Kerry Dooley Young

ORLANDO, Florida — Clinicians should keep in mind concerns about overdiagnosis of thyroid cancer when prescribing glucagon-like peptide 1 (GLP-1) drugs, as the US boxed warning about this risk for this class of medicines for certain tumors in mice could trigger excess screening, an expert endocrinologist said.

Speaking at the annual American Diabetes Association (ADA) 84th Scientific Sessions, Elizabeth N. Pearce, MD, MSc, a professor of medicine at Boston University, Boston, reviewed the different approaches US and European regulators have taken for the GLP-1 drugs. She also explained the current concerns about the wide use of thyroid screening in general and how these intersect with the rapid uptake of the GLP-1 drugs.

“We should not be screening for thyroid nodules before or during GLP-1 receptor agonist treatment just because the patients are on these medications,” said Dr. Pearce, who is also a former board president of the American Thyroid Association (ATA). “We do not want to contribute to this epidemic of overdiagnosis of thyroid cancer.”

The ATA and the US Preventive Services Task Force (USPSTF) are among the health organizations that have in recent years sought to boost public awareness of the potential risks for excess screening of thyroid nodules. In 2017, the USPSTF, which influences insurance coverage, recommended against routine screening for thyroid cancer in asymptomatic adults. At that time, the incidence of thyroid cancer detection had increased by 4.5% per year over a decade, faster than for any other cancer, but without a corresponding change in the mortality rate, USPSTF said.

“Unequivocally, the thyroid cancer mortality has not kept pace with thyroid cancer detection,” Dr. Pearce said at the ADA meeting. “We’ve been diagnosing a lot of small thyroid cancers that people would otherwise have been destined to die with and not die of.”

Dr. Pearce said clinicians should be careful not to overly restrict access to GLP-1 drugs due to concerns about thyroid cancer — and they should use care in screening nodules.

It’s possible that the weight loss experienced by people taking GLP-1 drugs may make preexisting thyroid nodules more prominent, Dr. Pearce said. It’s also likely that the US boxed warning on thyroid risk on GLP-1 drugs makes clinicians and patients more likely to look for these kinds of growths.

Dr. Pearce urged adherence to guidelines such as the ones the ATA published in 2015 for assessing nodules.

In an interview with this news organization, Dr. Pearce noted the frequency of CT scans in US medical practice in turning up many incidental thyroid nodules, a finding that can cause some panic for patients and their clinicians.

But it helps to put these findings in context, as by the age of 50, about 40% of women will have at least one thyroid nodule, making this a very common finding, she said.

“The vast majority are not malignant,” Dr. Pearce said. “When you explain this to patients, it alleviates anxiety.”
 

The US, European Union Differences

In the United States, the label for GLP-1 drugs starts with a boxed warning about thyroid C-cell tumors seen in rodents given these medicines in testing.

It’s unknown if the medicines could cause medullary thyroid carcinoma (MTC) in humans, the label adds. The drug is contraindicated in patients with a personal or family history of MTC or multiple endocrine neoplasia syndrome 2, the boxed warning says. This is based largely on data seen in laboratory rats.

“It’s a big black box warning that gets people’s attention,” Dr. Pearce said. “Important to note that if you practice in Europe, you will not be familiar with this labeling because it doesn’t exist there. They’ve never had this warning on the European package.”

The European Medicines Agency (EMA) does include information about the results of rodent studies as part of the discussion of known and potential risks for GLP-1 drugs but has not emphasized it in the same way as the US drug labels do.

For example, the public assessment report posted on the EMA website for semaglutide (Ozempic, Novo Nordisk) notes that nonlethal thyroid C-cell tumors “observed in rodents are a class effect for GLP-1 receptor agonists.” It’s possible that these may be due to a particular sensitivity in rodents, the report said.

“The relevance for humans is considered to be low but cannot be completely excluded,” the EMA report said in the product information section of the report.

There has been ongoing interest in the issue.

The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) in October concluded that the available evidence does not support a causal association between GLP-1 receptor agonists and thyroid cancer.

The EMA’s PRAC safety committee said it began assessing the evidence about a possible connection following the publication of a study in 2022 in the journal Diabetes Care. That paper reported on an analysis that suggested increased risk for all thyroid cancer and medullary thyroid cancer with the use of GLP-1 drugs, particularly after 1-3 years of treatment.

The EMA’s PRAC said that in making its decision, it also considered other published papers on this topic as well as clinical and postmarketing data on GLP-1 drugs.

In an email interview, Jean-Luc Faillie, MD, PhD, corresponding author of the Diabetes Care paper, called for continued “vigilance and prudence in clinical practice” with GLP-1 drugs.

His paper reported on a case-control analysis on the basis of reports from the French national healthcare insurance system database, looking at people who had taken GLP-1 drugs and similar people who had not.

Due to a lack of a specific diagnostic code for medullary thyroid cancers, the researchers used a composite definition combining thyroid cancer diagnosis with several calcitonin tests, a carcinoembryonic antigen test, or a specific treatment (vandetanib) to identify potential cases of this cancer.

It’s possible that this method could have led to overestimation of MTC among the cases of thyroid cancer, wrote Dr. Faillie, who is a professor at France’s Université de Montpellier, Montpellier, France, and part of its pharmacological vigilance service.

“Nevertheless, it’s crucial to emphasize that any potential overestimation of MTC cases would likely apply equally to both GLP-1 receptor agonist–exposed and unexposed groups,” Dr. Faillie wrote. “Therefore, it should not significantly impact our main findings regarding the suggested increased risk associated with GLP-1 receptor agonist use.”

Dr. Pearce disclosed honoraria for speaking at the Merck China Forum. Dr. Faille and his coauthors reported no conflicts of interest in the publication of their study. Their research was supported by the French Medicines Agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé, grant 2019S015) in the context of a partnership with the Health Product Epidemiology Scientific Interest Group (EPI-PHARE). The study was part of France’s Drugs Systematized Assessment in Real-Life Environment (DRUGS-SAFEr) research program.

A version of this article first appeared on Medscape.com.

ORLANDO, Florida — Clinicians should keep in mind concerns about overdiagnosis of thyroid cancer when prescribing glucagon-like peptide 1 (GLP-1) drugs, as the US boxed warning about this risk for this class of medicines for certain tumors in mice could trigger excess screening, an expert endocrinologist said.

Speaking at the annual American Diabetes Association (ADA) 84th Scientific Sessions, Elizabeth N. Pearce, MD, MSc, a professor of medicine at Boston University, Boston, reviewed the different approaches US and European regulators have taken for the GLP-1 drugs. She also explained the current concerns about the wide use of thyroid screening in general and how these intersect with the rapid uptake of the GLP-1 drugs.

“We should not be screening for thyroid nodules before or during GLP-1 receptor agonist treatment just because the patients are on these medications,” said Dr. Pearce, who is also a former board president of the American Thyroid Association (ATA). “We do not want to contribute to this epidemic of overdiagnosis of thyroid cancer.”

The ATA and the US Preventive Services Task Force (USPSTF) are among the health organizations that have in recent years sought to boost public awareness of the potential risks for excess screening of thyroid nodules. In 2017, the USPSTF, which influences insurance coverage, recommended against routine screening for thyroid cancer in asymptomatic adults. At that time, the incidence of thyroid cancer detection had increased by 4.5% per year over a decade, faster than for any other cancer, but without a corresponding change in the mortality rate, USPSTF said.

“Unequivocally, the thyroid cancer mortality has not kept pace with thyroid cancer detection,” Dr. Pearce said at the ADA meeting. “We’ve been diagnosing a lot of small thyroid cancers that people would otherwise have been destined to die with and not die of.”

Dr. Pearce said clinicians should be careful not to overly restrict access to GLP-1 drugs due to concerns about thyroid cancer — and they should use care in screening nodules.

It’s possible that the weight loss experienced by people taking GLP-1 drugs may make preexisting thyroid nodules more prominent, Dr. Pearce said. It’s also likely that the US boxed warning on thyroid risk on GLP-1 drugs makes clinicians and patients more likely to look for these kinds of growths.

Dr. Pearce urged adherence to guidelines such as the ones the ATA published in 2015 for assessing nodules.

In an interview with this news organization, Dr. Pearce noted the frequency of CT scans in US medical practice in turning up many incidental thyroid nodules, a finding that can cause some panic for patients and their clinicians.

But it helps to put these findings in context, as by the age of 50, about 40% of women will have at least one thyroid nodule, making this a very common finding, she said.

“The vast majority are not malignant,” Dr. Pearce said. “When you explain this to patients, it alleviates anxiety.”
 

The US, European Union Differences

In the United States, the label for GLP-1 drugs starts with a boxed warning about thyroid C-cell tumors seen in rodents given these medicines in testing.

It’s unknown if the medicines could cause medullary thyroid carcinoma (MTC) in humans, the label adds. The drug is contraindicated in patients with a personal or family history of MTC or multiple endocrine neoplasia syndrome 2, the boxed warning says. This is based largely on data seen in laboratory rats.

“It’s a big black box warning that gets people’s attention,” Dr. Pearce said. “Important to note that if you practice in Europe, you will not be familiar with this labeling because it doesn’t exist there. They’ve never had this warning on the European package.”

The European Medicines Agency (EMA) does include information about the results of rodent studies as part of the discussion of known and potential risks for GLP-1 drugs but has not emphasized it in the same way as the US drug labels do.

For example, the public assessment report posted on the EMA website for semaglutide (Ozempic, Novo Nordisk) notes that nonlethal thyroid C-cell tumors “observed in rodents are a class effect for GLP-1 receptor agonists.” It’s possible that these may be due to a particular sensitivity in rodents, the report said.

“The relevance for humans is considered to be low but cannot be completely excluded,” the EMA report said in the product information section of the report.

There has been ongoing interest in the issue.

The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) in October concluded that the available evidence does not support a causal association between GLP-1 receptor agonists and thyroid cancer.

The EMA’s PRAC safety committee said it began assessing the evidence about a possible connection following the publication of a study in 2022 in the journal Diabetes Care. That paper reported on an analysis that suggested increased risk for all thyroid cancer and medullary thyroid cancer with the use of GLP-1 drugs, particularly after 1-3 years of treatment.

The EMA’s PRAC said that in making its decision, it also considered other published papers on this topic as well as clinical and postmarketing data on GLP-1 drugs.

In an email interview, Jean-Luc Faillie, MD, PhD, corresponding author of the Diabetes Care paper, called for continued “vigilance and prudence in clinical practice” with GLP-1 drugs.

His paper reported on a case-control analysis on the basis of reports from the French national healthcare insurance system database, looking at people who had taken GLP-1 drugs and similar people who had not.

Due to a lack of a specific diagnostic code for medullary thyroid cancers, the researchers used a composite definition combining thyroid cancer diagnosis with several calcitonin tests, a carcinoembryonic antigen test, or a specific treatment (vandetanib) to identify potential cases of this cancer.

It’s possible that this method could have led to overestimation of MTC among the cases of thyroid cancer, wrote Dr. Faillie, who is a professor at France’s Université de Montpellier, Montpellier, France, and part of its pharmacological vigilance service.

“Nevertheless, it’s crucial to emphasize that any potential overestimation of MTC cases would likely apply equally to both GLP-1 receptor agonist–exposed and unexposed groups,” Dr. Faillie wrote. “Therefore, it should not significantly impact our main findings regarding the suggested increased risk associated with GLP-1 receptor agonist use.”

Dr. Pearce disclosed honoraria for speaking at the Merck China Forum. Dr. Faille and his coauthors reported no conflicts of interest in the publication of their study. Their research was supported by the French Medicines Agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé, grant 2019S015) in the context of a partnership with the Health Product Epidemiology Scientific Interest Group (EPI-PHARE). The study was part of France’s Drugs Systematized Assessment in Real-Life Environment (DRUGS-SAFEr) research program.

A version of this article first appeared on Medscape.com.

ORLANDO, Florida — Clinicians should keep in mind concerns about overdiagnosis of thyroid cancer when prescribing glucagon-like peptide 1 (GLP-1) drugs, as the US boxed warning about this risk for this class of medicines for certain tumors in mice could trigger excess screening, an expert endocrinologist said.

Speaking at the annual American Diabetes Association (ADA) 84th Scientific Sessions, Elizabeth N. Pearce, MD, MSc, a professor of medicine at Boston University, Boston, reviewed the different approaches US and European regulators have taken for the GLP-1 drugs. She also explained the current concerns about the wide use of thyroid screening in general and how these intersect with the rapid uptake of the GLP-1 drugs.

“We should not be screening for thyroid nodules before or during GLP-1 receptor agonist treatment just because the patients are on these medications,” said Dr. Pearce, who is also a former board president of the American Thyroid Association (ATA). “We do not want to contribute to this epidemic of overdiagnosis of thyroid cancer.”

The ATA and the US Preventive Services Task Force (USPSTF) are among the health organizations that have in recent years sought to boost public awareness of the potential risks for excess screening of thyroid nodules. In 2017, the USPSTF, which influences insurance coverage, recommended against routine screening for thyroid cancer in asymptomatic adults. At that time, the incidence of thyroid cancer detection had increased by 4.5% per year over a decade, faster than for any other cancer, but without a corresponding change in the mortality rate, USPSTF said.

“Unequivocally, the thyroid cancer mortality has not kept pace with thyroid cancer detection,” Dr. Pearce said at the ADA meeting. “We’ve been diagnosing a lot of small thyroid cancers that people would otherwise have been destined to die with and not die of.”

Dr. Pearce said clinicians should be careful not to overly restrict access to GLP-1 drugs due to concerns about thyroid cancer — and they should use care in screening nodules.

It’s possible that the weight loss experienced by people taking GLP-1 drugs may make preexisting thyroid nodules more prominent, Dr. Pearce said. It’s also likely that the US boxed warning on thyroid risk on GLP-1 drugs makes clinicians and patients more likely to look for these kinds of growths.

Dr. Pearce urged adherence to guidelines such as the ones the ATA published in 2015 for assessing nodules.

In an interview with this news organization, Dr. Pearce noted the frequency of CT scans in US medical practice in turning up many incidental thyroid nodules, a finding that can cause some panic for patients and their clinicians.

But it helps to put these findings in context, as by the age of 50, about 40% of women will have at least one thyroid nodule, making this a very common finding, she said.

“The vast majority are not malignant,” Dr. Pearce said. “When you explain this to patients, it alleviates anxiety.”
 

The US, European Union Differences

In the United States, the label for GLP-1 drugs starts with a boxed warning about thyroid C-cell tumors seen in rodents given these medicines in testing.

It’s unknown if the medicines could cause medullary thyroid carcinoma (MTC) in humans, the label adds. The drug is contraindicated in patients with a personal or family history of MTC or multiple endocrine neoplasia syndrome 2, the boxed warning says. This is based largely on data seen in laboratory rats.

“It’s a big black box warning that gets people’s attention,” Dr. Pearce said. “Important to note that if you practice in Europe, you will not be familiar with this labeling because it doesn’t exist there. They’ve never had this warning on the European package.”

The European Medicines Agency (EMA) does include information about the results of rodent studies as part of the discussion of known and potential risks for GLP-1 drugs but has not emphasized it in the same way as the US drug labels do.

For example, the public assessment report posted on the EMA website for semaglutide (Ozempic, Novo Nordisk) notes that nonlethal thyroid C-cell tumors “observed in rodents are a class effect for GLP-1 receptor agonists.” It’s possible that these may be due to a particular sensitivity in rodents, the report said.

“The relevance for humans is considered to be low but cannot be completely excluded,” the EMA report said in the product information section of the report.

There has been ongoing interest in the issue.

The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) in October concluded that the available evidence does not support a causal association between GLP-1 receptor agonists and thyroid cancer.

The EMA’s PRAC safety committee said it began assessing the evidence about a possible connection following the publication of a study in 2022 in the journal Diabetes Care. That paper reported on an analysis that suggested increased risk for all thyroid cancer and medullary thyroid cancer with the use of GLP-1 drugs, particularly after 1-3 years of treatment.

The EMA’s PRAC said that in making its decision, it also considered other published papers on this topic as well as clinical and postmarketing data on GLP-1 drugs.

In an email interview, Jean-Luc Faillie, MD, PhD, corresponding author of the Diabetes Care paper, called for continued “vigilance and prudence in clinical practice” with GLP-1 drugs.

His paper reported on a case-control analysis on the basis of reports from the French national healthcare insurance system database, looking at people who had taken GLP-1 drugs and similar people who had not.

Due to a lack of a specific diagnostic code for medullary thyroid cancers, the researchers used a composite definition combining thyroid cancer diagnosis with several calcitonin tests, a carcinoembryonic antigen test, or a specific treatment (vandetanib) to identify potential cases of this cancer.

It’s possible that this method could have led to overestimation of MTC among the cases of thyroid cancer, wrote Dr. Faillie, who is a professor at France’s Université de Montpellier, Montpellier, France, and part of its pharmacological vigilance service.

“Nevertheless, it’s crucial to emphasize that any potential overestimation of MTC cases would likely apply equally to both GLP-1 receptor agonist–exposed and unexposed groups,” Dr. Faillie wrote. “Therefore, it should not significantly impact our main findings regarding the suggested increased risk associated with GLP-1 receptor agonist use.”

Dr. Pearce disclosed honoraria for speaking at the Merck China Forum. Dr. Faille and his coauthors reported no conflicts of interest in the publication of their study. Their research was supported by the French Medicines Agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé, grant 2019S015) in the context of a partnership with the Health Product Epidemiology Scientific Interest Group (EPI-PHARE). The study was part of France’s Drugs Systematized Assessment in Real-Life Environment (DRUGS-SAFEr) research program.

A version of this article first appeared on Medscape.com.

The largest US physician organization wrestled with the professional risks and rewards of artificial intelligence (AI) at its annual meeting, delaying action even as it adopted new policies on prior authorization and other concerns for clinicians and patients.

Physicians and medical students at the annual meeting of the American Medical Association (AMA) House of Delegates in Chicago intensely debated a report and two key resolutions on AI but could not reach consensus, pushing off decision-making until a future meeting in November.

One resolution would establish “augmented intelligence” as the preferred term for AI, reflecting the desired role of these tools in supporting — not making — physicians’ decisions. The other resolution focused on insurers’ use of AI in determining medical necessity.

(See specific policies adopted at the meeting, held June 8-12, below.)

A comprehensive AMA trustees’ report on AI considered additional issues including requirements for disclosing AI use, liability for harms due to flawed application of AI, data privacy, and cybersecurity.

The AMA intends to “continue to methodically assess these issues and make informed recommendations in proposing new policy,” said Bobby Mukkamala, MD, an otolaryngologist from Flint, Michigan, who became the AMA’s new president-elect.

AMA members at the meeting largely applauded the aim of these AI proposals, but some objected to parts of the trustees’ report.

They raised questions about what, exactly, constitutes an AI-powered service and whether all AI tools need the kind of guardrails the AMA may seek. There also were concerns about calls to make AI use more transparent.

While transparency might be an admirable goal, it might prove too hard to achieve given that AI-powered tools and products are already woven into medical practice in ways that physicians may not know or understand, said Christopher Libby, MD, MPH, a clinical informaticist and emergency physician at Cedars Sinai Medical Center in Los Angeles.

“It’s hard for the practicing clinician to know how every piece of technology works in order to describe it to the patient,” Dr. Libby said at the meeting. “How many people here can identify when algorithms are used in their EHR today?”

He suggested asking for more transparency from the companies that make and sell AI-powered software and tools to insurers and healthcare systems.

Steven H. Kroft, MD, the editor of the American Journal of Clinical Pathology, raised concerns about the unintended harm that unchecked use of AI may pose to scientific research.

He asked the AMA to address “a significant omission in an otherwise comprehensive report” — the need to protect the integrity of study results that can direct patient care.

“While sham science is not a new issue, large language models make it far easier for authors to generate fake papers and far harder for editors, reviewers, and publishers to identify them,” Dr. Kroft said. “This is a rapidly growing phenomenon that is threatening the integrity of the literature. These papers become embedded in the evidence bases that drive clinical decision-making.”

AMA has been working with specialty societies and outside AI experts to refine an effective set of recommendations. The new policies, once finalized, are intended to build on steps AMA already has taken, including last year releasing principles for AI development, deployment, and use.
 

Congress Mulling

The AMA delegates are far from alone in facing AI policy challenges.

Leaders in Congress also are examining AI guardrails, with influential panels such as the Senate Finance and House Energy and Commerce committees holding hearings.

A key congressional AI effort to watch is the expected implementation of a bipartisan Senate “road map,” which Senate Majority Leader Chuck Schumer (D-NY) and colleagues released in May, said Miranda A. Franco, a senior policy advisor at the law firm Holland & Knight.

The product of many months of deliberation, this Senate road map identifies priorities for future legislation, including:

• Creating appropriate guardrails and safety measures to protect patients.
• Making healthcare and biomedical data available for machine learning and data science research while carefully addressing privacy issues.
• Providing transparency for clinicians and the public about the use of AI in medical products and clinical support services, including the data used to train models.
• Examining the Centers for Medicare & Medicaid Services’ reimbursement mechanisms as well as guardrails to ensure accountability, appropriate use, and broad application of AI across all populations.

Congress likely will address issues of AI in healthcare in piecemeal fashion, taking on different aspects of these challenges at different times, Ms. Franco said. The Senate road map gives the key committees directions on where to proceed in their efforts to develop new laws.

“I think this is all going to be slow and rolling, not big and sweeping,” Ms. Franco told this news organization. “I don’t think we’re going to see an encompassing AI bill.”
 

AMA Policies Adopted on Other Issues

At the June meeting, AMA delegates adopted the following policies aiming to:

• Increase oversight and accountability of health insurers’ use of prior authorization controls on patient access to care.
• Encourage policy changes allowing physicians to receive loan forgiveness when they practice in an Indian Health Service, Tribal, or Urban Indian Health Program, similar to physicians practicing in a Veterans Administration facility.
• Advocate for federal policy that limits a patient’s out-of-pocket cost to be the same or less than the amount that a patient with traditional Medicare plus a Medigap plan would pay.
• Oppose state or national legislation that could criminalize in vitro fertilization.
• Limit what the AMA calls the “expensive” cost for Medicare Advantage enrollees who need physician-administered drugs or biologics.
• Help physicians address the handling of de-identified patient data in a rapidly changing digital health ecosystem.
• Support efforts to decriminalize the possession of non-prescribed buprenorphine for personal use by individuals who lack access to a physician for the treatment of opioid use disorder.
• Expand access to hearing, vision, and dental care. The new AMA policy advocates working with state medical associations to support coverage of hearing exams, hearing aids, cochlear implants, and vision exams and aids. The revised AMA policy also supports working with the American Dental Association and other national organizations to improve access to dental care for people enrolled in Medicare, Medicaid, and CHIP programs.
• Increase enrollment of more women and sexual and gender minority populations in clinical trials.

A version of this article first appeared on Medscape.com.

The largest US physician organization wrestled with the professional risks and rewards of artificial intelligence (AI) at its annual meeting, delaying action even as it adopted new policies on prior authorization and other concerns for clinicians and patients.

Physicians and medical students at the annual meeting of the American Medical Association (AMA) House of Delegates in Chicago intensely debated a report and two key resolutions on AI but could not reach consensus, pushing off decision-making until a future meeting in November.

One resolution would establish “augmented intelligence” as the preferred term for AI, reflecting the desired role of these tools in supporting — not making — physicians’ decisions. The other resolution focused on insurers’ use of AI in determining medical necessity.

(See specific policies adopted at the meeting, held June 8-12, below.)

A comprehensive AMA trustees’ report on AI considered additional issues including requirements for disclosing AI use, liability for harms due to flawed application of AI, data privacy, and cybersecurity.

The AMA intends to “continue to methodically assess these issues and make informed recommendations in proposing new policy,” said Bobby Mukkamala, MD, an otolaryngologist from Flint, Michigan, who became the AMA’s new president-elect.

AMA members at the meeting largely applauded the aim of these AI proposals, but some objected to parts of the trustees’ report.

They raised questions about what, exactly, constitutes an AI-powered service and whether all AI tools need the kind of guardrails the AMA may seek. There also were concerns about calls to make AI use more transparent.

While transparency might be an admirable goal, it might prove too hard to achieve given that AI-powered tools and products are already woven into medical practice in ways that physicians may not know or understand, said Christopher Libby, MD, MPH, a clinical informaticist and emergency physician at Cedars Sinai Medical Center in Los Angeles.

“It’s hard for the practicing clinician to know how every piece of technology works in order to describe it to the patient,” Dr. Libby said at the meeting. “How many people here can identify when algorithms are used in their EHR today?”

He suggested asking for more transparency from the companies that make and sell AI-powered software and tools to insurers and healthcare systems.

Steven H. Kroft, MD, the editor of the American Journal of Clinical Pathology, raised concerns about the unintended harm that unchecked use of AI may pose to scientific research.

He asked the AMA to address “a significant omission in an otherwise comprehensive report” — the need to protect the integrity of study results that can direct patient care.

“While sham science is not a new issue, large language models make it far easier for authors to generate fake papers and far harder for editors, reviewers, and publishers to identify them,” Dr. Kroft said. “This is a rapidly growing phenomenon that is threatening the integrity of the literature. These papers become embedded in the evidence bases that drive clinical decision-making.”

AMA has been working with specialty societies and outside AI experts to refine an effective set of recommendations. The new policies, once finalized, are intended to build on steps AMA already has taken, including last year releasing principles for AI development, deployment, and use.
 

Congress Mulling

The AMA delegates are far from alone in facing AI policy challenges.

Leaders in Congress also are examining AI guardrails, with influential panels such as the Senate Finance and House Energy and Commerce committees holding hearings.

A key congressional AI effort to watch is the expected implementation of a bipartisan Senate “road map,” which Senate Majority Leader Chuck Schumer (D-NY) and colleagues released in May, said Miranda A. Franco, a senior policy advisor at the law firm Holland & Knight.

The product of many months of deliberation, this Senate road map identifies priorities for future legislation, including:

• Creating appropriate guardrails and safety measures to protect patients.
• Making healthcare and biomedical data available for machine learning and data science research while carefully addressing privacy issues.
• Providing transparency for clinicians and the public about the use of AI in medical products and clinical support services, including the data used to train models.
• Examining the Centers for Medicare & Medicaid Services’ reimbursement mechanisms as well as guardrails to ensure accountability, appropriate use, and broad application of AI across all populations.

Congress likely will address issues of AI in healthcare in piecemeal fashion, taking on different aspects of these challenges at different times, Ms. Franco said. The Senate road map gives the key committees directions on where to proceed in their efforts to develop new laws.

“I think this is all going to be slow and rolling, not big and sweeping,” Ms. Franco told this news organization. “I don’t think we’re going to see an encompassing AI bill.”
 

AMA Policies Adopted on Other Issues

At the June meeting, AMA delegates adopted the following policies aiming to:

• Increase oversight and accountability of health insurers’ use of prior authorization controls on patient access to care.
• Encourage policy changes allowing physicians to receive loan forgiveness when they practice in an Indian Health Service, Tribal, or Urban Indian Health Program, similar to physicians practicing in a Veterans Administration facility.
• Advocate for federal policy that limits a patient’s out-of-pocket cost to be the same or less than the amount that a patient with traditional Medicare plus a Medigap plan would pay.
• Oppose state or national legislation that could criminalize in vitro fertilization.
• Limit what the AMA calls the “expensive” cost for Medicare Advantage enrollees who need physician-administered drugs or biologics.
• Help physicians address the handling of de-identified patient data in a rapidly changing digital health ecosystem.
• Support efforts to decriminalize the possession of non-prescribed buprenorphine for personal use by individuals who lack access to a physician for the treatment of opioid use disorder.
• Expand access to hearing, vision, and dental care. The new AMA policy advocates working with state medical associations to support coverage of hearing exams, hearing aids, cochlear implants, and vision exams and aids. The revised AMA policy also supports working with the American Dental Association and other national organizations to improve access to dental care for people enrolled in Medicare, Medicaid, and CHIP programs.
• Increase enrollment of more women and sexual and gender minority populations in clinical trials.

A version of this article first appeared on Medscape.com.

The largest US physician organization wrestled with the professional risks and rewards of artificial intelligence (AI) at its annual meeting, delaying action even as it adopted new policies on prior authorization and other concerns for clinicians and patients.

Physicians and medical students at the annual meeting of the American Medical Association (AMA) House of Delegates in Chicago intensely debated a report and two key resolutions on AI but could not reach consensus, pushing off decision-making until a future meeting in November.

One resolution would establish “augmented intelligence” as the preferred term for AI, reflecting the desired role of these tools in supporting — not making — physicians’ decisions. The other resolution focused on insurers’ use of AI in determining medical necessity.

(See specific policies adopted at the meeting, held June 8-12, below.)

A comprehensive AMA trustees’ report on AI considered additional issues including requirements for disclosing AI use, liability for harms due to flawed application of AI, data privacy, and cybersecurity.

The AMA intends to “continue to methodically assess these issues and make informed recommendations in proposing new policy,” said Bobby Mukkamala, MD, an otolaryngologist from Flint, Michigan, who became the AMA’s new president-elect.

AMA members at the meeting largely applauded the aim of these AI proposals, but some objected to parts of the trustees’ report.

They raised questions about what, exactly, constitutes an AI-powered service and whether all AI tools need the kind of guardrails the AMA may seek. There also were concerns about calls to make AI use more transparent.

While transparency might be an admirable goal, it might prove too hard to achieve given that AI-powered tools and products are already woven into medical practice in ways that physicians may not know or understand, said Christopher Libby, MD, MPH, a clinical informaticist and emergency physician at Cedars Sinai Medical Center in Los Angeles.

“It’s hard for the practicing clinician to know how every piece of technology works in order to describe it to the patient,” Dr. Libby said at the meeting. “How many people here can identify when algorithms are used in their EHR today?”

He suggested asking for more transparency from the companies that make and sell AI-powered software and tools to insurers and healthcare systems.

Steven H. Kroft, MD, the editor of the American Journal of Clinical Pathology, raised concerns about the unintended harm that unchecked use of AI may pose to scientific research.

He asked the AMA to address “a significant omission in an otherwise comprehensive report” — the need to protect the integrity of study results that can direct patient care.

“While sham science is not a new issue, large language models make it far easier for authors to generate fake papers and far harder for editors, reviewers, and publishers to identify them,” Dr. Kroft said. “This is a rapidly growing phenomenon that is threatening the integrity of the literature. These papers become embedded in the evidence bases that drive clinical decision-making.”

AMA has been working with specialty societies and outside AI experts to refine an effective set of recommendations. The new policies, once finalized, are intended to build on steps AMA already has taken, including last year releasing principles for AI development, deployment, and use.
 

Congress Mulling

The AMA delegates are far from alone in facing AI policy challenges.

Leaders in Congress also are examining AI guardrails, with influential panels such as the Senate Finance and House Energy and Commerce committees holding hearings.

A key congressional AI effort to watch is the expected implementation of a bipartisan Senate “road map,” which Senate Majority Leader Chuck Schumer (D-NY) and colleagues released in May, said Miranda A. Franco, a senior policy advisor at the law firm Holland & Knight.

The product of many months of deliberation, this Senate road map identifies priorities for future legislation, including:

• Creating appropriate guardrails and safety measures to protect patients.
• Making healthcare and biomedical data available for machine learning and data science research while carefully addressing privacy issues.
• Providing transparency for clinicians and the public about the use of AI in medical products and clinical support services, including the data used to train models.
• Examining the Centers for Medicare & Medicaid Services’ reimbursement mechanisms as well as guardrails to ensure accountability, appropriate use, and broad application of AI across all populations.

Congress likely will address issues of AI in healthcare in piecemeal fashion, taking on different aspects of these challenges at different times, Ms. Franco said. The Senate road map gives the key committees directions on where to proceed in their efforts to develop new laws.

“I think this is all going to be slow and rolling, not big and sweeping,” Ms. Franco told this news organization. “I don’t think we’re going to see an encompassing AI bill.”
 

AMA Policies Adopted on Other Issues

At the June meeting, AMA delegates adopted the following policies aiming to:

• Increase oversight and accountability of health insurers’ use of prior authorization controls on patient access to care.
• Encourage policy changes allowing physicians to receive loan forgiveness when they practice in an Indian Health Service, Tribal, or Urban Indian Health Program, similar to physicians practicing in a Veterans Administration facility.
• Advocate for federal policy that limits a patient’s out-of-pocket cost to be the same or less than the amount that a patient with traditional Medicare plus a Medigap plan would pay.
• Oppose state or national legislation that could criminalize in vitro fertilization.
• Limit what the AMA calls the “expensive” cost for Medicare Advantage enrollees who need physician-administered drugs or biologics.
• Help physicians address the handling of de-identified patient data in a rapidly changing digital health ecosystem.
• Support efforts to decriminalize the possession of non-prescribed buprenorphine for personal use by individuals who lack access to a physician for the treatment of opioid use disorder.
• Expand access to hearing, vision, and dental care. The new AMA policy advocates working with state medical associations to support coverage of hearing exams, hearing aids, cochlear implants, and vision exams and aids. The revised AMA policy also supports working with the American Dental Association and other national organizations to improve access to dental care for people enrolled in Medicare, Medicaid, and CHIP programs.
• Increase enrollment of more women and sexual and gender minority populations in clinical trials.

A version of this article first appeared on Medscape.com.

An influential US panel may largely reaffirm its current recommendation in favor of screening older women to prevent osteoporotic fractures, while also repeating its call for more research to try to determine whether men would benefit from this kind of routine testing.

The US Preventive Services Task Force (USPSTF) on June 11 released a draft update of its recommendations on osteoporosis screening. The task force will accept comments on the draft through July 8. Federal law gives the USPSTF recommendations extra clout, requiring insurers to cover — without co-pay — services that get top marks “A” or “B” from the task force.

The task force intends to maintain a “B” recommendation on screening of older women, indicating that the evidence gathered to date suggests a moderate net benefit. But the draft includes a shift in the approach to this screening.

The USPSTF proposed saying that it recommends screening for osteoporosis in both women aged 65 years and older and postmenopausal women younger than 65 years who are at an increased risk for an osteoporotic fracture. The current recommendation, finalized in 2018, advises “screening for osteoporosis with bone measurement testing [emphasis added]” for these groups.

The proposed change in language — dropping the phrase “with bone measurement testing” — is intended to expand flexibility for clinicians, Esa Davis, MD, MPH, a member of USPSTF and a professor at the University of Maryland School of Medicine, Baltimore, told this news organization.

kurastomokibridichuwronushutodretrovametrofreslowesuclolajuthushotruswespecishoswovigekagespouekisusovogilispuhaswichakubraclubregumunumiclapritreclitrithawajikofrejocreshivekiuopacosletacruprocruclijephibicriclagogabospetok

cutedostochastovavukowrawilacrocluhuresavemeswediwretiniwroclolonoswutresliwot

Insufficient Evidence

The USPSTF’s “I” grade is different from a “D” grade, which is what the task force uses to recommend against the use of a service.

A “D” grade means the USPSTF says there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. (The USPSTF makes it easy to search online for grades given to preventive services, including those that got a “D.”)

The USPSTF is calling for more studies on the benefits and harms of screening for osteoporosis to prevent fractures and related morbidity and mortality in men.

“Men do get osteoporosis,” Dr. Davis said. “But unfortunately, the evidence isn’t there” to allow USPSTF to make a recommendation on screening approaches.

“Any man who has concerns about bone health should certainly talk to his clinician and figure out what is the best form of screening” he might want to do, she said.

There’s been a growing interest in the question of whether to screen men for osteoporosis and bone health. For example, Osteoporosis Canada last year updated a guideline to emphasize the need to assess older patients of both sexes for the risk for fractures. But the Canadian Task Force on Preventive Health Care in 2023 came to a conclusion in line with the USPSTF draft.

The Canadian task force recommended against routine screening in men, while adding that clinicians should be alert to changes in health that may indicate the patient has experienced or is at a higher risk for fragility fracture.
 

Risk Factors, Concerns About Tests

The USPSTF said that risk factors associated with fragility fractures are similar in men and women. These include:

• Increasing age
• Low body mass index
• Excessive alcohol intake
• Current smoking
• Chronic corticosteroid use
• History of prior fractures, falls within the past year, cerebrovascular accident, and diabetes
• Hypogonadism

The process of updating the USPSTF recommendations can serve as a chance to expand public awareness about osteoporosis, as many men may not know to raise the question of their fracture risk during medical appointments, Dr. Davis said.

“Clinicians need to be aware of the risk factors and to be able to have conversations with men,” she said.

Dr. Davis also cautioned about the need to be aware of limitations with clinical risk assessment tools. In the draft recommendation statement, the USPSTF noted that some tools and approaches may be less likely to identify Black, Hispanic, and Asian people as high risk, and subsequently, clinicians may be less likely to offer treatment to them compared with White people of the same age, bone mineral density, and clinical risk profile.

Dr. Davis had no relevant financial relationships. Dr. Jain received research funding from the Amgen Foundation.
 

A version of this article appeared on Medscape.com.

An influential US panel may largely reaffirm its current recommendation in favor of screening older women to prevent osteoporotic fractures, while also repeating its call for more research to try to determine whether men would benefit from this kind of routine testing.

The US Preventive Services Task Force (USPSTF) on June 11 released a draft update of its recommendations on osteoporosis screening. The task force will accept comments on the draft through July 8. Federal law gives the USPSTF recommendations extra clout, requiring insurers to cover — without co-pay — services that get top marks “A” or “B” from the task force.

The task force intends to maintain a “B” recommendation on screening of older women, indicating that the evidence gathered to date suggests a moderate net benefit. But the draft includes a shift in the approach to this screening.

The USPSTF proposed saying that it recommends screening for osteoporosis in both women aged 65 years and older and postmenopausal women younger than 65 years who are at an increased risk for an osteoporotic fracture. The current recommendation, finalized in 2018, advises “screening for osteoporosis with bone measurement testing [emphasis added]” for these groups.

The proposed change in language — dropping the phrase “with bone measurement testing” — is intended to expand flexibility for clinicians, Esa Davis, MD, MPH, a member of USPSTF and a professor at the University of Maryland School of Medicine, Baltimore, told this news organization.

kurastomokibridichuwronushutodretrovametrofreslowesuclolajuthushotruswespecishoswovigekagespouekisusovogilispuhaswichakubraclubregumunumiclapritreclitrithawajikofrejocreshivekiuopacosletacruprocruclijephibicriclagogabospetok

cutedostochastovavukowrawilacrocluhuresavemeswediwretiniwroclolonoswutresliwot

Insufficient Evidence

The USPSTF’s “I” grade is different from a “D” grade, which is what the task force uses to recommend against the use of a service.

A “D” grade means the USPSTF says there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. (The USPSTF makes it easy to search online for grades given to preventive services, including those that got a “D.”)

The USPSTF is calling for more studies on the benefits and harms of screening for osteoporosis to prevent fractures and related morbidity and mortality in men.

“Men do get osteoporosis,” Dr. Davis said. “But unfortunately, the evidence isn’t there” to allow USPSTF to make a recommendation on screening approaches.

“Any man who has concerns about bone health should certainly talk to his clinician and figure out what is the best form of screening” he might want to do, she said.

There’s been a growing interest in the question of whether to screen men for osteoporosis and bone health. For example, Osteoporosis Canada last year updated a guideline to emphasize the need to assess older patients of both sexes for the risk for fractures. But the Canadian Task Force on Preventive Health Care in 2023 came to a conclusion in line with the USPSTF draft.

The Canadian task force recommended against routine screening in men, while adding that clinicians should be alert to changes in health that may indicate the patient has experienced or is at a higher risk for fragility fracture.
 

Risk Factors, Concerns About Tests

The USPSTF said that risk factors associated with fragility fractures are similar in men and women. These include:

• Increasing age
• Low body mass index
• Excessive alcohol intake
• Current smoking
• Chronic corticosteroid use
• History of prior fractures, falls within the past year, cerebrovascular accident, and diabetes
• Hypogonadism

The process of updating the USPSTF recommendations can serve as a chance to expand public awareness about osteoporosis, as many men may not know to raise the question of their fracture risk during medical appointments, Dr. Davis said.

“Clinicians need to be aware of the risk factors and to be able to have conversations with men,” she said.

Dr. Davis also cautioned about the need to be aware of limitations with clinical risk assessment tools. In the draft recommendation statement, the USPSTF noted that some tools and approaches may be less likely to identify Black, Hispanic, and Asian people as high risk, and subsequently, clinicians may be less likely to offer treatment to them compared with White people of the same age, bone mineral density, and clinical risk profile.

Dr. Davis had no relevant financial relationships. Dr. Jain received research funding from the Amgen Foundation.
 

A version of this article appeared on Medscape.com.

An influential US panel may largely reaffirm its current recommendation in favor of screening older women to prevent osteoporotic fractures, while also repeating its call for more research to try to determine whether men would benefit from this kind of routine testing.

The US Preventive Services Task Force (USPSTF) on June 11 released a draft update of its recommendations on osteoporosis screening. The task force will accept comments on the draft through July 8. Federal law gives the USPSTF recommendations extra clout, requiring insurers to cover — without co-pay — services that get top marks “A” or “B” from the task force.

The task force intends to maintain a “B” recommendation on screening of older women, indicating that the evidence gathered to date suggests a moderate net benefit. But the draft includes a shift in the approach to this screening.

The USPSTF proposed saying that it recommends screening for osteoporosis in both women aged 65 years and older and postmenopausal women younger than 65 years who are at an increased risk for an osteoporotic fracture. The current recommendation, finalized in 2018, advises “screening for osteoporosis with bone measurement testing [emphasis added]” for these groups.

The proposed change in language — dropping the phrase “with bone measurement testing” — is intended to expand flexibility for clinicians, Esa Davis, MD, MPH, a member of USPSTF and a professor at the University of Maryland School of Medicine, Baltimore, told this news organization.

kurastomokibridichuwronushutodretrovametrofreslowesuclolajuthushotruswespecishoswovigekagespouekisusovogilispuhaswichakubraclubregumunumiclapritreclitrithawajikofrejocreshivekiuopacosletacruprocruclijephibicriclagogabospetok

cutedostochastovavukowrawilacrocluhuresavemeswediwretiniwroclolonoswutresliwot

Insufficient Evidence

The USPSTF’s “I” grade is different from a “D” grade, which is what the task force uses to recommend against the use of a service.

A “D” grade means the USPSTF says there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. (The USPSTF makes it easy to search online for grades given to preventive services, including those that got a “D.”)

The USPSTF is calling for more studies on the benefits and harms of screening for osteoporosis to prevent fractures and related morbidity and mortality in men.

“Men do get osteoporosis,” Dr. Davis said. “But unfortunately, the evidence isn’t there” to allow USPSTF to make a recommendation on screening approaches.

“Any man who has concerns about bone health should certainly talk to his clinician and figure out what is the best form of screening” he might want to do, she said.

There’s been a growing interest in the question of whether to screen men for osteoporosis and bone health. For example, Osteoporosis Canada last year updated a guideline to emphasize the need to assess older patients of both sexes for the risk for fractures. But the Canadian Task Force on Preventive Health Care in 2023 came to a conclusion in line with the USPSTF draft.

The Canadian task force recommended against routine screening in men, while adding that clinicians should be alert to changes in health that may indicate the patient has experienced or is at a higher risk for fragility fracture.
 

Risk Factors, Concerns About Tests

The USPSTF said that risk factors associated with fragility fractures are similar in men and women. These include:

• Increasing age
• Low body mass index
• Excessive alcohol intake
• Current smoking
• Chronic corticosteroid use
• History of prior fractures, falls within the past year, cerebrovascular accident, and diabetes
• Hypogonadism

The process of updating the USPSTF recommendations can serve as a chance to expand public awareness about osteoporosis, as many men may not know to raise the question of their fracture risk during medical appointments, Dr. Davis said.

“Clinicians need to be aware of the risk factors and to be able to have conversations with men,” she said.

Dr. Davis also cautioned about the need to be aware of limitations with clinical risk assessment tools. In the draft recommendation statement, the USPSTF noted that some tools and approaches may be less likely to identify Black, Hispanic, and Asian people as high risk, and subsequently, clinicians may be less likely to offer treatment to them compared with White people of the same age, bone mineral density, and clinical risk profile.

Dr. Davis had no relevant financial relationships. Dr. Jain received research funding from the Amgen Foundation.
 

A version of this article appeared on Medscape.com.

Some vitamin D tests may give misleading results despite progress made in recent years to improve the quality of these assays, according to the US Centers for Disease Control and Prevention (CDC).

Otoe Sugahara manager of the CDC Vitamin D Standardization-Certification Program (VDSCP), presented an update of her group’s work at ENDO 2024, the Endocrine Society’s annual meeting in Boston. 

“Though most vitamin D tests in our program have improved, there still remain some sample-specific inaccuracies. The CDC is working with program participants to address these situations,” Ms. Sugahara said in a statement released by the Endocrine Society.

For example, some assays measure other compounds besides 25-hydroxyvitamin D, which can falsely elevate results of some blood samples, Ms. Sugahara reported. Thus, some tests may be misclassified, with results seen as sufficient from samples that should have indicated a vitamin D deficiency.

“While most vitamin D tests are effective, it is important for healthcare providers to be aware of the potential inconsistencies associated with vitamin D tests to avoid misclassification of the patients,” Ms. Sugahara and coauthors said in an abstract provided by the Endocrine Society.

Ms. Sugahara’s report provided a snapshot of the state of longstanding efforts to improve the quality of a widely performed service in US healthcare: testing vitamin D levels.

These include an international collaboration that gave rise in 2010 to a vitamin D standardization program, from which the CDC’s VDSCP certification emerged. Among the leaders of these efforts was Christopher Sempos, PhD, then with the Office of Dietary Supplements at the National Institutes of Health.

Many clinicians may not be aware of the concerns about the accuracy of vitamin D tests that led to the drive for standardization, Dr. Sempos, now retired, said in an interview. And, in his view, it’s something that busy practitioners should not have to consider.

“They have literally thousands of diseases they have to be able to recognize and diagnose,” Dr. Sempos said. “They should be able to count on the laboratory system to give them accurate and precise data.”
 

‘Nudging’ Toward Better Results

The CDC’s certification program gives labs and companies detailed information about the analytical accuracy and precision of their vitamin D tests. 

This feedback has paid off with improved results, Andy Hoofnagle, MD, PhD, professor of laboratory medicine and pathology at the University of Washington in Seattle, told this news organization. It helps by “nudging manufacturers in the right direction,” he said.

“Some manufacturers reformulated, others recalibrated, which is a lot of effort on their part, so that when the patient get a number, it actually means the right thing,” said Dr. Hoofnagle, who is also chair of the Accuracy-Based Programs Committee of the College of American Pathologists.

“There are still many immunoassays on the market that aren’t giving the correct results, unfortunately, but the standardization certification program has really pushed the field in the right direction,” he said.

US scientists use two main types of technologies to measure vitamin D in the blood, Ms. Sugahara said. One is mass spectrometry, which separately measures 25-hydroxyvitamin D2 and D3 and sums the values. The other type, immunoassay, measures both compounds at the same time and reports one result for total 25-hydroxyvitamin D.

At the ENDO 2024 meeting, Ms. Sugahara reported generally positive trends seen in the VDSCP. For example, the program looks at specific tests’ bias, or the deviation of test results from the true value, as determined with the CDC’s reference method for vitamin D.

Average calibration bias was less than 1% for all assays in the VDSCP in 2022, Ms. Sugahara said. The average calibration bias for immunoassays was 0.86%, and for assays using mass spectrometry, it was 0.55%, Ms. Sugahara reported. 

These are improved results compared with 2019 data, in which mass spectrometry–based assays had a mean bias of 1.9% and immunoassays had a mean bias of 2.4%, the CDC told this news organization in an email exchange.

The CDC said the VDSCP supports laboratories and researchers from around the world, including ones based in the US, China, Australia, Japan, and Korea.
 

Call for Research

Vitamin D tests are widely administered despite questions about their benefit for people who do not appear likely to be deficient of it. 

The Endocrine Society’s newly released practice guideline recommends against routine testing of blood vitamin D levels in the general population.

Laboratory testing has increased over the years owing to studies reporting associations between blood vitamin D [25(OH)D] levels and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases, wrote Marie B. Demay, MD, of Harvard Medical School in Boston, and coauthors in the new guideline. It was published on June 3 in The Journal of Clinical Endocrinology & Metabolism.

‘”Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population,” they wrote.

It’s uncertain that “any putative benefits of screening would outweigh the increased burden and cost, and whether implementation of universal 25(OH)D screening would be feasible from a societal perspective,” Dr. Demay and coauthors added.

They noted that the influential US Preventive Services Task Force also has raised doubts about widespread use of vitamin D tests. 

The USPSTF has a somewhat different take from the Endocrine Society. The task force in 2021 reiterated its view that there is not enough evidence to recommend for or against widespread vitamin D testing for adults. The task force gave this test an I grade, meaning there is insufficient evidence to weigh the risks and benefits. That’s the same grade the task force gave it in 2014.

The USPSTF uses a grade of D to recommend against use of a test or service.

In an interview with this news organization, John Wong, MD, vice chair of the USPSTF, reiterated his group’s call for more research into the potential benefits and harms of vitamin D screening. 

One of the challenges in addressing this issue, Dr. Wong noted, has been the variability of test results. Therefore, efforts such as the CDC’s VDSCP in improving test quality may help in eventually building up the kind of evidence base needed for the task force to offer a more definitive judgment on the tests, he said.

Wong acknowledged it must be frustrating for clinicians and patients to hear that experts don’t have the evidence needed to make a broad call about whether routine vitamin D tests are beneficial.

“We really would like to have that evidence because we recognize that it’s an important health question to help everybody in this nation stay healthy and live longer,” Dr. Wong said.

A version of this article appeared on Medscape.com.

Some vitamin D tests may give misleading results despite progress made in recent years to improve the quality of these assays, according to the US Centers for Disease Control and Prevention (CDC).

Otoe Sugahara manager of the CDC Vitamin D Standardization-Certification Program (VDSCP), presented an update of her group’s work at ENDO 2024, the Endocrine Society’s annual meeting in Boston. 

“Though most vitamin D tests in our program have improved, there still remain some sample-specific inaccuracies. The CDC is working with program participants to address these situations,” Ms. Sugahara said in a statement released by the Endocrine Society.

For example, some assays measure other compounds besides 25-hydroxyvitamin D, which can falsely elevate results of some blood samples, Ms. Sugahara reported. Thus, some tests may be misclassified, with results seen as sufficient from samples that should have indicated a vitamin D deficiency.

“While most vitamin D tests are effective, it is important for healthcare providers to be aware of the potential inconsistencies associated with vitamin D tests to avoid misclassification of the patients,” Ms. Sugahara and coauthors said in an abstract provided by the Endocrine Society.

Ms. Sugahara’s report provided a snapshot of the state of longstanding efforts to improve the quality of a widely performed service in US healthcare: testing vitamin D levels.

These include an international collaboration that gave rise in 2010 to a vitamin D standardization program, from which the CDC’s VDSCP certification emerged. Among the leaders of these efforts was Christopher Sempos, PhD, then with the Office of Dietary Supplements at the National Institutes of Health.

Many clinicians may not be aware of the concerns about the accuracy of vitamin D tests that led to the drive for standardization, Dr. Sempos, now retired, said in an interview. And, in his view, it’s something that busy practitioners should not have to consider.

“They have literally thousands of diseases they have to be able to recognize and diagnose,” Dr. Sempos said. “They should be able to count on the laboratory system to give them accurate and precise data.”
 

‘Nudging’ Toward Better Results

The CDC’s certification program gives labs and companies detailed information about the analytical accuracy and precision of their vitamin D tests. 

This feedback has paid off with improved results, Andy Hoofnagle, MD, PhD, professor of laboratory medicine and pathology at the University of Washington in Seattle, told this news organization. It helps by “nudging manufacturers in the right direction,” he said.

“Some manufacturers reformulated, others recalibrated, which is a lot of effort on their part, so that when the patient get a number, it actually means the right thing,” said Dr. Hoofnagle, who is also chair of the Accuracy-Based Programs Committee of the College of American Pathologists.

“There are still many immunoassays on the market that aren’t giving the correct results, unfortunately, but the standardization certification program has really pushed the field in the right direction,” he said.

US scientists use two main types of technologies to measure vitamin D in the blood, Ms. Sugahara said. One is mass spectrometry, which separately measures 25-hydroxyvitamin D2 and D3 and sums the values. The other type, immunoassay, measures both compounds at the same time and reports one result for total 25-hydroxyvitamin D.

At the ENDO 2024 meeting, Ms. Sugahara reported generally positive trends seen in the VDSCP. For example, the program looks at specific tests’ bias, or the deviation of test results from the true value, as determined with the CDC’s reference method for vitamin D.

Average calibration bias was less than 1% for all assays in the VDSCP in 2022, Ms. Sugahara said. The average calibration bias for immunoassays was 0.86%, and for assays using mass spectrometry, it was 0.55%, Ms. Sugahara reported. 

These are improved results compared with 2019 data, in which mass spectrometry–based assays had a mean bias of 1.9% and immunoassays had a mean bias of 2.4%, the CDC told this news organization in an email exchange.

The CDC said the VDSCP supports laboratories and researchers from around the world, including ones based in the US, China, Australia, Japan, and Korea.
 

Call for Research

Vitamin D tests are widely administered despite questions about their benefit for people who do not appear likely to be deficient of it. 

The Endocrine Society’s newly released practice guideline recommends against routine testing of blood vitamin D levels in the general population.

Laboratory testing has increased over the years owing to studies reporting associations between blood vitamin D [25(OH)D] levels and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases, wrote Marie B. Demay, MD, of Harvard Medical School in Boston, and coauthors in the new guideline. It was published on June 3 in The Journal of Clinical Endocrinology & Metabolism.

‘”Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population,” they wrote.

It’s uncertain that “any putative benefits of screening would outweigh the increased burden and cost, and whether implementation of universal 25(OH)D screening would be feasible from a societal perspective,” Dr. Demay and coauthors added.

They noted that the influential US Preventive Services Task Force also has raised doubts about widespread use of vitamin D tests. 

The USPSTF has a somewhat different take from the Endocrine Society. The task force in 2021 reiterated its view that there is not enough evidence to recommend for or against widespread vitamin D testing for adults. The task force gave this test an I grade, meaning there is insufficient evidence to weigh the risks and benefits. That’s the same grade the task force gave it in 2014.

The USPSTF uses a grade of D to recommend against use of a test or service.

In an interview with this news organization, John Wong, MD, vice chair of the USPSTF, reiterated his group’s call for more research into the potential benefits and harms of vitamin D screening. 

One of the challenges in addressing this issue, Dr. Wong noted, has been the variability of test results. Therefore, efforts such as the CDC’s VDSCP in improving test quality may help in eventually building up the kind of evidence base needed for the task force to offer a more definitive judgment on the tests, he said.

Wong acknowledged it must be frustrating for clinicians and patients to hear that experts don’t have the evidence needed to make a broad call about whether routine vitamin D tests are beneficial.

“We really would like to have that evidence because we recognize that it’s an important health question to help everybody in this nation stay healthy and live longer,” Dr. Wong said.

A version of this article appeared on Medscape.com.

Some vitamin D tests may give misleading results despite progress made in recent years to improve the quality of these assays, according to the US Centers for Disease Control and Prevention (CDC).

Otoe Sugahara manager of the CDC Vitamin D Standardization-Certification Program (VDSCP), presented an update of her group’s work at ENDO 2024, the Endocrine Society’s annual meeting in Boston. 

“Though most vitamin D tests in our program have improved, there still remain some sample-specific inaccuracies. The CDC is working with program participants to address these situations,” Ms. Sugahara said in a statement released by the Endocrine Society.

For example, some assays measure other compounds besides 25-hydroxyvitamin D, which can falsely elevate results of some blood samples, Ms. Sugahara reported. Thus, some tests may be misclassified, with results seen as sufficient from samples that should have indicated a vitamin D deficiency.

“While most vitamin D tests are effective, it is important for healthcare providers to be aware of the potential inconsistencies associated with vitamin D tests to avoid misclassification of the patients,” Ms. Sugahara and coauthors said in an abstract provided by the Endocrine Society.

Ms. Sugahara’s report provided a snapshot of the state of longstanding efforts to improve the quality of a widely performed service in US healthcare: testing vitamin D levels.

These include an international collaboration that gave rise in 2010 to a vitamin D standardization program, from which the CDC’s VDSCP certification emerged. Among the leaders of these efforts was Christopher Sempos, PhD, then with the Office of Dietary Supplements at the National Institutes of Health.

Many clinicians may not be aware of the concerns about the accuracy of vitamin D tests that led to the drive for standardization, Dr. Sempos, now retired, said in an interview. And, in his view, it’s something that busy practitioners should not have to consider.

“They have literally thousands of diseases they have to be able to recognize and diagnose,” Dr. Sempos said. “They should be able to count on the laboratory system to give them accurate and precise data.”
 

‘Nudging’ Toward Better Results

The CDC’s certification program gives labs and companies detailed information about the analytical accuracy and precision of their vitamin D tests. 

This feedback has paid off with improved results, Andy Hoofnagle, MD, PhD, professor of laboratory medicine and pathology at the University of Washington in Seattle, told this news organization. It helps by “nudging manufacturers in the right direction,” he said.

“Some manufacturers reformulated, others recalibrated, which is a lot of effort on their part, so that when the patient get a number, it actually means the right thing,” said Dr. Hoofnagle, who is also chair of the Accuracy-Based Programs Committee of the College of American Pathologists.

“There are still many immunoassays on the market that aren’t giving the correct results, unfortunately, but the standardization certification program has really pushed the field in the right direction,” he said.

US scientists use two main types of technologies to measure vitamin D in the blood, Ms. Sugahara said. One is mass spectrometry, which separately measures 25-hydroxyvitamin D2 and D3 and sums the values. The other type, immunoassay, measures both compounds at the same time and reports one result for total 25-hydroxyvitamin D.

At the ENDO 2024 meeting, Ms. Sugahara reported generally positive trends seen in the VDSCP. For example, the program looks at specific tests’ bias, or the deviation of test results from the true value, as determined with the CDC’s reference method for vitamin D.

Average calibration bias was less than 1% for all assays in the VDSCP in 2022, Ms. Sugahara said. The average calibration bias for immunoassays was 0.86%, and for assays using mass spectrometry, it was 0.55%, Ms. Sugahara reported. 

These are improved results compared with 2019 data, in which mass spectrometry–based assays had a mean bias of 1.9% and immunoassays had a mean bias of 2.4%, the CDC told this news organization in an email exchange.

The CDC said the VDSCP supports laboratories and researchers from around the world, including ones based in the US, China, Australia, Japan, and Korea.
 

Call for Research

Vitamin D tests are widely administered despite questions about their benefit for people who do not appear likely to be deficient of it. 

The Endocrine Society’s newly released practice guideline recommends against routine testing of blood vitamin D levels in the general population.

Laboratory testing has increased over the years owing to studies reporting associations between blood vitamin D [25(OH)D] levels and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases, wrote Marie B. Demay, MD, of Harvard Medical School in Boston, and coauthors in the new guideline. It was published on June 3 in The Journal of Clinical Endocrinology & Metabolism.

‘”Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population,” they wrote.

It’s uncertain that “any putative benefits of screening would outweigh the increased burden and cost, and whether implementation of universal 25(OH)D screening would be feasible from a societal perspective,” Dr. Demay and coauthors added.

They noted that the influential US Preventive Services Task Force also has raised doubts about widespread use of vitamin D tests. 

The USPSTF has a somewhat different take from the Endocrine Society. The task force in 2021 reiterated its view that there is not enough evidence to recommend for or against widespread vitamin D testing for adults. The task force gave this test an I grade, meaning there is insufficient evidence to weigh the risks and benefits. That’s the same grade the task force gave it in 2014.

The USPSTF uses a grade of D to recommend against use of a test or service.

In an interview with this news organization, John Wong, MD, vice chair of the USPSTF, reiterated his group’s call for more research into the potential benefits and harms of vitamin D screening. 

One of the challenges in addressing this issue, Dr. Wong noted, has been the variability of test results. Therefore, efforts such as the CDC’s VDSCP in improving test quality may help in eventually building up the kind of evidence base needed for the task force to offer a more definitive judgment on the tests, he said.

Wong acknowledged it must be frustrating for clinicians and patients to hear that experts don’t have the evidence needed to make a broad call about whether routine vitamin D tests are beneficial.

“We really would like to have that evidence because we recognize that it’s an important health question to help everybody in this nation stay healthy and live longer,” Dr. Wong said.

A version of this article appeared on Medscape.com.

Charles Powell, MD, said he sometimes has a hard time persuading patients to start on low-dose vaginal estrogen, which can help prevent urinary tract infections and ease other symptoms of menopause.

Many women fear taking these vaginal products because of what Dr. Powell considers excessively strong warnings about the risk for cancer and cardiovascular disease linked to daily estrogen pills that were issued in the early 2000s.

He is advocating for the US Food and Drug Administration (FDA) to remove the boxed warning on low-dose estrogen. His efforts are separate from his roles as an associate professor of urology at the Indiana University School of Medicine, and as a member of the American Urological Association (AUA), Dr. Powell said.

In his quest to find out how to change labeling, Dr. Powell has gained a quick education about drug regulation. He has enlisted Representative Jim Baird (R-IN) and Senator Mike Braun (R-IN) to contact the FDA on his behalf, while congressional staff guided him through the hurdles of getting the warning label changed. For instance, a manufacturer of low-dose estrogen may need to become involved.

“You don’t learn this in med school,” Dr. Powell said in an interview.

With this work, Dr. Powell is wading into a long-standing argument between the FDA and some clinicians and researchers about the potential harms of low-dose estrogen.

He is doing so at a time of increased interest in understanding genitourinary syndrome of menopause (GSM), a term coined a decade ago by the International Society for the Study of Women’s Sexual Health and the North American Menopause Society to cover “a constellation of conditions” related to urogenital atrophy.

Symptoms of GSM include vaginal dryness and burning and recurrent urinary tract infections.

The federal government in 2022 began a project budgeted with nearly $1 million to review evidence on treatments, including vaginal and low-dose estrogen. The aim is to eventually help the AUA develop clinical guidelines for addressing GSM.

In addition, a bipartisan Senate bill introduced in May calls for authorizing $125 million over 5 years for the National Institutes of Health (NIH) to fund research on menopause. Senator Patty Murray (D-WA), the lead sponsor of the bill, is a longtime advocate for women’s health and serves as chairwoman for the Senate Appropriations Committee, which largely sets the NIH budget.

“The bottom line is, for too long, menopause has been overlooked, underinvested in and left behind,” Sen. Murray said during a May 2 press conference. “It is well past time to stop treating menopause like some kind of secret and start treating it like the major mainstream public health issue it is.”

Evidence Demands

Increased federal funding for menopause research could help efforts to change the warning label on low-dose estrogen, according to JoAnn Manson, MD, chief of preventive medicine at Brigham and Women’s Hospital in Boston.

Dr. Manson was a leader of the Women’s Health Initiative (WHI), a major federally funded research project launched in 1991 to investigate if hormone therapy and diet could protect older women from chronic diseases related to aging.

Before the WHI, clinicians prescribed hormones to prevent cardiovascular disease, based on evidence from earlier research.

But in 2002, a WHI trial that compared estrogen-progestin tablets with placebo was halted early because of disturbing findings, including an association with higher risk for breast cancer and cardiovascular disease.

Compared with placebo, for every 10,000 women taking estrogen plus progestin annually, incidences of cardiovascular disease, stroke, pulmonary embolism, and invasive breast cancer were seven to eight times higher.

In January 2003, the FDA announced it would put a boxed warning about cardiovascular risk and cancer risk on estrogen products, reflecting the WHI finding.

The agency at the time said clinicians should work with patients to assess risks and benefits of these products to manage the effects of menopause.

But more news on the potential harms of estrogen followed in 2004: A WHI study comparing estrogen-only pills with placebo produced signals of a small increased risk for stroke, although it also indicated no excess risk for breast cancer for at least 6.8 years of use.

Dr. Manson and the North American Menopause Society in 2016 filed a petition with the FDA to remove the boxed warning that appears on the front of low-dose estrogen products. The group wanted the information on risks moved to the usual warning section of the label.

Two years later, the FDA rejected the petition, citing the absence of “well-controlled studies,” to prove low-dose topical estrogen poses less risk to women than the high-dose pills studied in the WHI.

The FDA told this news organization that it stands by the decisions in its rejection of the petition.

Persuading the FDA to revise the labels on low-dose estrogen products likely will require evidence from randomized, large-scale studies, Dr. Manson said. The agency has not been satisfied to date with findings from other kinds of studies, including observational research.

“Once that evidence is available that the benefit-risk profile is different for different formulations and the evidence is compelling and definitive, that warning should change,” Dr. Manson told this news organization.

But the warning continues to have a chilling effect on patient willingness to use low-dose vaginal estrogen, even with the FDA’s continued endorsement of estrogen for menopause symptoms, clinicians told this news organization.

Risa Kagan, MD, a gynecologist at Sutter Health in Berkeley, California, said in many cases her patients’ partners also need to be reassured. Dr. Kagan said she still sees women who have had to discontinue sexual intercourse because of pain. In some cases, the patients will bring the medicine home only to find that the warnings frighten their spouses.

“The spouse says, ‘Oh my God, I don’t want you to get dementia, to get breast cancer, it’s not worth it, so let’s keep doing outercourse’,” meaning sexual relations without penetration, Dr. Kagan said.

Difficult Messaging

From the initial unveiling of disappointing WHI results, clinicians and researchers have stressed that women could continue using estrogen products for managing symptoms of menopause, even while advising strongly against their continued use with the intention of preventing heart disease.

Newly published findings from follow-ups of WHI participants may give clinicians and patients even more confidence for the use of estrogen products in early menopause.

According to the study, which Dr. Manson coauthored, younger women have a low risk for cardiovascular disease and other associated conditions when taking hormone therapy. Risks attributed to these drugs were less than one additional adverse event per 1000 women annually. This population may also derive significant quality-of-life benefits for symptom relief.

Dr. Manson told this news organization that estrogen in lower doses and delivered through the skin as a patch or gel may further reduce risks.

“The WHI findings should never be used as a reason to deny hormone therapy to women in early menopause with bothersome menopausal symptoms,” Dr. Manson said. “Many women are good candidates for treatment and, in shared decision-making with their clinicians, should be able to receive appropriate and personalized healthcare for their needs.”

But the current FDA warning label makes it difficult to help women understand the risk and benefits of low-dose estrogen, according to Stephanie Faubion, MD, MBA, medical director at the North American Menopause Society and director of Mayo Clinic’s Center for Women’s Health in Jacksonville, Florida.

Clinicians now must set aside time to explain the warnings to women when they prescribe low-dose estrogen, Dr. Faubion said.

“The package insert is going to look scary: I prepare women for that because otherwise they often won’t even fill it or use it.”
 

A version of this article appeared on Medscape.com .

Charles Powell, MD, said he sometimes has a hard time persuading patients to start on low-dose vaginal estrogen, which can help prevent urinary tract infections and ease other symptoms of menopause.

Many women fear taking these vaginal products because of what Dr. Powell considers excessively strong warnings about the risk for cancer and cardiovascular disease linked to daily estrogen pills that were issued in the early 2000s.

He is advocating for the US Food and Drug Administration (FDA) to remove the boxed warning on low-dose estrogen. His efforts are separate from his roles as an associate professor of urology at the Indiana University School of Medicine, and as a member of the American Urological Association (AUA), Dr. Powell said.

In his quest to find out how to change labeling, Dr. Powell has gained a quick education about drug regulation. He has enlisted Representative Jim Baird (R-IN) and Senator Mike Braun (R-IN) to contact the FDA on his behalf, while congressional staff guided him through the hurdles of getting the warning label changed. For instance, a manufacturer of low-dose estrogen may need to become involved.

“You don’t learn this in med school,” Dr. Powell said in an interview.

With this work, Dr. Powell is wading into a long-standing argument between the FDA and some clinicians and researchers about the potential harms of low-dose estrogen.

He is doing so at a time of increased interest in understanding genitourinary syndrome of menopause (GSM), a term coined a decade ago by the International Society for the Study of Women’s Sexual Health and the North American Menopause Society to cover “a constellation of conditions” related to urogenital atrophy.

Symptoms of GSM include vaginal dryness and burning and recurrent urinary tract infections.

The federal government in 2022 began a project budgeted with nearly $1 million to review evidence on treatments, including vaginal and low-dose estrogen. The aim is to eventually help the AUA develop clinical guidelines for addressing GSM.

In addition, a bipartisan Senate bill introduced in May calls for authorizing $125 million over 5 years for the National Institutes of Health (NIH) to fund research on menopause. Senator Patty Murray (D-WA), the lead sponsor of the bill, is a longtime advocate for women’s health and serves as chairwoman for the Senate Appropriations Committee, which largely sets the NIH budget.

“The bottom line is, for too long, menopause has been overlooked, underinvested in and left behind,” Sen. Murray said during a May 2 press conference. “It is well past time to stop treating menopause like some kind of secret and start treating it like the major mainstream public health issue it is.”

Evidence Demands

Increased federal funding for menopause research could help efforts to change the warning label on low-dose estrogen, according to JoAnn Manson, MD, chief of preventive medicine at Brigham and Women’s Hospital in Boston.

Dr. Manson was a leader of the Women’s Health Initiative (WHI), a major federally funded research project launched in 1991 to investigate if hormone therapy and diet could protect older women from chronic diseases related to aging.

Before the WHI, clinicians prescribed hormones to prevent cardiovascular disease, based on evidence from earlier research.

But in 2002, a WHI trial that compared estrogen-progestin tablets with placebo was halted early because of disturbing findings, including an association with higher risk for breast cancer and cardiovascular disease.

Compared with placebo, for every 10,000 women taking estrogen plus progestin annually, incidences of cardiovascular disease, stroke, pulmonary embolism, and invasive breast cancer were seven to eight times higher.

In January 2003, the FDA announced it would put a boxed warning about cardiovascular risk and cancer risk on estrogen products, reflecting the WHI finding.

The agency at the time said clinicians should work with patients to assess risks and benefits of these products to manage the effects of menopause.

But more news on the potential harms of estrogen followed in 2004: A WHI study comparing estrogen-only pills with placebo produced signals of a small increased risk for stroke, although it also indicated no excess risk for breast cancer for at least 6.8 years of use.

Dr. Manson and the North American Menopause Society in 2016 filed a petition with the FDA to remove the boxed warning that appears on the front of low-dose estrogen products. The group wanted the information on risks moved to the usual warning section of the label.

Two years later, the FDA rejected the petition, citing the absence of “well-controlled studies,” to prove low-dose topical estrogen poses less risk to women than the high-dose pills studied in the WHI.

The FDA told this news organization that it stands by the decisions in its rejection of the petition.

Persuading the FDA to revise the labels on low-dose estrogen products likely will require evidence from randomized, large-scale studies, Dr. Manson said. The agency has not been satisfied to date with findings from other kinds of studies, including observational research.

“Once that evidence is available that the benefit-risk profile is different for different formulations and the evidence is compelling and definitive, that warning should change,” Dr. Manson told this news organization.

But the warning continues to have a chilling effect on patient willingness to use low-dose vaginal estrogen, even with the FDA’s continued endorsement of estrogen for menopause symptoms, clinicians told this news organization.

Risa Kagan, MD, a gynecologist at Sutter Health in Berkeley, California, said in many cases her patients’ partners also need to be reassured. Dr. Kagan said she still sees women who have had to discontinue sexual intercourse because of pain. In some cases, the patients will bring the medicine home only to find that the warnings frighten their spouses.

“The spouse says, ‘Oh my God, I don’t want you to get dementia, to get breast cancer, it’s not worth it, so let’s keep doing outercourse’,” meaning sexual relations without penetration, Dr. Kagan said.

Difficult Messaging

From the initial unveiling of disappointing WHI results, clinicians and researchers have stressed that women could continue using estrogen products for managing symptoms of menopause, even while advising strongly against their continued use with the intention of preventing heart disease.

Newly published findings from follow-ups of WHI participants may give clinicians and patients even more confidence for the use of estrogen products in early menopause.

According to the study, which Dr. Manson coauthored, younger women have a low risk for cardiovascular disease and other associated conditions when taking hormone therapy. Risks attributed to these drugs were less than one additional adverse event per 1000 women annually. This population may also derive significant quality-of-life benefits for symptom relief.

Dr. Manson told this news organization that estrogen in lower doses and delivered through the skin as a patch or gel may further reduce risks.

“The WHI findings should never be used as a reason to deny hormone therapy to women in early menopause with bothersome menopausal symptoms,” Dr. Manson said. “Many women are good candidates for treatment and, in shared decision-making with their clinicians, should be able to receive appropriate and personalized healthcare for their needs.”

But the current FDA warning label makes it difficult to help women understand the risk and benefits of low-dose estrogen, according to Stephanie Faubion, MD, MBA, medical director at the North American Menopause Society and director of Mayo Clinic’s Center for Women’s Health in Jacksonville, Florida.

Clinicians now must set aside time to explain the warnings to women when they prescribe low-dose estrogen, Dr. Faubion said.

“The package insert is going to look scary: I prepare women for that because otherwise they often won’t even fill it or use it.”
 

A version of this article appeared on Medscape.com .

Charles Powell, MD, said he sometimes has a hard time persuading patients to start on low-dose vaginal estrogen, which can help prevent urinary tract infections and ease other symptoms of menopause.

Many women fear taking these vaginal products because of what Dr. Powell considers excessively strong warnings about the risk for cancer and cardiovascular disease linked to daily estrogen pills that were issued in the early 2000s.

He is advocating for the US Food and Drug Administration (FDA) to remove the boxed warning on low-dose estrogen. His efforts are separate from his roles as an associate professor of urology at the Indiana University School of Medicine, and as a member of the American Urological Association (AUA), Dr. Powell said.

In his quest to find out how to change labeling, Dr. Powell has gained a quick education about drug regulation. He has enlisted Representative Jim Baird (R-IN) and Senator Mike Braun (R-IN) to contact the FDA on his behalf, while congressional staff guided him through the hurdles of getting the warning label changed. For instance, a manufacturer of low-dose estrogen may need to become involved.

“You don’t learn this in med school,” Dr. Powell said in an interview.

With this work, Dr. Powell is wading into a long-standing argument between the FDA and some clinicians and researchers about the potential harms of low-dose estrogen.

He is doing so at a time of increased interest in understanding genitourinary syndrome of menopause (GSM), a term coined a decade ago by the International Society for the Study of Women’s Sexual Health and the North American Menopause Society to cover “a constellation of conditions” related to urogenital atrophy.

Symptoms of GSM include vaginal dryness and burning and recurrent urinary tract infections.

The federal government in 2022 began a project budgeted with nearly $1 million to review evidence on treatments, including vaginal and low-dose estrogen. The aim is to eventually help the AUA develop clinical guidelines for addressing GSM.

In addition, a bipartisan Senate bill introduced in May calls for authorizing $125 million over 5 years for the National Institutes of Health (NIH) to fund research on menopause. Senator Patty Murray (D-WA), the lead sponsor of the bill, is a longtime advocate for women’s health and serves as chairwoman for the Senate Appropriations Committee, which largely sets the NIH budget.

“The bottom line is, for too long, menopause has been overlooked, underinvested in and left behind,” Sen. Murray said during a May 2 press conference. “It is well past time to stop treating menopause like some kind of secret and start treating it like the major mainstream public health issue it is.”

Evidence Demands

Increased federal funding for menopause research could help efforts to change the warning label on low-dose estrogen, according to JoAnn Manson, MD, chief of preventive medicine at Brigham and Women’s Hospital in Boston.

Dr. Manson was a leader of the Women’s Health Initiative (WHI), a major federally funded research project launched in 1991 to investigate if hormone therapy and diet could protect older women from chronic diseases related to aging.

Before the WHI, clinicians prescribed hormones to prevent cardiovascular disease, based on evidence from earlier research.

But in 2002, a WHI trial that compared estrogen-progestin tablets with placebo was halted early because of disturbing findings, including an association with higher risk for breast cancer and cardiovascular disease.

Compared with placebo, for every 10,000 women taking estrogen plus progestin annually, incidences of cardiovascular disease, stroke, pulmonary embolism, and invasive breast cancer were seven to eight times higher.

In January 2003, the FDA announced it would put a boxed warning about cardiovascular risk and cancer risk on estrogen products, reflecting the WHI finding.

The agency at the time said clinicians should work with patients to assess risks and benefits of these products to manage the effects of menopause.

But more news on the potential harms of estrogen followed in 2004: A WHI study comparing estrogen-only pills with placebo produced signals of a small increased risk for stroke, although it also indicated no excess risk for breast cancer for at least 6.8 years of use.

Dr. Manson and the North American Menopause Society in 2016 filed a petition with the FDA to remove the boxed warning that appears on the front of low-dose estrogen products. The group wanted the information on risks moved to the usual warning section of the label.

Two years later, the FDA rejected the petition, citing the absence of “well-controlled studies,” to prove low-dose topical estrogen poses less risk to women than the high-dose pills studied in the WHI.

The FDA told this news organization that it stands by the decisions in its rejection of the petition.

Persuading the FDA to revise the labels on low-dose estrogen products likely will require evidence from randomized, large-scale studies, Dr. Manson said. The agency has not been satisfied to date with findings from other kinds of studies, including observational research.

“Once that evidence is available that the benefit-risk profile is different for different formulations and the evidence is compelling and definitive, that warning should change,” Dr. Manson told this news organization.

But the warning continues to have a chilling effect on patient willingness to use low-dose vaginal estrogen, even with the FDA’s continued endorsement of estrogen for menopause symptoms, clinicians told this news organization.

Risa Kagan, MD, a gynecologist at Sutter Health in Berkeley, California, said in many cases her patients’ partners also need to be reassured. Dr. Kagan said she still sees women who have had to discontinue sexual intercourse because of pain. In some cases, the patients will bring the medicine home only to find that the warnings frighten their spouses.

“The spouse says, ‘Oh my God, I don’t want you to get dementia, to get breast cancer, it’s not worth it, so let’s keep doing outercourse’,” meaning sexual relations without penetration, Dr. Kagan said.

Difficult Messaging

From the initial unveiling of disappointing WHI results, clinicians and researchers have stressed that women could continue using estrogen products for managing symptoms of menopause, even while advising strongly against their continued use with the intention of preventing heart disease.

Newly published findings from follow-ups of WHI participants may give clinicians and patients even more confidence for the use of estrogen products in early menopause.

According to the study, which Dr. Manson coauthored, younger women have a low risk for cardiovascular disease and other associated conditions when taking hormone therapy. Risks attributed to these drugs were less than one additional adverse event per 1000 women annually. This population may also derive significant quality-of-life benefits for symptom relief.

Dr. Manson told this news organization that estrogen in lower doses and delivered through the skin as a patch or gel may further reduce risks.

“The WHI findings should never be used as a reason to deny hormone therapy to women in early menopause with bothersome menopausal symptoms,” Dr. Manson said. “Many women are good candidates for treatment and, in shared decision-making with their clinicians, should be able to receive appropriate and personalized healthcare for their needs.”

But the current FDA warning label makes it difficult to help women understand the risk and benefits of low-dose estrogen, according to Stephanie Faubion, MD, MBA, medical director at the North American Menopause Society and director of Mayo Clinic’s Center for Women’s Health in Jacksonville, Florida.

Clinicians now must set aside time to explain the warnings to women when they prescribe low-dose estrogen, Dr. Faubion said.

“The package insert is going to look scary: I prepare women for that because otherwise they often won’t even fill it or use it.”
 

A version of this article appeared on Medscape.com .

Women who are considered to be at average risk for breast cancer should have mammograms every other year starting at age 40 years until age 74, according to the latest recommendations from the US Preventive Services Task Force (USPSTF).

In its updated recommendations published April 30 in JAMA, the USPSTF also made an urgent call to address reasons why Black women are more likely to die from breast cancer than are White women and pressed for more research to address persisting questions about how best to screen for cancer in dense breasts, which about 40% of women have. The USPSTF highlighted evidence gaps on the benefits and harms of continuing mammography after age 75 years as well.

The updated USPSTF recommendations were first unveiled last year in a draft version. 

In 2016, the task force recommended biennial mammograms for women starting 10 years later, at age 50 years, while stressing a need for clinicians and patients to weigh the risks and benefits of screening for those in their 40s. 

The shift to a general recommendation to start at age 40 years is based on a broad review of available data on mammography, including modeling from Cancer Intervention and Surveillance Modeling Network (CISNET).

Alongside the USPSTF report, JAMA published three separate editorials — a reflection of the controversy that these breast cancer screening recommendations often generate. 

In one editorial, published in JAMA Network Open, Lydia E. Pace, MD, MPH, and Nancy L. Keating, MD, MPH, highlighted that though screening earlier will prevent more deaths from breast cancer, it will also lead to more false positive findings and increase rates of overdiagnosis. 

Dr. Pace and Dr. Keating explained that the modeling study commissioned by the USPSTF estimated that screening every 2 years starting at age 40 years would avoid an additional 1.3 breast cancer deaths compared with screening at age 50 years. Among Black women, screening every 2 years starting at age 40 years would avert an extra 1.8 breast cancer deaths per 1000 people screened. 

However, the model also found that screening every 2 years starting at age 40 years would lead to more false positive tests — a rate of about 8.5% vs 7.8% for those starting at age 50.

“Given mammography screening’s modest benefits, we feel that all women — and particularly those aged 40 to 49 years —should be counseled about the benefits and harms of mammography and supported in deciding whether the balance of benefits to harms fits with their priorities and values,” wrote Dr. Pace and Dr. Keating, who specialize in internal medicine.

In a second editorial, in JAMA, Joann G. Elmore, MD, MPH, of UCLA, and Christoph I. Lee, MD, MS, of the University of Washington, Seattle, noted that the revised recommendations “shed light on 2 major issues that demand greater attention: addressing health inequities related to breast cancer outcomes and ensuring benefits for all women amid rapid screening technological advancements.” 

The USPSTF’s decision to recommend an earlier start age for routine mammography was partly intended to begin to address the fact that Black women are about 40% more likely to die from breast cancer than are White women.

“Despite greater absolute benefits of screening for Black women, the modeling study and systematic review underscore that mammography’s benefits (ie, breast cancer deaths averted) are modest for both Black women and the general population,” wrote Dr. Elmore and Dr. Lee.

The editorialists also cautioned against adopting artificial intelligence (AI) support tools too rapidly, criticizing the USPSTF for overlooking this “pressing issue.” 

“While AI algorithms show promise for enhancing cancer detection, their impact on patient outcomes and the balance between benefit and harms remain uncertain,” the editorialists wrote.

In a third editorial, in JAMA Oncology, Wendie A. Berg, MD, PhD, a radiologist at the University of Pittsburgh, argued that though the updated recommendations are “an important step forward,” they don’t go far enough.

Dr. Berg, for instance, noted her surprise “ to see the USPSTF recommendation only for biennial, rather than annual, screening among women aged 40 to 74 years.”

Compared with no screening, annual screening would reduce rates of breast cancer mortality (35.2%) more than biennial (28.4%) screening does among women aged 40-74 years, according to the CISNET modeling that informed the USPSTF’s decision.

Plus, Dr. Berg noted, regular risk assessments should begin at age 25 years “to identify women at high risk who should start annual MRI screenings.”

The American College of Radiology (ACR) offered similar views in a statement, saying the recommendations “do not go far enough to save more women’s lives.” It urged a more aggressive screening schedule, which starts at age 40 years but occurs annually vs biennially and continues past age 74 years. Like Dr. Berg, the ACR advocated for breast cancer risk assessments to begin at age 25 years.

The American Cancer Society also recommended annual mammography screening, starting as early as age 40 years in average-risk women, with high-risk women receiving a breast MRI and a mammogram every year starting at age 30 years. 
 

Ongoing Uncertainties 

The USPSTF’s 2024 update highlighted persistent evidence gaps in several key areas. 

The USPSTF, for instance, highlighted insufficient evidence on the benefits and harms of continuing to screen women who are 75 years or older as well as the benefits and harms of supplemental screening with breast ultrasonography or MRI in women with dense breasts who had a negative screening mammogram.

In the update, USPSTF noted that it’s still clear what proportion of ductal carcinoma in situ involves lesions detected by screening would not have ultimately caused harm. 

For women with dense breasts, the USPSTF said that “research is needed to help clinicians and patients understand the best strategy for breast cancer screening in women found to have dense breasts,” which includes supplemental screening.

Women with dense breasts should still get mammograms, but there is not enough evidence for a blanket statement about which benefit they might get from additional screening, Carol Mangione, MD, past chair of USPSTF, told this news organization. 

“We don’t want to send a message that the mammogram doesn’t have value in that group, because it does have high value,” said Dr. Mangione, chief of the division of general internal medicine and health services research at UCLA Health. 

Women with dense breasts should work with primary care clinicians who can take a holistic view of their preferences and needs, allowing them to make an informed choice about additional screening, she said.

“But we can’t make a global population choice because we don’t have the studies to do that,” Dr. Mangione said.
 

A version of this article appeared on Medscape.com.

Women who are considered to be at average risk for breast cancer should have mammograms every other year starting at age 40 years until age 74, according to the latest recommendations from the US Preventive Services Task Force (USPSTF).

In its updated recommendations published April 30 in JAMA, the USPSTF also made an urgent call to address reasons why Black women are more likely to die from breast cancer than are White women and pressed for more research to address persisting questions about how best to screen for cancer in dense breasts, which about 40% of women have. The USPSTF highlighted evidence gaps on the benefits and harms of continuing mammography after age 75 years as well.

The updated USPSTF recommendations were first unveiled last year in a draft version. 

In 2016, the task force recommended biennial mammograms for women starting 10 years later, at age 50 years, while stressing a need for clinicians and patients to weigh the risks and benefits of screening for those in their 40s. 

The shift to a general recommendation to start at age 40 years is based on a broad review of available data on mammography, including modeling from Cancer Intervention and Surveillance Modeling Network (CISNET).

Alongside the USPSTF report, JAMA published three separate editorials — a reflection of the controversy that these breast cancer screening recommendations often generate. 

In one editorial, published in JAMA Network Open, Lydia E. Pace, MD, MPH, and Nancy L. Keating, MD, MPH, highlighted that though screening earlier will prevent more deaths from breast cancer, it will also lead to more false positive findings and increase rates of overdiagnosis. 

Dr. Pace and Dr. Keating explained that the modeling study commissioned by the USPSTF estimated that screening every 2 years starting at age 40 years would avoid an additional 1.3 breast cancer deaths compared with screening at age 50 years. Among Black women, screening every 2 years starting at age 40 years would avert an extra 1.8 breast cancer deaths per 1000 people screened. 

However, the model also found that screening every 2 years starting at age 40 years would lead to more false positive tests — a rate of about 8.5% vs 7.8% for those starting at age 50.

“Given mammography screening’s modest benefits, we feel that all women — and particularly those aged 40 to 49 years —should be counseled about the benefits and harms of mammography and supported in deciding whether the balance of benefits to harms fits with their priorities and values,” wrote Dr. Pace and Dr. Keating, who specialize in internal medicine.

In a second editorial, in JAMA, Joann G. Elmore, MD, MPH, of UCLA, and Christoph I. Lee, MD, MS, of the University of Washington, Seattle, noted that the revised recommendations “shed light on 2 major issues that demand greater attention: addressing health inequities related to breast cancer outcomes and ensuring benefits for all women amid rapid screening technological advancements.” 

The USPSTF’s decision to recommend an earlier start age for routine mammography was partly intended to begin to address the fact that Black women are about 40% more likely to die from breast cancer than are White women.

“Despite greater absolute benefits of screening for Black women, the modeling study and systematic review underscore that mammography’s benefits (ie, breast cancer deaths averted) are modest for both Black women and the general population,” wrote Dr. Elmore and Dr. Lee.

The editorialists also cautioned against adopting artificial intelligence (AI) support tools too rapidly, criticizing the USPSTF for overlooking this “pressing issue.” 

“While AI algorithms show promise for enhancing cancer detection, their impact on patient outcomes and the balance between benefit and harms remain uncertain,” the editorialists wrote.

In a third editorial, in JAMA Oncology, Wendie A. Berg, MD, PhD, a radiologist at the University of Pittsburgh, argued that though the updated recommendations are “an important step forward,” they don’t go far enough.

Dr. Berg, for instance, noted her surprise “ to see the USPSTF recommendation only for biennial, rather than annual, screening among women aged 40 to 74 years.”

Compared with no screening, annual screening would reduce rates of breast cancer mortality (35.2%) more than biennial (28.4%) screening does among women aged 40-74 years, according to the CISNET modeling that informed the USPSTF’s decision.

Plus, Dr. Berg noted, regular risk assessments should begin at age 25 years “to identify women at high risk who should start annual MRI screenings.”

The American College of Radiology (ACR) offered similar views in a statement, saying the recommendations “do not go far enough to save more women’s lives.” It urged a more aggressive screening schedule, which starts at age 40 years but occurs annually vs biennially and continues past age 74 years. Like Dr. Berg, the ACR advocated for breast cancer risk assessments to begin at age 25 years.

The American Cancer Society also recommended annual mammography screening, starting as early as age 40 years in average-risk women, with high-risk women receiving a breast MRI and a mammogram every year starting at age 30 years. 
 

Ongoing Uncertainties 

The USPSTF’s 2024 update highlighted persistent evidence gaps in several key areas. 

The USPSTF, for instance, highlighted insufficient evidence on the benefits and harms of continuing to screen women who are 75 years or older as well as the benefits and harms of supplemental screening with breast ultrasonography or MRI in women with dense breasts who had a negative screening mammogram.

In the update, USPSTF noted that it’s still clear what proportion of ductal carcinoma in situ involves lesions detected by screening would not have ultimately caused harm. 

For women with dense breasts, the USPSTF said that “research is needed to help clinicians and patients understand the best strategy for breast cancer screening in women found to have dense breasts,” which includes supplemental screening.

Women with dense breasts should still get mammograms, but there is not enough evidence for a blanket statement about which benefit they might get from additional screening, Carol Mangione, MD, past chair of USPSTF, told this news organization. 

“We don’t want to send a message that the mammogram doesn’t have value in that group, because it does have high value,” said Dr. Mangione, chief of the division of general internal medicine and health services research at UCLA Health. 

Women with dense breasts should work with primary care clinicians who can take a holistic view of their preferences and needs, allowing them to make an informed choice about additional screening, she said.

“But we can’t make a global population choice because we don’t have the studies to do that,” Dr. Mangione said.
 

A version of this article appeared on Medscape.com.

Women who are considered to be at average risk for breast cancer should have mammograms every other year starting at age 40 years until age 74, according to the latest recommendations from the US Preventive Services Task Force (USPSTF).

In its updated recommendations published April 30 in JAMA, the USPSTF also made an urgent call to address reasons why Black women are more likely to die from breast cancer than are White women and pressed for more research to address persisting questions about how best to screen for cancer in dense breasts, which about 40% of women have. The USPSTF highlighted evidence gaps on the benefits and harms of continuing mammography after age 75 years as well.

The updated USPSTF recommendations were first unveiled last year in a draft version. 

In 2016, the task force recommended biennial mammograms for women starting 10 years later, at age 50 years, while stressing a need for clinicians and patients to weigh the risks and benefits of screening for those in their 40s. 

The shift to a general recommendation to start at age 40 years is based on a broad review of available data on mammography, including modeling from Cancer Intervention and Surveillance Modeling Network (CISNET).

Alongside the USPSTF report, JAMA published three separate editorials — a reflection of the controversy that these breast cancer screening recommendations often generate. 

In one editorial, published in JAMA Network Open, Lydia E. Pace, MD, MPH, and Nancy L. Keating, MD, MPH, highlighted that though screening earlier will prevent more deaths from breast cancer, it will also lead to more false positive findings and increase rates of overdiagnosis. 

Dr. Pace and Dr. Keating explained that the modeling study commissioned by the USPSTF estimated that screening every 2 years starting at age 40 years would avoid an additional 1.3 breast cancer deaths compared with screening at age 50 years. Among Black women, screening every 2 years starting at age 40 years would avert an extra 1.8 breast cancer deaths per 1000 people screened. 

However, the model also found that screening every 2 years starting at age 40 years would lead to more false positive tests — a rate of about 8.5% vs 7.8% for those starting at age 50.

“Given mammography screening’s modest benefits, we feel that all women — and particularly those aged 40 to 49 years —should be counseled about the benefits and harms of mammography and supported in deciding whether the balance of benefits to harms fits with their priorities and values,” wrote Dr. Pace and Dr. Keating, who specialize in internal medicine.

In a second editorial, in JAMA, Joann G. Elmore, MD, MPH, of UCLA, and Christoph I. Lee, MD, MS, of the University of Washington, Seattle, noted that the revised recommendations “shed light on 2 major issues that demand greater attention: addressing health inequities related to breast cancer outcomes and ensuring benefits for all women amid rapid screening technological advancements.” 

The USPSTF’s decision to recommend an earlier start age for routine mammography was partly intended to begin to address the fact that Black women are about 40% more likely to die from breast cancer than are White women.

“Despite greater absolute benefits of screening for Black women, the modeling study and systematic review underscore that mammography’s benefits (ie, breast cancer deaths averted) are modest for both Black women and the general population,” wrote Dr. Elmore and Dr. Lee.

The editorialists also cautioned against adopting artificial intelligence (AI) support tools too rapidly, criticizing the USPSTF for overlooking this “pressing issue.” 

“While AI algorithms show promise for enhancing cancer detection, their impact on patient outcomes and the balance between benefit and harms remain uncertain,” the editorialists wrote.

In a third editorial, in JAMA Oncology, Wendie A. Berg, MD, PhD, a radiologist at the University of Pittsburgh, argued that though the updated recommendations are “an important step forward,” they don’t go far enough.

Dr. Berg, for instance, noted her surprise “ to see the USPSTF recommendation only for biennial, rather than annual, screening among women aged 40 to 74 years.”

Compared with no screening, annual screening would reduce rates of breast cancer mortality (35.2%) more than biennial (28.4%) screening does among women aged 40-74 years, according to the CISNET modeling that informed the USPSTF’s decision.

Plus, Dr. Berg noted, regular risk assessments should begin at age 25 years “to identify women at high risk who should start annual MRI screenings.”

The American College of Radiology (ACR) offered similar views in a statement, saying the recommendations “do not go far enough to save more women’s lives.” It urged a more aggressive screening schedule, which starts at age 40 years but occurs annually vs biennially and continues past age 74 years. Like Dr. Berg, the ACR advocated for breast cancer risk assessments to begin at age 25 years.

The American Cancer Society also recommended annual mammography screening, starting as early as age 40 years in average-risk women, with high-risk women receiving a breast MRI and a mammogram every year starting at age 30 years. 
 

Ongoing Uncertainties 

The USPSTF’s 2024 update highlighted persistent evidence gaps in several key areas. 

The USPSTF, for instance, highlighted insufficient evidence on the benefits and harms of continuing to screen women who are 75 years or older as well as the benefits and harms of supplemental screening with breast ultrasonography or MRI in women with dense breasts who had a negative screening mammogram.

In the update, USPSTF noted that it’s still clear what proportion of ductal carcinoma in situ involves lesions detected by screening would not have ultimately caused harm. 

For women with dense breasts, the USPSTF said that “research is needed to help clinicians and patients understand the best strategy for breast cancer screening in women found to have dense breasts,” which includes supplemental screening.

Women with dense breasts should still get mammograms, but there is not enough evidence for a blanket statement about which benefit they might get from additional screening, Carol Mangione, MD, past chair of USPSTF, told this news organization. 

“We don’t want to send a message that the mammogram doesn’t have value in that group, because it does have high value,” said Dr. Mangione, chief of the division of general internal medicine and health services research at UCLA Health. 

Women with dense breasts should work with primary care clinicians who can take a holistic view of their preferences and needs, allowing them to make an informed choice about additional screening, she said.

“But we can’t make a global population choice because we don’t have the studies to do that,” Dr. Mangione said.
 

A version of this article appeared on Medscape.com.

Physician practice ownership by corporations, including health insurers, private equity firms, and large pharmacy chains, reached 30.1% as of January for the first time surpassing ownership by hospitals and health systems (28.4%), according to a new report.

As a result, about three in five physician practices are now owned by nonphysicians.

In early 2020, corporations owned just about 17% of US medical practices, while hospitals and health systems owned about 25%, according to the report released Thursday by nonprofit Physician Advocacy Institute (PAI). But corporate ownership of medical groups surged during the pandemic.

These trends raise questions about how best to protect patients and physicians in a changing employment landscape, said Kelly Kenney, PAI’s chief executive officer, in a statement.

“Corporate entities are assuming control of physician practices and changing the face of medicine in the United States with little to no scrutiny from regulators,” Ms. Kenney said.

The research, conducted by consulting group Avalere for PAI, used the IQVIA OneKey database that contains physician and practice location information on hospital and health system ownership.

By 2022-2023, there was a 7.3% increase in the percentage of practices owned by hospitals and 5.9% increase in the percentage of physicians employed by these organizations, PAI said. In the same time frame, there was an 11% increase in the percentage of practices owned by corporations and a 3.0% increase in the percentage of physicians employed by these entities.

“Physicians have an ethical responsibility to their patients’ health,” Ms. Kenney said. “Corporate entities have a fiduciary responsibility to their shareholders and are motivated to put profits first…these interests can conflict with providing the best medical care to patients.”
 

Federal Scrutiny Increases

However, both federal and state regulators are paying more attention to what happens to patients and physicians when corporations acquire practices.

“Given recent trends, we are concerned that some transactions may generate profits for those firms at the expense of patients’ health, workers’ safety, quality of care, and affordable healthcare for patients and taxpayers,” said the Federal Trade Commission (FTC) and the Justice (DOJ) and Health and Human Services (HHS) departments.

This statement appears in those agencies’ joint request for information (RFI) announced in March. An RFI is a tool that federal agencies can use to gauge the level of both support and opposition they would face if they were to try to change policies. Public comments are due May 6.

Corporations and advocacy groups often submit detailed comments outlining reasons why the federal government should or should not act on an issue. But individuals also can make their case in this forum.

The FTC, DOJ, and HHS are looking broadly at consolidation in healthcare, but they also spell out potential concerns related to acquisition of physician practices.

For example, they asked clinicians and support staff to provide feedback about whether acquisitions lead to changes in:

• Take-home pay
• Staffing levels
• Workplace safety
• Compensation model (eg, from fixed salary to volume based)
• Policies regarding patient referrals
• Mix of patients
• The volume of patients
• The way providers practice medicine (eg, incentives, prescribing decisions, forced protocols, restrictions on time spent with patients, or mandatory coding practices)
• Administrative or managerial organization (eg, transition to a management services organization).

A version of this article appeared on Medscape.com.

Physician practice ownership by corporations, including health insurers, private equity firms, and large pharmacy chains, reached 30.1% as of January for the first time surpassing ownership by hospitals and health systems (28.4%), according to a new report.

As a result, about three in five physician practices are now owned by nonphysicians.

In early 2020, corporations owned just about 17% of US medical practices, while hospitals and health systems owned about 25%, according to the report released Thursday by nonprofit Physician Advocacy Institute (PAI). But corporate ownership of medical groups surged during the pandemic.

These trends raise questions about how best to protect patients and physicians in a changing employment landscape, said Kelly Kenney, PAI’s chief executive officer, in a statement.

“Corporate entities are assuming control of physician practices and changing the face of medicine in the United States with little to no scrutiny from regulators,” Ms. Kenney said.

The research, conducted by consulting group Avalere for PAI, used the IQVIA OneKey database that contains physician and practice location information on hospital and health system ownership.

By 2022-2023, there was a 7.3% increase in the percentage of practices owned by hospitals and 5.9% increase in the percentage of physicians employed by these organizations, PAI said. In the same time frame, there was an 11% increase in the percentage of practices owned by corporations and a 3.0% increase in the percentage of physicians employed by these entities.

“Physicians have an ethical responsibility to their patients’ health,” Ms. Kenney said. “Corporate entities have a fiduciary responsibility to their shareholders and are motivated to put profits first…these interests can conflict with providing the best medical care to patients.”
 

Federal Scrutiny Increases

However, both federal and state regulators are paying more attention to what happens to patients and physicians when corporations acquire practices.

“Given recent trends, we are concerned that some transactions may generate profits for those firms at the expense of patients’ health, workers’ safety, quality of care, and affordable healthcare for patients and taxpayers,” said the Federal Trade Commission (FTC) and the Justice (DOJ) and Health and Human Services (HHS) departments.

This statement appears in those agencies’ joint request for information (RFI) announced in March. An RFI is a tool that federal agencies can use to gauge the level of both support and opposition they would face if they were to try to change policies. Public comments are due May 6.

Corporations and advocacy groups often submit detailed comments outlining reasons why the federal government should or should not act on an issue. But individuals also can make their case in this forum.

The FTC, DOJ, and HHS are looking broadly at consolidation in healthcare, but they also spell out potential concerns related to acquisition of physician practices.

For example, they asked clinicians and support staff to provide feedback about whether acquisitions lead to changes in:

• Take-home pay
• Staffing levels
• Workplace safety
• Compensation model (eg, from fixed salary to volume based)
• Policies regarding patient referrals
• Mix of patients
• The volume of patients
• The way providers practice medicine (eg, incentives, prescribing decisions, forced protocols, restrictions on time spent with patients, or mandatory coding practices)
• Administrative or managerial organization (eg, transition to a management services organization).

A version of this article appeared on Medscape.com.

Physician practice ownership by corporations, including health insurers, private equity firms, and large pharmacy chains, reached 30.1% as of January for the first time surpassing ownership by hospitals and health systems (28.4%), according to a new report.

As a result, about three in five physician practices are now owned by nonphysicians.

In early 2020, corporations owned just about 17% of US medical practices, while hospitals and health systems owned about 25%, according to the report released Thursday by nonprofit Physician Advocacy Institute (PAI). But corporate ownership of medical groups surged during the pandemic.

These trends raise questions about how best to protect patients and physicians in a changing employment landscape, said Kelly Kenney, PAI’s chief executive officer, in a statement.

“Corporate entities are assuming control of physician practices and changing the face of medicine in the United States with little to no scrutiny from regulators,” Ms. Kenney said.

The research, conducted by consulting group Avalere for PAI, used the IQVIA OneKey database that contains physician and practice location information on hospital and health system ownership.

By 2022-2023, there was a 7.3% increase in the percentage of practices owned by hospitals and 5.9% increase in the percentage of physicians employed by these organizations, PAI said. In the same time frame, there was an 11% increase in the percentage of practices owned by corporations and a 3.0% increase in the percentage of physicians employed by these entities.

“Physicians have an ethical responsibility to their patients’ health,” Ms. Kenney said. “Corporate entities have a fiduciary responsibility to their shareholders and are motivated to put profits first…these interests can conflict with providing the best medical care to patients.”
 

Federal Scrutiny Increases

However, both federal and state regulators are paying more attention to what happens to patients and physicians when corporations acquire practices.

“Given recent trends, we are concerned that some transactions may generate profits for those firms at the expense of patients’ health, workers’ safety, quality of care, and affordable healthcare for patients and taxpayers,” said the Federal Trade Commission (FTC) and the Justice (DOJ) and Health and Human Services (HHS) departments.

This statement appears in those agencies’ joint request for information (RFI) announced in March. An RFI is a tool that federal agencies can use to gauge the level of both support and opposition they would face if they were to try to change policies. Public comments are due May 6.

Corporations and advocacy groups often submit detailed comments outlining reasons why the federal government should or should not act on an issue. But individuals also can make their case in this forum.

The FTC, DOJ, and HHS are looking broadly at consolidation in healthcare, but they also spell out potential concerns related to acquisition of physician practices.

For example, they asked clinicians and support staff to provide feedback about whether acquisitions lead to changes in:

• Take-home pay
• Staffing levels
• Workplace safety
• Compensation model (eg, from fixed salary to volume based)
• Policies regarding patient referrals
• Mix of patients
• The volume of patients
• The way providers practice medicine (eg, incentives, prescribing decisions, forced protocols, restrictions on time spent with patients, or mandatory coding practices)
• Administrative or managerial organization (eg, transition to a management services organization).

A version of this article appeared on Medscape.com.

A panel of US government advisers unanimously backed use of highly sensitive tests that check for minimal residual disease (MRD) in efforts to accelerate approvals of drugs for multiple myeloma, an incurable blood cancer.

The Oncologic Drugs Advisory Committee (ODAC) of the US Food and Drug Administration (FDA) voted 12-0 on April 12 on the following question: Does the evidence support the use of MRD as an accelerated approval endpoint in multiple myeloma clinical trials?

The FDA is not bound to accept the recommendations of its panels, but often does so.

ODAC panelists said they felt comfortable in this recommendation because they expected the FDA to mandate confirmatory studies of any drugs to be given accelerated approval based on MRD data.

There’s a risk that MRD results might mislead regulators into clearing a drug later found to lack benefit, said Christopher Hourigan, DM, DPhil, an ODAC panelist and a physician-scientist at Virginia Tech, Blacksburg, Virginia, who treats people with blood cancer. Further tests would ultimately show if drugs cleared based on MRD data actually delivered benefits such as extending progression-free survival (PFS).

“That’s why we’re talking about accelerated approval,” Dr. Hourigan said. “There is harm to inaction. We’re not currently curing people in multiple myeloma. I’m not willing to make patients wait on principle for a theoretical perfect that may never come.”

“Our responsibility is to accept the world as messy and be agile enough to adapt and iterate that the evidence develops rather than create barriers to the work of discovering effective new therapies for these patients,” he added.

Advances in testing now allow for detection of the presence of malignant cells at orders of magnitude below previous assessments. MRD assays used in tracking what’s happening with myeloma generally have a sensitivity level of 10^-5, or a detection capacity of one cell of 100,000, said Ola Landgren, MD, PhD, of the University of Miami, Miami, Florida, during a presentation at the meeting.

The April 12 meeting was somewhat unusual for ODAC.

Instead of reviewing the benefits and risks of a specific drug, the panel reviewed results from two separate major research efforts done to see how MRD could be used in development of drugs.

These were Dr. Landgren’s EVIDENCE (Evaluating minimal residual disease as an intermediate clinical endpoint for multiple myeloma) meta-analysis, and the similar work of the i2TEAMM group, affiliated with the International Myeloma Foundation.

In its review, the FDA staff noted differences in the approaches of the two groups. In its analysis, the i2TEAMM removed information about patients with missing MRD data, while the University of Miami team retained information about these kinds of patients in the analyses and assigned their status to be MRD positive.

The FDA staff also noted in their review and presentations weaknesses in the case for MRD. For example, the FDA staff noted that the treatment effect on MRD negativity was not statistically significant in 4 of the 8 treatment comparisons in the work from Dr. Landgren and colleagues.

The FDA staff looked at what these analyses suggested at both an individual level and trial level. The data from these two research projects taken as a whole showed “strong individual-level” associations between negative MRD findings and later positive outcomes for patients, although trial-level associations were “weak to moderate” in some cases, the staff wrote.

The FDA staff concluded that the research appeared to support arguments in favor of the “prognostic value,” even with outstanding questions about how best to use this test.

In the briefing document for the meeting, the FDA also emphasized the need for new treatments.

Multiple myeloma remains an incurable disease with a 5-year relative survival rate of 59.8%, even after significant recent progress in treatment, the agency said. In the past decade, the FDA has approved 15 new drugs and greater than 20 new indications have been approved for the treatment of patients with multiple myeloma.

The FDA has been working with drugmakers and academic researchers for several years to address the potential of MRD in development of blood cancers. The agency in 2020 issued a guidance document on this issue.

Several ODAC members praised the i2TEAMM and Dr. Landgren’s EVIDENCE teams for their work, which took place across several nations and extended over many years.

“This was a herculean effort. It really changes the playbook for how we think about biomarkers across all cancer types,” said ODAC panelist Neil Vasan, MD, PhD, of Columbia University, New York, NY. “To me, the important word was reasonable. Is this a reasonable surrogate endpoint? Is this a reasonable intermediate endpoint? I think it is more than reasonable.”

Still, ODAC panelist Jorge Nieva, MD, raised a point of concern about how use of MRD as an endpoint could change the design of studies. He urged caution among researchers about potential ramping up of collection of MRD tests in search of more robust data, which could lead to more testing for patients.

“I have this tremendous fear that this is going to mean every myeloma protocol has a marrow biopsy every six weeks on the patients forever,” said Dr. Nieva of the Keck School of Medicine, University of Southern California, Los Angeles. “I just don’t want to see that happen. So I think we need to balance these two things.”

A panel of US government advisers unanimously backed use of highly sensitive tests that check for minimal residual disease (MRD) in efforts to accelerate approvals of drugs for multiple myeloma, an incurable blood cancer.

The Oncologic Drugs Advisory Committee (ODAC) of the US Food and Drug Administration (FDA) voted 12-0 on April 12 on the following question: Does the evidence support the use of MRD as an accelerated approval endpoint in multiple myeloma clinical trials?

The FDA is not bound to accept the recommendations of its panels, but often does so.

ODAC panelists said they felt comfortable in this recommendation because they expected the FDA to mandate confirmatory studies of any drugs to be given accelerated approval based on MRD data.

There’s a risk that MRD results might mislead regulators into clearing a drug later found to lack benefit, said Christopher Hourigan, DM, DPhil, an ODAC panelist and a physician-scientist at Virginia Tech, Blacksburg, Virginia, who treats people with blood cancer. Further tests would ultimately show if drugs cleared based on MRD data actually delivered benefits such as extending progression-free survival (PFS).

“That’s why we’re talking about accelerated approval,” Dr. Hourigan said. “There is harm to inaction. We’re not currently curing people in multiple myeloma. I’m not willing to make patients wait on principle for a theoretical perfect that may never come.”

“Our responsibility is to accept the world as messy and be agile enough to adapt and iterate that the evidence develops rather than create barriers to the work of discovering effective new therapies for these patients,” he added.

Advances in testing now allow for detection of the presence of malignant cells at orders of magnitude below previous assessments. MRD assays used in tracking what’s happening with myeloma generally have a sensitivity level of 10^-5, or a detection capacity of one cell of 100,000, said Ola Landgren, MD, PhD, of the University of Miami, Miami, Florida, during a presentation at the meeting.

The April 12 meeting was somewhat unusual for ODAC.

Instead of reviewing the benefits and risks of a specific drug, the panel reviewed results from two separate major research efforts done to see how MRD could be used in development of drugs.

These were Dr. Landgren’s EVIDENCE (Evaluating minimal residual disease as an intermediate clinical endpoint for multiple myeloma) meta-analysis, and the similar work of the i2TEAMM group, affiliated with the International Myeloma Foundation.

In its review, the FDA staff noted differences in the approaches of the two groups. In its analysis, the i2TEAMM removed information about patients with missing MRD data, while the University of Miami team retained information about these kinds of patients in the analyses and assigned their status to be MRD positive.

The FDA staff also noted in their review and presentations weaknesses in the case for MRD. For example, the FDA staff noted that the treatment effect on MRD negativity was not statistically significant in 4 of the 8 treatment comparisons in the work from Dr. Landgren and colleagues.

The FDA staff looked at what these analyses suggested at both an individual level and trial level. The data from these two research projects taken as a whole showed “strong individual-level” associations between negative MRD findings and later positive outcomes for patients, although trial-level associations were “weak to moderate” in some cases, the staff wrote.

The FDA staff concluded that the research appeared to support arguments in favor of the “prognostic value,” even with outstanding questions about how best to use this test.

In the briefing document for the meeting, the FDA also emphasized the need for new treatments.

Multiple myeloma remains an incurable disease with a 5-year relative survival rate of 59.8%, even after significant recent progress in treatment, the agency said. In the past decade, the FDA has approved 15 new drugs and greater than 20 new indications have been approved for the treatment of patients with multiple myeloma.

The FDA has been working with drugmakers and academic researchers for several years to address the potential of MRD in development of blood cancers. The agency in 2020 issued a guidance document on this issue.

Several ODAC members praised the i2TEAMM and Dr. Landgren’s EVIDENCE teams for their work, which took place across several nations and extended over many years.

“This was a herculean effort. It really changes the playbook for how we think about biomarkers across all cancer types,” said ODAC panelist Neil Vasan, MD, PhD, of Columbia University, New York, NY. “To me, the important word was reasonable. Is this a reasonable surrogate endpoint? Is this a reasonable intermediate endpoint? I think it is more than reasonable.”

Still, ODAC panelist Jorge Nieva, MD, raised a point of concern about how use of MRD as an endpoint could change the design of studies. He urged caution among researchers about potential ramping up of collection of MRD tests in search of more robust data, which could lead to more testing for patients.

“I have this tremendous fear that this is going to mean every myeloma protocol has a marrow biopsy every six weeks on the patients forever,” said Dr. Nieva of the Keck School of Medicine, University of Southern California, Los Angeles. “I just don’t want to see that happen. So I think we need to balance these two things.”

A panel of US government advisers unanimously backed use of highly sensitive tests that check for minimal residual disease (MRD) in efforts to accelerate approvals of drugs for multiple myeloma, an incurable blood cancer.

The Oncologic Drugs Advisory Committee (ODAC) of the US Food and Drug Administration (FDA) voted 12-0 on April 12 on the following question: Does the evidence support the use of MRD as an accelerated approval endpoint in multiple myeloma clinical trials?

The FDA is not bound to accept the recommendations of its panels, but often does so.

ODAC panelists said they felt comfortable in this recommendation because they expected the FDA to mandate confirmatory studies of any drugs to be given accelerated approval based on MRD data.

There’s a risk that MRD results might mislead regulators into clearing a drug later found to lack benefit, said Christopher Hourigan, DM, DPhil, an ODAC panelist and a physician-scientist at Virginia Tech, Blacksburg, Virginia, who treats people with blood cancer. Further tests would ultimately show if drugs cleared based on MRD data actually delivered benefits such as extending progression-free survival (PFS).

“That’s why we’re talking about accelerated approval,” Dr. Hourigan said. “There is harm to inaction. We’re not currently curing people in multiple myeloma. I’m not willing to make patients wait on principle for a theoretical perfect that may never come.”

“Our responsibility is to accept the world as messy and be agile enough to adapt and iterate that the evidence develops rather than create barriers to the work of discovering effective new therapies for these patients,” he added.

Advances in testing now allow for detection of the presence of malignant cells at orders of magnitude below previous assessments. MRD assays used in tracking what’s happening with myeloma generally have a sensitivity level of 10^-5, or a detection capacity of one cell of 100,000, said Ola Landgren, MD, PhD, of the University of Miami, Miami, Florida, during a presentation at the meeting.

The April 12 meeting was somewhat unusual for ODAC.

Instead of reviewing the benefits and risks of a specific drug, the panel reviewed results from two separate major research efforts done to see how MRD could be used in development of drugs.

These were Dr. Landgren’s EVIDENCE (Evaluating minimal residual disease as an intermediate clinical endpoint for multiple myeloma) meta-analysis, and the similar work of the i2TEAMM group, affiliated with the International Myeloma Foundation.

In its review, the FDA staff noted differences in the approaches of the two groups. In its analysis, the i2TEAMM removed information about patients with missing MRD data, while the University of Miami team retained information about these kinds of patients in the analyses and assigned their status to be MRD positive.

The FDA staff also noted in their review and presentations weaknesses in the case for MRD. For example, the FDA staff noted that the treatment effect on MRD negativity was not statistically significant in 4 of the 8 treatment comparisons in the work from Dr. Landgren and colleagues.

The FDA staff looked at what these analyses suggested at both an individual level and trial level. The data from these two research projects taken as a whole showed “strong individual-level” associations between negative MRD findings and later positive outcomes for patients, although trial-level associations were “weak to moderate” in some cases, the staff wrote.

The FDA staff concluded that the research appeared to support arguments in favor of the “prognostic value,” even with outstanding questions about how best to use this test.

In the briefing document for the meeting, the FDA also emphasized the need for new treatments.

Multiple myeloma remains an incurable disease with a 5-year relative survival rate of 59.8%, even after significant recent progress in treatment, the agency said. In the past decade, the FDA has approved 15 new drugs and greater than 20 new indications have been approved for the treatment of patients with multiple myeloma.

The FDA has been working with drugmakers and academic researchers for several years to address the potential of MRD in development of blood cancers. The agency in 2020 issued a guidance document on this issue.

Several ODAC members praised the i2TEAMM and Dr. Landgren’s EVIDENCE teams for their work, which took place across several nations and extended over many years.

“This was a herculean effort. It really changes the playbook for how we think about biomarkers across all cancer types,” said ODAC panelist Neil Vasan, MD, PhD, of Columbia University, New York, NY. “To me, the important word was reasonable. Is this a reasonable surrogate endpoint? Is this a reasonable intermediate endpoint? I think it is more than reasonable.”

Still, ODAC panelist Jorge Nieva, MD, raised a point of concern about how use of MRD as an endpoint could change the design of studies. He urged caution among researchers about potential ramping up of collection of MRD tests in search of more robust data, which could lead to more testing for patients.

“I have this tremendous fear that this is going to mean every myeloma protocol has a marrow biopsy every six weeks on the patients forever,” said Dr. Nieva of the Keck School of Medicine, University of Southern California, Los Angeles. “I just don’t want to see that happen. So I think we need to balance these two things.”

A group of researchers urged US regulators to revoke the approval of a test marketed for predicting risk for opioid addiction and said government health plans should not pay for the product. 

The focus of the request is AdvertD (SOLVD Health), which the US Food and Drug Administration (FDA) approved in December as the first test to use DNA to evaluate if people have an elevated risk for opioid use disorder (OUD). A sample obtained through a cheek swab is meant to help guide decisions about opioid prescriptions for patients not previously treated with these drugs, such as someone undergoing a planned surgery, the FDA said. 

But Michael T. Abrams, MPH, PhD, senior health researcher for Public Citizen’s Health Research Group, and 30 other physicians and researchers sent an April 4 letter to the Food and Drug Administration calling on the government to reconsider. 

Dr. Abrams and fellow signers of the letters, including longtime opioid watchdog Andrew Kolodny, MD, of Brandeis University, said the algorithm used in creating AvertD “fell into known pitfalls of genetic prediction that give the appearance of predicting genetic risk, without being a true measure of genetic risk.” 

“The harmful consequences of an invalid genetic test for OUD are clear. Patients who test negative, and their clinicians, may have a false sense of security about use of opioids,” the letter states. 

The letter adds that false-positive test results may result in harmful consequences, with clinicians refraining from prescribing needed opioids, a problem that may be magnified in minority populations. 

Among the signers of the letter is Alexander Hatoum, PhD, of Washington University, who conducted an independent evaluation of AdvertD, which he and his colleagues published in 2021 in Drug and Alcohol Dependency. 

Dr. Hatoum said many patients may not fully understand the limit of genetic testing in predicting conditions like risk for OUD, where many factors are at play. The availability of a test may lend the impression that a single DNA trait makes the difference, as happens with conditions like Huntington’s disease and cystic fibrosis, he said. 

“But it’s just not reality for most diseases,” Dr. Hatoum told this news organization. 

The FDA declined to comment on the letter and said its approval of the test was “another step forward” in efforts to prevent new cases of OUD. 

In 2021, a little more than three quarters of people who died by overdose in the United States involved opioids, or more than 80,000 people, according to the US Centers for Disease Control and Prevention. This figure includes prescription opioids, heroin, and fentanyl. 

While deaths from overdoses with prescription opioids peaked in 2017 at 17,029 people, that figure has decreased steadily. Meanwhile, synthetic opioids other than methadone — primarily fentanyl — were the main driver of drug overdose deaths with a nearly 7.5-fold increase from 2015 to 2021. 

The FDA agency said it had “a reasonable assurance of AvertD’s safety and effectiveness, taking into consideration available alternatives, patients’ perspectives, the public health need and the ability to address uncertainty through the collection of post-market data.” 

Slow Rollout

In a separate letter to the Centers for Medicare and Medicaid Services, Dr. Abrams, Dr. Kolodny, Dr. Hatoum, and the other signers repeated their arguments against the use of AdvertD and asked that the government not use federal funds to pay for the test. 

SOLVD is not yet selling AdvertD in the United States, and it has not yet set a price for the product. The Carlsbad, California-based company told this news organization in an email exchange that it is working with both Medicare and private insurers on questions of future coverage. 

AvertD correctly identified an elevated risk for OUD in about 82.8% of cases, equating to a false-negative rate of 18.2% of patients, the FDA said in its summary of on the data supporting the application. This measure is known as sensitivity, meaning it shows how often an individual has the condition addressed in the test. 

Meanwhile, the false positive rate was 20.8%, the FDA said. 

SOLVD published similar study results in 2021. 

The company failed to impress the FDA’s Clinical Chemistry and Clinical Toxicology Devices Panel, which in October 2022, said the probable risks of the test likely outweighed its benefits. 

Then, in November 2022, the FDA and National Institutes of Health (NIH) held a public workshop meeting  to consider the challenges and possibilities in developing tools to predict the risk of developing OUD. At that meeting, Keri Donaldson, MD, MSCE, the chief executive officer of SOLVD, said the company planned to conduct a controlled rollout of AdvertD on FDA approval. 

Dr. Donaldson said a “defined set” of clinicians would first access the test, allowing the company to understand how results would be used in clinical practice.

“Once a test gets into practice, you have to be very purposeful and thoughtful about how it’s used,” he said.

The FDA approved the test in December 2023, saying it had worked with the company on modifications to its test. It also said that the advisory committee’s feedback helped in the evaluation and ultimate approval of AdvertD. 

Even beyond the debate about the predictive ability of genetic tests for OUD are larger questions that physicians need time to ask patients in assessing their potential risk for addiction when prescribing narcotic painkillers, said Maya Hambright, MD, a physician in New York’s Hudson Valley who has been working mainly in addiction in response to the overdose crisis. 

Genetics are just one of many factors at play in causing people to become addicted to opioids, Dr. Hambright said. 

Physicians must also consider the lasting effects of emotional and physical trauma experienced at any age, but particularly in childhood, as well as what kind of social support a patient has in facing the illness or injury that may require opioids for pain, she said. 

“There is a time and place for narcotic medications to be prescribed appropriately, which means we have to do our due diligence,” Dr. Hambright told this news organization. “Regardless of the strides we make in research and development, we still must connect and communicate safely and effectively and compassionately with our patients.” 

A version of this article appeared on Medscape.com.

A group of researchers urged US regulators to revoke the approval of a test marketed for predicting risk for opioid addiction and said government health plans should not pay for the product. 

The focus of the request is AdvertD (SOLVD Health), which the US Food and Drug Administration (FDA) approved in December as the first test to use DNA to evaluate if people have an elevated risk for opioid use disorder (OUD). A sample obtained through a cheek swab is meant to help guide decisions about opioid prescriptions for patients not previously treated with these drugs, such as someone undergoing a planned surgery, the FDA said. 

But Michael T. Abrams, MPH, PhD, senior health researcher for Public Citizen’s Health Research Group, and 30 other physicians and researchers sent an April 4 letter to the Food and Drug Administration calling on the government to reconsider. 

Dr. Abrams and fellow signers of the letters, including longtime opioid watchdog Andrew Kolodny, MD, of Brandeis University, said the algorithm used in creating AvertD “fell into known pitfalls of genetic prediction that give the appearance of predicting genetic risk, without being a true measure of genetic risk.” 

“The harmful consequences of an invalid genetic test for OUD are clear. Patients who test negative, and their clinicians, may have a false sense of security about use of opioids,” the letter states. 

The letter adds that false-positive test results may result in harmful consequences, with clinicians refraining from prescribing needed opioids, a problem that may be magnified in minority populations. 

Among the signers of the letter is Alexander Hatoum, PhD, of Washington University, who conducted an independent evaluation of AdvertD, which he and his colleagues published in 2021 in Drug and Alcohol Dependency. 

Dr. Hatoum said many patients may not fully understand the limit of genetic testing in predicting conditions like risk for OUD, where many factors are at play. The availability of a test may lend the impression that a single DNA trait makes the difference, as happens with conditions like Huntington’s disease and cystic fibrosis, he said. 

“But it’s just not reality for most diseases,” Dr. Hatoum told this news organization. 

The FDA declined to comment on the letter and said its approval of the test was “another step forward” in efforts to prevent new cases of OUD. 

In 2021, a little more than three quarters of people who died by overdose in the United States involved opioids, or more than 80,000 people, according to the US Centers for Disease Control and Prevention. This figure includes prescription opioids, heroin, and fentanyl. 

While deaths from overdoses with prescription opioids peaked in 2017 at 17,029 people, that figure has decreased steadily. Meanwhile, synthetic opioids other than methadone — primarily fentanyl — were the main driver of drug overdose deaths with a nearly 7.5-fold increase from 2015 to 2021. 

The FDA agency said it had “a reasonable assurance of AvertD’s safety and effectiveness, taking into consideration available alternatives, patients’ perspectives, the public health need and the ability to address uncertainty through the collection of post-market data.” 

Slow Rollout

In a separate letter to the Centers for Medicare and Medicaid Services, Dr. Abrams, Dr. Kolodny, Dr. Hatoum, and the other signers repeated their arguments against the use of AdvertD and asked that the government not use federal funds to pay for the test. 

SOLVD is not yet selling AdvertD in the United States, and it has not yet set a price for the product. The Carlsbad, California-based company told this news organization in an email exchange that it is working with both Medicare and private insurers on questions of future coverage. 

AvertD correctly identified an elevated risk for OUD in about 82.8% of cases, equating to a false-negative rate of 18.2% of patients, the FDA said in its summary of on the data supporting the application. This measure is known as sensitivity, meaning it shows how often an individual has the condition addressed in the test. 

Meanwhile, the false positive rate was 20.8%, the FDA said. 

SOLVD published similar study results in 2021. 

The company failed to impress the FDA’s Clinical Chemistry and Clinical Toxicology Devices Panel, which in October 2022, said the probable risks of the test likely outweighed its benefits. 

Then, in November 2022, the FDA and National Institutes of Health (NIH) held a public workshop meeting  to consider the challenges and possibilities in developing tools to predict the risk of developing OUD. At that meeting, Keri Donaldson, MD, MSCE, the chief executive officer of SOLVD, said the company planned to conduct a controlled rollout of AdvertD on FDA approval. 

Dr. Donaldson said a “defined set” of clinicians would first access the test, allowing the company to understand how results would be used in clinical practice.

“Once a test gets into practice, you have to be very purposeful and thoughtful about how it’s used,” he said.

The FDA approved the test in December 2023, saying it had worked with the company on modifications to its test. It also said that the advisory committee’s feedback helped in the evaluation and ultimate approval of AdvertD. 

Even beyond the debate about the predictive ability of genetic tests for OUD are larger questions that physicians need time to ask patients in assessing their potential risk for addiction when prescribing narcotic painkillers, said Maya Hambright, MD, a physician in New York’s Hudson Valley who has been working mainly in addiction in response to the overdose crisis. 

Genetics are just one of many factors at play in causing people to become addicted to opioids, Dr. Hambright said. 

Physicians must also consider the lasting effects of emotional and physical trauma experienced at any age, but particularly in childhood, as well as what kind of social support a patient has in facing the illness or injury that may require opioids for pain, she said. 

“There is a time and place for narcotic medications to be prescribed appropriately, which means we have to do our due diligence,” Dr. Hambright told this news organization. “Regardless of the strides we make in research and development, we still must connect and communicate safely and effectively and compassionately with our patients.” 

A version of this article appeared on Medscape.com.

A group of researchers urged US regulators to revoke the approval of a test marketed for predicting risk for opioid addiction and said government health plans should not pay for the product. 

The focus of the request is AdvertD (SOLVD Health), which the US Food and Drug Administration (FDA) approved in December as the first test to use DNA to evaluate if people have an elevated risk for opioid use disorder (OUD). A sample obtained through a cheek swab is meant to help guide decisions about opioid prescriptions for patients not previously treated with these drugs, such as someone undergoing a planned surgery, the FDA said. 

But Michael T. Abrams, MPH, PhD, senior health researcher for Public Citizen’s Health Research Group, and 30 other physicians and researchers sent an April 4 letter to the Food and Drug Administration calling on the government to reconsider. 

Dr. Abrams and fellow signers of the letters, including longtime opioid watchdog Andrew Kolodny, MD, of Brandeis University, said the algorithm used in creating AvertD “fell into known pitfalls of genetic prediction that give the appearance of predicting genetic risk, without being a true measure of genetic risk.” 

“The harmful consequences of an invalid genetic test for OUD are clear. Patients who test negative, and their clinicians, may have a false sense of security about use of opioids,” the letter states. 

The letter adds that false-positive test results may result in harmful consequences, with clinicians refraining from prescribing needed opioids, a problem that may be magnified in minority populations. 

Among the signers of the letter is Alexander Hatoum, PhD, of Washington University, who conducted an independent evaluation of AdvertD, which he and his colleagues published in 2021 in Drug and Alcohol Dependency. 

Dr. Hatoum said many patients may not fully understand the limit of genetic testing in predicting conditions like risk for OUD, where many factors are at play. The availability of a test may lend the impression that a single DNA trait makes the difference, as happens with conditions like Huntington’s disease and cystic fibrosis, he said. 

“But it’s just not reality for most diseases,” Dr. Hatoum told this news organization. 

The FDA declined to comment on the letter and said its approval of the test was “another step forward” in efforts to prevent new cases of OUD. 

In 2021, a little more than three quarters of people who died by overdose in the United States involved opioids, or more than 80,000 people, according to the US Centers for Disease Control and Prevention. This figure includes prescription opioids, heroin, and fentanyl. 

While deaths from overdoses with prescription opioids peaked in 2017 at 17,029 people, that figure has decreased steadily. Meanwhile, synthetic opioids other than methadone — primarily fentanyl — were the main driver of drug overdose deaths with a nearly 7.5-fold increase from 2015 to 2021. 

The FDA agency said it had “a reasonable assurance of AvertD’s safety and effectiveness, taking into consideration available alternatives, patients’ perspectives, the public health need and the ability to address uncertainty through the collection of post-market data.” 

Slow Rollout

In a separate letter to the Centers for Medicare and Medicaid Services, Dr. Abrams, Dr. Kolodny, Dr. Hatoum, and the other signers repeated their arguments against the use of AdvertD and asked that the government not use federal funds to pay for the test. 

SOLVD is not yet selling AdvertD in the United States, and it has not yet set a price for the product. The Carlsbad, California-based company told this news organization in an email exchange that it is working with both Medicare and private insurers on questions of future coverage. 

AvertD correctly identified an elevated risk for OUD in about 82.8% of cases, equating to a false-negative rate of 18.2% of patients, the FDA said in its summary of on the data supporting the application. This measure is known as sensitivity, meaning it shows how often an individual has the condition addressed in the test. 

Meanwhile, the false positive rate was 20.8%, the FDA said. 

SOLVD published similar study results in 2021. 

The company failed to impress the FDA’s Clinical Chemistry and Clinical Toxicology Devices Panel, which in October 2022, said the probable risks of the test likely outweighed its benefits. 

Then, in November 2022, the FDA and National Institutes of Health (NIH) held a public workshop meeting  to consider the challenges and possibilities in developing tools to predict the risk of developing OUD. At that meeting, Keri Donaldson, MD, MSCE, the chief executive officer of SOLVD, said the company planned to conduct a controlled rollout of AdvertD on FDA approval. 

Dr. Donaldson said a “defined set” of clinicians would first access the test, allowing the company to understand how results would be used in clinical practice.

“Once a test gets into practice, you have to be very purposeful and thoughtful about how it’s used,” he said.

The FDA approved the test in December 2023, saying it had worked with the company on modifications to its test. It also said that the advisory committee’s feedback helped in the evaluation and ultimate approval of AdvertD. 

Even beyond the debate about the predictive ability of genetic tests for OUD are larger questions that physicians need time to ask patients in assessing their potential risk for addiction when prescribing narcotic painkillers, said Maya Hambright, MD, a physician in New York’s Hudson Valley who has been working mainly in addiction in response to the overdose crisis. 

Genetics are just one of many factors at play in causing people to become addicted to opioids, Dr. Hambright said. 

Physicians must also consider the lasting effects of emotional and physical trauma experienced at any age, but particularly in childhood, as well as what kind of social support a patient has in facing the illness or injury that may require opioids for pain, she said. 

“There is a time and place for narcotic medications to be prescribed appropriately, which means we have to do our due diligence,” Dr. Hambright told this news organization. “Regardless of the strides we make in research and development, we still must connect and communicate safely and effectively and compassionately with our patients.” 

A version of this article appeared on Medscape.com.

Regeneron Pharmaceuticals said in an interview that it may be the first company to have an accelerated approval application for its cancer drug rebuffed by the US Food and Drug Administration (FDA) due to concerns about the timing of completion of confirmatory research.

The company once had hoped to win this US clearance for odronextamab in relapsed/refractory (R/R) follicular lymphoma (FL) and in R/R diffuse large B-cell lymphoma (DLBCL) by March 31. Last year when Regeneron announced the FDA’s decision to grant priority review for odronextamab, the firm said that the end of this month was the US regulators’ target decision date.

But on March 25, Regeneron said the FDA issued two complete response letters (CRLs) in connection with odronextamab application. It will not approve the experimental medicine at this time.

In the release, Regeneron said the only approvability issue is related to the enrollment status of the confirmatory trials. The letters did not identify issues with the odronextamab clinical efficacy or safety, trial design, labeling, or manufacturing.

“While we acknowledge the general concerns that FDA has about sponsors failing to complete their postmarketing confirmatory trials, the relevant laws and regulatory guidances do not lay out rigid criteria for assessing whether the progress on a confirmatory trial is adequate to allow for an accelerated approval,” Tammy Allen, Regeneron’s director for product and pipeline communications, said in an email. “ And to our knowledge, this is the first time the FDA has issued a CRL for this reason.”

There has been rising concern in recent years about the gap between initial accelerated approvals for medicines and the completion of studies that show whether these promising therapies actually help patients live longer or better. Thus, a serious knowledge gap arises, often for many years, while patients and physicians use drugs with as yet unproven benefit. Recent studies highlighting this knowledge gap include work from Harvard’s Program on Regulation, Therapeutics, and Law (PORTAL) group and researchers at the University of Pennsylvania.

While Congress has long sought to speed approvals of new drugs, in 2022 lawmakers gave the FDA more clout for efforts to shorten the period of uncertainty between accelerated and traditional approval. Congress added a provision to a large spending package that said the federal government could require a study or studies to be underway prior to approval, or within a specified time period after the date of approval, of the applicable product.

“As this is new territory for us and for industry, we’re committed to working closely with them to address and plan on sharing updates on enrollment and regulatory timelines later this year,” Ms. Allen said.

The FDA generally does not comment on applications under review. In response to a question about Regeneron’s statements, an FDA spokeswoman pointed out by email that the 2022 law had made clear how the agency can decline approval if confirmatory clinical trials are not considered underway prior to approval.

Odronextamab is potentially part of a rapidly advancing field of lymphoma treatments, which include autologous chimeric antigen receptor (CAR T-cell) therapy in certain settings. There are severe constraints, though, on CAR-T therapy, including manufacturing delays and treatment-related toxicities. Odronextamab is part of what are called “off-the-shelf” drugs with the same aim as CAR-T. The bispecific antibodies (BsAb) are meant to teach the immune system to fight cancer.

Regeneron said it has been actively enrolling patients in multiple phase 3 trials for odronextamab as part of its OLYMPIA program. The company said this is intended to change the treatment paradigm of several B-cell non-Hodgkin lymphoma subtypes, including in earlier lines of therapy.

Enrollment in the dose-finding portion has begun, but the CRLs indicate that the confirmatory portions of these trials should be underway and that the timelines to completion should be agreed on prior to resubmission, Regeneron said. The company added that it is working closely with the FDA and investigators to bring odronextamab to patients with R/R FL and R/R DLBCL as quickly as possible. The company plans to share updates on enrollment and regulatory timelines later this year.

Regeneron Pharmaceuticals said in an interview that it may be the first company to have an accelerated approval application for its cancer drug rebuffed by the US Food and Drug Administration (FDA) due to concerns about the timing of completion of confirmatory research.

The company once had hoped to win this US clearance for odronextamab in relapsed/refractory (R/R) follicular lymphoma (FL) and in R/R diffuse large B-cell lymphoma (DLBCL) by March 31. Last year when Regeneron announced the FDA’s decision to grant priority review for odronextamab, the firm said that the end of this month was the US regulators’ target decision date.

But on March 25, Regeneron said the FDA issued two complete response letters (CRLs) in connection with odronextamab application. It will not approve the experimental medicine at this time.

In the release, Regeneron said the only approvability issue is related to the enrollment status of the confirmatory trials. The letters did not identify issues with the odronextamab clinical efficacy or safety, trial design, labeling, or manufacturing.

“While we acknowledge the general concerns that FDA has about sponsors failing to complete their postmarketing confirmatory trials, the relevant laws and regulatory guidances do not lay out rigid criteria for assessing whether the progress on a confirmatory trial is adequate to allow for an accelerated approval,” Tammy Allen, Regeneron’s director for product and pipeline communications, said in an email. “ And to our knowledge, this is the first time the FDA has issued a CRL for this reason.”

There has been rising concern in recent years about the gap between initial accelerated approvals for medicines and the completion of studies that show whether these promising therapies actually help patients live longer or better. Thus, a serious knowledge gap arises, often for many years, while patients and physicians use drugs with as yet unproven benefit. Recent studies highlighting this knowledge gap include work from Harvard’s Program on Regulation, Therapeutics, and Law (PORTAL) group and researchers at the University of Pennsylvania.

While Congress has long sought to speed approvals of new drugs, in 2022 lawmakers gave the FDA more clout for efforts to shorten the period of uncertainty between accelerated and traditional approval. Congress added a provision to a large spending package that said the federal government could require a study or studies to be underway prior to approval, or within a specified time period after the date of approval, of the applicable product.

“As this is new territory for us and for industry, we’re committed to working closely with them to address and plan on sharing updates on enrollment and regulatory timelines later this year,” Ms. Allen said.

The FDA generally does not comment on applications under review. In response to a question about Regeneron’s statements, an FDA spokeswoman pointed out by email that the 2022 law had made clear how the agency can decline approval if confirmatory clinical trials are not considered underway prior to approval.

Odronextamab is potentially part of a rapidly advancing field of lymphoma treatments, which include autologous chimeric antigen receptor (CAR T-cell) therapy in certain settings. There are severe constraints, though, on CAR-T therapy, including manufacturing delays and treatment-related toxicities. Odronextamab is part of what are called “off-the-shelf” drugs with the same aim as CAR-T. The bispecific antibodies (BsAb) are meant to teach the immune system to fight cancer.

Regeneron said it has been actively enrolling patients in multiple phase 3 trials for odronextamab as part of its OLYMPIA program. The company said this is intended to change the treatment paradigm of several B-cell non-Hodgkin lymphoma subtypes, including in earlier lines of therapy.

Enrollment in the dose-finding portion has begun, but the CRLs indicate that the confirmatory portions of these trials should be underway and that the timelines to completion should be agreed on prior to resubmission, Regeneron said. The company added that it is working closely with the FDA and investigators to bring odronextamab to patients with R/R FL and R/R DLBCL as quickly as possible. The company plans to share updates on enrollment and regulatory timelines later this year.

Regeneron Pharmaceuticals said in an interview that it may be the first company to have an accelerated approval application for its cancer drug rebuffed by the US Food and Drug Administration (FDA) due to concerns about the timing of completion of confirmatory research.

The company once had hoped to win this US clearance for odronextamab in relapsed/refractory (R/R) follicular lymphoma (FL) and in R/R diffuse large B-cell lymphoma (DLBCL) by March 31. Last year when Regeneron announced the FDA’s decision to grant priority review for odronextamab, the firm said that the end of this month was the US regulators’ target decision date.

But on March 25, Regeneron said the FDA issued two complete response letters (CRLs) in connection with odronextamab application. It will not approve the experimental medicine at this time.

In the release, Regeneron said the only approvability issue is related to the enrollment status of the confirmatory trials. The letters did not identify issues with the odronextamab clinical efficacy or safety, trial design, labeling, or manufacturing.

“While we acknowledge the general concerns that FDA has about sponsors failing to complete their postmarketing confirmatory trials, the relevant laws and regulatory guidances do not lay out rigid criteria for assessing whether the progress on a confirmatory trial is adequate to allow for an accelerated approval,” Tammy Allen, Regeneron’s director for product and pipeline communications, said in an email. “ And to our knowledge, this is the first time the FDA has issued a CRL for this reason.”

There has been rising concern in recent years about the gap between initial accelerated approvals for medicines and the completion of studies that show whether these promising therapies actually help patients live longer or better. Thus, a serious knowledge gap arises, often for many years, while patients and physicians use drugs with as yet unproven benefit. Recent studies highlighting this knowledge gap include work from Harvard’s Program on Regulation, Therapeutics, and Law (PORTAL) group and researchers at the University of Pennsylvania.

While Congress has long sought to speed approvals of new drugs, in 2022 lawmakers gave the FDA more clout for efforts to shorten the period of uncertainty between accelerated and traditional approval. Congress added a provision to a large spending package that said the federal government could require a study or studies to be underway prior to approval, or within a specified time period after the date of approval, of the applicable product.

“As this is new territory for us and for industry, we’re committed to working closely with them to address and plan on sharing updates on enrollment and regulatory timelines later this year,” Ms. Allen said.

The FDA generally does not comment on applications under review. In response to a question about Regeneron’s statements, an FDA spokeswoman pointed out by email that the 2022 law had made clear how the agency can decline approval if confirmatory clinical trials are not considered underway prior to approval.

Odronextamab is potentially part of a rapidly advancing field of lymphoma treatments, which include autologous chimeric antigen receptor (CAR T-cell) therapy in certain settings. There are severe constraints, though, on CAR-T therapy, including manufacturing delays and treatment-related toxicities. Odronextamab is part of what are called “off-the-shelf” drugs with the same aim as CAR-T. The bispecific antibodies (BsAb) are meant to teach the immune system to fight cancer.

Regeneron said it has been actively enrolling patients in multiple phase 3 trials for odronextamab as part of its OLYMPIA program. The company said this is intended to change the treatment paradigm of several B-cell non-Hodgkin lymphoma subtypes, including in earlier lines of therapy.

Enrollment in the dose-finding portion has begun, but the CRLs indicate that the confirmatory portions of these trials should be underway and that the timelines to completion should be agreed on prior to resubmission, Regeneron said. The company added that it is working closely with the FDA and investigators to bring odronextamab to patients with R/R FL and R/R DLBCL as quickly as possible. The company plans to share updates on enrollment and regulatory timelines later this year.