine, and subspecialty care — should receive training and ongoing professional development. Such professional development should include counseling, indications, contraindications, medication regimens, navigating required documentation and reporting, and anticipating possible side effects and complications.
A major challenge to internal medicine and other primary care physicians, subspecialists, and hospitalists addressing abortion is the inadequate training in and knowledge about providing this care. However, the entire spectrum of medical education (undergraduate, graduate, and continuing education) should evolve to address this lack.
Integrating this education into medical conferences and journals is a meaningful start, possibly in partnership with medical societies that have been teaching these skills for decades. Partnering with other specialties can also help us stay current on the local legal landscape and engage in collaborative advocacy.
Specifically, some resources for training can be found at:
- www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2014/11/abortion-training-and-education
- https://prochoice.org/providers/continuing-medical-education/
- www.reproductiveaccess.org/medicationabortion/
Some may have concerns that managing the possible complications of medication abortion is a reason for internal medicine to not be involved in abortion care. However, medication abortions are safe and effective for pregnancy termination and internal medicine physicians can refer patients with complications to peers in gynecology, family medicine, and emergency medicine should complications arise.8 We have managed countless other conditions this way, including most recently during the pandemic.
We live in a country with increasing barriers to care – now with laws in many states that prevent basic health care for women. Internal medicine doctors increasingly may see patients who need care urgently, particularly those who practice in states that neighbor those that prevent this access. We are calling for all who practice internal medicine to educate themselves, optimizing their skills within the full scope of medical practice to provide possibly lifesaving care and thereby address increased needs for medical services.
We must continue to advocate for our patients. The COVID-19 pandemic has reinforced the fact that internal medicine–trained physicians are able to care for conditions that are new and, as a profession, we are capable of rapidly switching practices and learning new modalities of care. It is time for us to extend this competency to care for patients who constitute half the population and are at risk: women.
Dr. Barrett is an internal medicine hospitalist based in Albuquerque, New Mexico; she completed a medical justice in advocacy fellowship in 2022. Dr. Radhakrishnan is an internal medicine physician educator who completed an equity matters fellowship in 2022 and is based in Scottsdale, Arizona. Neither reports conflicts of interest.
References
1. Harrison’s Principles of Internal Medicine, 20e. Jameson J et al., eds. McGraw Hill; 2018. Accessed Sept. 27, 2023.
2. Serchen J et al. Reproductive Health Policy in the United States: An American College of Physicians Policy Brief. Ann Intern Med.2023;176:364-6. epub 28 Feb. 2023.
3. Jatlaoui TC et al. Abortion Surveillance — United States, 2016. MMWR Surveill Summ 2019;68(No. SS-11):1-41.
4. Raymond EG and Grimes DA. The comparative safety of legal induced abortion and childbirth in the United States. Obstet Gynecol. 2012;119(2 Pt 1):215-9.
5. Ralph LJ et al. Self-reported Physical Health of Women Who Did and Did Not Terminate Pregnancy After Seeking Abortion Services: A Cohort Study. Ann Intern Med.2019;171:238-47. epub 11 June 2019.
6. Gerdts C et al. Side effects, physical health consequences, and mortality associated with abortion and birth after an unwanted pregnancy. Women’s Health Issues 2016;26:55-59.
7. Nobel K et al. Patient-reported experience with discussion of all options during pregnancy options counseling in the US south. Contraception. 2022;106:68-74.
8. Liu N and Ray JG. Short-Term Adverse Outcomes After Mifepristone–Misoprostol Versus Procedural Induced Abortion: A Population-Based Propensity-Weighted Study. Ann Intern Med.2023;176:145-53. epub 3 January 2023.
“No greater opportunity, responsibility, or obligation can fall to the lot of a human being than to become a physician. In the care of the suffering, [the physician] needs technical skill, scientific knowledge, and human understanding.”1 Internal medicine physicians have risen to this challenge for centuries. Today, it is time for us to use these skills to care for patients who need access to reproductive care — particularly medication abortion. Nationally accredited internal medicine training programs have not been required to provide abortion education, and this may evolve in the future.
However, considering the difficulty in people receiving contraception, the failure rate of contraception, the known risks from pregnancy, the increasing difficulty in accessing abortion, and the recent advocating to protect access to reproductive care by leadership of internal medicine and internal medicine subspecialty societies, we advocate that abortion must become a part of our education and practice.2
Most abortions are performed during the first trimester and can be managed with medications that are very safe.3 In fact, legal medication abortion is so safe that pregnancy in the United States has fourteen times the mortality risk as does legal medication abortion.4 Inability to access an abortion has widely documented negative health effects for women and their children.5,6
Within this context, it is important for internal medicine physicians to understand that the ability to access an abortion is the ability to access a life-saving procedure and there is no medical justification for restricting such a prescription any more than restricting any other standard medical therapy. Furthermore, the recent widespread criminalization of abortion gives new urgency to expanding the pool of physicians who understand this and are trained, able, and willing to prescribe medication abortion.
We understand that reproductive health care may not now be a component of clinical practice for some, but given the heterogeneity of internal medicine, we believe that some knowledge about medical abortion is an essential competency of foundational medical knowledge.7 The heterogeneity of practice in internal medicine lends itself to different levels of knowledge that should be embraced. Because of poor access to abortion, both ambulatory and hospital-based physicians will increasingly be required to care for patients who need abortion for medical or other reasons.
We advocate that all physicians — including those with internal medicine training — should understand counseling about choices and options (including an unbiased discussion of the options to continue or terminate the pregnancy), the safety of medication abortion in contrast to the risks from pregnancy, and where to refer someone seeking an abortion. In addition to this information, primary care physicians with a special interest in women’s health must have basic knowledge about mifepristone and misoprostol and how they work, the benefits and risks of these, and what the pregnant person seeking an abortion will experience.8
Lastly, physicians who wish to provide medication abortion — including in primary care, hospital medicine, and subspecialty care — should receive training and ongoing professional development. Such professional development should include counseling, indications, contraindications, medication regimens, navigating required documentation and reporting, and anticipating possible side effects and complications.
A major challenge to internal medicine and other primary care physicians, subspecialists, and hospitalists addressing abortion is the inadequate training in and knowledge about providing this care. However, the entire spectrum of medical education (undergraduate, graduate, and continuing education) should evolve to address this lack.
Integrating this education into medical conferences and journals is a meaningful start, possibly in partnership with medical societies that have been teaching these skills for decades. Partnering with other specialties can also help us stay current on the local legal landscape and engage in collaborative advocacy.
Specifically, some resources for training can be found at:
- www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2014/11/abortion-training-and-education
- https://prochoice.org/providers/continuing-medical-education/
- www.reproductiveaccess.org/medicationabortion/
Some may have concerns that managing the possible complications of medication abortion is a reason for internal medicine to not be involved in abortion care. However, medication abortions are safe and effective for pregnancy termination and internal medicine physicians can refer patients with complications to peers in gynecology, family medicine, and emergency medicine should complications arise.8 We have managed countless other conditions this way, including most recently during the pandemic.
We live in a country with increasing barriers to care – now with laws in many states that prevent basic health care for women. Internal medicine doctors increasingly may see patients who need care urgently, particularly those who practice in states that neighbor those that prevent this access. We are calling for all who practice internal medicine to educate themselves, optimizing their skills within the full scope of medical practice to provide possibly lifesaving care and thereby address increased needs for medical services.
We must continue to advocate for our patients. The COVID-19 pandemic has reinforced the fact that internal medicine–trained physicians are able to care for conditions that are new and, as a profession, we are capable of rapidly switching practices and learning new modalities of care. It is time for us to extend this competency to care for patients who constitute half the population and are at risk: women.
Dr. Barrett is an internal medicine hospitalist based in Albuquerque, New Mexico; she completed a medical justice in advocacy fellowship in 2022. Dr. Radhakrishnan is an internal medicine physician educator who completed an equity matters fellowship in 2022 and is based in Scottsdale, Arizona. Neither reports conflicts of interest.
References
1. Harrison’s Principles of Internal Medicine, 20e. Jameson J et al., eds. McGraw Hill; 2018. Accessed Sept. 27, 2023.
2. Serchen J et al. Reproductive Health Policy in the United States: An American College of Physicians Policy Brief. Ann Intern Med.2023;176:364-6. epub 28 Feb. 2023.
3. Jatlaoui TC et al. Abortion Surveillance — United States, 2016. MMWR Surveill Summ 2019;68(No. SS-11):1-41.
4. Raymond EG and Grimes DA. The comparative safety of legal induced abortion and childbirth in the United States. Obstet Gynecol. 2012;119(2 Pt 1):215-9.
5. Ralph LJ et al. Self-reported Physical Health of Women Who Did and Did Not Terminate Pregnancy After Seeking Abortion Services: A Cohort Study. Ann Intern Med.2019;171:238-47. epub 11 June 2019.
6. Gerdts C et al. Side effects, physical health consequences, and mortality associated with abortion and birth after an unwanted pregnancy. Women’s Health Issues 2016;26:55-59.
7. Nobel K et al. Patient-reported experience with discussion of all options during pregnancy options counseling in the US south. Contraception. 2022;106:68-74.
8. Liu N and Ray JG. Short-Term Adverse Outcomes After Mifepristone–Misoprostol Versus Procedural Induced Abortion: A Population-Based Propensity-Weighted Study. Ann Intern Med.2023;176:145-53. epub 3 January 2023.
Clock Watchers
The following scenario was discussed during a forum at a meeting recently:
Two employees managing the front desk are clock watchers, always the first to leave at 11:59 a.m. for lunch and at 4:59 p.m. for the end of the day no matter what is happening. This leaves the other employees stuck with their work.
I have seen clock watching often enough to know that it is widely practiced, and widely reviled by coworkers and managers alike. Generally, clock watchers — sometimes referred to in modern parlance as “quiet quitters” — radiate a palpable sense of “I don’t want to be here.”
; if that involves working past the usual “quitting time,” so be it. So your first task in dealing with this problem is to determine its cause. The clock watcher label may be unfair. There may be legitimate reasons for certain employees to leave work at precisely 4:59 every day. Perhaps they must pick up children, or they have a second job to get to. The label usually comes from a pattern of consistent, repeated behavior. And if more than one employee is exhibiting the same behavior in the same office, the likelihood of a valid explanation decreases proportionally.
A common cause of clock watching is a lack of employees’ commitment to their jobs. They don’t see the point in putting in extra effort, so they run out the door as soon as possible. There are many reasons why this might be the case. For example, the workload in your office may be too large to be accomplished in the time available by the number of people you employ. The solution might be to simply hire additional personnel.
Another common cause is a lack of communication between physicians, managers, and lower-level employees. If staffers are raising concerns or potential solutions, and management is not listening to their opinions or ideas, they will stop offering them. Alternatively, other staff members may not be pulling their weight. When there is a large imbalance in the contribution of team members, the higher performers will stop trying.
Over my 40 plus years in practice, I have had my share of clock watchers. I try the best I can not to let employees’ time commitment practices impact my valuation of their work. I always attempt to focus on quality and productivity. It isn’t easy, but I always try to address the issues behind clock watching behavior. As such, I can’t recall ever having to fire anyone for clock watching. Here are some of the strategies that have worked for me over the years:
1. Set clear expectations. Clearly communicate job responsibilities and expectations regarding time management and patient care. Ensure that all staff understand the importance of dedicating the necessary time to each patient, regardless of the time of day.
2. Foster a patient-centered culture. Cultivate a work environment that prioritizes patient care above all. This can help shift the focus from watching the clock to ensuring high-quality patient care.
3. Provide adequate breaks. Ensure that staff schedules include sufficient breaks. Overworked staff are more likely to watch the clock. Adequate rest periods can help alleviate this issue.
4. Offer flexibility where possible. If feasible, offer some degree of scheduling flexibility. This can help staff manage their personal time more effectively, potentially reducing the tendency to watch the clock.
5. Implement time management training. Offer training sessions focused on time management and efficiency. This can help staff manage their duties more effectively, reducing the need to constantly check the time.
6. Encourage open communication. Create an environment where staff feel comfortable discussing their concerns, including issues related to workload and time management. This can help identify and address specific factors contributing to clock watching.
7. Monitor and provide feedback. Regularly monitor staff performance and provide constructive feedback. If clock watching is observed, discuss it directly with the employee, focusing on the impact on patient care and the work environment.
8. Recognize and reward. Acknowledge and reward staff who consistently provide high-quality care and demonstrate effective time management. Recognition can motivate others to adjust their behavior.
9. Evaluate workloads. Regularly assess staff workloads to ensure they are manageable. Overburdened employees are more likely to engage in clock watching.
10. Lead by example. Management should model the behavior they wish to see in their staff. Demonstrating a commitment to patient care and effective time management can set a positive example.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
The following scenario was discussed during a forum at a meeting recently:
Two employees managing the front desk are clock watchers, always the first to leave at 11:59 a.m. for lunch and at 4:59 p.m. for the end of the day no matter what is happening. This leaves the other employees stuck with their work.
I have seen clock watching often enough to know that it is widely practiced, and widely reviled by coworkers and managers alike. Generally, clock watchers — sometimes referred to in modern parlance as “quiet quitters” — radiate a palpable sense of “I don’t want to be here.”
; if that involves working past the usual “quitting time,” so be it. So your first task in dealing with this problem is to determine its cause. The clock watcher label may be unfair. There may be legitimate reasons for certain employees to leave work at precisely 4:59 every day. Perhaps they must pick up children, or they have a second job to get to. The label usually comes from a pattern of consistent, repeated behavior. And if more than one employee is exhibiting the same behavior in the same office, the likelihood of a valid explanation decreases proportionally.
A common cause of clock watching is a lack of employees’ commitment to their jobs. They don’t see the point in putting in extra effort, so they run out the door as soon as possible. There are many reasons why this might be the case. For example, the workload in your office may be too large to be accomplished in the time available by the number of people you employ. The solution might be to simply hire additional personnel.
Another common cause is a lack of communication between physicians, managers, and lower-level employees. If staffers are raising concerns or potential solutions, and management is not listening to their opinions or ideas, they will stop offering them. Alternatively, other staff members may not be pulling their weight. When there is a large imbalance in the contribution of team members, the higher performers will stop trying.
Over my 40 plus years in practice, I have had my share of clock watchers. I try the best I can not to let employees’ time commitment practices impact my valuation of their work. I always attempt to focus on quality and productivity. It isn’t easy, but I always try to address the issues behind clock watching behavior. As such, I can’t recall ever having to fire anyone for clock watching. Here are some of the strategies that have worked for me over the years:
1. Set clear expectations. Clearly communicate job responsibilities and expectations regarding time management and patient care. Ensure that all staff understand the importance of dedicating the necessary time to each patient, regardless of the time of day.
2. Foster a patient-centered culture. Cultivate a work environment that prioritizes patient care above all. This can help shift the focus from watching the clock to ensuring high-quality patient care.
3. Provide adequate breaks. Ensure that staff schedules include sufficient breaks. Overworked staff are more likely to watch the clock. Adequate rest periods can help alleviate this issue.
4. Offer flexibility where possible. If feasible, offer some degree of scheduling flexibility. This can help staff manage their personal time more effectively, potentially reducing the tendency to watch the clock.
5. Implement time management training. Offer training sessions focused on time management and efficiency. This can help staff manage their duties more effectively, reducing the need to constantly check the time.
6. Encourage open communication. Create an environment where staff feel comfortable discussing their concerns, including issues related to workload and time management. This can help identify and address specific factors contributing to clock watching.
7. Monitor and provide feedback. Regularly monitor staff performance and provide constructive feedback. If clock watching is observed, discuss it directly with the employee, focusing on the impact on patient care and the work environment.
8. Recognize and reward. Acknowledge and reward staff who consistently provide high-quality care and demonstrate effective time management. Recognition can motivate others to adjust their behavior.
9. Evaluate workloads. Regularly assess staff workloads to ensure they are manageable. Overburdened employees are more likely to engage in clock watching.
10. Lead by example. Management should model the behavior they wish to see in their staff. Demonstrating a commitment to patient care and effective time management can set a positive example.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
The following scenario was discussed during a forum at a meeting recently:
Two employees managing the front desk are clock watchers, always the first to leave at 11:59 a.m. for lunch and at 4:59 p.m. for the end of the day no matter what is happening. This leaves the other employees stuck with their work.
I have seen clock watching often enough to know that it is widely practiced, and widely reviled by coworkers and managers alike. Generally, clock watchers — sometimes referred to in modern parlance as “quiet quitters” — radiate a palpable sense of “I don’t want to be here.”
; if that involves working past the usual “quitting time,” so be it. So your first task in dealing with this problem is to determine its cause. The clock watcher label may be unfair. There may be legitimate reasons for certain employees to leave work at precisely 4:59 every day. Perhaps they must pick up children, or they have a second job to get to. The label usually comes from a pattern of consistent, repeated behavior. And if more than one employee is exhibiting the same behavior in the same office, the likelihood of a valid explanation decreases proportionally.
A common cause of clock watching is a lack of employees’ commitment to their jobs. They don’t see the point in putting in extra effort, so they run out the door as soon as possible. There are many reasons why this might be the case. For example, the workload in your office may be too large to be accomplished in the time available by the number of people you employ. The solution might be to simply hire additional personnel.
Another common cause is a lack of communication between physicians, managers, and lower-level employees. If staffers are raising concerns or potential solutions, and management is not listening to their opinions or ideas, they will stop offering them. Alternatively, other staff members may not be pulling their weight. When there is a large imbalance in the contribution of team members, the higher performers will stop trying.
Over my 40 plus years in practice, I have had my share of clock watchers. I try the best I can not to let employees’ time commitment practices impact my valuation of their work. I always attempt to focus on quality and productivity. It isn’t easy, but I always try to address the issues behind clock watching behavior. As such, I can’t recall ever having to fire anyone for clock watching. Here are some of the strategies that have worked for me over the years:
1. Set clear expectations. Clearly communicate job responsibilities and expectations regarding time management and patient care. Ensure that all staff understand the importance of dedicating the necessary time to each patient, regardless of the time of day.
2. Foster a patient-centered culture. Cultivate a work environment that prioritizes patient care above all. This can help shift the focus from watching the clock to ensuring high-quality patient care.
3. Provide adequate breaks. Ensure that staff schedules include sufficient breaks. Overworked staff are more likely to watch the clock. Adequate rest periods can help alleviate this issue.
4. Offer flexibility where possible. If feasible, offer some degree of scheduling flexibility. This can help staff manage their personal time more effectively, potentially reducing the tendency to watch the clock.
5. Implement time management training. Offer training sessions focused on time management and efficiency. This can help staff manage their duties more effectively, reducing the need to constantly check the time.
6. Encourage open communication. Create an environment where staff feel comfortable discussing their concerns, including issues related to workload and time management. This can help identify and address specific factors contributing to clock watching.
7. Monitor and provide feedback. Regularly monitor staff performance and provide constructive feedback. If clock watching is observed, discuss it directly with the employee, focusing on the impact on patient care and the work environment.
8. Recognize and reward. Acknowledge and reward staff who consistently provide high-quality care and demonstrate effective time management. Recognition can motivate others to adjust their behavior.
9. Evaluate workloads. Regularly assess staff workloads to ensure they are manageable. Overburdened employees are more likely to engage in clock watching.
10. Lead by example. Management should model the behavior they wish to see in their staff. Demonstrating a commitment to patient care and effective time management can set a positive example.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
When the Next Big Thing Falls Short
Recently, Acadia Pharmaceuticals announced it was stopping trials on Nuplazid for indications outside of Parkinson’s disease psychosis.
I was impressed with what I saw in my office. Although I know there’s some controversy over the drug, the majority of studies do show efficacy, and in my little practice I clearly noticed improvements in patients with Parkinson’s disease who’d previously failed the more standard agents (note - I have no financial affiliation with Acadia Pharmaceuticals).
So, as a lay-neurologist, I expected the drug to work for other kinds of psychosis, particularly Alzheimer’s disease. All of us in practice know how much we need new options for that.
But when the clinical trials came, the drug didn’t work. It didn’t work for schizophrenia, either, Finally, Acadia threw in the towel and gave up.
I have no idea what happened. I’m sure others are wondering the same thing. On paper, I’d have thought it would work for Alzheimer’s psychosis, but in the real world it didn’t.
Is psychosis between the two disorders that different, with different neurotransmitter causes? Are the benefits in my patients with Parkinson’s disease really just from my own selection bias? Or is there just a lot we still don’t know?
Look at the graveyard full of amyloid-targeting drugs. Yeah, I know Leqembi is out there, and donanemab is in the wings, but are they anywhere near as good as we thought they’d be? Not at all.
At the same time, we’ve been waiting for the BTK drugs (not to be confused with a Korean pop band) for multiple sclerosis. They sounded like they were the Next Big Thing.
They may be, but recent data on one of them, evobrutinib, was less than encouraging. Of course, that shouldn’t extrapolate to the group as a whole, but it does leave you wondering why.
Medicine is always improving, but it’s also still a trial-and-error process. Just because something should work doesn’t mean it will, and it may be years before we know why.
It’s just a reminder that, here in 2024, we still have a lot to learn.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Recently, Acadia Pharmaceuticals announced it was stopping trials on Nuplazid for indications outside of Parkinson’s disease psychosis.
I was impressed with what I saw in my office. Although I know there’s some controversy over the drug, the majority of studies do show efficacy, and in my little practice I clearly noticed improvements in patients with Parkinson’s disease who’d previously failed the more standard agents (note - I have no financial affiliation with Acadia Pharmaceuticals).
So, as a lay-neurologist, I expected the drug to work for other kinds of psychosis, particularly Alzheimer’s disease. All of us in practice know how much we need new options for that.
But when the clinical trials came, the drug didn’t work. It didn’t work for schizophrenia, either, Finally, Acadia threw in the towel and gave up.
I have no idea what happened. I’m sure others are wondering the same thing. On paper, I’d have thought it would work for Alzheimer’s psychosis, but in the real world it didn’t.
Is psychosis between the two disorders that different, with different neurotransmitter causes? Are the benefits in my patients with Parkinson’s disease really just from my own selection bias? Or is there just a lot we still don’t know?
Look at the graveyard full of amyloid-targeting drugs. Yeah, I know Leqembi is out there, and donanemab is in the wings, but are they anywhere near as good as we thought they’d be? Not at all.
At the same time, we’ve been waiting for the BTK drugs (not to be confused with a Korean pop band) for multiple sclerosis. They sounded like they were the Next Big Thing.
They may be, but recent data on one of them, evobrutinib, was less than encouraging. Of course, that shouldn’t extrapolate to the group as a whole, but it does leave you wondering why.
Medicine is always improving, but it’s also still a trial-and-error process. Just because something should work doesn’t mean it will, and it may be years before we know why.
It’s just a reminder that, here in 2024, we still have a lot to learn.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Recently, Acadia Pharmaceuticals announced it was stopping trials on Nuplazid for indications outside of Parkinson’s disease psychosis.
I was impressed with what I saw in my office. Although I know there’s some controversy over the drug, the majority of studies do show efficacy, and in my little practice I clearly noticed improvements in patients with Parkinson’s disease who’d previously failed the more standard agents (note - I have no financial affiliation with Acadia Pharmaceuticals).
So, as a lay-neurologist, I expected the drug to work for other kinds of psychosis, particularly Alzheimer’s disease. All of us in practice know how much we need new options for that.
But when the clinical trials came, the drug didn’t work. It didn’t work for schizophrenia, either, Finally, Acadia threw in the towel and gave up.
I have no idea what happened. I’m sure others are wondering the same thing. On paper, I’d have thought it would work for Alzheimer’s psychosis, but in the real world it didn’t.
Is psychosis between the two disorders that different, with different neurotransmitter causes? Are the benefits in my patients with Parkinson’s disease really just from my own selection bias? Or is there just a lot we still don’t know?
Look at the graveyard full of amyloid-targeting drugs. Yeah, I know Leqembi is out there, and donanemab is in the wings, but are they anywhere near as good as we thought they’d be? Not at all.
At the same time, we’ve been waiting for the BTK drugs (not to be confused with a Korean pop band) for multiple sclerosis. They sounded like they were the Next Big Thing.
They may be, but recent data on one of them, evobrutinib, was less than encouraging. Of course, that shouldn’t extrapolate to the group as a whole, but it does leave you wondering why.
Medicine is always improving, but it’s also still a trial-and-error process. Just because something should work doesn’t mean it will, and it may be years before we know why.
It’s just a reminder that, here in 2024, we still have a lot to learn.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Using the Road Map
I had a premed college student with me, a young lady trying to figure out if medicine was for her, and what exactly a neurologist does.
The patient, a gentlemen in his mid-70s, had just left. He had some unusual symptoms. Not implausible, but the kind of case where the answers don’t come together easily. I’d ordered tests for the usual suspects and walked him up front.
When I got back she asked me “what do you think is wrong with him?”
Without thinking I said “I have no idea.” By this time I’d turned to some scheduling messages from my secretary, and didn’t register the student’s surprise for a moment.
I mean, I’m an attending physician. To her I’m the epitome of the career. I got accepted to (and survived) medical school. I made it through residency and fellowship and have almost 26 years of trench-earned experience behind me (hard to believe for me, too, sometimes). And yet I’d just said I didn’t know what was going on.
Reversing the roles and thinking back to the late 1980s, I probably would have felt the same way she did.
Of course “I have no idea” is a bit of unintentional hyperbole. I have some idea, just not a clear answer yet. I’d turned over the possible locations and causes, and so ordered tests to help narrow it down. As one of my attendings in residency used to say, “some days you need a rifle, some days a shotgun” to figure it out.
Being a doctor, even a good one (I hope I am, but not making any guarantees) doesn’t mean you know everything, or have the ability to figure it out immediately. Otherwise we wouldn’t need imaging, labs, and a host of other tests. Sherlock Holmes was a lot of things, but Watson was the doctor.
To those at the beginning of their careers, just like it was to us then, this is a revelation. Aren’t we supposed to know everything? We probably once believed we would, too, someday.
What combination of tests and decisions will hopefully lead us to the correct point.
Most of us realize that intuitively at this point, but it can be hard to explain to others. We have patients ask “what do you think is going on?” and we often have no answer other than “not sure yet, but I’ll try to find out.”
We don’t realize how far we’ve come until we see ourselves in someone who’s starting the same journey. And that’s something you can’t teach.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
I had a premed college student with me, a young lady trying to figure out if medicine was for her, and what exactly a neurologist does.
The patient, a gentlemen in his mid-70s, had just left. He had some unusual symptoms. Not implausible, but the kind of case where the answers don’t come together easily. I’d ordered tests for the usual suspects and walked him up front.
When I got back she asked me “what do you think is wrong with him?”
Without thinking I said “I have no idea.” By this time I’d turned to some scheduling messages from my secretary, and didn’t register the student’s surprise for a moment.
I mean, I’m an attending physician. To her I’m the epitome of the career. I got accepted to (and survived) medical school. I made it through residency and fellowship and have almost 26 years of trench-earned experience behind me (hard to believe for me, too, sometimes). And yet I’d just said I didn’t know what was going on.
Reversing the roles and thinking back to the late 1980s, I probably would have felt the same way she did.
Of course “I have no idea” is a bit of unintentional hyperbole. I have some idea, just not a clear answer yet. I’d turned over the possible locations and causes, and so ordered tests to help narrow it down. As one of my attendings in residency used to say, “some days you need a rifle, some days a shotgun” to figure it out.
Being a doctor, even a good one (I hope I am, but not making any guarantees) doesn’t mean you know everything, or have the ability to figure it out immediately. Otherwise we wouldn’t need imaging, labs, and a host of other tests. Sherlock Holmes was a lot of things, but Watson was the doctor.
To those at the beginning of their careers, just like it was to us then, this is a revelation. Aren’t we supposed to know everything? We probably once believed we would, too, someday.
What combination of tests and decisions will hopefully lead us to the correct point.
Most of us realize that intuitively at this point, but it can be hard to explain to others. We have patients ask “what do you think is going on?” and we often have no answer other than “not sure yet, but I’ll try to find out.”
We don’t realize how far we’ve come until we see ourselves in someone who’s starting the same journey. And that’s something you can’t teach.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
I had a premed college student with me, a young lady trying to figure out if medicine was for her, and what exactly a neurologist does.
The patient, a gentlemen in his mid-70s, had just left. He had some unusual symptoms. Not implausible, but the kind of case where the answers don’t come together easily. I’d ordered tests for the usual suspects and walked him up front.
When I got back she asked me “what do you think is wrong with him?”
Without thinking I said “I have no idea.” By this time I’d turned to some scheduling messages from my secretary, and didn’t register the student’s surprise for a moment.
I mean, I’m an attending physician. To her I’m the epitome of the career. I got accepted to (and survived) medical school. I made it through residency and fellowship and have almost 26 years of trench-earned experience behind me (hard to believe for me, too, sometimes). And yet I’d just said I didn’t know what was going on.
Reversing the roles and thinking back to the late 1980s, I probably would have felt the same way she did.
Of course “I have no idea” is a bit of unintentional hyperbole. I have some idea, just not a clear answer yet. I’d turned over the possible locations and causes, and so ordered tests to help narrow it down. As one of my attendings in residency used to say, “some days you need a rifle, some days a shotgun” to figure it out.
Being a doctor, even a good one (I hope I am, but not making any guarantees) doesn’t mean you know everything, or have the ability to figure it out immediately. Otherwise we wouldn’t need imaging, labs, and a host of other tests. Sherlock Holmes was a lot of things, but Watson was the doctor.
To those at the beginning of their careers, just like it was to us then, this is a revelation. Aren’t we supposed to know everything? We probably once believed we would, too, someday.
What combination of tests and decisions will hopefully lead us to the correct point.
Most of us realize that intuitively at this point, but it can be hard to explain to others. We have patients ask “what do you think is going on?” and we often have no answer other than “not sure yet, but I’ll try to find out.”
We don’t realize how far we’ve come until we see ourselves in someone who’s starting the same journey. And that’s something you can’t teach.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
ERISA Health Plan Lawsuits: Why Should We Care?
A recently filed lawsuit against Johnson & Johnson can serve as an example to use when advocating for patients who have insurance through their employers that can potentially hurt them physically and financially. When your patient has an employer-funded health insurance plan where the employer directly pays for all medical costs — called an ERISA plan for the federal law that governs employee benefit plans, the Employee Retirement Income Security Act — there are certain accountability, fairness, and fiduciary responsibilities that the employers must meet. These so-called ERISA plans do not have to follow state utilization management legislation that addresses harmful changes in insurers’ formularies and other policies, so when the plans are not properly overseen and do not mandate the delivery of proper care at the lowest cost, both the patient and employer may be losing out.
The J&J lawsuit serves as a bellwether warning to self-insured employers to demand transparency from their third-party administrators so as not to (knowingly or unknowingly) breach their fiduciary duty to their health plans and employees. These duties include ensuring reasonable plan costs as well as acting in the best interest of their employees. There were multiple complaints in the lawsuit by a J&J employee, stating that she paid a much higher price for her multiple sclerosis drug through the plan than the price she eventually found at a lower cost pharmacy. The allegations state that J&J failed to show prudence in its selection of a pharmacy benefit manager (PBM). In addition, the company failed to negotiate better drug pricing terms, and the design of the drug plan steered patients to the PBM specialty pharmacy, resulting in higher prices for the employees. All of these led to higher drug costs and premiums for employees, which, according to the lawsuit, is a breach of J&J’s fiduciary duties.
Why Should Rheumatologists Care About This?
With all insurance plans, it feels as though we are dealing with obstacles every day that keep us from giving the excellent rheumatologic care that our patients deserve. Self-insured employers now account for over 50% of commercial health plans, and as rheumatologists caring for the employees of these companies, we can use those transparency, accountability, and fiduciary responsibilities of the employer to ensure that our patients are getting the proper care at the lowest cost.
Not only is the J&J lawsuit a warning to self-insured employers, but a reminder to rheumatologists to be on the lookout for drug pricing issues and formulary construction that leads to higher pricing for employees and the plan. For example, make note if your patient is forced to fail a much higher priced self-injectable biologic before using a much lower cost infusible medication. Or if the plan mandates the use of the much higher priced adalimumab biosimilars over the lower priced biosimilars or even the highest priced JAK inhibitor over the lowest priced one. Let’s not forget mandated white bagging, which is often much more expensive to the plan than the buy-and-bill model through a rheumatologist’s office.
Recently, we have been able to help rheumatology practices get exemptions from white-bagging mandates that large self-insured employers often have in their plan documents. We have been able to show that the cost of obtaining the medication through specialty pharmacy (SP) is much higher than through the buy-and-bill model. Mandating that the plan spend more money on SP drugs, as opposed to allowing the rheumatologist to buy and bill, could easily be interpreted as a breach of fiduciary duty on the part of the employer by mandating a higher cost model.
CSRO Payer Issue Response Team
I have written about the Coalition of State Rheumatology Organizations (CSRO)’s Payer Issue Response Team (PIRT) in the past. Rheumatologists around the country can send to PIRT any problems that they are having with payers. A recent PIRT submission involved a white-bagging mandate for an employee of a very large international Fortune 500 company. This particular example is important because of the response by the VP of Global Benefits for this company. Express Scripts is the administrator of pharmacy benefits for this company. The rheumatologist was told that he could not buy and bill for an infusible medicine but would have to obtain the drug through Express Scripts’ SP. He then asked Express Scripts for the SP medication’s cost to the health plan in order to compare the SP price versus what the buy-and-bill model would cost this company. Express Scripts would not respond to this simple transparency question; often, PBMs claim that this is proprietary information.
I was able to speak with the company’s VP of Global Benefits regarding this issue. First of all, he stated that his company was not mandating white bagging. I explained to him that the plan documents had white bagging as the only option for acquisition of provider-administered drugs. A rheumatologist would have to apply for an exemption to buy and bill, and in this case, it was denied. This is essentially a mandate.
I gave the VP of Global Benefits an example of another large Fortune 500 company (UPS) that spent over $30,000 per year more on an infusible medication when obtained through SP than what it cost them under a buy-and-bill model. I had hoped that this example would impress upon the VP the importance of transparency in pricing and claims to prevent his company from unknowingly costing the health plan more and its being construed as a breach of fiduciary duty. It was explained to me by the VP of Global Benefits that his company is part of the National Drug Purchasers Coalition and they trust Express Scripts to do the right thing for them. As they say, “You can lead a horse to water, but can’t make it drink.”
Liability of a Plan That Physically Harms an Employee?
A slightly different example of a self-insured employer, presumably unknowingly, allowing its third-party administrator to mishandle the care of an employee was recently brought to me by a rheumatologist in North Carolina. She takes care of an employee who has rheumatoid arthritis with severe interstitial lung disease (ILD). The employee’s pulmonary status was stabilized on several courses of Rituxan (reference product of rituximab). Recently, BlueCross BlueShield of North Carolina, the third-party administrator of this employer’s plan, mandated a switch to a biosimilar of rituximab for the treatment of the ILD. The rheumatologist appealed the nonmedical switch but gave the patient the biosimilar so as not to delay care. Her patient’s condition is now deteriorating with progression of the ILD, and she once again has asked for an exemption to use Rituxan, which had initially stabilized the patient. Her staff told her that the BCBSNC rep said that the patient would have to have a life-threatening infusion reaction (and present the bill for the ambulance) before they would approve a return to the reference product. An employer that knowingly or unknowingly allows a third-party administrator to act in such a way as to endanger the life of an employee could be considered to be breaching its fiduciary duty. (Disclaimer: I am not an attorney — merely a rheumatologist with common sense. Nor am I making any qualitative statement about biosimilars.)
We now have a lawsuit to which you can refer when advocating for our patients who are employed by large, self-insured employers. It is unfortunate that it is not the third-party administrators or PBMs that can be sued, as they are generally not the fiduciaries for the plan. It is the unsuspecting employers who “trust” their brokers/consultants and the third-party administrators to do the right thing. Please continue to send us your payer issues. And if your patient works for a self-insured employer, I will continue to remind the CEO, CFO, and chief compliance officer that an employer with an ERISA health plan can potentially face legal action if the health plan’s actions or decisions cause harm to an employee’s health — physically or in the wallet.
Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s Vice President of Advocacy and Government Affairs and its immediate Past President, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].
A recently filed lawsuit against Johnson & Johnson can serve as an example to use when advocating for patients who have insurance through their employers that can potentially hurt them physically and financially. When your patient has an employer-funded health insurance plan where the employer directly pays for all medical costs — called an ERISA plan for the federal law that governs employee benefit plans, the Employee Retirement Income Security Act — there are certain accountability, fairness, and fiduciary responsibilities that the employers must meet. These so-called ERISA plans do not have to follow state utilization management legislation that addresses harmful changes in insurers’ formularies and other policies, so when the plans are not properly overseen and do not mandate the delivery of proper care at the lowest cost, both the patient and employer may be losing out.
The J&J lawsuit serves as a bellwether warning to self-insured employers to demand transparency from their third-party administrators so as not to (knowingly or unknowingly) breach their fiduciary duty to their health plans and employees. These duties include ensuring reasonable plan costs as well as acting in the best interest of their employees. There were multiple complaints in the lawsuit by a J&J employee, stating that she paid a much higher price for her multiple sclerosis drug through the plan than the price she eventually found at a lower cost pharmacy. The allegations state that J&J failed to show prudence in its selection of a pharmacy benefit manager (PBM). In addition, the company failed to negotiate better drug pricing terms, and the design of the drug plan steered patients to the PBM specialty pharmacy, resulting in higher prices for the employees. All of these led to higher drug costs and premiums for employees, which, according to the lawsuit, is a breach of J&J’s fiduciary duties.
Why Should Rheumatologists Care About This?
With all insurance plans, it feels as though we are dealing with obstacles every day that keep us from giving the excellent rheumatologic care that our patients deserve. Self-insured employers now account for over 50% of commercial health plans, and as rheumatologists caring for the employees of these companies, we can use those transparency, accountability, and fiduciary responsibilities of the employer to ensure that our patients are getting the proper care at the lowest cost.
Not only is the J&J lawsuit a warning to self-insured employers, but a reminder to rheumatologists to be on the lookout for drug pricing issues and formulary construction that leads to higher pricing for employees and the plan. For example, make note if your patient is forced to fail a much higher priced self-injectable biologic before using a much lower cost infusible medication. Or if the plan mandates the use of the much higher priced adalimumab biosimilars over the lower priced biosimilars or even the highest priced JAK inhibitor over the lowest priced one. Let’s not forget mandated white bagging, which is often much more expensive to the plan than the buy-and-bill model through a rheumatologist’s office.
Recently, we have been able to help rheumatology practices get exemptions from white-bagging mandates that large self-insured employers often have in their plan documents. We have been able to show that the cost of obtaining the medication through specialty pharmacy (SP) is much higher than through the buy-and-bill model. Mandating that the plan spend more money on SP drugs, as opposed to allowing the rheumatologist to buy and bill, could easily be interpreted as a breach of fiduciary duty on the part of the employer by mandating a higher cost model.
CSRO Payer Issue Response Team
I have written about the Coalition of State Rheumatology Organizations (CSRO)’s Payer Issue Response Team (PIRT) in the past. Rheumatologists around the country can send to PIRT any problems that they are having with payers. A recent PIRT submission involved a white-bagging mandate for an employee of a very large international Fortune 500 company. This particular example is important because of the response by the VP of Global Benefits for this company. Express Scripts is the administrator of pharmacy benefits for this company. The rheumatologist was told that he could not buy and bill for an infusible medicine but would have to obtain the drug through Express Scripts’ SP. He then asked Express Scripts for the SP medication’s cost to the health plan in order to compare the SP price versus what the buy-and-bill model would cost this company. Express Scripts would not respond to this simple transparency question; often, PBMs claim that this is proprietary information.
I was able to speak with the company’s VP of Global Benefits regarding this issue. First of all, he stated that his company was not mandating white bagging. I explained to him that the plan documents had white bagging as the only option for acquisition of provider-administered drugs. A rheumatologist would have to apply for an exemption to buy and bill, and in this case, it was denied. This is essentially a mandate.
I gave the VP of Global Benefits an example of another large Fortune 500 company (UPS) that spent over $30,000 per year more on an infusible medication when obtained through SP than what it cost them under a buy-and-bill model. I had hoped that this example would impress upon the VP the importance of transparency in pricing and claims to prevent his company from unknowingly costing the health plan more and its being construed as a breach of fiduciary duty. It was explained to me by the VP of Global Benefits that his company is part of the National Drug Purchasers Coalition and they trust Express Scripts to do the right thing for them. As they say, “You can lead a horse to water, but can’t make it drink.”
Liability of a Plan That Physically Harms an Employee?
A slightly different example of a self-insured employer, presumably unknowingly, allowing its third-party administrator to mishandle the care of an employee was recently brought to me by a rheumatologist in North Carolina. She takes care of an employee who has rheumatoid arthritis with severe interstitial lung disease (ILD). The employee’s pulmonary status was stabilized on several courses of Rituxan (reference product of rituximab). Recently, BlueCross BlueShield of North Carolina, the third-party administrator of this employer’s plan, mandated a switch to a biosimilar of rituximab for the treatment of the ILD. The rheumatologist appealed the nonmedical switch but gave the patient the biosimilar so as not to delay care. Her patient’s condition is now deteriorating with progression of the ILD, and she once again has asked for an exemption to use Rituxan, which had initially stabilized the patient. Her staff told her that the BCBSNC rep said that the patient would have to have a life-threatening infusion reaction (and present the bill for the ambulance) before they would approve a return to the reference product. An employer that knowingly or unknowingly allows a third-party administrator to act in such a way as to endanger the life of an employee could be considered to be breaching its fiduciary duty. (Disclaimer: I am not an attorney — merely a rheumatologist with common sense. Nor am I making any qualitative statement about biosimilars.)
We now have a lawsuit to which you can refer when advocating for our patients who are employed by large, self-insured employers. It is unfortunate that it is not the third-party administrators or PBMs that can be sued, as they are generally not the fiduciaries for the plan. It is the unsuspecting employers who “trust” their brokers/consultants and the third-party administrators to do the right thing. Please continue to send us your payer issues. And if your patient works for a self-insured employer, I will continue to remind the CEO, CFO, and chief compliance officer that an employer with an ERISA health plan can potentially face legal action if the health plan’s actions or decisions cause harm to an employee’s health — physically or in the wallet.
Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s Vice President of Advocacy and Government Affairs and its immediate Past President, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].
A recently filed lawsuit against Johnson & Johnson can serve as an example to use when advocating for patients who have insurance through their employers that can potentially hurt them physically and financially. When your patient has an employer-funded health insurance plan where the employer directly pays for all medical costs — called an ERISA plan for the federal law that governs employee benefit plans, the Employee Retirement Income Security Act — there are certain accountability, fairness, and fiduciary responsibilities that the employers must meet. These so-called ERISA plans do not have to follow state utilization management legislation that addresses harmful changes in insurers’ formularies and other policies, so when the plans are not properly overseen and do not mandate the delivery of proper care at the lowest cost, both the patient and employer may be losing out.
The J&J lawsuit serves as a bellwether warning to self-insured employers to demand transparency from their third-party administrators so as not to (knowingly or unknowingly) breach their fiduciary duty to their health plans and employees. These duties include ensuring reasonable plan costs as well as acting in the best interest of their employees. There were multiple complaints in the lawsuit by a J&J employee, stating that she paid a much higher price for her multiple sclerosis drug through the plan than the price she eventually found at a lower cost pharmacy. The allegations state that J&J failed to show prudence in its selection of a pharmacy benefit manager (PBM). In addition, the company failed to negotiate better drug pricing terms, and the design of the drug plan steered patients to the PBM specialty pharmacy, resulting in higher prices for the employees. All of these led to higher drug costs and premiums for employees, which, according to the lawsuit, is a breach of J&J’s fiduciary duties.
Why Should Rheumatologists Care About This?
With all insurance plans, it feels as though we are dealing with obstacles every day that keep us from giving the excellent rheumatologic care that our patients deserve. Self-insured employers now account for over 50% of commercial health plans, and as rheumatologists caring for the employees of these companies, we can use those transparency, accountability, and fiduciary responsibilities of the employer to ensure that our patients are getting the proper care at the lowest cost.
Not only is the J&J lawsuit a warning to self-insured employers, but a reminder to rheumatologists to be on the lookout for drug pricing issues and formulary construction that leads to higher pricing for employees and the plan. For example, make note if your patient is forced to fail a much higher priced self-injectable biologic before using a much lower cost infusible medication. Or if the plan mandates the use of the much higher priced adalimumab biosimilars over the lower priced biosimilars or even the highest priced JAK inhibitor over the lowest priced one. Let’s not forget mandated white bagging, which is often much more expensive to the plan than the buy-and-bill model through a rheumatologist’s office.
Recently, we have been able to help rheumatology practices get exemptions from white-bagging mandates that large self-insured employers often have in their plan documents. We have been able to show that the cost of obtaining the medication through specialty pharmacy (SP) is much higher than through the buy-and-bill model. Mandating that the plan spend more money on SP drugs, as opposed to allowing the rheumatologist to buy and bill, could easily be interpreted as a breach of fiduciary duty on the part of the employer by mandating a higher cost model.
CSRO Payer Issue Response Team
I have written about the Coalition of State Rheumatology Organizations (CSRO)’s Payer Issue Response Team (PIRT) in the past. Rheumatologists around the country can send to PIRT any problems that they are having with payers. A recent PIRT submission involved a white-bagging mandate for an employee of a very large international Fortune 500 company. This particular example is important because of the response by the VP of Global Benefits for this company. Express Scripts is the administrator of pharmacy benefits for this company. The rheumatologist was told that he could not buy and bill for an infusible medicine but would have to obtain the drug through Express Scripts’ SP. He then asked Express Scripts for the SP medication’s cost to the health plan in order to compare the SP price versus what the buy-and-bill model would cost this company. Express Scripts would not respond to this simple transparency question; often, PBMs claim that this is proprietary information.
I was able to speak with the company’s VP of Global Benefits regarding this issue. First of all, he stated that his company was not mandating white bagging. I explained to him that the plan documents had white bagging as the only option for acquisition of provider-administered drugs. A rheumatologist would have to apply for an exemption to buy and bill, and in this case, it was denied. This is essentially a mandate.
I gave the VP of Global Benefits an example of another large Fortune 500 company (UPS) that spent over $30,000 per year more on an infusible medication when obtained through SP than what it cost them under a buy-and-bill model. I had hoped that this example would impress upon the VP the importance of transparency in pricing and claims to prevent his company from unknowingly costing the health plan more and its being construed as a breach of fiduciary duty. It was explained to me by the VP of Global Benefits that his company is part of the National Drug Purchasers Coalition and they trust Express Scripts to do the right thing for them. As they say, “You can lead a horse to water, but can’t make it drink.”
Liability of a Plan That Physically Harms an Employee?
A slightly different example of a self-insured employer, presumably unknowingly, allowing its third-party administrator to mishandle the care of an employee was recently brought to me by a rheumatologist in North Carolina. She takes care of an employee who has rheumatoid arthritis with severe interstitial lung disease (ILD). The employee’s pulmonary status was stabilized on several courses of Rituxan (reference product of rituximab). Recently, BlueCross BlueShield of North Carolina, the third-party administrator of this employer’s plan, mandated a switch to a biosimilar of rituximab for the treatment of the ILD. The rheumatologist appealed the nonmedical switch but gave the patient the biosimilar so as not to delay care. Her patient’s condition is now deteriorating with progression of the ILD, and she once again has asked for an exemption to use Rituxan, which had initially stabilized the patient. Her staff told her that the BCBSNC rep said that the patient would have to have a life-threatening infusion reaction (and present the bill for the ambulance) before they would approve a return to the reference product. An employer that knowingly or unknowingly allows a third-party administrator to act in such a way as to endanger the life of an employee could be considered to be breaching its fiduciary duty. (Disclaimer: I am not an attorney — merely a rheumatologist with common sense. Nor am I making any qualitative statement about biosimilars.)
We now have a lawsuit to which you can refer when advocating for our patients who are employed by large, self-insured employers. It is unfortunate that it is not the third-party administrators or PBMs that can be sued, as they are generally not the fiduciaries for the plan. It is the unsuspecting employers who “trust” their brokers/consultants and the third-party administrators to do the right thing. Please continue to send us your payer issues. And if your patient works for a self-insured employer, I will continue to remind the CEO, CFO, and chief compliance officer that an employer with an ERISA health plan can potentially face legal action if the health plan’s actions or decisions cause harm to an employee’s health — physically or in the wallet.
Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s Vice President of Advocacy and Government Affairs and its immediate Past President, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].
A 35-year-old female presented with a 1-day history of eroded papules and vesicles distributed periorally
.1 While it predominantly affects children, it is important to note that it can also affect adults. Although it is not a life threatening infection, it can cause a painful rash and is highly contagious. The infection is easily spread in multiple ways, including via respiratory droplets, contact with vesicular or nasal secretions, or through fecal-oral transmission. Most cases occur during the summer and fall seasons but individuals can be infected at any time of the year.
HFMD typically starts with a few days of non-specific viral symptoms, such as fever, cough, sore throat, and fatigue. It is then followed by an eruption of intraoral macules and vesicles and a widespread distribution of oval shaped macules that predominantly involve the hands and feet.1 Both children and adults can present atypically. Atypical presentations include vesicles and bullae on extensor surfaces such as the forearms, as well as eruptions on the face or buttocks.2 Other atypical morphologies include eczema herpeticum-like, Gianotti-Crosti-like, and purpuric/petechiae.3 Atypical hand, food, and mouth disease cases are often caused by coxsackievirus A6, however other strains of coxsackievirus can also cause atypical symptoms.2,3
Our 35-year-old female patient presented with eroded papules and vesicles around the mouth. A diagnosis of atypical HFMD was made clinically in the following days when the patient developed the more classic intraoral and acral macules and vesicles.
Similar to our case, HFMD is most often diagnosed clinically. PCR testing from an active vesicle or nasopharyngeal swab can be obtained. Treatment for HFMD is supportive and symptoms generally resolve over 7-10 days. Over-the-counter analgesics, such as ibuprofen and acetaminophen, as well as oral analgesics that contain lidocaine or diphenhydramine are often helpful3. In this case, our patient improved over the course of seven days without needing therapy.
This case and the photos were submitted by Vanessa Ortega, BS, University of California, San Diego; Brooke Resh Sateesh, MD, and Justin Gordon, MD, San Diego Family Dermatology. The column was edited by Donna Bilu Martin, MD.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
References
1. Centers for Disease Control and Prevention. (2023, June 20). Symptoms of hand, foot, and mouth disease.
2. Drago F et al. J Am Acad Dermatol. 2017 Aug;77(2):e51-6. doi: 10.1016/j.jaad.2017.03.046.
3. Starkey SY et al. Pediatr Dermatol. 2024 Jan-Feb;41(1):23-7. doi: 10.1111/pde.15461.
.1 While it predominantly affects children, it is important to note that it can also affect adults. Although it is not a life threatening infection, it can cause a painful rash and is highly contagious. The infection is easily spread in multiple ways, including via respiratory droplets, contact with vesicular or nasal secretions, or through fecal-oral transmission. Most cases occur during the summer and fall seasons but individuals can be infected at any time of the year.
HFMD typically starts with a few days of non-specific viral symptoms, such as fever, cough, sore throat, and fatigue. It is then followed by an eruption of intraoral macules and vesicles and a widespread distribution of oval shaped macules that predominantly involve the hands and feet.1 Both children and adults can present atypically. Atypical presentations include vesicles and bullae on extensor surfaces such as the forearms, as well as eruptions on the face or buttocks.2 Other atypical morphologies include eczema herpeticum-like, Gianotti-Crosti-like, and purpuric/petechiae.3 Atypical hand, food, and mouth disease cases are often caused by coxsackievirus A6, however other strains of coxsackievirus can also cause atypical symptoms.2,3
Our 35-year-old female patient presented with eroded papules and vesicles around the mouth. A diagnosis of atypical HFMD was made clinically in the following days when the patient developed the more classic intraoral and acral macules and vesicles.
Similar to our case, HFMD is most often diagnosed clinically. PCR testing from an active vesicle or nasopharyngeal swab can be obtained. Treatment for HFMD is supportive and symptoms generally resolve over 7-10 days. Over-the-counter analgesics, such as ibuprofen and acetaminophen, as well as oral analgesics that contain lidocaine or diphenhydramine are often helpful3. In this case, our patient improved over the course of seven days without needing therapy.
This case and the photos were submitted by Vanessa Ortega, BS, University of California, San Diego; Brooke Resh Sateesh, MD, and Justin Gordon, MD, San Diego Family Dermatology. The column was edited by Donna Bilu Martin, MD.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
References
1. Centers for Disease Control and Prevention. (2023, June 20). Symptoms of hand, foot, and mouth disease.
2. Drago F et al. J Am Acad Dermatol. 2017 Aug;77(2):e51-6. doi: 10.1016/j.jaad.2017.03.046.
3. Starkey SY et al. Pediatr Dermatol. 2024 Jan-Feb;41(1):23-7. doi: 10.1111/pde.15461.
.1 While it predominantly affects children, it is important to note that it can also affect adults. Although it is not a life threatening infection, it can cause a painful rash and is highly contagious. The infection is easily spread in multiple ways, including via respiratory droplets, contact with vesicular or nasal secretions, or through fecal-oral transmission. Most cases occur during the summer and fall seasons but individuals can be infected at any time of the year.
HFMD typically starts with a few days of non-specific viral symptoms, such as fever, cough, sore throat, and fatigue. It is then followed by an eruption of intraoral macules and vesicles and a widespread distribution of oval shaped macules that predominantly involve the hands and feet.1 Both children and adults can present atypically. Atypical presentations include vesicles and bullae on extensor surfaces such as the forearms, as well as eruptions on the face or buttocks.2 Other atypical morphologies include eczema herpeticum-like, Gianotti-Crosti-like, and purpuric/petechiae.3 Atypical hand, food, and mouth disease cases are often caused by coxsackievirus A6, however other strains of coxsackievirus can also cause atypical symptoms.2,3
Our 35-year-old female patient presented with eroded papules and vesicles around the mouth. A diagnosis of atypical HFMD was made clinically in the following days when the patient developed the more classic intraoral and acral macules and vesicles.
Similar to our case, HFMD is most often diagnosed clinically. PCR testing from an active vesicle or nasopharyngeal swab can be obtained. Treatment for HFMD is supportive and symptoms generally resolve over 7-10 days. Over-the-counter analgesics, such as ibuprofen and acetaminophen, as well as oral analgesics that contain lidocaine or diphenhydramine are often helpful3. In this case, our patient improved over the course of seven days without needing therapy.
This case and the photos were submitted by Vanessa Ortega, BS, University of California, San Diego; Brooke Resh Sateesh, MD, and Justin Gordon, MD, San Diego Family Dermatology. The column was edited by Donna Bilu Martin, MD.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
References
1. Centers for Disease Control and Prevention. (2023, June 20). Symptoms of hand, foot, and mouth disease.
2. Drago F et al. J Am Acad Dermatol. 2017 Aug;77(2):e51-6. doi: 10.1016/j.jaad.2017.03.046.
3. Starkey SY et al. Pediatr Dermatol. 2024 Jan-Feb;41(1):23-7. doi: 10.1111/pde.15461.
Rosemary, Part 2
Used as a spice in various, particularly Mediterranean, cuisines and in traditional medicine for hundreds of years, this aromatic shrub has been the focus of substantial research this century to clarify its roles in skin care. It is used broadly in cosmetic formulations, particularly to preserve the product, and acts as a skin conditioner and fragrance in safe concentrations.1 Rosemary essential oil is also a popular choice frequently used in aromatherapy.2,3 This column focuses on recent promising results supporting the antioxidant and anti-photoaging activities, especially, of rosemary.
UV Protection and Rosemary in Combination
A 2021 study in mice authored by Auh and Madhavan showed that a mixture of marigold and rosemary extracts yielded anti-photoaging effects, with the botanical formula suppressing UV-induced damage.4
Seven years earlier, Pérez-Sánchez et al. combined rosemary and citrus extracts and found that they exerted protective effects against UV damage in human HaCaT keratinocytes as well as human volunteers after oral consumption. Significant increases in minimal erythema dose (MED) were seen in participants, with daily intake of 250 mg of botanical combination, at 8 weeks (34%) and 12 weeks (56%). The investigators attributed the photoprotective effects of the formula to rosemary polyphenols and diterpenes as well as citrus flavonoids.5
Evaluation of a human skin cell model by Sánchez-Marzo et al. in 2020 revealed that rosemary diterpenes were instrumental in an herbal extract that combined citrus, olive, and rosemary in conferring genoprotection against UV-induced DNA damage. The authors note that human trials are needed to overcome the limitations of the cellular model in ascertaining whether the tested herbal formulations can yield oral and/or topical photoprotection.6
Anti-Photoaging and Anti-Pollution
In 2022, Ibrahim et al. assessed a hexane extract of rosemary leaves for anti-photoaging activity. Their evaluation showed an abundance of triterpenoids, monoterpenoids, and phenolic diterpenes in rosemary, with in vitro assays verifying the anti-aging, antioxidant, and wound healing functions of the extract. Further, topical rosemary hexane extract–loaded lipid nanocapsules protected rat skin from UV radiation, as epidermal and dermal histological parameters improved, antioxidant biochemical balance was restored, and inflammatory markers and wrinkling were diminished. The researchers concluded that the use of rosemary hexane extract represents a safe, efficient, and cost-effective way to deliver anti-aging, photoprotective functions to cosmeceutical formulations.7
In March 2021, Nobile et al. published a report on their randomized, double-blind, placebo-controlled parallel group study to investigate the efficacy of a marketed polyphenol-enriched dietary supplement (Zeropollution, which contains four standardized herbal extracts: Olea europaea leaf, Lippia citriodora, S. rosmarinus, and Sophora japonica) in diminishing pollution-induced oxidative stress and in improving skin aging in 100 White and Asian women who were outdoor workers living in a polluted environment (Milan, Italy). Statistically significant improvements in reducing wrinkle depth and hyperpigmentation, enhancing elasticity and firmness, as well as promoting skin moisturization and diminishing transepidermal water loss were noted as early as 2 weeks after product consumption began, with inter-group and intra-group analysis verifying that all skin parameters were ameliorated in Asian and White subjects.8
Previously, Nobile et al. conducted a randomized, parallel-group study on 90 subjects to evaluate the photoprotective effects of a combination of rosemary and grapefruit (Citrus paradisi) extracts (Nutroxsun). The investigators also performed a pilot, randomized crossover study on five participants. Both studies included only females with Fitzpatrick skin phototypes I-III who manifested mild to moderate chronological aging or photoaging. Within as little as 2 weeks, treated individuals exhibited reductions in UVA- and UVB-induced skin changes. Skin elasticity improved in this group, with wrinkles diminishing along with skin redness and lipoperoxides. The investigators concluded that the oral blend of rosemary and grapefruit consumed long term merits consideration as an adjuvant approach to preventing the deleterious effects of solar exposure.9
In 2021, Hoskin et al. used ex vivo human biopsies exposed to diesel engine exhaust to study the impact of spray-dried algae-rosemary particles against pollution-induced damage. The spirulina-rosemary gel that was developed lowered levels of 4-hydroxynonenal protein adducts (4HNE-PA) as well as matrix metalloproteinase-9 (MMP-9) and reduced the loss of filaggrin. The researchers concluded that their topically applied spirulina-rosemary gel was effective in mitigating or preventing skin aging and cutaneous damage caused by diesel air pollution.10
Antioxidant, Antibacterial, and Anti-Inflammatory Activity
Based on a 2023 literature search by Li Pomi et al. of in vitro as well as in vivo animal and human studies involving S. rosmarinus and the skin, researchers reported on substantial evidence buttressing the antioxidant role of the botanical agent. They cautioned that, while data support the harnessing of the bioactive constituents of rosemary to address inflammatory and infectious skin conditions, large controlled trials remain necessary to establish its potential functions in dermatologic clinical practice.11
Ten years earlier, Park et al. determined that a phenolic diterpene from rosemary (carnosic acid) prevented UV-induced expression of MMP-1, MMP-3, and MMP-9 in human skin fibroblasts and keratinocytes in a concentration-dependent manner by suppressing reactive oxygen species and blocking through the inhibition of ROS and the suppression of extracellular signal-regulated kinase (ERK)-mediated AP-1 activation.12
Around the same time, Sienkiewicz et al. showed that rosemary essential oil exhibits antibacterial activity against the standard strain Escherichia coli ATCC 25922 and 60 other clinical strains of the bacteria.13
Further, anti-inflammatory properties have been attributed to rosemary essential oil, which are thought to be due to its suppression of nuclear factor kappa B transcription and inhibition of the arachidonic acid cascade.14
Other Functions of Rosemary
In 2022, Sutkowska-Skolimowska et al. demonstrated that rosemary extract in concentrations of 50 and 100mcg/mL significantly diminished accumulated collagen in the fibroblasts of four patients with severe and fatal osteogenesis imperfecta, suggesting that the botanical agent may have a role targeting cellular stress and inducing autophagy in therapy for this condition.15
In 2015, Akbari et al. established that 0.5% and 1% concentrations of rosemary essential oil were effective in facilitating the percutaneous absorption of diclofenac sodium topical gel.16
Conclusion
In Western culture, rosemary is thought of more as a spice to add flavor to food. However, there appears to be an emerging body of evidence suggesting various possible functions for rosemary in the dermatologic armamentarium. Much more research is necessary, though, to ascertain the most appropriate and optimal roles for this popular herb in skin care.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami, Florida. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a SaaS company used to generate skin care routines in office and as a ecommerce solution. Write to her at [email protected].
References
1. González-Minero FJ et al. Cosmetics. 2020 Oct 3;7(4):77.
2. Sayorwan W et al. Sci Pharm. 2013 Apr-Jun;81(2):531-42.
3. Pazyar N et al. Skin Pharmacol Physiol. 2014;27(6):303-10.
4. Auh JH and Madhavan J Biomed Pharmacother. 2021 Mar;135:111178.
5. Pérez-Sánchez A et al. J Photochem Photobiol B. 2014 Jul 5;136:12-8.
6. Sánchez-Marzo N et al. Antioxidants (Basel). 2020 Mar 20;9(3):255.
7. Ibrahim N et al. Sci Rep. 2022 Jul 30;12(1):13102.
8. Nobile V et al. Food Nutr Res. 2021 Mar 29:65.
9. Nobile V et al. Food Nutr Res. 2016 Jul 1;60:31871.
10. Hoskin R et al. Molecules. 2021 Jun 22;26(13):3781.
11. Li Pomi F et al. Antioxidants (Basel). 2023 Mar 9;12(3):680.
12. Park M et al. Exp Dermatol. 2013 May;22(5):336-41.
13. Sienkiewicz M et al. Molecules. 2013 Aug 5;18(8):9334-51.
14. Borges RS et al. J Ethnopharmacol. 2019 Jan 30;229:29-45.
15. Sutkowska-Skolimowska. Int J Mol Sci. 2022 Sep 7;23(18):10341.
16. Akbari J et al. Pharm Biol. 2015;53(10):1442-7.
Used as a spice in various, particularly Mediterranean, cuisines and in traditional medicine for hundreds of years, this aromatic shrub has been the focus of substantial research this century to clarify its roles in skin care. It is used broadly in cosmetic formulations, particularly to preserve the product, and acts as a skin conditioner and fragrance in safe concentrations.1 Rosemary essential oil is also a popular choice frequently used in aromatherapy.2,3 This column focuses on recent promising results supporting the antioxidant and anti-photoaging activities, especially, of rosemary.
UV Protection and Rosemary in Combination
A 2021 study in mice authored by Auh and Madhavan showed that a mixture of marigold and rosemary extracts yielded anti-photoaging effects, with the botanical formula suppressing UV-induced damage.4
Seven years earlier, Pérez-Sánchez et al. combined rosemary and citrus extracts and found that they exerted protective effects against UV damage in human HaCaT keratinocytes as well as human volunteers after oral consumption. Significant increases in minimal erythema dose (MED) were seen in participants, with daily intake of 250 mg of botanical combination, at 8 weeks (34%) and 12 weeks (56%). The investigators attributed the photoprotective effects of the formula to rosemary polyphenols and diterpenes as well as citrus flavonoids.5
Evaluation of a human skin cell model by Sánchez-Marzo et al. in 2020 revealed that rosemary diterpenes were instrumental in an herbal extract that combined citrus, olive, and rosemary in conferring genoprotection against UV-induced DNA damage. The authors note that human trials are needed to overcome the limitations of the cellular model in ascertaining whether the tested herbal formulations can yield oral and/or topical photoprotection.6
Anti-Photoaging and Anti-Pollution
In 2022, Ibrahim et al. assessed a hexane extract of rosemary leaves for anti-photoaging activity. Their evaluation showed an abundance of triterpenoids, monoterpenoids, and phenolic diterpenes in rosemary, with in vitro assays verifying the anti-aging, antioxidant, and wound healing functions of the extract. Further, topical rosemary hexane extract–loaded lipid nanocapsules protected rat skin from UV radiation, as epidermal and dermal histological parameters improved, antioxidant biochemical balance was restored, and inflammatory markers and wrinkling were diminished. The researchers concluded that the use of rosemary hexane extract represents a safe, efficient, and cost-effective way to deliver anti-aging, photoprotective functions to cosmeceutical formulations.7
In March 2021, Nobile et al. published a report on their randomized, double-blind, placebo-controlled parallel group study to investigate the efficacy of a marketed polyphenol-enriched dietary supplement (Zeropollution, which contains four standardized herbal extracts: Olea europaea leaf, Lippia citriodora, S. rosmarinus, and Sophora japonica) in diminishing pollution-induced oxidative stress and in improving skin aging in 100 White and Asian women who were outdoor workers living in a polluted environment (Milan, Italy). Statistically significant improvements in reducing wrinkle depth and hyperpigmentation, enhancing elasticity and firmness, as well as promoting skin moisturization and diminishing transepidermal water loss were noted as early as 2 weeks after product consumption began, with inter-group and intra-group analysis verifying that all skin parameters were ameliorated in Asian and White subjects.8
Previously, Nobile et al. conducted a randomized, parallel-group study on 90 subjects to evaluate the photoprotective effects of a combination of rosemary and grapefruit (Citrus paradisi) extracts (Nutroxsun). The investigators also performed a pilot, randomized crossover study on five participants. Both studies included only females with Fitzpatrick skin phototypes I-III who manifested mild to moderate chronological aging or photoaging. Within as little as 2 weeks, treated individuals exhibited reductions in UVA- and UVB-induced skin changes. Skin elasticity improved in this group, with wrinkles diminishing along with skin redness and lipoperoxides. The investigators concluded that the oral blend of rosemary and grapefruit consumed long term merits consideration as an adjuvant approach to preventing the deleterious effects of solar exposure.9
In 2021, Hoskin et al. used ex vivo human biopsies exposed to diesel engine exhaust to study the impact of spray-dried algae-rosemary particles against pollution-induced damage. The spirulina-rosemary gel that was developed lowered levels of 4-hydroxynonenal protein adducts (4HNE-PA) as well as matrix metalloproteinase-9 (MMP-9) and reduced the loss of filaggrin. The researchers concluded that their topically applied spirulina-rosemary gel was effective in mitigating or preventing skin aging and cutaneous damage caused by diesel air pollution.10
Antioxidant, Antibacterial, and Anti-Inflammatory Activity
Based on a 2023 literature search by Li Pomi et al. of in vitro as well as in vivo animal and human studies involving S. rosmarinus and the skin, researchers reported on substantial evidence buttressing the antioxidant role of the botanical agent. They cautioned that, while data support the harnessing of the bioactive constituents of rosemary to address inflammatory and infectious skin conditions, large controlled trials remain necessary to establish its potential functions in dermatologic clinical practice.11
Ten years earlier, Park et al. determined that a phenolic diterpene from rosemary (carnosic acid) prevented UV-induced expression of MMP-1, MMP-3, and MMP-9 in human skin fibroblasts and keratinocytes in a concentration-dependent manner by suppressing reactive oxygen species and blocking through the inhibition of ROS and the suppression of extracellular signal-regulated kinase (ERK)-mediated AP-1 activation.12
Around the same time, Sienkiewicz et al. showed that rosemary essential oil exhibits antibacterial activity against the standard strain Escherichia coli ATCC 25922 and 60 other clinical strains of the bacteria.13
Further, anti-inflammatory properties have been attributed to rosemary essential oil, which are thought to be due to its suppression of nuclear factor kappa B transcription and inhibition of the arachidonic acid cascade.14
Other Functions of Rosemary
In 2022, Sutkowska-Skolimowska et al. demonstrated that rosemary extract in concentrations of 50 and 100mcg/mL significantly diminished accumulated collagen in the fibroblasts of four patients with severe and fatal osteogenesis imperfecta, suggesting that the botanical agent may have a role targeting cellular stress and inducing autophagy in therapy for this condition.15
In 2015, Akbari et al. established that 0.5% and 1% concentrations of rosemary essential oil were effective in facilitating the percutaneous absorption of diclofenac sodium topical gel.16
Conclusion
In Western culture, rosemary is thought of more as a spice to add flavor to food. However, there appears to be an emerging body of evidence suggesting various possible functions for rosemary in the dermatologic armamentarium. Much more research is necessary, though, to ascertain the most appropriate and optimal roles for this popular herb in skin care.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami, Florida. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a SaaS company used to generate skin care routines in office and as a ecommerce solution. Write to her at [email protected].
References
1. González-Minero FJ et al. Cosmetics. 2020 Oct 3;7(4):77.
2. Sayorwan W et al. Sci Pharm. 2013 Apr-Jun;81(2):531-42.
3. Pazyar N et al. Skin Pharmacol Physiol. 2014;27(6):303-10.
4. Auh JH and Madhavan J Biomed Pharmacother. 2021 Mar;135:111178.
5. Pérez-Sánchez A et al. J Photochem Photobiol B. 2014 Jul 5;136:12-8.
6. Sánchez-Marzo N et al. Antioxidants (Basel). 2020 Mar 20;9(3):255.
7. Ibrahim N et al. Sci Rep. 2022 Jul 30;12(1):13102.
8. Nobile V et al. Food Nutr Res. 2021 Mar 29:65.
9. Nobile V et al. Food Nutr Res. 2016 Jul 1;60:31871.
10. Hoskin R et al. Molecules. 2021 Jun 22;26(13):3781.
11. Li Pomi F et al. Antioxidants (Basel). 2023 Mar 9;12(3):680.
12. Park M et al. Exp Dermatol. 2013 May;22(5):336-41.
13. Sienkiewicz M et al. Molecules. 2013 Aug 5;18(8):9334-51.
14. Borges RS et al. J Ethnopharmacol. 2019 Jan 30;229:29-45.
15. Sutkowska-Skolimowska. Int J Mol Sci. 2022 Sep 7;23(18):10341.
16. Akbari J et al. Pharm Biol. 2015;53(10):1442-7.
Used as a spice in various, particularly Mediterranean, cuisines and in traditional medicine for hundreds of years, this aromatic shrub has been the focus of substantial research this century to clarify its roles in skin care. It is used broadly in cosmetic formulations, particularly to preserve the product, and acts as a skin conditioner and fragrance in safe concentrations.1 Rosemary essential oil is also a popular choice frequently used in aromatherapy.2,3 This column focuses on recent promising results supporting the antioxidant and anti-photoaging activities, especially, of rosemary.
UV Protection and Rosemary in Combination
A 2021 study in mice authored by Auh and Madhavan showed that a mixture of marigold and rosemary extracts yielded anti-photoaging effects, with the botanical formula suppressing UV-induced damage.4
Seven years earlier, Pérez-Sánchez et al. combined rosemary and citrus extracts and found that they exerted protective effects against UV damage in human HaCaT keratinocytes as well as human volunteers after oral consumption. Significant increases in minimal erythema dose (MED) were seen in participants, with daily intake of 250 mg of botanical combination, at 8 weeks (34%) and 12 weeks (56%). The investigators attributed the photoprotective effects of the formula to rosemary polyphenols and diterpenes as well as citrus flavonoids.5
Evaluation of a human skin cell model by Sánchez-Marzo et al. in 2020 revealed that rosemary diterpenes were instrumental in an herbal extract that combined citrus, olive, and rosemary in conferring genoprotection against UV-induced DNA damage. The authors note that human trials are needed to overcome the limitations of the cellular model in ascertaining whether the tested herbal formulations can yield oral and/or topical photoprotection.6
Anti-Photoaging and Anti-Pollution
In 2022, Ibrahim et al. assessed a hexane extract of rosemary leaves for anti-photoaging activity. Their evaluation showed an abundance of triterpenoids, monoterpenoids, and phenolic diterpenes in rosemary, with in vitro assays verifying the anti-aging, antioxidant, and wound healing functions of the extract. Further, topical rosemary hexane extract–loaded lipid nanocapsules protected rat skin from UV radiation, as epidermal and dermal histological parameters improved, antioxidant biochemical balance was restored, and inflammatory markers and wrinkling were diminished. The researchers concluded that the use of rosemary hexane extract represents a safe, efficient, and cost-effective way to deliver anti-aging, photoprotective functions to cosmeceutical formulations.7
In March 2021, Nobile et al. published a report on their randomized, double-blind, placebo-controlled parallel group study to investigate the efficacy of a marketed polyphenol-enriched dietary supplement (Zeropollution, which contains four standardized herbal extracts: Olea europaea leaf, Lippia citriodora, S. rosmarinus, and Sophora japonica) in diminishing pollution-induced oxidative stress and in improving skin aging in 100 White and Asian women who were outdoor workers living in a polluted environment (Milan, Italy). Statistically significant improvements in reducing wrinkle depth and hyperpigmentation, enhancing elasticity and firmness, as well as promoting skin moisturization and diminishing transepidermal water loss were noted as early as 2 weeks after product consumption began, with inter-group and intra-group analysis verifying that all skin parameters were ameliorated in Asian and White subjects.8
Previously, Nobile et al. conducted a randomized, parallel-group study on 90 subjects to evaluate the photoprotective effects of a combination of rosemary and grapefruit (Citrus paradisi) extracts (Nutroxsun). The investigators also performed a pilot, randomized crossover study on five participants. Both studies included only females with Fitzpatrick skin phototypes I-III who manifested mild to moderate chronological aging or photoaging. Within as little as 2 weeks, treated individuals exhibited reductions in UVA- and UVB-induced skin changes. Skin elasticity improved in this group, with wrinkles diminishing along with skin redness and lipoperoxides. The investigators concluded that the oral blend of rosemary and grapefruit consumed long term merits consideration as an adjuvant approach to preventing the deleterious effects of solar exposure.9
In 2021, Hoskin et al. used ex vivo human biopsies exposed to diesel engine exhaust to study the impact of spray-dried algae-rosemary particles against pollution-induced damage. The spirulina-rosemary gel that was developed lowered levels of 4-hydroxynonenal protein adducts (4HNE-PA) as well as matrix metalloproteinase-9 (MMP-9) and reduced the loss of filaggrin. The researchers concluded that their topically applied spirulina-rosemary gel was effective in mitigating or preventing skin aging and cutaneous damage caused by diesel air pollution.10
Antioxidant, Antibacterial, and Anti-Inflammatory Activity
Based on a 2023 literature search by Li Pomi et al. of in vitro as well as in vivo animal and human studies involving S. rosmarinus and the skin, researchers reported on substantial evidence buttressing the antioxidant role of the botanical agent. They cautioned that, while data support the harnessing of the bioactive constituents of rosemary to address inflammatory and infectious skin conditions, large controlled trials remain necessary to establish its potential functions in dermatologic clinical practice.11
Ten years earlier, Park et al. determined that a phenolic diterpene from rosemary (carnosic acid) prevented UV-induced expression of MMP-1, MMP-3, and MMP-9 in human skin fibroblasts and keratinocytes in a concentration-dependent manner by suppressing reactive oxygen species and blocking through the inhibition of ROS and the suppression of extracellular signal-regulated kinase (ERK)-mediated AP-1 activation.12
Around the same time, Sienkiewicz et al. showed that rosemary essential oil exhibits antibacterial activity against the standard strain Escherichia coli ATCC 25922 and 60 other clinical strains of the bacteria.13
Further, anti-inflammatory properties have been attributed to rosemary essential oil, which are thought to be due to its suppression of nuclear factor kappa B transcription and inhibition of the arachidonic acid cascade.14
Other Functions of Rosemary
In 2022, Sutkowska-Skolimowska et al. demonstrated that rosemary extract in concentrations of 50 and 100mcg/mL significantly diminished accumulated collagen in the fibroblasts of four patients with severe and fatal osteogenesis imperfecta, suggesting that the botanical agent may have a role targeting cellular stress and inducing autophagy in therapy for this condition.15
In 2015, Akbari et al. established that 0.5% and 1% concentrations of rosemary essential oil were effective in facilitating the percutaneous absorption of diclofenac sodium topical gel.16
Conclusion
In Western culture, rosemary is thought of more as a spice to add flavor to food. However, there appears to be an emerging body of evidence suggesting various possible functions for rosemary in the dermatologic armamentarium. Much more research is necessary, though, to ascertain the most appropriate and optimal roles for this popular herb in skin care.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami, Florida. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a SaaS company used to generate skin care routines in office and as a ecommerce solution. Write to her at [email protected].
References
1. González-Minero FJ et al. Cosmetics. 2020 Oct 3;7(4):77.
2. Sayorwan W et al. Sci Pharm. 2013 Apr-Jun;81(2):531-42.
3. Pazyar N et al. Skin Pharmacol Physiol. 2014;27(6):303-10.
4. Auh JH and Madhavan J Biomed Pharmacother. 2021 Mar;135:111178.
5. Pérez-Sánchez A et al. J Photochem Photobiol B. 2014 Jul 5;136:12-8.
6. Sánchez-Marzo N et al. Antioxidants (Basel). 2020 Mar 20;9(3):255.
7. Ibrahim N et al. Sci Rep. 2022 Jul 30;12(1):13102.
8. Nobile V et al. Food Nutr Res. 2021 Mar 29:65.
9. Nobile V et al. Food Nutr Res. 2016 Jul 1;60:31871.
10. Hoskin R et al. Molecules. 2021 Jun 22;26(13):3781.
11. Li Pomi F et al. Antioxidants (Basel). 2023 Mar 9;12(3):680.
12. Park M et al. Exp Dermatol. 2013 May;22(5):336-41.
13. Sienkiewicz M et al. Molecules. 2013 Aug 5;18(8):9334-51.
14. Borges RS et al. J Ethnopharmacol. 2019 Jan 30;229:29-45.
15. Sutkowska-Skolimowska. Int J Mol Sci. 2022 Sep 7;23(18):10341.
16. Akbari J et al. Pharm Biol. 2015;53(10):1442-7.
Vitamin D Supplements May Be a Double-Edged Sword
This transcript has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson of the Yale School of Medicine.
Imagine, if you will, the great Cathedral of Our Lady of Correlation. You walk through the majestic oak doors depicting the link between ice cream sales and shark attacks, past the rose window depicting the cardiovascular benefits of red wine, and down the aisles frescoed in dramatic images showing how Facebook usage is associated with less life satisfaction. And then you reach the altar, the holy of holies where, emblazoned in shimmering pyrite, you see the patron saint of this church: vitamin D.
Yes, if you’ve watched this space, then you know that I have little truck with the wildly popular supplement. In all of clinical research, I believe that there is no molecule with stronger data for correlation and weaker data for causation.
Low serum vitamin D levels have been linked to higher risks for heart disease, cancer, falls, COVID, dementia, C diff, and others. And yet, when we do randomized trials of vitamin D supplementation — the thing that can prove that the low level was causally linked to the outcome of interest — we get negative results.
Trials aren’t perfect, of course, and we’ll talk in a moment about a big one that had some issues. But we are at a point where we need to either be vitamin D apologists, saying, “Forget what those lying RCTs tell you and buy this supplement” — an $800 million-a-year industry, by the way — or conclude that vitamin D levels are a convenient marker of various lifestyle factors that are associated with better outcomes: markers of exercise, getting outside, eating a varied diet.
Or perhaps vitamin D supplements have real effects. It’s just that the beneficial effects are matched by the harmful ones. Stay tuned.
The Women’s Health Initiative remains among the largest randomized trials of vitamin D and calcium supplementation ever conducted — and a major contributor to the negative outcomes of vitamin D trials.
But if you dig into the inclusion and exclusion criteria for this trial, you’ll find that individuals were allowed to continue taking vitamins and supplements while they were in the trial, regardless of their randomization status. In fact, the majority took supplements at baseline, and more took supplements over time.
That means, of course, that people in the placebo group, who were getting sugar pills instead of vitamin D and calcium, may have been taking vitamin D and calcium on the side. That would certainly bias the results of the trial toward the null, which is what the primary analyses showed. To wit, the original analysis of the Women’s Health Initiative trial showed no effect of randomization to vitamin D supplementation on improving cancer or cardiovascular outcomes.
But the Women’s Health Initiative trial started 30 years ago. Today, with the benefit of decades of follow-up, we can re-investigate — and perhaps re-litigate — those findings, courtesy of this study, “Long-Term Effect of Randomization to Calcium and Vitamin D Supplementation on Health in Older Women” appearing in Annals of Internal Medicine.
Dr Cynthia Thomson, of the Mel and Enid Zuckerman College of Public Health at the University of Arizona, and colleagues led this updated analysis focused on two findings that had been hinted at, but not statistically confirmed, in other vitamin D studies: a potential for the supplement to reduce the risk for cancer, and a potential for it to increase the risk for heart disease.
The randomized trial itself only lasted 7 years. What we are seeing in this analysis of 36,282 women is outcomes that happened at any time from randomization to the end of 2023 — around 20 years after the randomization to supplementation stopped. But, the researchers would argue, that’s probably okay. Cancer and heart disease take time to develop; we see lung cancer long after people stop smoking. So a history of consistent vitamin D supplementation may indeed be protective — or harmful.
Here are the top-line results. Those randomized to vitamin D and calcium supplementation had a 7% reduction in the rate of death from cancer, driven primarily by a reduction in colorectal cancer. This was statistically significant. Also statistically significant? Those randomized to supplementation had a 6% increase in the rate of death from cardiovascular disease. Put those findings together and what do you get? Stone-cold nothing, in terms of overall mortality.
Okay, you say, but what about all that supplementation that was happening outside of the context of the trial, biasing our results toward the null?
The researchers finally clue us in.
First of all, I’ll tell you that, yes, people who were supplementing outside of the trial had higher baseline vitamin D levels — a median of 54.5 nmol/L vs 32.8 nmol/L. This may be because they were supplementing with vitamin D, but it could also be because people who take supplements tend to do other healthy things — another correlation to add to the great cathedral.
To get a better view of the real effects of randomization, the authors restricted the analysis to just those who did not use outside supplements. If vitamin D supplements help, then these are the people they should help. This group had about a 11% reduction in the incidence of cancer — statistically significant — and a 7% reduction in cancer mortality that did not meet the bar for statistical significance.
There was no increase in cardiovascular disease among this group. But this small effect on cancer was nowhere near enough to significantly reduce the rate of all-cause mortality.
Among those using supplements, vitamin D supplementation didn’t really move the needle on any outcome.
I know what you’re thinking: How many of these women were vitamin D deficient when we got started? These results may simply be telling us that people who have normal vitamin D levels are fine to go without supplementation.
Nearly three fourths of women who were not taking supplements entered the trial with vitamin D levels below the 50 nmol/L cutoff that the authors suggest would qualify for deficiency. Around half of those who used supplements were deficient. And yet, frustratingly, I could not find data on the effect of randomization to supplementation stratified by baseline vitamin D level. I even reached out to Dr Thomson to ask about this. She replied, “We did not stratify on baseline values because the numbers are too small statistically to test this.” Sorry.
In the meantime, I can tell you that for your “average woman,” vitamin D supplementation likely has no effect on mortality. It might modestly reduce the risk for certain cancers while increasing the risk for heart disease (probably through coronary calcification). So, there might be some room for personalization here. Perhaps women with a strong family history of cancer or other risk factors would do better with supplements, and those with a high risk for heart disease would do worse. Seems like a strategy that could be tested in a clinical trial. But maybe we could ask the participants to give up their extracurricular supplement use before they enter the trial. F. Perry Wilson, MD, MSCE, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn’t, is available now.
This transcript has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson of the Yale School of Medicine.
Imagine, if you will, the great Cathedral of Our Lady of Correlation. You walk through the majestic oak doors depicting the link between ice cream sales and shark attacks, past the rose window depicting the cardiovascular benefits of red wine, and down the aisles frescoed in dramatic images showing how Facebook usage is associated with less life satisfaction. And then you reach the altar, the holy of holies where, emblazoned in shimmering pyrite, you see the patron saint of this church: vitamin D.
Yes, if you’ve watched this space, then you know that I have little truck with the wildly popular supplement. In all of clinical research, I believe that there is no molecule with stronger data for correlation and weaker data for causation.
Low serum vitamin D levels have been linked to higher risks for heart disease, cancer, falls, COVID, dementia, C diff, and others. And yet, when we do randomized trials of vitamin D supplementation — the thing that can prove that the low level was causally linked to the outcome of interest — we get negative results.
Trials aren’t perfect, of course, and we’ll talk in a moment about a big one that had some issues. But we are at a point where we need to either be vitamin D apologists, saying, “Forget what those lying RCTs tell you and buy this supplement” — an $800 million-a-year industry, by the way — or conclude that vitamin D levels are a convenient marker of various lifestyle factors that are associated with better outcomes: markers of exercise, getting outside, eating a varied diet.
Or perhaps vitamin D supplements have real effects. It’s just that the beneficial effects are matched by the harmful ones. Stay tuned.
The Women’s Health Initiative remains among the largest randomized trials of vitamin D and calcium supplementation ever conducted — and a major contributor to the negative outcomes of vitamin D trials.
But if you dig into the inclusion and exclusion criteria for this trial, you’ll find that individuals were allowed to continue taking vitamins and supplements while they were in the trial, regardless of their randomization status. In fact, the majority took supplements at baseline, and more took supplements over time.
That means, of course, that people in the placebo group, who were getting sugar pills instead of vitamin D and calcium, may have been taking vitamin D and calcium on the side. That would certainly bias the results of the trial toward the null, which is what the primary analyses showed. To wit, the original analysis of the Women’s Health Initiative trial showed no effect of randomization to vitamin D supplementation on improving cancer or cardiovascular outcomes.
But the Women’s Health Initiative trial started 30 years ago. Today, with the benefit of decades of follow-up, we can re-investigate — and perhaps re-litigate — those findings, courtesy of this study, “Long-Term Effect of Randomization to Calcium and Vitamin D Supplementation on Health in Older Women” appearing in Annals of Internal Medicine.
Dr Cynthia Thomson, of the Mel and Enid Zuckerman College of Public Health at the University of Arizona, and colleagues led this updated analysis focused on two findings that had been hinted at, but not statistically confirmed, in other vitamin D studies: a potential for the supplement to reduce the risk for cancer, and a potential for it to increase the risk for heart disease.
The randomized trial itself only lasted 7 years. What we are seeing in this analysis of 36,282 women is outcomes that happened at any time from randomization to the end of 2023 — around 20 years after the randomization to supplementation stopped. But, the researchers would argue, that’s probably okay. Cancer and heart disease take time to develop; we see lung cancer long after people stop smoking. So a history of consistent vitamin D supplementation may indeed be protective — or harmful.
Here are the top-line results. Those randomized to vitamin D and calcium supplementation had a 7% reduction in the rate of death from cancer, driven primarily by a reduction in colorectal cancer. This was statistically significant. Also statistically significant? Those randomized to supplementation had a 6% increase in the rate of death from cardiovascular disease. Put those findings together and what do you get? Stone-cold nothing, in terms of overall mortality.
Okay, you say, but what about all that supplementation that was happening outside of the context of the trial, biasing our results toward the null?
The researchers finally clue us in.
First of all, I’ll tell you that, yes, people who were supplementing outside of the trial had higher baseline vitamin D levels — a median of 54.5 nmol/L vs 32.8 nmol/L. This may be because they were supplementing with vitamin D, but it could also be because people who take supplements tend to do other healthy things — another correlation to add to the great cathedral.
To get a better view of the real effects of randomization, the authors restricted the analysis to just those who did not use outside supplements. If vitamin D supplements help, then these are the people they should help. This group had about a 11% reduction in the incidence of cancer — statistically significant — and a 7% reduction in cancer mortality that did not meet the bar for statistical significance.
There was no increase in cardiovascular disease among this group. But this small effect on cancer was nowhere near enough to significantly reduce the rate of all-cause mortality.
Among those using supplements, vitamin D supplementation didn’t really move the needle on any outcome.
I know what you’re thinking: How many of these women were vitamin D deficient when we got started? These results may simply be telling us that people who have normal vitamin D levels are fine to go without supplementation.
Nearly three fourths of women who were not taking supplements entered the trial with vitamin D levels below the 50 nmol/L cutoff that the authors suggest would qualify for deficiency. Around half of those who used supplements were deficient. And yet, frustratingly, I could not find data on the effect of randomization to supplementation stratified by baseline vitamin D level. I even reached out to Dr Thomson to ask about this. She replied, “We did not stratify on baseline values because the numbers are too small statistically to test this.” Sorry.
In the meantime, I can tell you that for your “average woman,” vitamin D supplementation likely has no effect on mortality. It might modestly reduce the risk for certain cancers while increasing the risk for heart disease (probably through coronary calcification). So, there might be some room for personalization here. Perhaps women with a strong family history of cancer or other risk factors would do better with supplements, and those with a high risk for heart disease would do worse. Seems like a strategy that could be tested in a clinical trial. But maybe we could ask the participants to give up their extracurricular supplement use before they enter the trial. F. Perry Wilson, MD, MSCE, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn’t, is available now.
This transcript has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson of the Yale School of Medicine.
Imagine, if you will, the great Cathedral of Our Lady of Correlation. You walk through the majestic oak doors depicting the link between ice cream sales and shark attacks, past the rose window depicting the cardiovascular benefits of red wine, and down the aisles frescoed in dramatic images showing how Facebook usage is associated with less life satisfaction. And then you reach the altar, the holy of holies where, emblazoned in shimmering pyrite, you see the patron saint of this church: vitamin D.
Yes, if you’ve watched this space, then you know that I have little truck with the wildly popular supplement. In all of clinical research, I believe that there is no molecule with stronger data for correlation and weaker data for causation.
Low serum vitamin D levels have been linked to higher risks for heart disease, cancer, falls, COVID, dementia, C diff, and others. And yet, when we do randomized trials of vitamin D supplementation — the thing that can prove that the low level was causally linked to the outcome of interest — we get negative results.
Trials aren’t perfect, of course, and we’ll talk in a moment about a big one that had some issues. But we are at a point where we need to either be vitamin D apologists, saying, “Forget what those lying RCTs tell you and buy this supplement” — an $800 million-a-year industry, by the way — or conclude that vitamin D levels are a convenient marker of various lifestyle factors that are associated with better outcomes: markers of exercise, getting outside, eating a varied diet.
Or perhaps vitamin D supplements have real effects. It’s just that the beneficial effects are matched by the harmful ones. Stay tuned.
The Women’s Health Initiative remains among the largest randomized trials of vitamin D and calcium supplementation ever conducted — and a major contributor to the negative outcomes of vitamin D trials.
But if you dig into the inclusion and exclusion criteria for this trial, you’ll find that individuals were allowed to continue taking vitamins and supplements while they were in the trial, regardless of their randomization status. In fact, the majority took supplements at baseline, and more took supplements over time.
That means, of course, that people in the placebo group, who were getting sugar pills instead of vitamin D and calcium, may have been taking vitamin D and calcium on the side. That would certainly bias the results of the trial toward the null, which is what the primary analyses showed. To wit, the original analysis of the Women’s Health Initiative trial showed no effect of randomization to vitamin D supplementation on improving cancer or cardiovascular outcomes.
But the Women’s Health Initiative trial started 30 years ago. Today, with the benefit of decades of follow-up, we can re-investigate — and perhaps re-litigate — those findings, courtesy of this study, “Long-Term Effect of Randomization to Calcium and Vitamin D Supplementation on Health in Older Women” appearing in Annals of Internal Medicine.
Dr Cynthia Thomson, of the Mel and Enid Zuckerman College of Public Health at the University of Arizona, and colleagues led this updated analysis focused on two findings that had been hinted at, but not statistically confirmed, in other vitamin D studies: a potential for the supplement to reduce the risk for cancer, and a potential for it to increase the risk for heart disease.
The randomized trial itself only lasted 7 years. What we are seeing in this analysis of 36,282 women is outcomes that happened at any time from randomization to the end of 2023 — around 20 years after the randomization to supplementation stopped. But, the researchers would argue, that’s probably okay. Cancer and heart disease take time to develop; we see lung cancer long after people stop smoking. So a history of consistent vitamin D supplementation may indeed be protective — or harmful.
Here are the top-line results. Those randomized to vitamin D and calcium supplementation had a 7% reduction in the rate of death from cancer, driven primarily by a reduction in colorectal cancer. This was statistically significant. Also statistically significant? Those randomized to supplementation had a 6% increase in the rate of death from cardiovascular disease. Put those findings together and what do you get? Stone-cold nothing, in terms of overall mortality.
Okay, you say, but what about all that supplementation that was happening outside of the context of the trial, biasing our results toward the null?
The researchers finally clue us in.
First of all, I’ll tell you that, yes, people who were supplementing outside of the trial had higher baseline vitamin D levels — a median of 54.5 nmol/L vs 32.8 nmol/L. This may be because they were supplementing with vitamin D, but it could also be because people who take supplements tend to do other healthy things — another correlation to add to the great cathedral.
To get a better view of the real effects of randomization, the authors restricted the analysis to just those who did not use outside supplements. If vitamin D supplements help, then these are the people they should help. This group had about a 11% reduction in the incidence of cancer — statistically significant — and a 7% reduction in cancer mortality that did not meet the bar for statistical significance.
There was no increase in cardiovascular disease among this group. But this small effect on cancer was nowhere near enough to significantly reduce the rate of all-cause mortality.
Among those using supplements, vitamin D supplementation didn’t really move the needle on any outcome.
I know what you’re thinking: How many of these women were vitamin D deficient when we got started? These results may simply be telling us that people who have normal vitamin D levels are fine to go without supplementation.
Nearly three fourths of women who were not taking supplements entered the trial with vitamin D levels below the 50 nmol/L cutoff that the authors suggest would qualify for deficiency. Around half of those who used supplements were deficient. And yet, frustratingly, I could not find data on the effect of randomization to supplementation stratified by baseline vitamin D level. I even reached out to Dr Thomson to ask about this. She replied, “We did not stratify on baseline values because the numbers are too small statistically to test this.” Sorry.
In the meantime, I can tell you that for your “average woman,” vitamin D supplementation likely has no effect on mortality. It might modestly reduce the risk for certain cancers while increasing the risk for heart disease (probably through coronary calcification). So, there might be some room for personalization here. Perhaps women with a strong family history of cancer or other risk factors would do better with supplements, and those with a high risk for heart disease would do worse. Seems like a strategy that could be tested in a clinical trial. But maybe we could ask the participants to give up their extracurricular supplement use before they enter the trial. F. Perry Wilson, MD, MSCE, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn’t, is available now.
Survival Advantage of Adjuvant IO ‘Big News’ in Renal Cancer
This transcript has been edited for clarity.
Hi. I’m Brian Rini. I’m an Ingram Professor of Medicine at Vanderbilt-Ingram Cancer Center in Nashville, Tennessee. I think there’s three main areas: adjuvant therapy in kidney cancer, frontline therapy in advanced disease, and the refractory space.
To open with adjuvant therapy, the biggest news in kidney cancer, and probably all of GU cancer at ASCO GU this year, was the adjuvant pembrolizumab overall survival data. This KEYNOTE study had previously shown disease-free survival advantages over placebo in a population with high-risk resected kidney cancer. There was a trend toward overall survival, but it was not significant in those early analyses.
Now with nearly 5 years of follow-up, we see an overall survival advantage, with a hazard ratio in the 0.6 range — so, about a 40% reduction in the risk for death among these patients receiving adjuvant pembrolizumab (pembro). This was really important for the field. It’s been difficult to show a survival advantage, even in diseases like melanoma, which is considered at least as much, if not more immune responsive, and I think puts into perspective whether to offer this drug to high-risk resected patients. And it certainly needs to be considered for this population.
I think the balance on that — and this came out in some of the questions after the session — was around how many of the placebo recipients got salvage immune therapy, which would be a standard of care. But in the countries where this was done, it’s not really clear how many actually got therapy. We know most patients got some salvage therapy, be it local or systemic, and about half the patients got immune therapy. But some more granular detail would be necessary.
The other thing I would mention is that this was paired with the previous presentation, which was adjuvant nivolumab. It was a very similar study, a similar drug in a similar setting, but it did not show any advantages of either disease-free or overall survival. This comes on the heels of other negative studies and a negative ipilimumab/nivolumab (ipi/nivo) study in this setting, part of the same study.
The reasons for these discrepancies are not entirely clear. There’s differences in populations and duration of therapy and mechanism, and all sorts of things. I don’t think anybody’s really been able to come up with one reason why we have some negative immune trials in kidney cancer and one shiningly positive one. But be that as it may, I think the take-home was that adjuvant pembro is certainly a standard of care in high-risk disease, and a benefit/risk discussion needs to be had with each individual patient. And I think pembro will be the building block for future studies, some of which are ongoing.
The second major area of update was in frontline kidney cancer. There weren’t a lot of new data, but there were updates to the existing trials. As you may know, frontline immune-based doublet is a standard of care in this disease: either ipi/nivo or one of the immuno-oncology/tyrosine kinase inhibitor (IO/TKI) regimens. We had two updates. One was an 8-year update on ipi/nivo. It’s a really long follow-up for these patients now, and what was observed was that these results remain remarkably consistent.
The hazard ratios for benefit in terms of survival and durability of response are really consistent over the past several years — again, a hallmark of immune therapy. Over half the responders are still responding now, many years later. I think that only strengthens the position of ipi/nivo as a choice for advanced clear cell kidney cancer patients. Again, there are good long-term toxicity data, and some patients can remain off treatment in what’s called treatment-free survival. So, an important update. We look forward to future, probably 10-year, data.
The CheckMate 9ER cabozantinib/nivolumab (cabo/nivo) study was updated now with many years of follow-up, as some of the other IO/TKI regimens have as well. And I think there is a similar theme, although a few years behind in maturity from the ipi/nivo data. It shows persistence of benefit. With IO/TKI regimens, a lot of the benefit is up front. It’s high response rates. It’s progression-free survival (PFS). But we’re starting to see some of that durability.
Where it’ll land, if there will be a tail of the curve and where it will be, is unclear, but these updates are important in terms of counseling patients. Patients want to know not just what’s going to happen at their first scan but also years from now. And they’re planning to be around years from now. So, I think these data are important.
The last thing I’ll mention is a health-related quality-of-life update from what was called the 005 trial of belzutifan, an oral HIF inhibitor, compared with everolimus. We heard data at the European Society for Medical Oncology (ESMO) Congress 2023 on a PFS and response-rate advantage. The drug was approved by the US Food and Drug Administration (FDA) in late December, and now we see some quality-of-life data.
Quality-of-life questionnaires and scales have a lot of imperfections. I don’t think they necessarily capture everything we want. But in this case, it was fairly clean in that belzutifan is known to be a well-tolerated agent. The toxicity profile is clean. It’s been used for years in patients with Von Hippel-Lindau syndrome, certainly in the trials for years, and has shown good tolerance over time. So, I view these data as complementary to what we already knew about the drug, but they’re nice to see.
It’s nice to see datasets come together and show the same thing: Not only is the drug active in a refractory renal cell carcinoma (RCC) setting, but also it’s really well tolerated and does not adversely impact patients› quality of life. I use this drug a lot in refractory kidney cancer, and because it’s so well tolerated. That means it’s also combinable. And there are some very large studies in the front-end second-line space combining it, in a space where people believe that it has more activity. But there are some complementary data as we wait for the overall survival signal, hopefully, from this regimen.
So, there have been some exciting updates, mostly in the adjuvant space but also in some other spaces in kidney cancer and building upon some of the clinical advances that we had seen from previous meetings. I’m Brian Rini, and I appreciate you attending.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Hi. I’m Brian Rini. I’m an Ingram Professor of Medicine at Vanderbilt-Ingram Cancer Center in Nashville, Tennessee. I think there’s three main areas: adjuvant therapy in kidney cancer, frontline therapy in advanced disease, and the refractory space.
To open with adjuvant therapy, the biggest news in kidney cancer, and probably all of GU cancer at ASCO GU this year, was the adjuvant pembrolizumab overall survival data. This KEYNOTE study had previously shown disease-free survival advantages over placebo in a population with high-risk resected kidney cancer. There was a trend toward overall survival, but it was not significant in those early analyses.
Now with nearly 5 years of follow-up, we see an overall survival advantage, with a hazard ratio in the 0.6 range — so, about a 40% reduction in the risk for death among these patients receiving adjuvant pembrolizumab (pembro). This was really important for the field. It’s been difficult to show a survival advantage, even in diseases like melanoma, which is considered at least as much, if not more immune responsive, and I think puts into perspective whether to offer this drug to high-risk resected patients. And it certainly needs to be considered for this population.
I think the balance on that — and this came out in some of the questions after the session — was around how many of the placebo recipients got salvage immune therapy, which would be a standard of care. But in the countries where this was done, it’s not really clear how many actually got therapy. We know most patients got some salvage therapy, be it local or systemic, and about half the patients got immune therapy. But some more granular detail would be necessary.
The other thing I would mention is that this was paired with the previous presentation, which was adjuvant nivolumab. It was a very similar study, a similar drug in a similar setting, but it did not show any advantages of either disease-free or overall survival. This comes on the heels of other negative studies and a negative ipilimumab/nivolumab (ipi/nivo) study in this setting, part of the same study.
The reasons for these discrepancies are not entirely clear. There’s differences in populations and duration of therapy and mechanism, and all sorts of things. I don’t think anybody’s really been able to come up with one reason why we have some negative immune trials in kidney cancer and one shiningly positive one. But be that as it may, I think the take-home was that adjuvant pembro is certainly a standard of care in high-risk disease, and a benefit/risk discussion needs to be had with each individual patient. And I think pembro will be the building block for future studies, some of which are ongoing.
The second major area of update was in frontline kidney cancer. There weren’t a lot of new data, but there were updates to the existing trials. As you may know, frontline immune-based doublet is a standard of care in this disease: either ipi/nivo or one of the immuno-oncology/tyrosine kinase inhibitor (IO/TKI) regimens. We had two updates. One was an 8-year update on ipi/nivo. It’s a really long follow-up for these patients now, and what was observed was that these results remain remarkably consistent.
The hazard ratios for benefit in terms of survival and durability of response are really consistent over the past several years — again, a hallmark of immune therapy. Over half the responders are still responding now, many years later. I think that only strengthens the position of ipi/nivo as a choice for advanced clear cell kidney cancer patients. Again, there are good long-term toxicity data, and some patients can remain off treatment in what’s called treatment-free survival. So, an important update. We look forward to future, probably 10-year, data.
The CheckMate 9ER cabozantinib/nivolumab (cabo/nivo) study was updated now with many years of follow-up, as some of the other IO/TKI regimens have as well. And I think there is a similar theme, although a few years behind in maturity from the ipi/nivo data. It shows persistence of benefit. With IO/TKI regimens, a lot of the benefit is up front. It’s high response rates. It’s progression-free survival (PFS). But we’re starting to see some of that durability.
Where it’ll land, if there will be a tail of the curve and where it will be, is unclear, but these updates are important in terms of counseling patients. Patients want to know not just what’s going to happen at their first scan but also years from now. And they’re planning to be around years from now. So, I think these data are important.
The last thing I’ll mention is a health-related quality-of-life update from what was called the 005 trial of belzutifan, an oral HIF inhibitor, compared with everolimus. We heard data at the European Society for Medical Oncology (ESMO) Congress 2023 on a PFS and response-rate advantage. The drug was approved by the US Food and Drug Administration (FDA) in late December, and now we see some quality-of-life data.
Quality-of-life questionnaires and scales have a lot of imperfections. I don’t think they necessarily capture everything we want. But in this case, it was fairly clean in that belzutifan is known to be a well-tolerated agent. The toxicity profile is clean. It’s been used for years in patients with Von Hippel-Lindau syndrome, certainly in the trials for years, and has shown good tolerance over time. So, I view these data as complementary to what we already knew about the drug, but they’re nice to see.
It’s nice to see datasets come together and show the same thing: Not only is the drug active in a refractory renal cell carcinoma (RCC) setting, but also it’s really well tolerated and does not adversely impact patients› quality of life. I use this drug a lot in refractory kidney cancer, and because it’s so well tolerated. That means it’s also combinable. And there are some very large studies in the front-end second-line space combining it, in a space where people believe that it has more activity. But there are some complementary data as we wait for the overall survival signal, hopefully, from this regimen.
So, there have been some exciting updates, mostly in the adjuvant space but also in some other spaces in kidney cancer and building upon some of the clinical advances that we had seen from previous meetings. I’m Brian Rini, and I appreciate you attending.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Hi. I’m Brian Rini. I’m an Ingram Professor of Medicine at Vanderbilt-Ingram Cancer Center in Nashville, Tennessee. I think there’s three main areas: adjuvant therapy in kidney cancer, frontline therapy in advanced disease, and the refractory space.
To open with adjuvant therapy, the biggest news in kidney cancer, and probably all of GU cancer at ASCO GU this year, was the adjuvant pembrolizumab overall survival data. This KEYNOTE study had previously shown disease-free survival advantages over placebo in a population with high-risk resected kidney cancer. There was a trend toward overall survival, but it was not significant in those early analyses.
Now with nearly 5 years of follow-up, we see an overall survival advantage, with a hazard ratio in the 0.6 range — so, about a 40% reduction in the risk for death among these patients receiving adjuvant pembrolizumab (pembro). This was really important for the field. It’s been difficult to show a survival advantage, even in diseases like melanoma, which is considered at least as much, if not more immune responsive, and I think puts into perspective whether to offer this drug to high-risk resected patients. And it certainly needs to be considered for this population.
I think the balance on that — and this came out in some of the questions after the session — was around how many of the placebo recipients got salvage immune therapy, which would be a standard of care. But in the countries where this was done, it’s not really clear how many actually got therapy. We know most patients got some salvage therapy, be it local or systemic, and about half the patients got immune therapy. But some more granular detail would be necessary.
The other thing I would mention is that this was paired with the previous presentation, which was adjuvant nivolumab. It was a very similar study, a similar drug in a similar setting, but it did not show any advantages of either disease-free or overall survival. This comes on the heels of other negative studies and a negative ipilimumab/nivolumab (ipi/nivo) study in this setting, part of the same study.
The reasons for these discrepancies are not entirely clear. There’s differences in populations and duration of therapy and mechanism, and all sorts of things. I don’t think anybody’s really been able to come up with one reason why we have some negative immune trials in kidney cancer and one shiningly positive one. But be that as it may, I think the take-home was that adjuvant pembro is certainly a standard of care in high-risk disease, and a benefit/risk discussion needs to be had with each individual patient. And I think pembro will be the building block for future studies, some of which are ongoing.
The second major area of update was in frontline kidney cancer. There weren’t a lot of new data, but there were updates to the existing trials. As you may know, frontline immune-based doublet is a standard of care in this disease: either ipi/nivo or one of the immuno-oncology/tyrosine kinase inhibitor (IO/TKI) regimens. We had two updates. One was an 8-year update on ipi/nivo. It’s a really long follow-up for these patients now, and what was observed was that these results remain remarkably consistent.
The hazard ratios for benefit in terms of survival and durability of response are really consistent over the past several years — again, a hallmark of immune therapy. Over half the responders are still responding now, many years later. I think that only strengthens the position of ipi/nivo as a choice for advanced clear cell kidney cancer patients. Again, there are good long-term toxicity data, and some patients can remain off treatment in what’s called treatment-free survival. So, an important update. We look forward to future, probably 10-year, data.
The CheckMate 9ER cabozantinib/nivolumab (cabo/nivo) study was updated now with many years of follow-up, as some of the other IO/TKI regimens have as well. And I think there is a similar theme, although a few years behind in maturity from the ipi/nivo data. It shows persistence of benefit. With IO/TKI regimens, a lot of the benefit is up front. It’s high response rates. It’s progression-free survival (PFS). But we’re starting to see some of that durability.
Where it’ll land, if there will be a tail of the curve and where it will be, is unclear, but these updates are important in terms of counseling patients. Patients want to know not just what’s going to happen at their first scan but also years from now. And they’re planning to be around years from now. So, I think these data are important.
The last thing I’ll mention is a health-related quality-of-life update from what was called the 005 trial of belzutifan, an oral HIF inhibitor, compared with everolimus. We heard data at the European Society for Medical Oncology (ESMO) Congress 2023 on a PFS and response-rate advantage. The drug was approved by the US Food and Drug Administration (FDA) in late December, and now we see some quality-of-life data.
Quality-of-life questionnaires and scales have a lot of imperfections. I don’t think they necessarily capture everything we want. But in this case, it was fairly clean in that belzutifan is known to be a well-tolerated agent. The toxicity profile is clean. It’s been used for years in patients with Von Hippel-Lindau syndrome, certainly in the trials for years, and has shown good tolerance over time. So, I view these data as complementary to what we already knew about the drug, but they’re nice to see.
It’s nice to see datasets come together and show the same thing: Not only is the drug active in a refractory renal cell carcinoma (RCC) setting, but also it’s really well tolerated and does not adversely impact patients› quality of life. I use this drug a lot in refractory kidney cancer, and because it’s so well tolerated. That means it’s also combinable. And there are some very large studies in the front-end second-line space combining it, in a space where people believe that it has more activity. But there are some complementary data as we wait for the overall survival signal, hopefully, from this regimen.
So, there have been some exciting updates, mostly in the adjuvant space but also in some other spaces in kidney cancer and building upon some of the clinical advances that we had seen from previous meetings. I’m Brian Rini, and I appreciate you attending.
A version of this article first appeared on Medscape.com.