Feature

Cannabis use is becoming increasingly common among people with diabetes. A recent US prevalence study estimated that 9% adults with diabetes used cannabis in the last month, a 33.7% increase between 2021 and 2022. Nearly half (48.9%) of users were younger than 50 years.

Cannabis use is also increasing sharply among those aged 65 years or older, many of whom have diabetes and other chronic conditions. In this demographic, the perceived risk surrounding regular cannabis use has dropped significantly, even as the data tell another story — that they are particularly at risk from emergency department visits for cannabis poisoning.

As legalization continues and cannabis products proliferate, endocrinologists will likely face more patients of all ages seeking advice about its use. Yet with few evidence-based resources to turn to, endocrinologists advising patients in this area are mostly left fending for themselves.
 

Evidence ‘Limited’

“The evidence on cannabis is limited mainly because of its scheduling in the United States,” Jay Shubrook, DO, a professor and diabetologist at College of Osteopathic Medicine, Touro University California, in Vallejo, California, told this news organization. 

“It was declared to be a schedule I drug in the 1970s, which meant it was ‘dangerous’ and ‘had no medical benefit.’ This made it hard to access and study in human trials.” 

That will likely change soon. On May 16, 2024, the US Department of Justice submitted a proposal to move marijuana from a schedule I to a schedule III drug under the Controlled Substances Act, emphasizing its accepted medical use. If approved, the door will open to more investigators seeking to study the effects of cannabis. 

Yet, even in Canada, where recreational use has been legal since 2018 and cannabis is sold widely with government support, there are little hard data to guide practice. In 2019, Diabetes Canada issued a position statement on recreational cannabis use in people with type 1 diabetes (T1D) and type 2 diabetes (T2D). It sought to evaluate the effects of cannabis on metabolic factors and diabetes complications, as well as self-management behaviors in those aged 13 years or older.

The authors noted that five of the six studies upon which the statement was based did not consider or report the routes of cannabis administration, which have differing risks. In addition, their recommendations were based on grade D evidence and consensus.
 

What Patients Are Taking

Cannabis — also known as marijuana, weed, pot, or bud — refers to the dried flowers, leaves, stems, and seeds of the cannabis plant. The plant contains more than 100 compounds, including tetrahydrocannabinol (THC), which is responsible for the euphoric “high,” and other active compounds, including cannabidiol (CBD), which by itself is not mind-altering.

Cannabis can be ingested in several ways. It can be smoked (ie, joints, blunts, pipes, and water pipes), ingested in edible form (mixed or infused into foods), and inhaled using electronic vaporizing devices (ie, e-cigarettes or vape pens).

Compounds in cannabis can also be extracted to make oils and concentrates that can be vaped or inhaled. Smoking oils, concentrates, and extracts from the cannabis plant, known as “dabbing,” are on the rise in the United States.

There are no validated or standard dosage recommendations for cannabis strains and formulations, THC/CBD ratios, or modes of administration. Therefore, the Canadian Pharmacists Association prepared a guide for finding a safe and effective dose for medical purposes. GoodRx, a website with information on prescription drug prices, says that larger doses of THC pose greater risks, noting that the potency of cannabis has increased from 4% in 1995 to about 14% in 2019.
 

Potential Risks and Benefits: Canadian and US Perspectives

Health and safety risks vary with each of the different ways of using cannabis for individuals with and without diabetes, depending on a host of patient- and product-specific factors.

In a recent article proposing a “THC unit” for Canada’s legal cannabis market, researchers reported that consumers lack familiarity with THC levels, don’t know what constitutes a “low” or “high” THC amount, have trouble dosing, overconsume, and commonly experience adverse health events from cannabis use.

A recent study suggested that most clinicians are similarly uninformed, with “a lack of knowledge of beneficial effects, adverse effects, and of how to advise patients,” even for medical cannabis.

Diabetes Canada takes a stab at summarizing what’s known with respect to cannabis and diabetes, stating that:

“Research on recreational cannabis use suggests it may negatively impact diabetes metabolic factors and self-management behaviors. The safety of recreational cannabis use has not been demonstrated, whereas regular cannabis use is associated with worsening glycemic control, more diabetes-related complications, and poorer self-care behaviors, such as adequate glucose monitoring, adherence to medications, and compliance with dietary and physical activity recommendations for people living with both type 1 and type 2 diabetes.”

The American Diabetes Association’s information on cannabis consists of a patient-oriented article on CBD oil. The article stated:

“There’s a lot of hype surrounding CBD oil and diabetes. There is no noticeable effect on blood glucose (blood sugar) or insulin levels in people with type 2 diabetes. Researchers continue to study the effects of CBD on diabetes in animal studies.”

It concludes that:

“Although many claims continue to be made about CBD oil, there is little evidence of any benefit. It’s certainly not an alternative to traditional diabetes management. The safety of CBD is also unknown — it may have dangerous side effects that we won’t know about unless further research is done.”
 

A Roundup of Recent Studies

A smattering of recent studies have touched on various aspects of cannabis consumption and diabetes.

Angela Bryan, PhD, professor and co-director of CUChange at the University of Colorado Boulder, has been evaluating cannabis use in young adults (ages 21-40 years) in the SONIC study. Dr. Bryan reported at the American Diabetes Association (ADA) 84th Scientific Sessions that cannabis users were more likely to have a lower body mass index and less likely to develop T2D. Furthermore, chronic cannabis users were less likely to have measures of inflammation and no loss of insulin sensitivity.

Another study by Dr. Bryan’s group found that CBD-dominant forms of cannabis were associated with acute tension reduction, which might lead to longer-term reductions in anxiety. Bryan said the findings could be relevant in the context of diabetes distress.

Similarly positive results were found in a 15-week, double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD spray for neuropathic pain among treatment-resistant patients. The investigators reported that “clinically important improvements” were seen in pain, sleep quality, and subjective impressions of pain. Another small study of inhaled cannabis in treatment-refractory patients found a dose-dependent reduction in diabetic peripheral neuropathy pain.

Findings from a 9-year longitudinal study of approximately 18,000 Swedish men and women suggested no association between cannabis and subsequent T2D development after controlling for age, although these authors also called for longer follow-up and more detailed information about cannabis use to make “more robust” conclusions.

On the other side of the spectrum, a “rapid” review of recreational cannabis use in people with T1D and T2D found that recreational cannabis use may negatively impact diabetes metabolic factors and self-management behaviors and may increase risks for peripheral arterial occlusion, myocardial infarction, and renal disease. However, the authors cautioned that more robust research is needed to confirm the potential impact of cannabis on diabetes.
 

How to Advise Patients

When Dr. Shubrook was working with patients with diabetes in his family medicine practice in Ohio, cannabis wasn’t legal. 

“’Don’t ask, don’t tell’ was the way we handled it then,” he said. 

By contrast, in California, where he’s currently located, “it’s pretty well accepted and legal, and patients volunteer information about use, even if it’s recreational,” he said. “Realizing this was something we could talk about was really eye-opening to me.” 

Talking to patients about cannabis use is a “20-minute conversation that details what they’re doing,” he said. He proceeds by asking questions: Are you using for recreational or medicinal purposes? What do you take? What do you take it for? Does it work? 

“People will tell you,” Dr. Shubrook said. “They know exactly what it works or doesn’t work for and how it affects their glucose control, which in most cases is only minimally.”

He tells patients he would prefer they don’t inhale cannabis, given the risks posed to the lungs. 

“Edibles may have a slower onset of effect, but depending on what they’re adding it to, glucose might be affected,” he noted. “And I have seen that chronic use can lead to hyperemesis syndrome.”

Overall, he said, “Take the time to talk to your patients about cannabis — it will allow them to be honest with you, and you can improve the specificity and safety of its use. If cannabis is legal in your state, encourage people to go to legal dispensaries, which will reduce the risk of it being laced with another drug that could increase the danger of use.”

A recent US prevalence study found that people with diabetes who use cannabis likely engage in other substance and psychoactive substance use, including tobacco use, binge drinking, and misuse of opioids and stimulants. 

“Use of these additional substances could further exacerbate the health risks associated with diabetes and also emphasizes the importance of addressing polysubstance use among adults with diabetes,” the study’s author Benjamin H. Han, MD, Division of Geriatrics, Gerontology and Palliative Care, Department of Medicine, US San Diego School of Medicine in La Jolla, California, told this news organization.

“We were surprised at how strong the associations were, especially with use of substances that can increase cardiovascular risk,” Dr. Han added. “And given the strong association we found between cannabis use and use of other psychoactive substances in diabetes, clinicians must screen all their patients for psychoactive substance use.” 

Diabetes Canada’s position paper states that despite the limited evidence, “there were sufficient data to begin developing recommendations for type 1 and type 2 diabetes about education, counseling, and management related to recreational cannabis use.” 

Their recommendations include the following:

• Healthcare professionals should engage their patients in discussions about substance use on a regular basis, with a nonjudgmental approach.
• The use of recreational cannabis is not recommended for adolescents and adults with diabetes.
• People with T1D should avoid recreational cannabis use because of the increased risk for diabetic ketoacidosis.
• For adults with T1D or T2D who intend to use cannabis recreationally, individualized assessment and counseling should be offered to inform them of the general risks of cannabis, with a focus on harm reduction and reduction of the risk for potential adverse effects on diabetes management and complications.
• People with T1D or T2D should be offered education on and encouraged to read public information available through resources from various Canadian health authorities about the general risks of cannabis use to reduce the risk for nondiabetes-related adverse effects of cannabis consumption.

Of note, in 2018, the Canadian government produced an exhaustive compendium of information on cannabis for healthcare professionals that includes information relevant to managing patients with diabetes. 

Dr. Shubrook and Dr. Han reported no competing interests.
 

A version of this article appeared on Medscape.com.

Cannabis use is becoming increasingly common among people with diabetes. A recent US prevalence study estimated that 9% adults with diabetes used cannabis in the last month, a 33.7% increase between 2021 and 2022. Nearly half (48.9%) of users were younger than 50 years.

Cannabis use is also increasing sharply among those aged 65 years or older, many of whom have diabetes and other chronic conditions. In this demographic, the perceived risk surrounding regular cannabis use has dropped significantly, even as the data tell another story — that they are particularly at risk from emergency department visits for cannabis poisoning.

As legalization continues and cannabis products proliferate, endocrinologists will likely face more patients of all ages seeking advice about its use. Yet with few evidence-based resources to turn to, endocrinologists advising patients in this area are mostly left fending for themselves.
 

Evidence ‘Limited’

“The evidence on cannabis is limited mainly because of its scheduling in the United States,” Jay Shubrook, DO, a professor and diabetologist at College of Osteopathic Medicine, Touro University California, in Vallejo, California, told this news organization. 

“It was declared to be a schedule I drug in the 1970s, which meant it was ‘dangerous’ and ‘had no medical benefit.’ This made it hard to access and study in human trials.” 

That will likely change soon. On May 16, 2024, the US Department of Justice submitted a proposal to move marijuana from a schedule I to a schedule III drug under the Controlled Substances Act, emphasizing its accepted medical use. If approved, the door will open to more investigators seeking to study the effects of cannabis. 

Yet, even in Canada, where recreational use has been legal since 2018 and cannabis is sold widely with government support, there are little hard data to guide practice. In 2019, Diabetes Canada issued a position statement on recreational cannabis use in people with type 1 diabetes (T1D) and type 2 diabetes (T2D). It sought to evaluate the effects of cannabis on metabolic factors and diabetes complications, as well as self-management behaviors in those aged 13 years or older.

The authors noted that five of the six studies upon which the statement was based did not consider or report the routes of cannabis administration, which have differing risks. In addition, their recommendations were based on grade D evidence and consensus.
 

What Patients Are Taking

Cannabis — also known as marijuana, weed, pot, or bud — refers to the dried flowers, leaves, stems, and seeds of the cannabis plant. The plant contains more than 100 compounds, including tetrahydrocannabinol (THC), which is responsible for the euphoric “high,” and other active compounds, including cannabidiol (CBD), which by itself is not mind-altering.

Cannabis can be ingested in several ways. It can be smoked (ie, joints, blunts, pipes, and water pipes), ingested in edible form (mixed or infused into foods), and inhaled using electronic vaporizing devices (ie, e-cigarettes or vape pens).

Compounds in cannabis can also be extracted to make oils and concentrates that can be vaped or inhaled. Smoking oils, concentrates, and extracts from the cannabis plant, known as “dabbing,” are on the rise in the United States.

There are no validated or standard dosage recommendations for cannabis strains and formulations, THC/CBD ratios, or modes of administration. Therefore, the Canadian Pharmacists Association prepared a guide for finding a safe and effective dose for medical purposes. GoodRx, a website with information on prescription drug prices, says that larger doses of THC pose greater risks, noting that the potency of cannabis has increased from 4% in 1995 to about 14% in 2019.
 

Potential Risks and Benefits: Canadian and US Perspectives

Health and safety risks vary with each of the different ways of using cannabis for individuals with and without diabetes, depending on a host of patient- and product-specific factors.

In a recent article proposing a “THC unit” for Canada’s legal cannabis market, researchers reported that consumers lack familiarity with THC levels, don’t know what constitutes a “low” or “high” THC amount, have trouble dosing, overconsume, and commonly experience adverse health events from cannabis use.

A recent study suggested that most clinicians are similarly uninformed, with “a lack of knowledge of beneficial effects, adverse effects, and of how to advise patients,” even for medical cannabis.

Diabetes Canada takes a stab at summarizing what’s known with respect to cannabis and diabetes, stating that:

“Research on recreational cannabis use suggests it may negatively impact diabetes metabolic factors and self-management behaviors. The safety of recreational cannabis use has not been demonstrated, whereas regular cannabis use is associated with worsening glycemic control, more diabetes-related complications, and poorer self-care behaviors, such as adequate glucose monitoring, adherence to medications, and compliance with dietary and physical activity recommendations for people living with both type 1 and type 2 diabetes.”

The American Diabetes Association’s information on cannabis consists of a patient-oriented article on CBD oil. The article stated:

“There’s a lot of hype surrounding CBD oil and diabetes. There is no noticeable effect on blood glucose (blood sugar) or insulin levels in people with type 2 diabetes. Researchers continue to study the effects of CBD on diabetes in animal studies.”

It concludes that:

“Although many claims continue to be made about CBD oil, there is little evidence of any benefit. It’s certainly not an alternative to traditional diabetes management. The safety of CBD is also unknown — it may have dangerous side effects that we won’t know about unless further research is done.”
 

A Roundup of Recent Studies

A smattering of recent studies have touched on various aspects of cannabis consumption and diabetes.

Angela Bryan, PhD, professor and co-director of CUChange at the University of Colorado Boulder, has been evaluating cannabis use in young adults (ages 21-40 years) in the SONIC study. Dr. Bryan reported at the American Diabetes Association (ADA) 84th Scientific Sessions that cannabis users were more likely to have a lower body mass index and less likely to develop T2D. Furthermore, chronic cannabis users were less likely to have measures of inflammation and no loss of insulin sensitivity.

Another study by Dr. Bryan’s group found that CBD-dominant forms of cannabis were associated with acute tension reduction, which might lead to longer-term reductions in anxiety. Bryan said the findings could be relevant in the context of diabetes distress.

Similarly positive results were found in a 15-week, double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD spray for neuropathic pain among treatment-resistant patients. The investigators reported that “clinically important improvements” were seen in pain, sleep quality, and subjective impressions of pain. Another small study of inhaled cannabis in treatment-refractory patients found a dose-dependent reduction in diabetic peripheral neuropathy pain.

Findings from a 9-year longitudinal study of approximately 18,000 Swedish men and women suggested no association between cannabis and subsequent T2D development after controlling for age, although these authors also called for longer follow-up and more detailed information about cannabis use to make “more robust” conclusions.

On the other side of the spectrum, a “rapid” review of recreational cannabis use in people with T1D and T2D found that recreational cannabis use may negatively impact diabetes metabolic factors and self-management behaviors and may increase risks for peripheral arterial occlusion, myocardial infarction, and renal disease. However, the authors cautioned that more robust research is needed to confirm the potential impact of cannabis on diabetes.
 

How to Advise Patients

When Dr. Shubrook was working with patients with diabetes in his family medicine practice in Ohio, cannabis wasn’t legal. 

“’Don’t ask, don’t tell’ was the way we handled it then,” he said. 

By contrast, in California, where he’s currently located, “it’s pretty well accepted and legal, and patients volunteer information about use, even if it’s recreational,” he said. “Realizing this was something we could talk about was really eye-opening to me.” 

Talking to patients about cannabis use is a “20-minute conversation that details what they’re doing,” he said. He proceeds by asking questions: Are you using for recreational or medicinal purposes? What do you take? What do you take it for? Does it work? 

“People will tell you,” Dr. Shubrook said. “They know exactly what it works or doesn’t work for and how it affects their glucose control, which in most cases is only minimally.”

He tells patients he would prefer they don’t inhale cannabis, given the risks posed to the lungs. 

“Edibles may have a slower onset of effect, but depending on what they’re adding it to, glucose might be affected,” he noted. “And I have seen that chronic use can lead to hyperemesis syndrome.”

Overall, he said, “Take the time to talk to your patients about cannabis — it will allow them to be honest with you, and you can improve the specificity and safety of its use. If cannabis is legal in your state, encourage people to go to legal dispensaries, which will reduce the risk of it being laced with another drug that could increase the danger of use.”

A recent US prevalence study found that people with diabetes who use cannabis likely engage in other substance and psychoactive substance use, including tobacco use, binge drinking, and misuse of opioids and stimulants. 

“Use of these additional substances could further exacerbate the health risks associated with diabetes and also emphasizes the importance of addressing polysubstance use among adults with diabetes,” the study’s author Benjamin H. Han, MD, Division of Geriatrics, Gerontology and Palliative Care, Department of Medicine, US San Diego School of Medicine in La Jolla, California, told this news organization.

“We were surprised at how strong the associations were, especially with use of substances that can increase cardiovascular risk,” Dr. Han added. “And given the strong association we found between cannabis use and use of other psychoactive substances in diabetes, clinicians must screen all their patients for psychoactive substance use.” 

Diabetes Canada’s position paper states that despite the limited evidence, “there were sufficient data to begin developing recommendations for type 1 and type 2 diabetes about education, counseling, and management related to recreational cannabis use.” 

Their recommendations include the following:

• Healthcare professionals should engage their patients in discussions about substance use on a regular basis, with a nonjudgmental approach.
• The use of recreational cannabis is not recommended for adolescents and adults with diabetes.
• People with T1D should avoid recreational cannabis use because of the increased risk for diabetic ketoacidosis.
• For adults with T1D or T2D who intend to use cannabis recreationally, individualized assessment and counseling should be offered to inform them of the general risks of cannabis, with a focus on harm reduction and reduction of the risk for potential adverse effects on diabetes management and complications.
• People with T1D or T2D should be offered education on and encouraged to read public information available through resources from various Canadian health authorities about the general risks of cannabis use to reduce the risk for nondiabetes-related adverse effects of cannabis consumption.

Of note, in 2018, the Canadian government produced an exhaustive compendium of information on cannabis for healthcare professionals that includes information relevant to managing patients with diabetes. 

Dr. Shubrook and Dr. Han reported no competing interests.
 

A version of this article appeared on Medscape.com.

Cannabis use is becoming increasingly common among people with diabetes. A recent US prevalence study estimated that 9% adults with diabetes used cannabis in the last month, a 33.7% increase between 2021 and 2022. Nearly half (48.9%) of users were younger than 50 years.

Cannabis use is also increasing sharply among those aged 65 years or older, many of whom have diabetes and other chronic conditions. In this demographic, the perceived risk surrounding regular cannabis use has dropped significantly, even as the data tell another story — that they are particularly at risk from emergency department visits for cannabis poisoning.

As legalization continues and cannabis products proliferate, endocrinologists will likely face more patients of all ages seeking advice about its use. Yet with few evidence-based resources to turn to, endocrinologists advising patients in this area are mostly left fending for themselves.
 

Evidence ‘Limited’

“The evidence on cannabis is limited mainly because of its scheduling in the United States,” Jay Shubrook, DO, a professor and diabetologist at College of Osteopathic Medicine, Touro University California, in Vallejo, California, told this news organization. 

“It was declared to be a schedule I drug in the 1970s, which meant it was ‘dangerous’ and ‘had no medical benefit.’ This made it hard to access and study in human trials.” 

That will likely change soon. On May 16, 2024, the US Department of Justice submitted a proposal to move marijuana from a schedule I to a schedule III drug under the Controlled Substances Act, emphasizing its accepted medical use. If approved, the door will open to more investigators seeking to study the effects of cannabis. 

Yet, even in Canada, where recreational use has been legal since 2018 and cannabis is sold widely with government support, there are little hard data to guide practice. In 2019, Diabetes Canada issued a position statement on recreational cannabis use in people with type 1 diabetes (T1D) and type 2 diabetes (T2D). It sought to evaluate the effects of cannabis on metabolic factors and diabetes complications, as well as self-management behaviors in those aged 13 years or older.

The authors noted that five of the six studies upon which the statement was based did not consider or report the routes of cannabis administration, which have differing risks. In addition, their recommendations were based on grade D evidence and consensus.
 

What Patients Are Taking

Cannabis — also known as marijuana, weed, pot, or bud — refers to the dried flowers, leaves, stems, and seeds of the cannabis plant. The plant contains more than 100 compounds, including tetrahydrocannabinol (THC), which is responsible for the euphoric “high,” and other active compounds, including cannabidiol (CBD), which by itself is not mind-altering.

Cannabis can be ingested in several ways. It can be smoked (ie, joints, blunts, pipes, and water pipes), ingested in edible form (mixed or infused into foods), and inhaled using electronic vaporizing devices (ie, e-cigarettes or vape pens).

Compounds in cannabis can also be extracted to make oils and concentrates that can be vaped or inhaled. Smoking oils, concentrates, and extracts from the cannabis plant, known as “dabbing,” are on the rise in the United States.

There are no validated or standard dosage recommendations for cannabis strains and formulations, THC/CBD ratios, or modes of administration. Therefore, the Canadian Pharmacists Association prepared a guide for finding a safe and effective dose for medical purposes. GoodRx, a website with information on prescription drug prices, says that larger doses of THC pose greater risks, noting that the potency of cannabis has increased from 4% in 1995 to about 14% in 2019.
 

Potential Risks and Benefits: Canadian and US Perspectives

Health and safety risks vary with each of the different ways of using cannabis for individuals with and without diabetes, depending on a host of patient- and product-specific factors.

In a recent article proposing a “THC unit” for Canada’s legal cannabis market, researchers reported that consumers lack familiarity with THC levels, don’t know what constitutes a “low” or “high” THC amount, have trouble dosing, overconsume, and commonly experience adverse health events from cannabis use.

A recent study suggested that most clinicians are similarly uninformed, with “a lack of knowledge of beneficial effects, adverse effects, and of how to advise patients,” even for medical cannabis.

Diabetes Canada takes a stab at summarizing what’s known with respect to cannabis and diabetes, stating that:

“Research on recreational cannabis use suggests it may negatively impact diabetes metabolic factors and self-management behaviors. The safety of recreational cannabis use has not been demonstrated, whereas regular cannabis use is associated with worsening glycemic control, more diabetes-related complications, and poorer self-care behaviors, such as adequate glucose monitoring, adherence to medications, and compliance with dietary and physical activity recommendations for people living with both type 1 and type 2 diabetes.”

The American Diabetes Association’s information on cannabis consists of a patient-oriented article on CBD oil. The article stated:

“There’s a lot of hype surrounding CBD oil and diabetes. There is no noticeable effect on blood glucose (blood sugar) or insulin levels in people with type 2 diabetes. Researchers continue to study the effects of CBD on diabetes in animal studies.”

It concludes that:

“Although many claims continue to be made about CBD oil, there is little evidence of any benefit. It’s certainly not an alternative to traditional diabetes management. The safety of CBD is also unknown — it may have dangerous side effects that we won’t know about unless further research is done.”
 

A Roundup of Recent Studies

A smattering of recent studies have touched on various aspects of cannabis consumption and diabetes.

Angela Bryan, PhD, professor and co-director of CUChange at the University of Colorado Boulder, has been evaluating cannabis use in young adults (ages 21-40 years) in the SONIC study. Dr. Bryan reported at the American Diabetes Association (ADA) 84th Scientific Sessions that cannabis users were more likely to have a lower body mass index and less likely to develop T2D. Furthermore, chronic cannabis users were less likely to have measures of inflammation and no loss of insulin sensitivity.

Another study by Dr. Bryan’s group found that CBD-dominant forms of cannabis were associated with acute tension reduction, which might lead to longer-term reductions in anxiety. Bryan said the findings could be relevant in the context of diabetes distress.

Similarly positive results were found in a 15-week, double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD spray for neuropathic pain among treatment-resistant patients. The investigators reported that “clinically important improvements” were seen in pain, sleep quality, and subjective impressions of pain. Another small study of inhaled cannabis in treatment-refractory patients found a dose-dependent reduction in diabetic peripheral neuropathy pain.

Findings from a 9-year longitudinal study of approximately 18,000 Swedish men and women suggested no association between cannabis and subsequent T2D development after controlling for age, although these authors also called for longer follow-up and more detailed information about cannabis use to make “more robust” conclusions.

On the other side of the spectrum, a “rapid” review of recreational cannabis use in people with T1D and T2D found that recreational cannabis use may negatively impact diabetes metabolic factors and self-management behaviors and may increase risks for peripheral arterial occlusion, myocardial infarction, and renal disease. However, the authors cautioned that more robust research is needed to confirm the potential impact of cannabis on diabetes.
 

How to Advise Patients

When Dr. Shubrook was working with patients with diabetes in his family medicine practice in Ohio, cannabis wasn’t legal. 

“’Don’t ask, don’t tell’ was the way we handled it then,” he said. 

By contrast, in California, where he’s currently located, “it’s pretty well accepted and legal, and patients volunteer information about use, even if it’s recreational,” he said. “Realizing this was something we could talk about was really eye-opening to me.” 

Talking to patients about cannabis use is a “20-minute conversation that details what they’re doing,” he said. He proceeds by asking questions: Are you using for recreational or medicinal purposes? What do you take? What do you take it for? Does it work? 

“People will tell you,” Dr. Shubrook said. “They know exactly what it works or doesn’t work for and how it affects their glucose control, which in most cases is only minimally.”

He tells patients he would prefer they don’t inhale cannabis, given the risks posed to the lungs. 

“Edibles may have a slower onset of effect, but depending on what they’re adding it to, glucose might be affected,” he noted. “And I have seen that chronic use can lead to hyperemesis syndrome.”

Overall, he said, “Take the time to talk to your patients about cannabis — it will allow them to be honest with you, and you can improve the specificity and safety of its use. If cannabis is legal in your state, encourage people to go to legal dispensaries, which will reduce the risk of it being laced with another drug that could increase the danger of use.”

A recent US prevalence study found that people with diabetes who use cannabis likely engage in other substance and psychoactive substance use, including tobacco use, binge drinking, and misuse of opioids and stimulants. 

“Use of these additional substances could further exacerbate the health risks associated with diabetes and also emphasizes the importance of addressing polysubstance use among adults with diabetes,” the study’s author Benjamin H. Han, MD, Division of Geriatrics, Gerontology and Palliative Care, Department of Medicine, US San Diego School of Medicine in La Jolla, California, told this news organization.

“We were surprised at how strong the associations were, especially with use of substances that can increase cardiovascular risk,” Dr. Han added. “And given the strong association we found between cannabis use and use of other psychoactive substances in diabetes, clinicians must screen all their patients for psychoactive substance use.” 

Diabetes Canada’s position paper states that despite the limited evidence, “there were sufficient data to begin developing recommendations for type 1 and type 2 diabetes about education, counseling, and management related to recreational cannabis use.” 

Their recommendations include the following:

• Healthcare professionals should engage their patients in discussions about substance use on a regular basis, with a nonjudgmental approach.
• The use of recreational cannabis is not recommended for adolescents and adults with diabetes.
• People with T1D should avoid recreational cannabis use because of the increased risk for diabetic ketoacidosis.
• For adults with T1D or T2D who intend to use cannabis recreationally, individualized assessment and counseling should be offered to inform them of the general risks of cannabis, with a focus on harm reduction and reduction of the risk for potential adverse effects on diabetes management and complications.
• People with T1D or T2D should be offered education on and encouraged to read public information available through resources from various Canadian health authorities about the general risks of cannabis use to reduce the risk for nondiabetes-related adverse effects of cannabis consumption.

Of note, in 2018, the Canadian government produced an exhaustive compendium of information on cannabis for healthcare professionals that includes information relevant to managing patients with diabetes. 

Dr. Shubrook and Dr. Han reported no competing interests.
 

A version of this article appeared on Medscape.com.

Palliative care has proven to be one of the most promising fields for research on interventions with psychedelic substances. One of the most prominent researchers in this area was the American psychopharmacologist Roland Griffiths, PhD.

In 2016, Dr. Griffiths and his team at Johns Hopkins University in Baltimore, Maryland, published one of the most relevant contributions to the field by demonstrating in a placebo-controlled study that psilocybin can reduce depressive and anxiety symptoms in patients with cancer. The study, conducted with 51 patients diagnosed with advanced-stage cancer, compared the effects of a low dose and a high dose of psilocybin, showing that the high dose resulted in improvements in mood, quality of life, and sense of life, reducing death-related anxiety.

In 2021, after a routine examination, Dr. Griffiths himself was diagnosed with advanced colon cancer. Unexpectedly, the researcher found himself in the position of his research subjects. In an interview with The New York Times in April 2023, he stated that, after some resistance, he agreed to undergo an LSD session.

In the conversation, he revealed that he had a 50% chance of being alive by Halloween. Despite the diagnosis, he showed no discouragement. “As a scientist, I feel like a kid in a candy store, considering all the research and questions that need to be answered about psychedelics and the theme of human flourishing,” he said.

In his last months of life, in the various appearances and interviews he gave, Dr. Griffiths demonstrated a perception of life uncommon in people facing death. “I’m excited to communicate, to shake off the dust and tell people: ‘Come on, wake up!’ ”

He passed away on October 16, 2023, at age 77 years, opening new horizons for clinical research with psychedelics and becoming an example of the therapeutic potential of these substances.
 

Innovative Treatments

“I believe this will be one of the next conditions, if not the next condition, to be considered for the designation of innovative treatment in future psilocybin regulation in the United States, where the field is more advanced,” said Lucas Maia, PhD, a psychopharmacologist and researcher affiliated with the Advanced Center for Psychedelic Medicine (CAMP) at the Federal University of Rio Grande do Norte (UFRN) and the Interdisciplinary Cooperation for Ayahuasca Research and Outreach (ICARO) at the State University of Campinas in São Paulo, Brazil.

Currently, MDMA (for the treatment of posttraumatic stress disorder), psilocybin (for depressive disorder), and MM120 (an LSD analogue used to treat generalized anxiety disorder) are the only psychedelic substances that have received the designation of innovative treatment by the Food and Drug Administration (FDA).

In 2022, Dr. Maia and a colleague from ICARO, Ana Cláudia Mesquita Garcia, PhD, a professor at the School of Nursing at the Federal University of Alfenas in Brazil and leader of the Interdisciplinary Center for Studies in Palliative Care, published a systematic review in the Journal of Pain and Symptom Management that evaluated the use of psychedelic-assisted treatments for symptom control in patients with serious or terminal illnesses.

Of the 20 articles reviewed, 9 (45%) used LSD, 5 (25%) psilocybin, 2 (10%) dipropyltryptamine (DPT), 1 (5%) used ketamine, and 1 (5%) used MDMA. In 10% of the studies, LSD and DPT were combined. Altogether, 347 participants (54%) received LSD, 116 (18%) psilocybin, 81 (13%) LSD and DPT, 64 (10%) DPT, 18 (3%) MDMA, and 14 (2%) ketamine.

The conclusion of the study is that psychedelics provide therapeutic effects on physical, psychological, social, and existential outcomes. They are associated with a reduction in pain and improvement in sleep. A decrease in depressive and anxiety symptoms is also observed; such symptoms are common in patients with serious diseases. In addition, interpersonal relationships become closer and more empathetic. Finally, there is a reduction in the fear of death and suffering, an increase in acceptance, and a redefinition of the disease.

In 55% of the studies, the adverse effects were mild to moderate and transient. They included nausea, vomiting, dry mouth, and fatigue, as well as anxiety, panic, and hallucinations. The researchers concluded that the scarcity and difficulty of access to professional training in psychedelic-assisted treatments represent a significant challenge for the advancement of these interventions, especially in countries in the Global South.

Another systematic review and meta-analysis published in July by researchers at the University of Michigan in Ann Arbor, Michigan, included seven studies with 132 participants and showed significant improvements in quality of life, pain control, and anxiety relief after psychedelic-assisted psychotherapy with psilocybin. The combined effects indicated statistically significant reductions in anxiety symptoms after 4.0-4.5 months and after 6.0-6.5 months post administration, compared with the initial evaluations.

One of the most advanced research studies currently being conducted is led by Stephen Ross, MD, a psychiatrist affiliated with New York University’s Langone Medical Center, New York City. The phase 2b clinical study is randomized, double blind, and placebo controlled, and involves 300 participants. The study aims to evaluate the effects of psilocybin-assisted psychotherapy on psychiatric and existential distress in patients with advanced cancer. Its expected completion date is in 2027.

“We still lack effective interventions in minimizing psychological, spiritual, and existential suffering,” said Dr. Garcia. “In this sense, respecting the contraindications of a physical nature (including pre-existing illnesses at study initiation, disease staging, patient functionality level, comorbidities, concurrent pharmacological treatments, etc) and of a psychiatric nature for the use of psychedelics, depending on the clinical picture, end-of-life patients facing existential crises and psychological suffering will likely benefit more from psychedelic-assisted psychotherapy, which highlights the need for more research and the integration of this treatment into clinical practice.”
 

Changing Perceptions

Since 2021, the Cancer Institute of the State of São Paulo (Icesp) has been providing palliative treatment with ketamine — an atypical psychedelic — following a rigorous and carefully monitored clinical protocol. The substance is already used off label to treat refractory depressive disorder. In addition, in 2020, Brazil’s National Health Surveillance Agency approved the use of Spravato, an intranasal antidepressant based on the ketamine derivative esketamine.

Icesp has hospice beds for clinical oncology patients, and a pain management team evaluates which patients meet the inclusion criteria for ketamine use. In addition to difficult-to-control pain, it is important that the patient present emotional, existential, or spiritual symptoms that amplify that pain.

After this evaluation, a psychoeducation process takes place, in which the patient receives clear information about the treatment, its potential benefits and risks, and understands how ketamine can be a viable option for managing their symptoms. Finally, it is essential that the patient accept the referral and demonstrate a willingness to participate in the treatment, agreeing to the proposed terms.

The treatment takes place in a hospital environment, with an ambiance that aims to provide comfort and safety. Clinicians consider not only the substance dose (such as 0.5 mg/kg) but also the emotional state (“set”) and the treatment environment (“setting”). The experience is facilitated through psychological support for the patient during and after treatment.

According to Alessandro Campolina, MD, PhD, a researcher at the Center for Translational Oncology Research at Icesp, it is important to highlight that quality of life is intrinsically linked to the patient’s self-perception, including how they see themselves in terms of health and in the context in which they live.

The doctor explains that psychedelic interventions can provide a “window of opportunity,” allowing a qualified clinician to help the patient explore new perspectives based on their experiences.

“Often, although the intensity of pain remains the same, the way the patient perceives it can change significantly. For example, a patient may report that, despite the pain, they now feel less concerned about it because they were able to contemplate more significant aspects of their life,” said Dr. Campolina.

“This observation shows that treatment is not limited to addressing the pain or primary symptoms, but also addresses the associated suffering. While some patients have profound insights, many others experience more subtle changes that, under the guidance of a competent therapist, can turn into valuable clinical insights, thus improving quality of life and how they deal with their pathologies.”

Dr. Griffiths exemplified this in the interview with the Times when he reflected on his own cancer. He came to believe, as if guided an external observer, that “there is a meaning and a purpose in this [disease] that go beyond your understanding, and the way you are dealing with it is exactly how you should.”

Toshio Chiba, MD, chief physician of the Palliative Care Service at Icesp, emphasized that ketamine is already in use. “It is not feasible to wait years for the approval of psilocybin or for the FDA’s decision on MDMA, especially if the patient needs immediate care,” he said.

Furthermore, recreational and therapeutic uses are distinct. “It is essential to note that responsibilities are shared between the professional and the patient,” said Dr. Chiba. “In the therapeutic setting, there is an ethical and civil responsibility of the medical professional, as well as the patient actively engaging in treatment.”

Early palliative care can also facilitate the establishment of care goals. “I prefer to avoid terms like ‘coping’ or ‘fighting the disease,’” said Dr. Chiba. “Nowadays, dealing with cancer is more about coexisting with the disease properly, as treatments can last for years. 

“Of course, there are still highly lethal tumors. However, for neoplasms like breast, colorectal, and prostate cancers, we often talk about 5, 10, or even 15 years of coexistence [with the condition]. The lack of this information [about the disease, treatments, and existential issues] can generate distress in some patients, who end up excessively worrying about the future,” he added.

But palliative treatment with psychedelics as a panacea, he said.

In addition, Marcelo Falchi, MD, medical director of CAMP at UFRN, also emphasized that psychedelics are not a risk-free intervention. Substances like LSD and psilocybin, for example, can cause increases in blood pressure and tachycardia, which, may limit their use for patients at high cardiovascular risk. Crises of anxiety or dissociative symptoms also may occur, and they require mitigation strategies such as psychological support and attention to set and setting.

“But research seems to agree that the risks can be managed effectively through a diligent process, allowing for the responsible exploration of the therapeutic potential of psychedelics,” said Dr. Falchi, who is responsible for CAMP’s postgraduate course in psychedelic therapies. The program provides training in substances used in Brazil, such as ketamine and ibogaine.

The use of psychedelics in palliative care requires a significant shift in how professionals relate to patients.

Unlike in traditional practice, where the prescription is followed by quick consultations, palliative care with psychedelics requires deep and continuous involvement, as Dr. Campolina pointed out. “We joke that it’s not a high-tech specialty, but ‘high touch,’ because it demands the constant presence of the doctor or therapist with the patient. This can involve sessions of several hours, with frequent monitoring and regular contact after sessions. This dynamic emphasizes the importance of human touch and connection during the process, reflecting a new way of practicing medicine.”

In his last months of life, Dr. Griffiths sought to emphasize this point, suggesting that, from a broader perspective, doctors and patients face the same fundamental questions. “We all know we are terminal,” he said. “Essentially, we shouldn’t need a stage 4 cancer diagnosis to awaken to this reality.”

This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Palliative care has proven to be one of the most promising fields for research on interventions with psychedelic substances. One of the most prominent researchers in this area was the American psychopharmacologist Roland Griffiths, PhD.

In 2016, Dr. Griffiths and his team at Johns Hopkins University in Baltimore, Maryland, published one of the most relevant contributions to the field by demonstrating in a placebo-controlled study that psilocybin can reduce depressive and anxiety symptoms in patients with cancer. The study, conducted with 51 patients diagnosed with advanced-stage cancer, compared the effects of a low dose and a high dose of psilocybin, showing that the high dose resulted in improvements in mood, quality of life, and sense of life, reducing death-related anxiety.

In 2021, after a routine examination, Dr. Griffiths himself was diagnosed with advanced colon cancer. Unexpectedly, the researcher found himself in the position of his research subjects. In an interview with The New York Times in April 2023, he stated that, after some resistance, he agreed to undergo an LSD session.

In the conversation, he revealed that he had a 50% chance of being alive by Halloween. Despite the diagnosis, he showed no discouragement. “As a scientist, I feel like a kid in a candy store, considering all the research and questions that need to be answered about psychedelics and the theme of human flourishing,” he said.

In his last months of life, in the various appearances and interviews he gave, Dr. Griffiths demonstrated a perception of life uncommon in people facing death. “I’m excited to communicate, to shake off the dust and tell people: ‘Come on, wake up!’ ”

He passed away on October 16, 2023, at age 77 years, opening new horizons for clinical research with psychedelics and becoming an example of the therapeutic potential of these substances.
 

Innovative Treatments

“I believe this will be one of the next conditions, if not the next condition, to be considered for the designation of innovative treatment in future psilocybin regulation in the United States, where the field is more advanced,” said Lucas Maia, PhD, a psychopharmacologist and researcher affiliated with the Advanced Center for Psychedelic Medicine (CAMP) at the Federal University of Rio Grande do Norte (UFRN) and the Interdisciplinary Cooperation for Ayahuasca Research and Outreach (ICARO) at the State University of Campinas in São Paulo, Brazil.

Currently, MDMA (for the treatment of posttraumatic stress disorder), psilocybin (for depressive disorder), and MM120 (an LSD analogue used to treat generalized anxiety disorder) are the only psychedelic substances that have received the designation of innovative treatment by the Food and Drug Administration (FDA).

In 2022, Dr. Maia and a colleague from ICARO, Ana Cláudia Mesquita Garcia, PhD, a professor at the School of Nursing at the Federal University of Alfenas in Brazil and leader of the Interdisciplinary Center for Studies in Palliative Care, published a systematic review in the Journal of Pain and Symptom Management that evaluated the use of psychedelic-assisted treatments for symptom control in patients with serious or terminal illnesses.

Of the 20 articles reviewed, 9 (45%) used LSD, 5 (25%) psilocybin, 2 (10%) dipropyltryptamine (DPT), 1 (5%) used ketamine, and 1 (5%) used MDMA. In 10% of the studies, LSD and DPT were combined. Altogether, 347 participants (54%) received LSD, 116 (18%) psilocybin, 81 (13%) LSD and DPT, 64 (10%) DPT, 18 (3%) MDMA, and 14 (2%) ketamine.

The conclusion of the study is that psychedelics provide therapeutic effects on physical, psychological, social, and existential outcomes. They are associated with a reduction in pain and improvement in sleep. A decrease in depressive and anxiety symptoms is also observed; such symptoms are common in patients with serious diseases. In addition, interpersonal relationships become closer and more empathetic. Finally, there is a reduction in the fear of death and suffering, an increase in acceptance, and a redefinition of the disease.

In 55% of the studies, the adverse effects were mild to moderate and transient. They included nausea, vomiting, dry mouth, and fatigue, as well as anxiety, panic, and hallucinations. The researchers concluded that the scarcity and difficulty of access to professional training in psychedelic-assisted treatments represent a significant challenge for the advancement of these interventions, especially in countries in the Global South.

Another systematic review and meta-analysis published in July by researchers at the University of Michigan in Ann Arbor, Michigan, included seven studies with 132 participants and showed significant improvements in quality of life, pain control, and anxiety relief after psychedelic-assisted psychotherapy with psilocybin. The combined effects indicated statistically significant reductions in anxiety symptoms after 4.0-4.5 months and after 6.0-6.5 months post administration, compared with the initial evaluations.

One of the most advanced research studies currently being conducted is led by Stephen Ross, MD, a psychiatrist affiliated with New York University’s Langone Medical Center, New York City. The phase 2b clinical study is randomized, double blind, and placebo controlled, and involves 300 participants. The study aims to evaluate the effects of psilocybin-assisted psychotherapy on psychiatric and existential distress in patients with advanced cancer. Its expected completion date is in 2027.

“We still lack effective interventions in minimizing psychological, spiritual, and existential suffering,” said Dr. Garcia. “In this sense, respecting the contraindications of a physical nature (including pre-existing illnesses at study initiation, disease staging, patient functionality level, comorbidities, concurrent pharmacological treatments, etc) and of a psychiatric nature for the use of psychedelics, depending on the clinical picture, end-of-life patients facing existential crises and psychological suffering will likely benefit more from psychedelic-assisted psychotherapy, which highlights the need for more research and the integration of this treatment into clinical practice.”
 

Changing Perceptions

Since 2021, the Cancer Institute of the State of São Paulo (Icesp) has been providing palliative treatment with ketamine — an atypical psychedelic — following a rigorous and carefully monitored clinical protocol. The substance is already used off label to treat refractory depressive disorder. In addition, in 2020, Brazil’s National Health Surveillance Agency approved the use of Spravato, an intranasal antidepressant based on the ketamine derivative esketamine.

Icesp has hospice beds for clinical oncology patients, and a pain management team evaluates which patients meet the inclusion criteria for ketamine use. In addition to difficult-to-control pain, it is important that the patient present emotional, existential, or spiritual symptoms that amplify that pain.

After this evaluation, a psychoeducation process takes place, in which the patient receives clear information about the treatment, its potential benefits and risks, and understands how ketamine can be a viable option for managing their symptoms. Finally, it is essential that the patient accept the referral and demonstrate a willingness to participate in the treatment, agreeing to the proposed terms.

The treatment takes place in a hospital environment, with an ambiance that aims to provide comfort and safety. Clinicians consider not only the substance dose (such as 0.5 mg/kg) but also the emotional state (“set”) and the treatment environment (“setting”). The experience is facilitated through psychological support for the patient during and after treatment.

According to Alessandro Campolina, MD, PhD, a researcher at the Center for Translational Oncology Research at Icesp, it is important to highlight that quality of life is intrinsically linked to the patient’s self-perception, including how they see themselves in terms of health and in the context in which they live.

The doctor explains that psychedelic interventions can provide a “window of opportunity,” allowing a qualified clinician to help the patient explore new perspectives based on their experiences.

“Often, although the intensity of pain remains the same, the way the patient perceives it can change significantly. For example, a patient may report that, despite the pain, they now feel less concerned about it because they were able to contemplate more significant aspects of their life,” said Dr. Campolina.

“This observation shows that treatment is not limited to addressing the pain or primary symptoms, but also addresses the associated suffering. While some patients have profound insights, many others experience more subtle changes that, under the guidance of a competent therapist, can turn into valuable clinical insights, thus improving quality of life and how they deal with their pathologies.”

Dr. Griffiths exemplified this in the interview with the Times when he reflected on his own cancer. He came to believe, as if guided an external observer, that “there is a meaning and a purpose in this [disease] that go beyond your understanding, and the way you are dealing with it is exactly how you should.”

Toshio Chiba, MD, chief physician of the Palliative Care Service at Icesp, emphasized that ketamine is already in use. “It is not feasible to wait years for the approval of psilocybin or for the FDA’s decision on MDMA, especially if the patient needs immediate care,” he said.

Furthermore, recreational and therapeutic uses are distinct. “It is essential to note that responsibilities are shared between the professional and the patient,” said Dr. Chiba. “In the therapeutic setting, there is an ethical and civil responsibility of the medical professional, as well as the patient actively engaging in treatment.”

Early palliative care can also facilitate the establishment of care goals. “I prefer to avoid terms like ‘coping’ or ‘fighting the disease,’” said Dr. Chiba. “Nowadays, dealing with cancer is more about coexisting with the disease properly, as treatments can last for years. 

“Of course, there are still highly lethal tumors. However, for neoplasms like breast, colorectal, and prostate cancers, we often talk about 5, 10, or even 15 years of coexistence [with the condition]. The lack of this information [about the disease, treatments, and existential issues] can generate distress in some patients, who end up excessively worrying about the future,” he added.

But palliative treatment with psychedelics as a panacea, he said.

In addition, Marcelo Falchi, MD, medical director of CAMP at UFRN, also emphasized that psychedelics are not a risk-free intervention. Substances like LSD and psilocybin, for example, can cause increases in blood pressure and tachycardia, which, may limit their use for patients at high cardiovascular risk. Crises of anxiety or dissociative symptoms also may occur, and they require mitigation strategies such as psychological support and attention to set and setting.

“But research seems to agree that the risks can be managed effectively through a diligent process, allowing for the responsible exploration of the therapeutic potential of psychedelics,” said Dr. Falchi, who is responsible for CAMP’s postgraduate course in psychedelic therapies. The program provides training in substances used in Brazil, such as ketamine and ibogaine.

The use of psychedelics in palliative care requires a significant shift in how professionals relate to patients.

Unlike in traditional practice, where the prescription is followed by quick consultations, palliative care with psychedelics requires deep and continuous involvement, as Dr. Campolina pointed out. “We joke that it’s not a high-tech specialty, but ‘high touch,’ because it demands the constant presence of the doctor or therapist with the patient. This can involve sessions of several hours, with frequent monitoring and regular contact after sessions. This dynamic emphasizes the importance of human touch and connection during the process, reflecting a new way of practicing medicine.”

In his last months of life, Dr. Griffiths sought to emphasize this point, suggesting that, from a broader perspective, doctors and patients face the same fundamental questions. “We all know we are terminal,” he said. “Essentially, we shouldn’t need a stage 4 cancer diagnosis to awaken to this reality.”

This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Palliative care has proven to be one of the most promising fields for research on interventions with psychedelic substances. One of the most prominent researchers in this area was the American psychopharmacologist Roland Griffiths, PhD.

In 2016, Dr. Griffiths and his team at Johns Hopkins University in Baltimore, Maryland, published one of the most relevant contributions to the field by demonstrating in a placebo-controlled study that psilocybin can reduce depressive and anxiety symptoms in patients with cancer. The study, conducted with 51 patients diagnosed with advanced-stage cancer, compared the effects of a low dose and a high dose of psilocybin, showing that the high dose resulted in improvements in mood, quality of life, and sense of life, reducing death-related anxiety.

In 2021, after a routine examination, Dr. Griffiths himself was diagnosed with advanced colon cancer. Unexpectedly, the researcher found himself in the position of his research subjects. In an interview with The New York Times in April 2023, he stated that, after some resistance, he agreed to undergo an LSD session.

In the conversation, he revealed that he had a 50% chance of being alive by Halloween. Despite the diagnosis, he showed no discouragement. “As a scientist, I feel like a kid in a candy store, considering all the research and questions that need to be answered about psychedelics and the theme of human flourishing,” he said.

In his last months of life, in the various appearances and interviews he gave, Dr. Griffiths demonstrated a perception of life uncommon in people facing death. “I’m excited to communicate, to shake off the dust and tell people: ‘Come on, wake up!’ ”

He passed away on October 16, 2023, at age 77 years, opening new horizons for clinical research with psychedelics and becoming an example of the therapeutic potential of these substances.
 

Innovative Treatments

“I believe this will be one of the next conditions, if not the next condition, to be considered for the designation of innovative treatment in future psilocybin regulation in the United States, where the field is more advanced,” said Lucas Maia, PhD, a psychopharmacologist and researcher affiliated with the Advanced Center for Psychedelic Medicine (CAMP) at the Federal University of Rio Grande do Norte (UFRN) and the Interdisciplinary Cooperation for Ayahuasca Research and Outreach (ICARO) at the State University of Campinas in São Paulo, Brazil.

Currently, MDMA (for the treatment of posttraumatic stress disorder), psilocybin (for depressive disorder), and MM120 (an LSD analogue used to treat generalized anxiety disorder) are the only psychedelic substances that have received the designation of innovative treatment by the Food and Drug Administration (FDA).

In 2022, Dr. Maia and a colleague from ICARO, Ana Cláudia Mesquita Garcia, PhD, a professor at the School of Nursing at the Federal University of Alfenas in Brazil and leader of the Interdisciplinary Center for Studies in Palliative Care, published a systematic review in the Journal of Pain and Symptom Management that evaluated the use of psychedelic-assisted treatments for symptom control in patients with serious or terminal illnesses.

Of the 20 articles reviewed, 9 (45%) used LSD, 5 (25%) psilocybin, 2 (10%) dipropyltryptamine (DPT), 1 (5%) used ketamine, and 1 (5%) used MDMA. In 10% of the studies, LSD and DPT were combined. Altogether, 347 participants (54%) received LSD, 116 (18%) psilocybin, 81 (13%) LSD and DPT, 64 (10%) DPT, 18 (3%) MDMA, and 14 (2%) ketamine.

The conclusion of the study is that psychedelics provide therapeutic effects on physical, psychological, social, and existential outcomes. They are associated with a reduction in pain and improvement in sleep. A decrease in depressive and anxiety symptoms is also observed; such symptoms are common in patients with serious diseases. In addition, interpersonal relationships become closer and more empathetic. Finally, there is a reduction in the fear of death and suffering, an increase in acceptance, and a redefinition of the disease.

In 55% of the studies, the adverse effects were mild to moderate and transient. They included nausea, vomiting, dry mouth, and fatigue, as well as anxiety, panic, and hallucinations. The researchers concluded that the scarcity and difficulty of access to professional training in psychedelic-assisted treatments represent a significant challenge for the advancement of these interventions, especially in countries in the Global South.

Another systematic review and meta-analysis published in July by researchers at the University of Michigan in Ann Arbor, Michigan, included seven studies with 132 participants and showed significant improvements in quality of life, pain control, and anxiety relief after psychedelic-assisted psychotherapy with psilocybin. The combined effects indicated statistically significant reductions in anxiety symptoms after 4.0-4.5 months and after 6.0-6.5 months post administration, compared with the initial evaluations.

One of the most advanced research studies currently being conducted is led by Stephen Ross, MD, a psychiatrist affiliated with New York University’s Langone Medical Center, New York City. The phase 2b clinical study is randomized, double blind, and placebo controlled, and involves 300 participants. The study aims to evaluate the effects of psilocybin-assisted psychotherapy on psychiatric and existential distress in patients with advanced cancer. Its expected completion date is in 2027.

“We still lack effective interventions in minimizing psychological, spiritual, and existential suffering,” said Dr. Garcia. “In this sense, respecting the contraindications of a physical nature (including pre-existing illnesses at study initiation, disease staging, patient functionality level, comorbidities, concurrent pharmacological treatments, etc) and of a psychiatric nature for the use of psychedelics, depending on the clinical picture, end-of-life patients facing existential crises and psychological suffering will likely benefit more from psychedelic-assisted psychotherapy, which highlights the need for more research and the integration of this treatment into clinical practice.”
 

Changing Perceptions

Since 2021, the Cancer Institute of the State of São Paulo (Icesp) has been providing palliative treatment with ketamine — an atypical psychedelic — following a rigorous and carefully monitored clinical protocol. The substance is already used off label to treat refractory depressive disorder. In addition, in 2020, Brazil’s National Health Surveillance Agency approved the use of Spravato, an intranasal antidepressant based on the ketamine derivative esketamine.

Icesp has hospice beds for clinical oncology patients, and a pain management team evaluates which patients meet the inclusion criteria for ketamine use. In addition to difficult-to-control pain, it is important that the patient present emotional, existential, or spiritual symptoms that amplify that pain.

After this evaluation, a psychoeducation process takes place, in which the patient receives clear information about the treatment, its potential benefits and risks, and understands how ketamine can be a viable option for managing their symptoms. Finally, it is essential that the patient accept the referral and demonstrate a willingness to participate in the treatment, agreeing to the proposed terms.

The treatment takes place in a hospital environment, with an ambiance that aims to provide comfort and safety. Clinicians consider not only the substance dose (such as 0.5 mg/kg) but also the emotional state (“set”) and the treatment environment (“setting”). The experience is facilitated through psychological support for the patient during and after treatment.

According to Alessandro Campolina, MD, PhD, a researcher at the Center for Translational Oncology Research at Icesp, it is important to highlight that quality of life is intrinsically linked to the patient’s self-perception, including how they see themselves in terms of health and in the context in which they live.

The doctor explains that psychedelic interventions can provide a “window of opportunity,” allowing a qualified clinician to help the patient explore new perspectives based on their experiences.

“Often, although the intensity of pain remains the same, the way the patient perceives it can change significantly. For example, a patient may report that, despite the pain, they now feel less concerned about it because they were able to contemplate more significant aspects of their life,” said Dr. Campolina.

“This observation shows that treatment is not limited to addressing the pain or primary symptoms, but also addresses the associated suffering. While some patients have profound insights, many others experience more subtle changes that, under the guidance of a competent therapist, can turn into valuable clinical insights, thus improving quality of life and how they deal with their pathologies.”

Dr. Griffiths exemplified this in the interview with the Times when he reflected on his own cancer. He came to believe, as if guided an external observer, that “there is a meaning and a purpose in this [disease] that go beyond your understanding, and the way you are dealing with it is exactly how you should.”

Toshio Chiba, MD, chief physician of the Palliative Care Service at Icesp, emphasized that ketamine is already in use. “It is not feasible to wait years for the approval of psilocybin or for the FDA’s decision on MDMA, especially if the patient needs immediate care,” he said.

Furthermore, recreational and therapeutic uses are distinct. “It is essential to note that responsibilities are shared between the professional and the patient,” said Dr. Chiba. “In the therapeutic setting, there is an ethical and civil responsibility of the medical professional, as well as the patient actively engaging in treatment.”

Early palliative care can also facilitate the establishment of care goals. “I prefer to avoid terms like ‘coping’ or ‘fighting the disease,’” said Dr. Chiba. “Nowadays, dealing with cancer is more about coexisting with the disease properly, as treatments can last for years. 

“Of course, there are still highly lethal tumors. However, for neoplasms like breast, colorectal, and prostate cancers, we often talk about 5, 10, or even 15 years of coexistence [with the condition]. The lack of this information [about the disease, treatments, and existential issues] can generate distress in some patients, who end up excessively worrying about the future,” he added.

But palliative treatment with psychedelics as a panacea, he said.

In addition, Marcelo Falchi, MD, medical director of CAMP at UFRN, also emphasized that psychedelics are not a risk-free intervention. Substances like LSD and psilocybin, for example, can cause increases in blood pressure and tachycardia, which, may limit their use for patients at high cardiovascular risk. Crises of anxiety or dissociative symptoms also may occur, and they require mitigation strategies such as psychological support and attention to set and setting.

“But research seems to agree that the risks can be managed effectively through a diligent process, allowing for the responsible exploration of the therapeutic potential of psychedelics,” said Dr. Falchi, who is responsible for CAMP’s postgraduate course in psychedelic therapies. The program provides training in substances used in Brazil, such as ketamine and ibogaine.

The use of psychedelics in palliative care requires a significant shift in how professionals relate to patients.

Unlike in traditional practice, where the prescription is followed by quick consultations, palliative care with psychedelics requires deep and continuous involvement, as Dr. Campolina pointed out. “We joke that it’s not a high-tech specialty, but ‘high touch,’ because it demands the constant presence of the doctor or therapist with the patient. This can involve sessions of several hours, with frequent monitoring and regular contact after sessions. This dynamic emphasizes the importance of human touch and connection during the process, reflecting a new way of practicing medicine.”

In his last months of life, Dr. Griffiths sought to emphasize this point, suggesting that, from a broader perspective, doctors and patients face the same fundamental questions. “We all know we are terminal,” he said. “Essentially, we shouldn’t need a stage 4 cancer diagnosis to awaken to this reality.”

This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Salaries for millennial physicians are slightly increasing, but clinicians still face pay disparities across location, practice type, and gender.

Medscape Medical News reviewed survey data from more than 1200 practicing doctors under age 40 across 29 specialties over a 4-month period starting in October 2023.

The average annual total compensation (including any bonuses) for young clinicians rose from $326,000 to $338,000, about 4%, between 2022 and 2023. Among millennials, primary care physicians saw a 5% increase. But a large pay gap exists between fields: Specialists under age 40 earned an average of $357,000 in 2023, compared with the average primary care clinician salary of $271,000.

“Procedures are reimbursed too high, while very little value is placed on primary care,” one survey respondent complained.

The type of practice plays a major part in compensation. Millennial doctors in office-based, single-specialty group practices earned an average of $358,000 per year, followed by those in office-based multispecialty group practices at 355,000 per year. Those in outpatient clinics earned $278,000 per year.

“I believe the practice situation is a huge portion of compensation,” said Tiffany Di Pietro, DO, a cardiologist and internal medicine physician in Fort Lauderdale, Florida. “Owning your own private practice is generally more lucrative (if you have good business sense), but it is also quite a bit more time-consuming, whereas employed physicians usually make less but have fewer concerns with staffing and overhead.”

Like in previous years, a gender pay gap equated to men outearning women. Female physicians under age 40 of any kind earned about $302,000 per year, 24% less than their male counterparts, on average.

Millennial doctors in the Midwest brought home the biggest earnings, with an average salary of $343,000 vs $332,000 on the West Coast.

Millennial physicians also reported higher levels of dissatisfaction. In the 2022 report, 46% said they were not paid fairly. That figure rose to 49%. Just 68% of millennial doctors would choose medicine again if they could do things over, down from 76% in the 2021 report.

“Doctors go through multiple years of school and then have to act like we are working at Dunkin’ Donuts — like we’re on an assembly line,” one survey respondent said. “We should not have to be paid per patient seen but valued for 8-9 years of training.”

Despite these complaints, close to 7 out of 10 millennial respondents said pay was not a major factor in what area of medicine they chose, with 29% saying it played no role at all in their decision.

Psychiatrists and anesthesiologists were the happiest with their earnings, with 61% of both specialties reporting that they felt fairly paid. They were followed by dermatologists and emergency medicine doctors, both of whom 60% reported fair earnings.

Many millennial doctors are finding ways to make money outside of their practice, with 18% securing other medical-related work, 15% doing medical moonlighting, and 5% taking on non–medical-related work.

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

Salaries for millennial physicians are slightly increasing, but clinicians still face pay disparities across location, practice type, and gender.

Medscape Medical News reviewed survey data from more than 1200 practicing doctors under age 40 across 29 specialties over a 4-month period starting in October 2023.

The average annual total compensation (including any bonuses) for young clinicians rose from $326,000 to $338,000, about 4%, between 2022 and 2023. Among millennials, primary care physicians saw a 5% increase. But a large pay gap exists between fields: Specialists under age 40 earned an average of $357,000 in 2023, compared with the average primary care clinician salary of $271,000.

“Procedures are reimbursed too high, while very little value is placed on primary care,” one survey respondent complained.

The type of practice plays a major part in compensation. Millennial doctors in office-based, single-specialty group practices earned an average of $358,000 per year, followed by those in office-based multispecialty group practices at 355,000 per year. Those in outpatient clinics earned $278,000 per year.

“I believe the practice situation is a huge portion of compensation,” said Tiffany Di Pietro, DO, a cardiologist and internal medicine physician in Fort Lauderdale, Florida. “Owning your own private practice is generally more lucrative (if you have good business sense), but it is also quite a bit more time-consuming, whereas employed physicians usually make less but have fewer concerns with staffing and overhead.”

Like in previous years, a gender pay gap equated to men outearning women. Female physicians under age 40 of any kind earned about $302,000 per year, 24% less than their male counterparts, on average.

Millennial doctors in the Midwest brought home the biggest earnings, with an average salary of $343,000 vs $332,000 on the West Coast.

Millennial physicians also reported higher levels of dissatisfaction. In the 2022 report, 46% said they were not paid fairly. That figure rose to 49%. Just 68% of millennial doctors would choose medicine again if they could do things over, down from 76% in the 2021 report.

“Doctors go through multiple years of school and then have to act like we are working at Dunkin’ Donuts — like we’re on an assembly line,” one survey respondent said. “We should not have to be paid per patient seen but valued for 8-9 years of training.”

Despite these complaints, close to 7 out of 10 millennial respondents said pay was not a major factor in what area of medicine they chose, with 29% saying it played no role at all in their decision.

Psychiatrists and anesthesiologists were the happiest with their earnings, with 61% of both specialties reporting that they felt fairly paid. They were followed by dermatologists and emergency medicine doctors, both of whom 60% reported fair earnings.

Many millennial doctors are finding ways to make money outside of their practice, with 18% securing other medical-related work, 15% doing medical moonlighting, and 5% taking on non–medical-related work.

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

Salaries for millennial physicians are slightly increasing, but clinicians still face pay disparities across location, practice type, and gender.

Medscape Medical News reviewed survey data from more than 1200 practicing doctors under age 40 across 29 specialties over a 4-month period starting in October 2023.

The average annual total compensation (including any bonuses) for young clinicians rose from $326,000 to $338,000, about 4%, between 2022 and 2023. Among millennials, primary care physicians saw a 5% increase. But a large pay gap exists between fields: Specialists under age 40 earned an average of $357,000 in 2023, compared with the average primary care clinician salary of $271,000.

“Procedures are reimbursed too high, while very little value is placed on primary care,” one survey respondent complained.

The type of practice plays a major part in compensation. Millennial doctors in office-based, single-specialty group practices earned an average of $358,000 per year, followed by those in office-based multispecialty group practices at 355,000 per year. Those in outpatient clinics earned $278,000 per year.

“I believe the practice situation is a huge portion of compensation,” said Tiffany Di Pietro, DO, a cardiologist and internal medicine physician in Fort Lauderdale, Florida. “Owning your own private practice is generally more lucrative (if you have good business sense), but it is also quite a bit more time-consuming, whereas employed physicians usually make less but have fewer concerns with staffing and overhead.”

Like in previous years, a gender pay gap equated to men outearning women. Female physicians under age 40 of any kind earned about $302,000 per year, 24% less than their male counterparts, on average.

Millennial doctors in the Midwest brought home the biggest earnings, with an average salary of $343,000 vs $332,000 on the West Coast.

Millennial physicians also reported higher levels of dissatisfaction. In the 2022 report, 46% said they were not paid fairly. That figure rose to 49%. Just 68% of millennial doctors would choose medicine again if they could do things over, down from 76% in the 2021 report.

“Doctors go through multiple years of school and then have to act like we are working at Dunkin’ Donuts — like we’re on an assembly line,” one survey respondent said. “We should not have to be paid per patient seen but valued for 8-9 years of training.”

Despite these complaints, close to 7 out of 10 millennial respondents said pay was not a major factor in what area of medicine they chose, with 29% saying it played no role at all in their decision.

Psychiatrists and anesthesiologists were the happiest with their earnings, with 61% of both specialties reporting that they felt fairly paid. They were followed by dermatologists and emergency medicine doctors, both of whom 60% reported fair earnings.

Many millennial doctors are finding ways to make money outside of their practice, with 18% securing other medical-related work, 15% doing medical moonlighting, and 5% taking on non–medical-related work.

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

Fantine Giap, MD, sat across from a 21-year-old with a rare sarcoma at the base of her skull. 

Despite the large tumor, nestled in a sensitive area, the Boston-based radiation oncologist could envision a bright future for her patient. 

She and the other members of the patient’s care team had an impressive cancer-fighting arsenal at her fingertips. The team had recommended surgery, followed by proton therapy — a sophisticated tool able to deliver concentrated, razor-focused radiation to the once apple-sized growth, while sparing the fragile brain stem, optic nerve, and spinal cord. 

Surgery went as planned. But as the days and weeks wore on and insurance prior authorization for the proton therapy never came, the tumor roared back, leading to more surgeries and more complications. Ultimately, the young woman needed a tracheostomy and a feeding tube. 

By the time insurance said yes, more than 1 year from her initial visit, the future the team had envisioned seemed out of reach. 

“Unfortunately for this patient, it went from a potentially curable situation to a likely not curable situation,” recalled Dr. Giap, a clinician at Massachusetts General Hospital and instructor at Harvard Medical School, Boston. “I wanted to cry every day that she waited.’’ 

While a stark example, such insurance delays are not uncommon, according to new research published in JAMA Network Open.

The study of 206 denials in radiation oncology concluded that more than two-thirds were ultimately approved on appeal without changes, but often these approvals came only after costly delays that potentially compromised patient care.

Other studies have found that number to be even higher, with more than 86% of prior authorization requests ultimately approved with few changes.

‘’It gives you the idea that this entire process might be a little futile — that it’s just wasting people’s time,’’ said Fumiko Chino, MD, coauthor on the JAMA study and now an assistant professor in radiation oncology at MD Anderson Cancer Center in Houston. ‘’The problem is cancer doesn’t wait for bureaucracy.’’
 

Barriers at Every Step

As Dr. Chino and her study coauthors explained, advancements like intensity-modulated radiation therapy and stereotactic radiosurgery have allowed a new generation of specialists to treat previously untreatable cancers in ways that maximize tumor-killing power while minimizing collateral damage. But these tools require sophisticated planning, imaging, simulations and execution — all of which are subject to increased insurance scrutiny.

‘’We face barriers pretty much every step of the way for every patient,’’ said Dr. Chino.

To investigate how such barriers impact care, Dr. Chino and colleagues at Memorial Sloan Kettering Cancer Center — where she worked until July — looked at 206 cases in which payers denied prior authorization for radiation therapy from November 1, 2021 to December 8, 2022. 

The team found that 62% were ultimately approved without any change to technique or dose, while 28% were authorized, but with lower doses or less sophisticated techniques. Four people, however, never got authorization at all — three abandoned treatment altogether, and one sought treatment at another institution.

Treatment delays ranged from 1 day to 49 days. Eighty-three patients died.

Would some of them have lived if it weren’t for prior authorization?

Dr. Chino cannot say for sure, but did note that certain cancers, like cervical cancer, can grow so quickly that every day of delayed treatment makes them harder to control. 

Patients with metastatic or late-stage cancers are often denied more aggressive treatments by insurers who, in essence, “assume that they are going to die from their disease anyway,” Dr. Chino said. 

She views this as tragically shortsighted.

‘’There’s actually a strong body of evidence to show that if you treat even metastatic stage IV diseases aggressively, you can prolong not just quality of life but also quantity,’’ she said. 

In cases where the cancer is more localized and insurance mandates lower doses or cheaper techniques, the consequences can be equally heartbreaking.

‘’It’s like saying instead of taking an extra-strength Tylenol you can only have a baby aspirin,’’ she said. ‘’Their pain is less likely to be controlled, their disease is less likely to be controlled, and they are more likely to need retreatment.’’

Prior authorization delays can also significantly stress patients at the most vulnerable point of their lives.

In another recent study, Dr. Chino found that 69% of patients with cancer reported prior authorization-related delays in care, with one-third waiting a month or longer. One in five never got the care their doctors recommended, and 20% reported spending more than 11 hours on the phone haggling with their insurance companies. 

Most patients rated the process as ‘’bad’’ or ‘’horrible,’’ and said it fueled anxiety.

Such delays can be hard on clinicians and the healthcare system too. 

One 2022 study found that a typical academic radiation oncology practice spent about a half-million dollars per year seeking insurance preauthorization. Nationally, that number exceeds $40 million.

Then there is the burnout factor. 

Dr. Giap, an early-career physician who specializes in rare, aggressive sarcomas, works at an institution that helped pioneer proton therapy. She says it pains her to tell a desperate patient, like the 21-year-old, who has traveled to her from out of state that they have to wait. 

‘’Knowing that the majority of the cases are ultimately approved and that this wait is often unnecessary makes it even tougher,’’ she said.

Dr. Chino, a breast cancer specialist, has taken to warning patients before the alarming insurance letter arrives in the mail that their insurance may delay authorizing their care. But she tells patients that she will do everything she can to fight for them and develops a back-up plan to pivot to quickly, if needed.

‘’No one goes into medicine to spend their time talking to insurance companies,’’ said Dr. Chino.

The national trade group, America’s Health Insurance Plans (AHIP), did not return repeated requests for an interview for this story. But their official position, as stated on their website, is that “prior authorization is one of many tools health insurance providers use to promote safe, timely, evidence-based, affordable, and efficient care.”

Both Dr. Giap and Dr. Chino believe that prior authorization was developed with good intentions: to save healthcare costs and rein in treatments that don’t necessarily benefit patients. 

But, in their specialty, the burden has proliferated to a point that Dr. Chino characterizes as ‘’unconscionable.’’

She believes that policy changes like the proposed Improving Seniors’ Timely Access to Care Act — which would require real-time decisions for procedures that are routinely approved — could go a long way in improving patient care.

Meanwhile, Dr. Giap said, more research and professional guidelines are necessary to bolster insurance company confidence in newer technologies, particularly for rare cancers.

Her patient ultimately got her proton therapy and is ‘’doing relatively well, all things considered.’’

But not all the stories end like this.

Dr. Chino will never forget a patient with a cancer growing so rapidly she could see it protruding through her chest wall. She called for an urgent PET scan to see where else in the body the cancer might be brewing and rushed the planning process for radiation therapy, both of which faced prior authorization barriers. That scan — which ultimately showed the cancer had spread — was delayed for months.*

If the team had had those imaging results upfront, she said, they would have recommended a completely different course of treatment.

And her patient might be alive today.

‘’Unfortunately,” Dr. Chino said, “the people with the very worst prior authorization stories aren’t here anymore to tell you about them.”

*Correction,  10/4/24: An earlier version of this article erroneously stated that Dr. Chino called for surgery for her patient. She actually called for a PET scan and an urgent radiation start.

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

Fantine Giap, MD, sat across from a 21-year-old with a rare sarcoma at the base of her skull. 

Despite the large tumor, nestled in a sensitive area, the Boston-based radiation oncologist could envision a bright future for her patient. 

She and the other members of the patient’s care team had an impressive cancer-fighting arsenal at her fingertips. The team had recommended surgery, followed by proton therapy — a sophisticated tool able to deliver concentrated, razor-focused radiation to the once apple-sized growth, while sparing the fragile brain stem, optic nerve, and spinal cord. 

Surgery went as planned. But as the days and weeks wore on and insurance prior authorization for the proton therapy never came, the tumor roared back, leading to more surgeries and more complications. Ultimately, the young woman needed a tracheostomy and a feeding tube. 

By the time insurance said yes, more than 1 year from her initial visit, the future the team had envisioned seemed out of reach. 

“Unfortunately for this patient, it went from a potentially curable situation to a likely not curable situation,” recalled Dr. Giap, a clinician at Massachusetts General Hospital and instructor at Harvard Medical School, Boston. “I wanted to cry every day that she waited.’’ 

While a stark example, such insurance delays are not uncommon, according to new research published in JAMA Network Open.

The study of 206 denials in radiation oncology concluded that more than two-thirds were ultimately approved on appeal without changes, but often these approvals came only after costly delays that potentially compromised patient care.

Other studies have found that number to be even higher, with more than 86% of prior authorization requests ultimately approved with few changes.

‘’It gives you the idea that this entire process might be a little futile — that it’s just wasting people’s time,’’ said Fumiko Chino, MD, coauthor on the JAMA study and now an assistant professor in radiation oncology at MD Anderson Cancer Center in Houston. ‘’The problem is cancer doesn’t wait for bureaucracy.’’
 

Barriers at Every Step

As Dr. Chino and her study coauthors explained, advancements like intensity-modulated radiation therapy and stereotactic radiosurgery have allowed a new generation of specialists to treat previously untreatable cancers in ways that maximize tumor-killing power while minimizing collateral damage. But these tools require sophisticated planning, imaging, simulations and execution — all of which are subject to increased insurance scrutiny.

‘’We face barriers pretty much every step of the way for every patient,’’ said Dr. Chino.

To investigate how such barriers impact care, Dr. Chino and colleagues at Memorial Sloan Kettering Cancer Center — where she worked until July — looked at 206 cases in which payers denied prior authorization for radiation therapy from November 1, 2021 to December 8, 2022. 

The team found that 62% were ultimately approved without any change to technique or dose, while 28% were authorized, but with lower doses or less sophisticated techniques. Four people, however, never got authorization at all — three abandoned treatment altogether, and one sought treatment at another institution.

Treatment delays ranged from 1 day to 49 days. Eighty-three patients died.

Would some of them have lived if it weren’t for prior authorization?

Dr. Chino cannot say for sure, but did note that certain cancers, like cervical cancer, can grow so quickly that every day of delayed treatment makes them harder to control. 

Patients with metastatic or late-stage cancers are often denied more aggressive treatments by insurers who, in essence, “assume that they are going to die from their disease anyway,” Dr. Chino said. 

She views this as tragically shortsighted.

‘’There’s actually a strong body of evidence to show that if you treat even metastatic stage IV diseases aggressively, you can prolong not just quality of life but also quantity,’’ she said. 

In cases where the cancer is more localized and insurance mandates lower doses or cheaper techniques, the consequences can be equally heartbreaking.

‘’It’s like saying instead of taking an extra-strength Tylenol you can only have a baby aspirin,’’ she said. ‘’Their pain is less likely to be controlled, their disease is less likely to be controlled, and they are more likely to need retreatment.’’

Prior authorization delays can also significantly stress patients at the most vulnerable point of their lives.

In another recent study, Dr. Chino found that 69% of patients with cancer reported prior authorization-related delays in care, with one-third waiting a month or longer. One in five never got the care their doctors recommended, and 20% reported spending more than 11 hours on the phone haggling with their insurance companies. 

Most patients rated the process as ‘’bad’’ or ‘’horrible,’’ and said it fueled anxiety.

Such delays can be hard on clinicians and the healthcare system too. 

One 2022 study found that a typical academic radiation oncology practice spent about a half-million dollars per year seeking insurance preauthorization. Nationally, that number exceeds $40 million.

Then there is the burnout factor. 

Dr. Giap, an early-career physician who specializes in rare, aggressive sarcomas, works at an institution that helped pioneer proton therapy. She says it pains her to tell a desperate patient, like the 21-year-old, who has traveled to her from out of state that they have to wait. 

‘’Knowing that the majority of the cases are ultimately approved and that this wait is often unnecessary makes it even tougher,’’ she said.

Dr. Chino, a breast cancer specialist, has taken to warning patients before the alarming insurance letter arrives in the mail that their insurance may delay authorizing their care. But she tells patients that she will do everything she can to fight for them and develops a back-up plan to pivot to quickly, if needed.

‘’No one goes into medicine to spend their time talking to insurance companies,’’ said Dr. Chino.

The national trade group, America’s Health Insurance Plans (AHIP), did not return repeated requests for an interview for this story. But their official position, as stated on their website, is that “prior authorization is one of many tools health insurance providers use to promote safe, timely, evidence-based, affordable, and efficient care.”

Both Dr. Giap and Dr. Chino believe that prior authorization was developed with good intentions: to save healthcare costs and rein in treatments that don’t necessarily benefit patients. 

But, in their specialty, the burden has proliferated to a point that Dr. Chino characterizes as ‘’unconscionable.’’

She believes that policy changes like the proposed Improving Seniors’ Timely Access to Care Act — which would require real-time decisions for procedures that are routinely approved — could go a long way in improving patient care.

Meanwhile, Dr. Giap said, more research and professional guidelines are necessary to bolster insurance company confidence in newer technologies, particularly for rare cancers.

Her patient ultimately got her proton therapy and is ‘’doing relatively well, all things considered.’’

But not all the stories end like this.

Dr. Chino will never forget a patient with a cancer growing so rapidly she could see it protruding through her chest wall. She called for an urgent PET scan to see where else in the body the cancer might be brewing and rushed the planning process for radiation therapy, both of which faced prior authorization barriers. That scan — which ultimately showed the cancer had spread — was delayed for months.*

If the team had had those imaging results upfront, she said, they would have recommended a completely different course of treatment.

And her patient might be alive today.

‘’Unfortunately,” Dr. Chino said, “the people with the very worst prior authorization stories aren’t here anymore to tell you about them.”

*Correction,  10/4/24: An earlier version of this article erroneously stated that Dr. Chino called for surgery for her patient. She actually called for a PET scan and an urgent radiation start.

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

Fantine Giap, MD, sat across from a 21-year-old with a rare sarcoma at the base of her skull. 

Despite the large tumor, nestled in a sensitive area, the Boston-based radiation oncologist could envision a bright future for her patient. 

She and the other members of the patient’s care team had an impressive cancer-fighting arsenal at her fingertips. The team had recommended surgery, followed by proton therapy — a sophisticated tool able to deliver concentrated, razor-focused radiation to the once apple-sized growth, while sparing the fragile brain stem, optic nerve, and spinal cord. 

Surgery went as planned. But as the days and weeks wore on and insurance prior authorization for the proton therapy never came, the tumor roared back, leading to more surgeries and more complications. Ultimately, the young woman needed a tracheostomy and a feeding tube. 

By the time insurance said yes, more than 1 year from her initial visit, the future the team had envisioned seemed out of reach. 

“Unfortunately for this patient, it went from a potentially curable situation to a likely not curable situation,” recalled Dr. Giap, a clinician at Massachusetts General Hospital and instructor at Harvard Medical School, Boston. “I wanted to cry every day that she waited.’’ 

While a stark example, such insurance delays are not uncommon, according to new research published in JAMA Network Open.

The study of 206 denials in radiation oncology concluded that more than two-thirds were ultimately approved on appeal without changes, but often these approvals came only after costly delays that potentially compromised patient care.

Other studies have found that number to be even higher, with more than 86% of prior authorization requests ultimately approved with few changes.

‘’It gives you the idea that this entire process might be a little futile — that it’s just wasting people’s time,’’ said Fumiko Chino, MD, coauthor on the JAMA study and now an assistant professor in radiation oncology at MD Anderson Cancer Center in Houston. ‘’The problem is cancer doesn’t wait for bureaucracy.’’
 

Barriers at Every Step

As Dr. Chino and her study coauthors explained, advancements like intensity-modulated radiation therapy and stereotactic radiosurgery have allowed a new generation of specialists to treat previously untreatable cancers in ways that maximize tumor-killing power while minimizing collateral damage. But these tools require sophisticated planning, imaging, simulations and execution — all of which are subject to increased insurance scrutiny.

‘’We face barriers pretty much every step of the way for every patient,’’ said Dr. Chino.

To investigate how such barriers impact care, Dr. Chino and colleagues at Memorial Sloan Kettering Cancer Center — where she worked until July — looked at 206 cases in which payers denied prior authorization for radiation therapy from November 1, 2021 to December 8, 2022. 

The team found that 62% were ultimately approved without any change to technique or dose, while 28% were authorized, but with lower doses or less sophisticated techniques. Four people, however, never got authorization at all — three abandoned treatment altogether, and one sought treatment at another institution.

Treatment delays ranged from 1 day to 49 days. Eighty-three patients died.

Would some of them have lived if it weren’t for prior authorization?

Dr. Chino cannot say for sure, but did note that certain cancers, like cervical cancer, can grow so quickly that every day of delayed treatment makes them harder to control. 

Patients with metastatic or late-stage cancers are often denied more aggressive treatments by insurers who, in essence, “assume that they are going to die from their disease anyway,” Dr. Chino said. 

She views this as tragically shortsighted.

‘’There’s actually a strong body of evidence to show that if you treat even metastatic stage IV diseases aggressively, you can prolong not just quality of life but also quantity,’’ she said. 

In cases where the cancer is more localized and insurance mandates lower doses or cheaper techniques, the consequences can be equally heartbreaking.

‘’It’s like saying instead of taking an extra-strength Tylenol you can only have a baby aspirin,’’ she said. ‘’Their pain is less likely to be controlled, their disease is less likely to be controlled, and they are more likely to need retreatment.’’

Prior authorization delays can also significantly stress patients at the most vulnerable point of their lives.

In another recent study, Dr. Chino found that 69% of patients with cancer reported prior authorization-related delays in care, with one-third waiting a month or longer. One in five never got the care their doctors recommended, and 20% reported spending more than 11 hours on the phone haggling with their insurance companies. 

Most patients rated the process as ‘’bad’’ or ‘’horrible,’’ and said it fueled anxiety.

Such delays can be hard on clinicians and the healthcare system too. 

One 2022 study found that a typical academic radiation oncology practice spent about a half-million dollars per year seeking insurance preauthorization. Nationally, that number exceeds $40 million.

Then there is the burnout factor. 

Dr. Giap, an early-career physician who specializes in rare, aggressive sarcomas, works at an institution that helped pioneer proton therapy. She says it pains her to tell a desperate patient, like the 21-year-old, who has traveled to her from out of state that they have to wait. 

‘’Knowing that the majority of the cases are ultimately approved and that this wait is often unnecessary makes it even tougher,’’ she said.

Dr. Chino, a breast cancer specialist, has taken to warning patients before the alarming insurance letter arrives in the mail that their insurance may delay authorizing their care. But she tells patients that she will do everything she can to fight for them and develops a back-up plan to pivot to quickly, if needed.

‘’No one goes into medicine to spend their time talking to insurance companies,’’ said Dr. Chino.

The national trade group, America’s Health Insurance Plans (AHIP), did not return repeated requests for an interview for this story. But their official position, as stated on their website, is that “prior authorization is one of many tools health insurance providers use to promote safe, timely, evidence-based, affordable, and efficient care.”

Both Dr. Giap and Dr. Chino believe that prior authorization was developed with good intentions: to save healthcare costs and rein in treatments that don’t necessarily benefit patients. 

But, in their specialty, the burden has proliferated to a point that Dr. Chino characterizes as ‘’unconscionable.’’

She believes that policy changes like the proposed Improving Seniors’ Timely Access to Care Act — which would require real-time decisions for procedures that are routinely approved — could go a long way in improving patient care.

Meanwhile, Dr. Giap said, more research and professional guidelines are necessary to bolster insurance company confidence in newer technologies, particularly for rare cancers.

Her patient ultimately got her proton therapy and is ‘’doing relatively well, all things considered.’’

But not all the stories end like this.

Dr. Chino will never forget a patient with a cancer growing so rapidly she could see it protruding through her chest wall. She called for an urgent PET scan to see where else in the body the cancer might be brewing and rushed the planning process for radiation therapy, both of which faced prior authorization barriers. That scan — which ultimately showed the cancer had spread — was delayed for months.*

If the team had had those imaging results upfront, she said, they would have recommended a completely different course of treatment.

And her patient might be alive today.

‘’Unfortunately,” Dr. Chino said, “the people with the very worst prior authorization stories aren’t here anymore to tell you about them.”

*Correction,  10/4/24: An earlier version of this article erroneously stated that Dr. Chino called for surgery for her patient. She actually called for a PET scan and an urgent radiation start.

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

There’s a new morning ritual in Pinedale, Wyoming, a town of about 2000, nestled against the Wind River Mountains.

Friends and neighbors in the oil- and gas-rich community “take their morning coffee and pull up” to watch workers building the county’s first hospital, said Kari DeWitt, the project’s public relations director.

“I think it’s just gratitude,” Ms. DeWitt said.

Sublette County is the only one in Wyoming — where counties span thousands of square miles — without a hospital. The 10-bed, 40,000-square-foot hospital, with a similarly sized attached long-term care facility, is slated to open by the summer of 2025.

Ms. DeWitt, who also is executive director of the Sublette County Health Foundation, has an office at the town’s health clinic with a window view of the construction.

Pinedale’s residents have good reason to be excited. New full-service hospitals with inpatient beds are rare in rural America, where declining population has spurred decades of downsizing and closures. Yet, a few communities in Wyoming and others in Kansas and Georgia are defying the trend.

“To be honest with you, it even seems strange to me,” said Wyoming Hospital Association President Eric Boley. Small rural “hospitals are really struggling all across the country,” he said.

There is no official tally of new hospitals being built in rural America, but industry experts such as Mr. Boley said they’re rare. Typically, health-related construction projects in rural areas are for smaller urgent care centers or stand-alone emergency facilities or are replacements for old hospitals.

About half of rural hospitals lost money in the prior year, according to Chartis, a health analytics and consulting firm. And nearly 150 rural hospitals have closed or converted to smaller operations since 2010, according to data collected by the University of North Carolina’s Cecil G. Sheps Center for Health Services Research.

To stem the tide of closures, Congress created a new rural emergency hospital designation that allowed struggling hospitals to close their inpatient units and provide only outpatient and emergency services. Since January 2023, when the program took effect, 32 of the more than 1700 eligible rural hospitals — from Georgia to New Mexico — have joined the program, according to data from the Centers for Medicare & Medicaid Services.

Tony Breitlow is healthcare studio director for EUA, which has extensive experience working for rural health care systems. Mr. Breitlow said his national architecture and engineering firm’s work expands, replaces, or revamps older buildings, many of which were constructed during the middle of the last century.

The work, Mr. Breitlow said, is part of health care “systems figuring out how to remain robust and viable.”

Freeman Health System, based in Joplin, Missouri, announced plans last year to build a new 50-bed hospital across the state line in Kansas. Paula Baker, Freeman’s president and chief executive, said the system is building for patients in the southeastern corner of the state who travel 45 minutes or more to its bigger Joplin facilities for care.

Freeman’s new hospital, with construction on the building expected to begin in the spring, will be less than 10 miles away from an older, 64-bed hospital that has existed for decades. Kansas is one of more than a dozen states with no “certificate of need” law that would require health providers to obtain approval from the state before offering new services or building or expanding facilities.

Ms. Baker also said Freeman plans to operate emergency services and a small 10-bed outpost in Fort Scott, Kansas, opening early next year in a corner of a hospital that closed in late 2018. Residents there “cried, they cheered, they hugged me,” Ms. Baker said, adding that the “level of appreciation and gratitude that they felt and they displayed was overwhelming to me.”

Michael Topchik, executive director of the Chartis Center for Rural Health, said regional healthcare systems in the Upper Midwest have been particularly active in competing for patients by, among other things, building new hospitals.

And while private corporate money can drive construction, many rural hospital projects tap government programs, especially those supported by the US Department of Agriculture, Mr. Topchik said. That, he said, “surprises a lot of people.”

Since 2021, the USDA’s rural Community Facilities Programs have awarded $2.24 billion in loans and grants to 68 rural hospitals for work that was not related to an emergency or disaster, according to data analyzed by KFF Health News and confirmed by the agency. The federal program is funded through what is often known as the farm bill, which faces a September congressional renewal deadline.

Nearly all the projects are replacements or expansions and updates of older facilities.

The USDA confirmed that three new or planned Wyoming hospitals received federal funding. Hospital projects in Riverton and Saratoga received loans of $37.2 million and $18.3 million, respectively. Pinedale’s hospital received a $29.2 million loan from the agency.

Wyoming’s new construction is rare in a state where more than 80% of rural hospitals reported losses in the third quarter of 2023, according to Chartis. The state association’s Mr. Boley said he worries about several hospitals that have less than 10 days’ cash on hand “day and night.”

Pinedale’s project loan was approved after the community submitted a feasibility study to the USDA that included local clinics and a long-term care facility. “It’s pretty remote and right up in the mountains,” Mr. Boley said.

Pinedale’s Ms. DeWitt said the community was missing key services, such as blood transfusions, which are often necessary when there is a trauma like a car crash or if a pregnant woman faces severe complications. Local ambulances drove 94,000 miles last year, she said.

Ms. DeWitt began working to raise support for the new hospital after her own pregnancy-related trauma in 2014. She was bleeding heavily and arrived at the local health clinic believing it operated like a hospital.

“It was shocking to hear, ‘No, we’re not a hospital. We can’t do blood transfusions. We’re just going to have to pray you live for the next 45 minutes,’ ” Ms. DeWitt said.

Ms. DeWitt had to be airlifted to Idaho, where she delivered a few minutes after landing. When the hospital financing went on the ballot in 2020, Ms. DeWitt — fully recovered, with healthy grade-schoolers at home — began making five calls a night to rally support for a county tax increase to help fund the hospital.

“By improving health care, I think we improve everybody’s chances of survival. You know, it’s pretty basic,” Ms. DeWitt said.

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

There’s a new morning ritual in Pinedale, Wyoming, a town of about 2000, nestled against the Wind River Mountains.

Friends and neighbors in the oil- and gas-rich community “take their morning coffee and pull up” to watch workers building the county’s first hospital, said Kari DeWitt, the project’s public relations director.

“I think it’s just gratitude,” Ms. DeWitt said.

Sublette County is the only one in Wyoming — where counties span thousands of square miles — without a hospital. The 10-bed, 40,000-square-foot hospital, with a similarly sized attached long-term care facility, is slated to open by the summer of 2025.

Ms. DeWitt, who also is executive director of the Sublette County Health Foundation, has an office at the town’s health clinic with a window view of the construction.

Pinedale’s residents have good reason to be excited. New full-service hospitals with inpatient beds are rare in rural America, where declining population has spurred decades of downsizing and closures. Yet, a few communities in Wyoming and others in Kansas and Georgia are defying the trend.

“To be honest with you, it even seems strange to me,” said Wyoming Hospital Association President Eric Boley. Small rural “hospitals are really struggling all across the country,” he said.

There is no official tally of new hospitals being built in rural America, but industry experts such as Mr. Boley said they’re rare. Typically, health-related construction projects in rural areas are for smaller urgent care centers or stand-alone emergency facilities or are replacements for old hospitals.

About half of rural hospitals lost money in the prior year, according to Chartis, a health analytics and consulting firm. And nearly 150 rural hospitals have closed or converted to smaller operations since 2010, according to data collected by the University of North Carolina’s Cecil G. Sheps Center for Health Services Research.

To stem the tide of closures, Congress created a new rural emergency hospital designation that allowed struggling hospitals to close their inpatient units and provide only outpatient and emergency services. Since January 2023, when the program took effect, 32 of the more than 1700 eligible rural hospitals — from Georgia to New Mexico — have joined the program, according to data from the Centers for Medicare & Medicaid Services.

Tony Breitlow is healthcare studio director for EUA, which has extensive experience working for rural health care systems. Mr. Breitlow said his national architecture and engineering firm’s work expands, replaces, or revamps older buildings, many of which were constructed during the middle of the last century.

The work, Mr. Breitlow said, is part of health care “systems figuring out how to remain robust and viable.”

Freeman Health System, based in Joplin, Missouri, announced plans last year to build a new 50-bed hospital across the state line in Kansas. Paula Baker, Freeman’s president and chief executive, said the system is building for patients in the southeastern corner of the state who travel 45 minutes or more to its bigger Joplin facilities for care.

Freeman’s new hospital, with construction on the building expected to begin in the spring, will be less than 10 miles away from an older, 64-bed hospital that has existed for decades. Kansas is one of more than a dozen states with no “certificate of need” law that would require health providers to obtain approval from the state before offering new services or building or expanding facilities.

Ms. Baker also said Freeman plans to operate emergency services and a small 10-bed outpost in Fort Scott, Kansas, opening early next year in a corner of a hospital that closed in late 2018. Residents there “cried, they cheered, they hugged me,” Ms. Baker said, adding that the “level of appreciation and gratitude that they felt and they displayed was overwhelming to me.”

Michael Topchik, executive director of the Chartis Center for Rural Health, said regional healthcare systems in the Upper Midwest have been particularly active in competing for patients by, among other things, building new hospitals.

And while private corporate money can drive construction, many rural hospital projects tap government programs, especially those supported by the US Department of Agriculture, Mr. Topchik said. That, he said, “surprises a lot of people.”

Since 2021, the USDA’s rural Community Facilities Programs have awarded $2.24 billion in loans and grants to 68 rural hospitals for work that was not related to an emergency or disaster, according to data analyzed by KFF Health News and confirmed by the agency. The federal program is funded through what is often known as the farm bill, which faces a September congressional renewal deadline.

Nearly all the projects are replacements or expansions and updates of older facilities.

The USDA confirmed that three new or planned Wyoming hospitals received federal funding. Hospital projects in Riverton and Saratoga received loans of $37.2 million and $18.3 million, respectively. Pinedale’s hospital received a $29.2 million loan from the agency.

Wyoming’s new construction is rare in a state where more than 80% of rural hospitals reported losses in the third quarter of 2023, according to Chartis. The state association’s Mr. Boley said he worries about several hospitals that have less than 10 days’ cash on hand “day and night.”

Pinedale’s project loan was approved after the community submitted a feasibility study to the USDA that included local clinics and a long-term care facility. “It’s pretty remote and right up in the mountains,” Mr. Boley said.

Pinedale’s Ms. DeWitt said the community was missing key services, such as blood transfusions, which are often necessary when there is a trauma like a car crash or if a pregnant woman faces severe complications. Local ambulances drove 94,000 miles last year, she said.

Ms. DeWitt began working to raise support for the new hospital after her own pregnancy-related trauma in 2014. She was bleeding heavily and arrived at the local health clinic believing it operated like a hospital.

“It was shocking to hear, ‘No, we’re not a hospital. We can’t do blood transfusions. We’re just going to have to pray you live for the next 45 minutes,’ ” Ms. DeWitt said.

Ms. DeWitt had to be airlifted to Idaho, where she delivered a few minutes after landing. When the hospital financing went on the ballot in 2020, Ms. DeWitt — fully recovered, with healthy grade-schoolers at home — began making five calls a night to rally support for a county tax increase to help fund the hospital.

“By improving health care, I think we improve everybody’s chances of survival. You know, it’s pretty basic,” Ms. DeWitt said.

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

There’s a new morning ritual in Pinedale, Wyoming, a town of about 2000, nestled against the Wind River Mountains.

Friends and neighbors in the oil- and gas-rich community “take their morning coffee and pull up” to watch workers building the county’s first hospital, said Kari DeWitt, the project’s public relations director.

“I think it’s just gratitude,” Ms. DeWitt said.

Sublette County is the only one in Wyoming — where counties span thousands of square miles — without a hospital. The 10-bed, 40,000-square-foot hospital, with a similarly sized attached long-term care facility, is slated to open by the summer of 2025.

Ms. DeWitt, who also is executive director of the Sublette County Health Foundation, has an office at the town’s health clinic with a window view of the construction.

Pinedale’s residents have good reason to be excited. New full-service hospitals with inpatient beds are rare in rural America, where declining population has spurred decades of downsizing and closures. Yet, a few communities in Wyoming and others in Kansas and Georgia are defying the trend.

“To be honest with you, it even seems strange to me,” said Wyoming Hospital Association President Eric Boley. Small rural “hospitals are really struggling all across the country,” he said.

There is no official tally of new hospitals being built in rural America, but industry experts such as Mr. Boley said they’re rare. Typically, health-related construction projects in rural areas are for smaller urgent care centers or stand-alone emergency facilities or are replacements for old hospitals.

About half of rural hospitals lost money in the prior year, according to Chartis, a health analytics and consulting firm. And nearly 150 rural hospitals have closed or converted to smaller operations since 2010, according to data collected by the University of North Carolina’s Cecil G. Sheps Center for Health Services Research.

To stem the tide of closures, Congress created a new rural emergency hospital designation that allowed struggling hospitals to close their inpatient units and provide only outpatient and emergency services. Since January 2023, when the program took effect, 32 of the more than 1700 eligible rural hospitals — from Georgia to New Mexico — have joined the program, according to data from the Centers for Medicare & Medicaid Services.

Tony Breitlow is healthcare studio director for EUA, which has extensive experience working for rural health care systems. Mr. Breitlow said his national architecture and engineering firm’s work expands, replaces, or revamps older buildings, many of which were constructed during the middle of the last century.

The work, Mr. Breitlow said, is part of health care “systems figuring out how to remain robust and viable.”

Freeman Health System, based in Joplin, Missouri, announced plans last year to build a new 50-bed hospital across the state line in Kansas. Paula Baker, Freeman’s president and chief executive, said the system is building for patients in the southeastern corner of the state who travel 45 minutes or more to its bigger Joplin facilities for care.

Freeman’s new hospital, with construction on the building expected to begin in the spring, will be less than 10 miles away from an older, 64-bed hospital that has existed for decades. Kansas is one of more than a dozen states with no “certificate of need” law that would require health providers to obtain approval from the state before offering new services or building or expanding facilities.

Ms. Baker also said Freeman plans to operate emergency services and a small 10-bed outpost in Fort Scott, Kansas, opening early next year in a corner of a hospital that closed in late 2018. Residents there “cried, they cheered, they hugged me,” Ms. Baker said, adding that the “level of appreciation and gratitude that they felt and they displayed was overwhelming to me.”

Michael Topchik, executive director of the Chartis Center for Rural Health, said regional healthcare systems in the Upper Midwest have been particularly active in competing for patients by, among other things, building new hospitals.

And while private corporate money can drive construction, many rural hospital projects tap government programs, especially those supported by the US Department of Agriculture, Mr. Topchik said. That, he said, “surprises a lot of people.”

Since 2021, the USDA’s rural Community Facilities Programs have awarded $2.24 billion in loans and grants to 68 rural hospitals for work that was not related to an emergency or disaster, according to data analyzed by KFF Health News and confirmed by the agency. The federal program is funded through what is often known as the farm bill, which faces a September congressional renewal deadline.

Nearly all the projects are replacements or expansions and updates of older facilities.

The USDA confirmed that three new or planned Wyoming hospitals received federal funding. Hospital projects in Riverton and Saratoga received loans of $37.2 million and $18.3 million, respectively. Pinedale’s hospital received a $29.2 million loan from the agency.

Wyoming’s new construction is rare in a state where more than 80% of rural hospitals reported losses in the third quarter of 2023, according to Chartis. The state association’s Mr. Boley said he worries about several hospitals that have less than 10 days’ cash on hand “day and night.”

Pinedale’s project loan was approved after the community submitted a feasibility study to the USDA that included local clinics and a long-term care facility. “It’s pretty remote and right up in the mountains,” Mr. Boley said.

Pinedale’s Ms. DeWitt said the community was missing key services, such as blood transfusions, which are often necessary when there is a trauma like a car crash or if a pregnant woman faces severe complications. Local ambulances drove 94,000 miles last year, she said.

Ms. DeWitt began working to raise support for the new hospital after her own pregnancy-related trauma in 2014. She was bleeding heavily and arrived at the local health clinic believing it operated like a hospital.

“It was shocking to hear, ‘No, we’re not a hospital. We can’t do blood transfusions. We’re just going to have to pray you live for the next 45 minutes,’ ” Ms. DeWitt said.

Ms. DeWitt had to be airlifted to Idaho, where she delivered a few minutes after landing. When the hospital financing went on the ballot in 2020, Ms. DeWitt — fully recovered, with healthy grade-schoolers at home — began making five calls a night to rally support for a county tax increase to help fund the hospital.

“By improving health care, I think we improve everybody’s chances of survival. You know, it’s pretty basic,” Ms. DeWitt said.

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

Gitanjali Srivastava, MD, professor of medicine, pediatrics, and surgery, and medical director of obesity medicine at Vanderbilt University School of Medicine in Nashville, Tennessee, was nearly 10 years into practicing pediatric medicine when she graduated from the obesity medicine fellowship at Massachusetts General Hospital in Boston in 2013. “We were the very first sort of fellows to speak of then; there were no standards or curriculum,” she said.

Obesity was already epidemic, but stigma and bias were still pervasive in the medical community and within the public. After graduating, Dr. Srivastava spent months vying for a position with hospital CEOs. She traveled across the country explaining the specialty and its value, going into detail about the budget, business model, space requirement, and revenue potential of obesity medicine. 

Today marks a very different era.

Obesity medicine is exploding. Patients are spilling into doctors’ offices looking for obesity treatment. Healthcare systems are seeking out obesity specialists and building metabolic health centers. Since 2020, the number of doctors board-certified by the American Board of Obesity Medicine has nearly doubled, and the number of obesity medicine fellowships across the country has more than doubled. Next month, another 2115 doctors from primary care, surgery, orthopedics, pediatrics, fertility, endocrinology, and beyond will sit for the 2024 exam. The once niche specialty is quickly becoming intertwined with most of modern medicine.
 

The Need to Treat

It’s no mystery that the rapid expansion of obesity medicine coincides with the US Food and Drug Administration’s approval of GLP-1 injections. The drugs’ radical weight loss properties have captured headlines and driven up patient demand. Meanwhile, doctors are finally able to offer effective treatment for a disease that affects 40% of US adults.

“We are finally treating it as a chronic disease, not as a lifestyle,” said Marcio Griebeler, MD, director of the obesity medicine fellowship at the Cleveland Clinic. And “I think it’s fulfilling for physicians,” he said. 

For so long, the advice for obesity was about lifestyle. Move more, eat less, and harness willpower, “which really is a fallacy,” said Kimberly Gudzune, MD, MPH, an obesity medicine specialist and chief medical officer for the American Board of Obesity Medicine (ABOM) Foundation. For people with obesity, “your brain is operating differently,” she said. “Your body really is set up to work against you.” 

Brianna Johnson-Rabbett, MD, medical director of the ABOM, told this news organization that with the advent of GLP-1s, “there’s a clearer recognition that obesity is a disease that needs to be treated like other diseases.” Some of that is thanks to clinical trial data showing that just as with other diseases such as high blood pressure or diabetes, obesity can be treated with medication and it resurges when the medication is stopped, she said.

Doctors don’t have to go looking for patients with obesity, dr. Griebeler added. Now that treatment options exist, they’re showing up in droves at the doctor’s office — all the doctors’ offices. In primary care, endocrinology, surgery, pediatrics — a wide variety of doctors are being asked about obesity drugs, Dr. Griebeler noted.

And while doctors are often just as excited as patients about the potential for treatment, many find themselves under-equipped when it comes to obesity. “More physicians are ... recognizing the value in treating this, and some are realizing, “Oh gosh, I never learned how to do this,” said Dr. Gudzune.
 

Information Patients Have Been Waiting For

Medical training has traditionally devoted minimal, if any, curriculum to obesity and metabolism. “To be honest, we didn’t really cover this at all in my training,” said Nina Paddu, MD, obesity medicine specialist at Maimonides Medical Center in New York City who finished her training only 2 years ago. “The guidance even in residency was ‘let’s send them to nutrition’ and ‘recommend exercising.’ ”

In addition to the medical education gap, until recently there was a “paucity of robust evidence,” Dr. Srivastava said. Leaders in the field wanted to establish standards and guidelines, but there wasn’t enough strong evidence on obesity and its treatments to build them, she said. 

Only in the last 5 years or so has the evidence-based understanding of obesity’s pathophysiology truly accelerated: The brain’s driving roles, its interplay with hormones, and its interactions with other diseases. “We are just at the cusp of understanding all the different factors,” Dr. Gudzune said.

But already endocrinologists, surgeons, fertility specialists, gynecologists, and oncologists, to name a few, see the critical overlap with their own field. “Conditions were once suspected of being intertwined [with obesity], and now we have data to connect them,” Dr. Srivastava said. For example, there’s now data connecting semaglutide to a 20% reduction in cardiovascular events for people with obesity. That’s a game changer for multiple specialties, she told this news organization. 
 

Getting Trained in Obesity Management

The recent uptick in obesity insights and increased patient need has doctors from every career stage seeking additional training.

The ABOM offers two board certification pathways: 60 hours of CME credits or a 12-month fellowship. Both paths require doctors to pass the board’s exam. 

Many doctors incorporate the training into their existing practice. The CME credit pathway, especially, is designed to help get doctors up to speed without requiring them to upend their lives for a fellowship.

Dr. Srivastava said that the fellowship is more consuming and immersive. While it’s often younger doctors just out of training who apply to fellowship, every year, “I’m astonished at the number of talented physicians with clinical and research experience who want to immerse themselves in a fellowship experience.”

Some doctors return to their previous specialties after fellowship. But many will go on to take obesity medicine–specific roles or set aside clinic hours for obesity medicine. Their credentials are “really attractive to institutions, especially those looking to open up obesity medicine or weight management programs,” said Dr. Srivastava.

Dr. Paddu, who finished her obesity medicine fellowship this year, said there are a variety of obesity medicine jobs to choose from — far different from Dr. Srivastava’s job search 15 years ago. Dr. Paddu’s new role combines 2 days of primary care with 2 days devoted to obesity medicine and 1 day each week set aside for administrative work so she can build up the hospital’s new metabolic health clinic. 
 

Still Not Enough Obesity Specialists

As with all things, rapid growth requires careful oversight. “Part of the responsibility of the board is to think critically of how the field is growing” and conduct ongoing monitoring, Dr. Gudzune said.

This is also why the board’s credentials are time-limited and must be recertified, Dr. Johnson-Rabbett added. 

But even with the rise in certified doctors and obesity medicine positions, the 8263 doctors certified by ABOM are only a tiny fraction of US physicians. As a result, there’s genuine likelihood that many patients seeking GLP-1s or other obesity treatment don’t yet have access to the holistic care they need. Plus, doctors may still not have obesity expertise within their networks.

“The field has grown rapidly, but it’s still such a small field relative to the patient need,” said Dr. Gudzune.
 

A version of this article appeared on Medscape.com.

Gitanjali Srivastava, MD, professor of medicine, pediatrics, and surgery, and medical director of obesity medicine at Vanderbilt University School of Medicine in Nashville, Tennessee, was nearly 10 years into practicing pediatric medicine when she graduated from the obesity medicine fellowship at Massachusetts General Hospital in Boston in 2013. “We were the very first sort of fellows to speak of then; there were no standards or curriculum,” she said.

Obesity was already epidemic, but stigma and bias were still pervasive in the medical community and within the public. After graduating, Dr. Srivastava spent months vying for a position with hospital CEOs. She traveled across the country explaining the specialty and its value, going into detail about the budget, business model, space requirement, and revenue potential of obesity medicine. 

Today marks a very different era.

Obesity medicine is exploding. Patients are spilling into doctors’ offices looking for obesity treatment. Healthcare systems are seeking out obesity specialists and building metabolic health centers. Since 2020, the number of doctors board-certified by the American Board of Obesity Medicine has nearly doubled, and the number of obesity medicine fellowships across the country has more than doubled. Next month, another 2115 doctors from primary care, surgery, orthopedics, pediatrics, fertility, endocrinology, and beyond will sit for the 2024 exam. The once niche specialty is quickly becoming intertwined with most of modern medicine.
 

The Need to Treat

It’s no mystery that the rapid expansion of obesity medicine coincides with the US Food and Drug Administration’s approval of GLP-1 injections. The drugs’ radical weight loss properties have captured headlines and driven up patient demand. Meanwhile, doctors are finally able to offer effective treatment for a disease that affects 40% of US adults.

“We are finally treating it as a chronic disease, not as a lifestyle,” said Marcio Griebeler, MD, director of the obesity medicine fellowship at the Cleveland Clinic. And “I think it’s fulfilling for physicians,” he said. 

For so long, the advice for obesity was about lifestyle. Move more, eat less, and harness willpower, “which really is a fallacy,” said Kimberly Gudzune, MD, MPH, an obesity medicine specialist and chief medical officer for the American Board of Obesity Medicine (ABOM) Foundation. For people with obesity, “your brain is operating differently,” she said. “Your body really is set up to work against you.” 

Brianna Johnson-Rabbett, MD, medical director of the ABOM, told this news organization that with the advent of GLP-1s, “there’s a clearer recognition that obesity is a disease that needs to be treated like other diseases.” Some of that is thanks to clinical trial data showing that just as with other diseases such as high blood pressure or diabetes, obesity can be treated with medication and it resurges when the medication is stopped, she said.

Doctors don’t have to go looking for patients with obesity, dr. Griebeler added. Now that treatment options exist, they’re showing up in droves at the doctor’s office — all the doctors’ offices. In primary care, endocrinology, surgery, pediatrics — a wide variety of doctors are being asked about obesity drugs, Dr. Griebeler noted.

And while doctors are often just as excited as patients about the potential for treatment, many find themselves under-equipped when it comes to obesity. “More physicians are ... recognizing the value in treating this, and some are realizing, “Oh gosh, I never learned how to do this,” said Dr. Gudzune.
 

Information Patients Have Been Waiting For

Medical training has traditionally devoted minimal, if any, curriculum to obesity and metabolism. “To be honest, we didn’t really cover this at all in my training,” said Nina Paddu, MD, obesity medicine specialist at Maimonides Medical Center in New York City who finished her training only 2 years ago. “The guidance even in residency was ‘let’s send them to nutrition’ and ‘recommend exercising.’ ”

In addition to the medical education gap, until recently there was a “paucity of robust evidence,” Dr. Srivastava said. Leaders in the field wanted to establish standards and guidelines, but there wasn’t enough strong evidence on obesity and its treatments to build them, she said. 

Only in the last 5 years or so has the evidence-based understanding of obesity’s pathophysiology truly accelerated: The brain’s driving roles, its interplay with hormones, and its interactions with other diseases. “We are just at the cusp of understanding all the different factors,” Dr. Gudzune said.

But already endocrinologists, surgeons, fertility specialists, gynecologists, and oncologists, to name a few, see the critical overlap with their own field. “Conditions were once suspected of being intertwined [with obesity], and now we have data to connect them,” Dr. Srivastava said. For example, there’s now data connecting semaglutide to a 20% reduction in cardiovascular events for people with obesity. That’s a game changer for multiple specialties, she told this news organization. 
 

Getting Trained in Obesity Management

The recent uptick in obesity insights and increased patient need has doctors from every career stage seeking additional training.

The ABOM offers two board certification pathways: 60 hours of CME credits or a 12-month fellowship. Both paths require doctors to pass the board’s exam. 

Many doctors incorporate the training into their existing practice. The CME credit pathway, especially, is designed to help get doctors up to speed without requiring them to upend their lives for a fellowship.

Dr. Srivastava said that the fellowship is more consuming and immersive. While it’s often younger doctors just out of training who apply to fellowship, every year, “I’m astonished at the number of talented physicians with clinical and research experience who want to immerse themselves in a fellowship experience.”

Some doctors return to their previous specialties after fellowship. But many will go on to take obesity medicine–specific roles or set aside clinic hours for obesity medicine. Their credentials are “really attractive to institutions, especially those looking to open up obesity medicine or weight management programs,” said Dr. Srivastava.

Dr. Paddu, who finished her obesity medicine fellowship this year, said there are a variety of obesity medicine jobs to choose from — far different from Dr. Srivastava’s job search 15 years ago. Dr. Paddu’s new role combines 2 days of primary care with 2 days devoted to obesity medicine and 1 day each week set aside for administrative work so she can build up the hospital’s new metabolic health clinic. 
 

Still Not Enough Obesity Specialists

As with all things, rapid growth requires careful oversight. “Part of the responsibility of the board is to think critically of how the field is growing” and conduct ongoing monitoring, Dr. Gudzune said.

This is also why the board’s credentials are time-limited and must be recertified, Dr. Johnson-Rabbett added. 

But even with the rise in certified doctors and obesity medicine positions, the 8263 doctors certified by ABOM are only a tiny fraction of US physicians. As a result, there’s genuine likelihood that many patients seeking GLP-1s or other obesity treatment don’t yet have access to the holistic care they need. Plus, doctors may still not have obesity expertise within their networks.

“The field has grown rapidly, but it’s still such a small field relative to the patient need,” said Dr. Gudzune.
 

A version of this article appeared on Medscape.com.

Gitanjali Srivastava, MD, professor of medicine, pediatrics, and surgery, and medical director of obesity medicine at Vanderbilt University School of Medicine in Nashville, Tennessee, was nearly 10 years into practicing pediatric medicine when she graduated from the obesity medicine fellowship at Massachusetts General Hospital in Boston in 2013. “We were the very first sort of fellows to speak of then; there were no standards or curriculum,” she said.

Obesity was already epidemic, but stigma and bias were still pervasive in the medical community and within the public. After graduating, Dr. Srivastava spent months vying for a position with hospital CEOs. She traveled across the country explaining the specialty and its value, going into detail about the budget, business model, space requirement, and revenue potential of obesity medicine. 

Today marks a very different era.

Obesity medicine is exploding. Patients are spilling into doctors’ offices looking for obesity treatment. Healthcare systems are seeking out obesity specialists and building metabolic health centers. Since 2020, the number of doctors board-certified by the American Board of Obesity Medicine has nearly doubled, and the number of obesity medicine fellowships across the country has more than doubled. Next month, another 2115 doctors from primary care, surgery, orthopedics, pediatrics, fertility, endocrinology, and beyond will sit for the 2024 exam. The once niche specialty is quickly becoming intertwined with most of modern medicine.
 

The Need to Treat

It’s no mystery that the rapid expansion of obesity medicine coincides with the US Food and Drug Administration’s approval of GLP-1 injections. The drugs’ radical weight loss properties have captured headlines and driven up patient demand. Meanwhile, doctors are finally able to offer effective treatment for a disease that affects 40% of US adults.

“We are finally treating it as a chronic disease, not as a lifestyle,” said Marcio Griebeler, MD, director of the obesity medicine fellowship at the Cleveland Clinic. And “I think it’s fulfilling for physicians,” he said. 

For so long, the advice for obesity was about lifestyle. Move more, eat less, and harness willpower, “which really is a fallacy,” said Kimberly Gudzune, MD, MPH, an obesity medicine specialist and chief medical officer for the American Board of Obesity Medicine (ABOM) Foundation. For people with obesity, “your brain is operating differently,” she said. “Your body really is set up to work against you.” 

Brianna Johnson-Rabbett, MD, medical director of the ABOM, told this news organization that with the advent of GLP-1s, “there’s a clearer recognition that obesity is a disease that needs to be treated like other diseases.” Some of that is thanks to clinical trial data showing that just as with other diseases such as high blood pressure or diabetes, obesity can be treated with medication and it resurges when the medication is stopped, she said.

Doctors don’t have to go looking for patients with obesity, dr. Griebeler added. Now that treatment options exist, they’re showing up in droves at the doctor’s office — all the doctors’ offices. In primary care, endocrinology, surgery, pediatrics — a wide variety of doctors are being asked about obesity drugs, Dr. Griebeler noted.

And while doctors are often just as excited as patients about the potential for treatment, many find themselves under-equipped when it comes to obesity. “More physicians are ... recognizing the value in treating this, and some are realizing, “Oh gosh, I never learned how to do this,” said Dr. Gudzune.
 

Information Patients Have Been Waiting For

Medical training has traditionally devoted minimal, if any, curriculum to obesity and metabolism. “To be honest, we didn’t really cover this at all in my training,” said Nina Paddu, MD, obesity medicine specialist at Maimonides Medical Center in New York City who finished her training only 2 years ago. “The guidance even in residency was ‘let’s send them to nutrition’ and ‘recommend exercising.’ ”

In addition to the medical education gap, until recently there was a “paucity of robust evidence,” Dr. Srivastava said. Leaders in the field wanted to establish standards and guidelines, but there wasn’t enough strong evidence on obesity and its treatments to build them, she said. 

Only in the last 5 years or so has the evidence-based understanding of obesity’s pathophysiology truly accelerated: The brain’s driving roles, its interplay with hormones, and its interactions with other diseases. “We are just at the cusp of understanding all the different factors,” Dr. Gudzune said.

But already endocrinologists, surgeons, fertility specialists, gynecologists, and oncologists, to name a few, see the critical overlap with their own field. “Conditions were once suspected of being intertwined [with obesity], and now we have data to connect them,” Dr. Srivastava said. For example, there’s now data connecting semaglutide to a 20% reduction in cardiovascular events for people with obesity. That’s a game changer for multiple specialties, she told this news organization. 
 

Getting Trained in Obesity Management

The recent uptick in obesity insights and increased patient need has doctors from every career stage seeking additional training.

The ABOM offers two board certification pathways: 60 hours of CME credits or a 12-month fellowship. Both paths require doctors to pass the board’s exam. 

Many doctors incorporate the training into their existing practice. The CME credit pathway, especially, is designed to help get doctors up to speed without requiring them to upend their lives for a fellowship.

Dr. Srivastava said that the fellowship is more consuming and immersive. While it’s often younger doctors just out of training who apply to fellowship, every year, “I’m astonished at the number of talented physicians with clinical and research experience who want to immerse themselves in a fellowship experience.”

Some doctors return to their previous specialties after fellowship. But many will go on to take obesity medicine–specific roles or set aside clinic hours for obesity medicine. Their credentials are “really attractive to institutions, especially those looking to open up obesity medicine or weight management programs,” said Dr. Srivastava.

Dr. Paddu, who finished her obesity medicine fellowship this year, said there are a variety of obesity medicine jobs to choose from — far different from Dr. Srivastava’s job search 15 years ago. Dr. Paddu’s new role combines 2 days of primary care with 2 days devoted to obesity medicine and 1 day each week set aside for administrative work so she can build up the hospital’s new metabolic health clinic. 
 

Still Not Enough Obesity Specialists

As with all things, rapid growth requires careful oversight. “Part of the responsibility of the board is to think critically of how the field is growing” and conduct ongoing monitoring, Dr. Gudzune said.

This is also why the board’s credentials are time-limited and must be recertified, Dr. Johnson-Rabbett added. 

But even with the rise in certified doctors and obesity medicine positions, the 8263 doctors certified by ABOM are only a tiny fraction of US physicians. As a result, there’s genuine likelihood that many patients seeking GLP-1s or other obesity treatment don’t yet have access to the holistic care they need. Plus, doctors may still not have obesity expertise within their networks.

“The field has grown rapidly, but it’s still such a small field relative to the patient need,” said Dr. Gudzune.
 

A version of this article appeared on Medscape.com.

Common complaints of abdominal pain, fever, shortness of breath, or rash can signal more serious disease that should be referred to specialty care or might be related to benign conditions.

Combine the vague nature of many patients’ descriptions and the pressure of short visits, and clinicians have a recipe for all manner of diagnostic error.

An estimated 5% of US adults who seek outpatient care each year experience a diagnostic error. Most Americans will eventually have this experience, according to a 2015 report from the National Academy of Medicine.

The most frequently missed diagnoses in primary care involve conditions such as pneumonia, decompensated heart failure, acute renal failure, cancer, urinary tract infection, and pyelonephritis.

“It’s not one or two or three types of diagnosis that are missed: We miss a lot of things, especially in primary care,” said Hardeep Singh, MD, MPH, a patient safety researcher at the Michael E. DeBakey VA Medical Center and the Baylor College of Medicine in Houston, Texas.

One of the most serious errors is to miss cancer, with failing to follow‐up on abnormal tests ranking consistently as one of the leading causes of malpractice claims. But most diagnostic errors do not lead to lawsuits, although they often result in missed and delayed opportunities for patients to get needed care.

In interviews with this news organization, experts who have studied the root causes of diagnostic error suggested primary care clinicians focus on several practices to avoid mistakes: Ask questions with humility and curiosity, use checklists, and brainstorm with patients the potential root cause of symptoms.
 

Humility and Curiosity 

Clinicians should remain aware of the potential for errors and reach out for assistance when needed, keeping an open mind that common symptoms may, in rare cases, signal serious illness, Dr. Singh said.

Dr. Singh recommends continual review with what he calls “byte-sized” learning through digital tools such as the Human Diagnosis app and podcasts and webinars offered by Clinical Problem Solvers.

Continuing education activities such as classes for Maintenance of Certification (MOC) can help keep physicians up to date and alert for cases where seemingly common symptoms may turn out to be something serious, said Richard M. Wardrop, III, MD, PhD, an internal medicine physician at the Cleveland Clinic in Ohio, and chair of the internal medicine board at the American Board of Internal Medicine.

“I’ve been in practice for 20 years. I’m double board certified in peds and medicine, and I regularly teach students and residents and mentor other physicians, but the further I go in my career and in practice, the more humble I become,” Dr. Wardrop told this news organization.

He said he recently spent a few hours on MOC for pediatrics and found the review was helpful in his practice in medicine.

“If I find myself taking care of a patient in a newborn nursery anytime soon, I’m going to understand the new hyperbilirubinemia guidelines,” Dr. Wardrop said. “That takes time and energy, but when I was done with the questions for this quarter, I felt good about myself.”
 

Checking It Twice

Clinicians should incorporate checklists into daily practice. Reviewing these with patients can not only help rule out an illness but also serve as a nonconfrontational method to inquire about issues patients may find uncomfortable, said John Ely, MD, MSPH, professor emeritus of family medicine at the University of Iowa Carver College of Medicine in Iowa City.

Clinicians could benefit from the approach used in aviation, where checklists are a required and routine part of a pilot’s job, Dr. Ely said.

Although clinicians may assume patients expect them to work from memory and knowledge without this aide, many will see using a checklist as a sign of providing thorough care, he said.

Checklists can also open a pathway for discussions about potentially difficult or touchy issues in short visits. For example, a patient might feel defensive if a clinician asks about depression during a visit for abdominal pain. But incorporating a question in a checklist allows for a different framing of the question.

“A clinician could say ‘I didn’t say you were depressed because of your abdominal pain, I brought it up because it’s on the list,’” Dr. Ely said. The checklist is “a very easy way to bring up those things.”

Dr. Ely said he has cared for a few patients who sought help for abdominal pain that turned out to be linked to sexual abuse in their past. Dr. Ely used a checklist with these patients to review possible causes for their illness. He recalled one of these patients who had suffered sexual abuse and had depression, neither of which was readily apparent.

“There was nothing about her affect that appeared to be depressed, and she had seen multiple physicians unable to make a diagnosis,” Dr. Ely said. “She had worked up for multiple other diseases and this had never come up before.”
 

Cooperation 

“Coproduction” is how Kathryn McDonald, PhD, describes an ideal path to getting an accurate diagnosis. The intent is for clinicians to enlist patients in helping them in finding the root cause of symptoms.

“It’s bringing the patient into knowing that they are in a partnership to coproduce, knowing that there is a process going on,” said Dr. McDonald, who is codirector of the Armstrong Institute Center for Diagnostic Excellence at Johns Hopkins University in Baltimore, Maryland.

In many cases, patients seek reassurance for ruling out a suspected condition, which the physician can sometimes provide. In others, clinicians may not be able to offer a concrete diagnosis.

“There are times when uncertainty is more pervasive and I will ask patients, ‘Let’s brainstorm this together,’” Dr. Wardrop said.

A version of this article appeared on Medscape.com.

Common complaints of abdominal pain, fever, shortness of breath, or rash can signal more serious disease that should be referred to specialty care or might be related to benign conditions.

Combine the vague nature of many patients’ descriptions and the pressure of short visits, and clinicians have a recipe for all manner of diagnostic error.

An estimated 5% of US adults who seek outpatient care each year experience a diagnostic error. Most Americans will eventually have this experience, according to a 2015 report from the National Academy of Medicine.

The most frequently missed diagnoses in primary care involve conditions such as pneumonia, decompensated heart failure, acute renal failure, cancer, urinary tract infection, and pyelonephritis.

“It’s not one or two or three types of diagnosis that are missed: We miss a lot of things, especially in primary care,” said Hardeep Singh, MD, MPH, a patient safety researcher at the Michael E. DeBakey VA Medical Center and the Baylor College of Medicine in Houston, Texas.

One of the most serious errors is to miss cancer, with failing to follow‐up on abnormal tests ranking consistently as one of the leading causes of malpractice claims. But most diagnostic errors do not lead to lawsuits, although they often result in missed and delayed opportunities for patients to get needed care.

In interviews with this news organization, experts who have studied the root causes of diagnostic error suggested primary care clinicians focus on several practices to avoid mistakes: Ask questions with humility and curiosity, use checklists, and brainstorm with patients the potential root cause of symptoms.
 

Humility and Curiosity 

Clinicians should remain aware of the potential for errors and reach out for assistance when needed, keeping an open mind that common symptoms may, in rare cases, signal serious illness, Dr. Singh said.

Dr. Singh recommends continual review with what he calls “byte-sized” learning through digital tools such as the Human Diagnosis app and podcasts and webinars offered by Clinical Problem Solvers.

Continuing education activities such as classes for Maintenance of Certification (MOC) can help keep physicians up to date and alert for cases where seemingly common symptoms may turn out to be something serious, said Richard M. Wardrop, III, MD, PhD, an internal medicine physician at the Cleveland Clinic in Ohio, and chair of the internal medicine board at the American Board of Internal Medicine.

“I’ve been in practice for 20 years. I’m double board certified in peds and medicine, and I regularly teach students and residents and mentor other physicians, but the further I go in my career and in practice, the more humble I become,” Dr. Wardrop told this news organization.

He said he recently spent a few hours on MOC for pediatrics and found the review was helpful in his practice in medicine.

“If I find myself taking care of a patient in a newborn nursery anytime soon, I’m going to understand the new hyperbilirubinemia guidelines,” Dr. Wardrop said. “That takes time and energy, but when I was done with the questions for this quarter, I felt good about myself.”
 

Checking It Twice

Clinicians should incorporate checklists into daily practice. Reviewing these with patients can not only help rule out an illness but also serve as a nonconfrontational method to inquire about issues patients may find uncomfortable, said John Ely, MD, MSPH, professor emeritus of family medicine at the University of Iowa Carver College of Medicine in Iowa City.

Clinicians could benefit from the approach used in aviation, where checklists are a required and routine part of a pilot’s job, Dr. Ely said.

Although clinicians may assume patients expect them to work from memory and knowledge without this aide, many will see using a checklist as a sign of providing thorough care, he said.

Checklists can also open a pathway for discussions about potentially difficult or touchy issues in short visits. For example, a patient might feel defensive if a clinician asks about depression during a visit for abdominal pain. But incorporating a question in a checklist allows for a different framing of the question.

“A clinician could say ‘I didn’t say you were depressed because of your abdominal pain, I brought it up because it’s on the list,’” Dr. Ely said. The checklist is “a very easy way to bring up those things.”

Dr. Ely said he has cared for a few patients who sought help for abdominal pain that turned out to be linked to sexual abuse in their past. Dr. Ely used a checklist with these patients to review possible causes for their illness. He recalled one of these patients who had suffered sexual abuse and had depression, neither of which was readily apparent.

“There was nothing about her affect that appeared to be depressed, and she had seen multiple physicians unable to make a diagnosis,” Dr. Ely said. “She had worked up for multiple other diseases and this had never come up before.”
 

Cooperation 

“Coproduction” is how Kathryn McDonald, PhD, describes an ideal path to getting an accurate diagnosis. The intent is for clinicians to enlist patients in helping them in finding the root cause of symptoms.

“It’s bringing the patient into knowing that they are in a partnership to coproduce, knowing that there is a process going on,” said Dr. McDonald, who is codirector of the Armstrong Institute Center for Diagnostic Excellence at Johns Hopkins University in Baltimore, Maryland.

In many cases, patients seek reassurance for ruling out a suspected condition, which the physician can sometimes provide. In others, clinicians may not be able to offer a concrete diagnosis.

“There are times when uncertainty is more pervasive and I will ask patients, ‘Let’s brainstorm this together,’” Dr. Wardrop said.

A version of this article appeared on Medscape.com.

Common complaints of abdominal pain, fever, shortness of breath, or rash can signal more serious disease that should be referred to specialty care or might be related to benign conditions.

Combine the vague nature of many patients’ descriptions and the pressure of short visits, and clinicians have a recipe for all manner of diagnostic error.

An estimated 5% of US adults who seek outpatient care each year experience a diagnostic error. Most Americans will eventually have this experience, according to a 2015 report from the National Academy of Medicine.

The most frequently missed diagnoses in primary care involve conditions such as pneumonia, decompensated heart failure, acute renal failure, cancer, urinary tract infection, and pyelonephritis.

“It’s not one or two or three types of diagnosis that are missed: We miss a lot of things, especially in primary care,” said Hardeep Singh, MD, MPH, a patient safety researcher at the Michael E. DeBakey VA Medical Center and the Baylor College of Medicine in Houston, Texas.

One of the most serious errors is to miss cancer, with failing to follow‐up on abnormal tests ranking consistently as one of the leading causes of malpractice claims. But most diagnostic errors do not lead to lawsuits, although they often result in missed and delayed opportunities for patients to get needed care.

In interviews with this news organization, experts who have studied the root causes of diagnostic error suggested primary care clinicians focus on several practices to avoid mistakes: Ask questions with humility and curiosity, use checklists, and brainstorm with patients the potential root cause of symptoms.
 

Humility and Curiosity 

Clinicians should remain aware of the potential for errors and reach out for assistance when needed, keeping an open mind that common symptoms may, in rare cases, signal serious illness, Dr. Singh said.

Dr. Singh recommends continual review with what he calls “byte-sized” learning through digital tools such as the Human Diagnosis app and podcasts and webinars offered by Clinical Problem Solvers.

Continuing education activities such as classes for Maintenance of Certification (MOC) can help keep physicians up to date and alert for cases where seemingly common symptoms may turn out to be something serious, said Richard M. Wardrop, III, MD, PhD, an internal medicine physician at the Cleveland Clinic in Ohio, and chair of the internal medicine board at the American Board of Internal Medicine.

“I’ve been in practice for 20 years. I’m double board certified in peds and medicine, and I regularly teach students and residents and mentor other physicians, but the further I go in my career and in practice, the more humble I become,” Dr. Wardrop told this news organization.

He said he recently spent a few hours on MOC for pediatrics and found the review was helpful in his practice in medicine.

“If I find myself taking care of a patient in a newborn nursery anytime soon, I’m going to understand the new hyperbilirubinemia guidelines,” Dr. Wardrop said. “That takes time and energy, but when I was done with the questions for this quarter, I felt good about myself.”
 

Checking It Twice

Clinicians should incorporate checklists into daily practice. Reviewing these with patients can not only help rule out an illness but also serve as a nonconfrontational method to inquire about issues patients may find uncomfortable, said John Ely, MD, MSPH, professor emeritus of family medicine at the University of Iowa Carver College of Medicine in Iowa City.

Clinicians could benefit from the approach used in aviation, where checklists are a required and routine part of a pilot’s job, Dr. Ely said.

Although clinicians may assume patients expect them to work from memory and knowledge without this aide, many will see using a checklist as a sign of providing thorough care, he said.

Checklists can also open a pathway for discussions about potentially difficult or touchy issues in short visits. For example, a patient might feel defensive if a clinician asks about depression during a visit for abdominal pain. But incorporating a question in a checklist allows for a different framing of the question.

“A clinician could say ‘I didn’t say you were depressed because of your abdominal pain, I brought it up because it’s on the list,’” Dr. Ely said. The checklist is “a very easy way to bring up those things.”

Dr. Ely said he has cared for a few patients who sought help for abdominal pain that turned out to be linked to sexual abuse in their past. Dr. Ely used a checklist with these patients to review possible causes for their illness. He recalled one of these patients who had suffered sexual abuse and had depression, neither of which was readily apparent.

“There was nothing about her affect that appeared to be depressed, and she had seen multiple physicians unable to make a diagnosis,” Dr. Ely said. “She had worked up for multiple other diseases and this had never come up before.”
 

Cooperation 

“Coproduction” is how Kathryn McDonald, PhD, describes an ideal path to getting an accurate diagnosis. The intent is for clinicians to enlist patients in helping them in finding the root cause of symptoms.

“It’s bringing the patient into knowing that they are in a partnership to coproduce, knowing that there is a process going on,” said Dr. McDonald, who is codirector of the Armstrong Institute Center for Diagnostic Excellence at Johns Hopkins University in Baltimore, Maryland.

In many cases, patients seek reassurance for ruling out a suspected condition, which the physician can sometimes provide. In others, clinicians may not be able to offer a concrete diagnosis.

“There are times when uncertainty is more pervasive and I will ask patients, ‘Let’s brainstorm this together,’” Dr. Wardrop said.

A version of this article appeared on Medscape.com.

The global withdrawal of voxelotor (Oxbryta, Pfizer) has left clinicians who treat sickle cell disease (SCD) with the urgent task of reaching patients taking the medicine, while trying to understand why it was taken off the market.

The National Alliance of Sickle Cell Centers issued a statement urging patients not to stop voxelotor abruptly. Instead, they should work out plans with their physicians and medical teams for weaning plans.

“Don’t lose faith. This a step backward, but we will stay on the path to better outcomes for everyone,” said the alliance in a statement to patients and clinicians.

On September 25, Pfizer said it would withdraw all lots of voxelotor in all markets where it is approved. The New York–based drugmaker also said it was discontinuing all active voxelotor clinical trials and expanded access programs worldwide. The cause was data that suggested “an imbalance in vaso-occlusive crises and fatal events which require further assessment.”

Pfizer told this news organization in an email exchange that it is focused on analyzing the data and will share updates in the future about presenting or publishing on this issue.

The withdrawal came amid increased scrutiny of the drug by the European Medicines Agency (EMA). The EMA in July began a review of voxelotor after data from a clinical trial showed that a higher number of deaths occurred with the drug than with placebo and another trial showed the total number of deaths was higher than anticipated.

On September 26, the EMA’s human medicines committee recommended suspending the marketing authorization of voxelotor, citing new safety data that emerged during the review. The drug had received marketing authorization for the European Union in 2022, the agency said.

The US Food and Drug Administration (FDA), which first cleared voxelotor for sale in 2019, also said it has been conducting a safety review of the drug. The agency continues to examine post-marketing clinical trial data for voxelotor, the real-world registry studies, and data from the FDA Adverse Event Reporting System. At the conclusion of this review, the FDA will communicate any additional findings, if necessary, the agency said.

The FDA said it appeared that more deaths and a higher rate of vaso-occlusive crisis occurred in patients taking voxelotor vs placebo in post-marketing clinical trials.

“Pfizer also observed a higher rate of vaso-occlusive crisis in patients with sickle cell disease receiving Oxbryta in two real-world registry studies,” the FDA said. “Based on the totality of clinical data, Pfizer has determined the benefit of Oxbryta does not outweigh the risk.”
 

Gene Therapy, Tried-and-True Hydroxyurea (HU)

As a field, SCD has drawn more interest in recent years, with significant gains made lately in cutting-edge projects.

The FDA in December approved two gene-editing treatments for patients aged 12 years or older. These are considered “milestone treatments” for a debilitating and potentially life-threatening blood disorder that affects about 100,000 people in the United States. Exagamglogene autotemcel (Casgevy, Vertex Pharmaceuticals and CRISPR Therapeutics) is the first to use the gene-editing tool CRISPR. And lovotibeglogene autotemcel (Lyfgenia, bluebird bio) uses a different gene-editing tool called a lentiviral vector.

These advances have been covered widely by the news media but are not expected to be widely available, with the cost of these extensive treatments estimated around $2-$3 million per patient.

“Gene therapy is amazing in that it can offer a cure, but it’s very expensive and not all patients are suitable for it. Some have so much existing organ damage that it’s not an option for them,” said John Wood, MD, PhD, director of cardiovascular MRI at Children’s Hospital Los Angeles, Los Angeles, who does research on SCD.

“So it really is a great treatment for a very few people,” he said in an interview.

The mainstay of treatment for SCD remains a drug that Lydia Pecker, MD, a pediatric hematologist at Johns Hopkins University in Baltimore, describes as the “first, oldest, and best”: HU.

The FDA approved this in 1998 for use in SCD. It reduces the frequency of painful crises and acute chest syndrome and other complications of SCD that otherwise could be serious or even lethal, Pecker said.

“Older doctors can tell you that what they experienced with sickle cell disease in the hospitals has been completely transformed because of the high uptake of the drug,” she said, adding that it made a “profound” change. “We just don’t have data for any other agent that’s quite like that.”

Voxelotor had been a good second drug to add for some patients, in addition to HU and blood transfusions, Dr. Pecker noted. It was a first-line drug for those for whom transfusion and HU were not options, which constitutes a relatively small number of patients, she said.

“So we have, in the last 5 years, felt more hopeful because we had something else to offer,” she said.

Alexis A. Thompson, MD, MPH, chief of the Division of Hematology at Children’s Hospital of Philadelphia in Pennsylvania, said in an interview that her organization also had patients who appeared to benefit from voxelotor, some of whom had been participants in clinical trials.

Dr. Thompson, who has been a top researcher involved in the study of gene therapy, urged the need for companies to keep seeking to expand the options for people with SCD, even after the setback with voxelotor.

“I hope that there’s an appreciation for the need for continued investment in this very serious condition, for which there are insufficient options for treatments,” Dr. Thompson said. “So ongoing investment is really needed if we expect to make progress.”

Dr. Pecker disclosed ties with Novartis, Afimmune, the American Society of Hematology, and the National Institutes of Health. Thompson reported relationships with bluebird bio, Beam, Editas, Novartis, and Novo Nordisk.
 

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

The global withdrawal of voxelotor (Oxbryta, Pfizer) has left clinicians who treat sickle cell disease (SCD) with the urgent task of reaching patients taking the medicine, while trying to understand why it was taken off the market.

The National Alliance of Sickle Cell Centers issued a statement urging patients not to stop voxelotor abruptly. Instead, they should work out plans with their physicians and medical teams for weaning plans.

“Don’t lose faith. This a step backward, but we will stay on the path to better outcomes for everyone,” said the alliance in a statement to patients and clinicians.

On September 25, Pfizer said it would withdraw all lots of voxelotor in all markets where it is approved. The New York–based drugmaker also said it was discontinuing all active voxelotor clinical trials and expanded access programs worldwide. The cause was data that suggested “an imbalance in vaso-occlusive crises and fatal events which require further assessment.”

Pfizer told this news organization in an email exchange that it is focused on analyzing the data and will share updates in the future about presenting or publishing on this issue.

The withdrawal came amid increased scrutiny of the drug by the European Medicines Agency (EMA). The EMA in July began a review of voxelotor after data from a clinical trial showed that a higher number of deaths occurred with the drug than with placebo and another trial showed the total number of deaths was higher than anticipated.

On September 26, the EMA’s human medicines committee recommended suspending the marketing authorization of voxelotor, citing new safety data that emerged during the review. The drug had received marketing authorization for the European Union in 2022, the agency said.

The US Food and Drug Administration (FDA), which first cleared voxelotor for sale in 2019, also said it has been conducting a safety review of the drug. The agency continues to examine post-marketing clinical trial data for voxelotor, the real-world registry studies, and data from the FDA Adverse Event Reporting System. At the conclusion of this review, the FDA will communicate any additional findings, if necessary, the agency said.

The FDA said it appeared that more deaths and a higher rate of vaso-occlusive crisis occurred in patients taking voxelotor vs placebo in post-marketing clinical trials.

“Pfizer also observed a higher rate of vaso-occlusive crisis in patients with sickle cell disease receiving Oxbryta in two real-world registry studies,” the FDA said. “Based on the totality of clinical data, Pfizer has determined the benefit of Oxbryta does not outweigh the risk.”
 

Gene Therapy, Tried-and-True Hydroxyurea (HU)

As a field, SCD has drawn more interest in recent years, with significant gains made lately in cutting-edge projects.

The FDA in December approved two gene-editing treatments for patients aged 12 years or older. These are considered “milestone treatments” for a debilitating and potentially life-threatening blood disorder that affects about 100,000 people in the United States. Exagamglogene autotemcel (Casgevy, Vertex Pharmaceuticals and CRISPR Therapeutics) is the first to use the gene-editing tool CRISPR. And lovotibeglogene autotemcel (Lyfgenia, bluebird bio) uses a different gene-editing tool called a lentiviral vector.

These advances have been covered widely by the news media but are not expected to be widely available, with the cost of these extensive treatments estimated around $2-$3 million per patient.

“Gene therapy is amazing in that it can offer a cure, but it’s very expensive and not all patients are suitable for it. Some have so much existing organ damage that it’s not an option for them,” said John Wood, MD, PhD, director of cardiovascular MRI at Children’s Hospital Los Angeles, Los Angeles, who does research on SCD.

“So it really is a great treatment for a very few people,” he said in an interview.

The mainstay of treatment for SCD remains a drug that Lydia Pecker, MD, a pediatric hematologist at Johns Hopkins University in Baltimore, describes as the “first, oldest, and best”: HU.

The FDA approved this in 1998 for use in SCD. It reduces the frequency of painful crises and acute chest syndrome and other complications of SCD that otherwise could be serious or even lethal, Pecker said.

“Older doctors can tell you that what they experienced with sickle cell disease in the hospitals has been completely transformed because of the high uptake of the drug,” she said, adding that it made a “profound” change. “We just don’t have data for any other agent that’s quite like that.”

Voxelotor had been a good second drug to add for some patients, in addition to HU and blood transfusions, Dr. Pecker noted. It was a first-line drug for those for whom transfusion and HU were not options, which constitutes a relatively small number of patients, she said.

“So we have, in the last 5 years, felt more hopeful because we had something else to offer,” she said.

Alexis A. Thompson, MD, MPH, chief of the Division of Hematology at Children’s Hospital of Philadelphia in Pennsylvania, said in an interview that her organization also had patients who appeared to benefit from voxelotor, some of whom had been participants in clinical trials.

Dr. Thompson, who has been a top researcher involved in the study of gene therapy, urged the need for companies to keep seeking to expand the options for people with SCD, even after the setback with voxelotor.

“I hope that there’s an appreciation for the need for continued investment in this very serious condition, for which there are insufficient options for treatments,” Dr. Thompson said. “So ongoing investment is really needed if we expect to make progress.”

Dr. Pecker disclosed ties with Novartis, Afimmune, the American Society of Hematology, and the National Institutes of Health. Thompson reported relationships with bluebird bio, Beam, Editas, Novartis, and Novo Nordisk.
 

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

The global withdrawal of voxelotor (Oxbryta, Pfizer) has left clinicians who treat sickle cell disease (SCD) with the urgent task of reaching patients taking the medicine, while trying to understand why it was taken off the market.

The National Alliance of Sickle Cell Centers issued a statement urging patients not to stop voxelotor abruptly. Instead, they should work out plans with their physicians and medical teams for weaning plans.

“Don’t lose faith. This a step backward, but we will stay on the path to better outcomes for everyone,” said the alliance in a statement to patients and clinicians.

On September 25, Pfizer said it would withdraw all lots of voxelotor in all markets where it is approved. The New York–based drugmaker also said it was discontinuing all active voxelotor clinical trials and expanded access programs worldwide. The cause was data that suggested “an imbalance in vaso-occlusive crises and fatal events which require further assessment.”

Pfizer told this news organization in an email exchange that it is focused on analyzing the data and will share updates in the future about presenting or publishing on this issue.

The withdrawal came amid increased scrutiny of the drug by the European Medicines Agency (EMA). The EMA in July began a review of voxelotor after data from a clinical trial showed that a higher number of deaths occurred with the drug than with placebo and another trial showed the total number of deaths was higher than anticipated.

On September 26, the EMA’s human medicines committee recommended suspending the marketing authorization of voxelotor, citing new safety data that emerged during the review. The drug had received marketing authorization for the European Union in 2022, the agency said.

The US Food and Drug Administration (FDA), which first cleared voxelotor for sale in 2019, also said it has been conducting a safety review of the drug. The agency continues to examine post-marketing clinical trial data for voxelotor, the real-world registry studies, and data from the FDA Adverse Event Reporting System. At the conclusion of this review, the FDA will communicate any additional findings, if necessary, the agency said.

The FDA said it appeared that more deaths and a higher rate of vaso-occlusive crisis occurred in patients taking voxelotor vs placebo in post-marketing clinical trials.

“Pfizer also observed a higher rate of vaso-occlusive crisis in patients with sickle cell disease receiving Oxbryta in two real-world registry studies,” the FDA said. “Based on the totality of clinical data, Pfizer has determined the benefit of Oxbryta does not outweigh the risk.”
 

Gene Therapy, Tried-and-True Hydroxyurea (HU)

As a field, SCD has drawn more interest in recent years, with significant gains made lately in cutting-edge projects.

The FDA in December approved two gene-editing treatments for patients aged 12 years or older. These are considered “milestone treatments” for a debilitating and potentially life-threatening blood disorder that affects about 100,000 people in the United States. Exagamglogene autotemcel (Casgevy, Vertex Pharmaceuticals and CRISPR Therapeutics) is the first to use the gene-editing tool CRISPR. And lovotibeglogene autotemcel (Lyfgenia, bluebird bio) uses a different gene-editing tool called a lentiviral vector.

These advances have been covered widely by the news media but are not expected to be widely available, with the cost of these extensive treatments estimated around $2-$3 million per patient.

“Gene therapy is amazing in that it can offer a cure, but it’s very expensive and not all patients are suitable for it. Some have so much existing organ damage that it’s not an option for them,” said John Wood, MD, PhD, director of cardiovascular MRI at Children’s Hospital Los Angeles, Los Angeles, who does research on SCD.

“So it really is a great treatment for a very few people,” he said in an interview.

The mainstay of treatment for SCD remains a drug that Lydia Pecker, MD, a pediatric hematologist at Johns Hopkins University in Baltimore, describes as the “first, oldest, and best”: HU.

The FDA approved this in 1998 for use in SCD. It reduces the frequency of painful crises and acute chest syndrome and other complications of SCD that otherwise could be serious or even lethal, Pecker said.

“Older doctors can tell you that what they experienced with sickle cell disease in the hospitals has been completely transformed because of the high uptake of the drug,” she said, adding that it made a “profound” change. “We just don’t have data for any other agent that’s quite like that.”

Voxelotor had been a good second drug to add for some patients, in addition to HU and blood transfusions, Dr. Pecker noted. It was a first-line drug for those for whom transfusion and HU were not options, which constitutes a relatively small number of patients, she said.

“So we have, in the last 5 years, felt more hopeful because we had something else to offer,” she said.

Alexis A. Thompson, MD, MPH, chief of the Division of Hematology at Children’s Hospital of Philadelphia in Pennsylvania, said in an interview that her organization also had patients who appeared to benefit from voxelotor, some of whom had been participants in clinical trials.

Dr. Thompson, who has been a top researcher involved in the study of gene therapy, urged the need for companies to keep seeking to expand the options for people with SCD, even after the setback with voxelotor.

“I hope that there’s an appreciation for the need for continued investment in this very serious condition, for which there are insufficient options for treatments,” Dr. Thompson said. “So ongoing investment is really needed if we expect to make progress.”

Dr. Pecker disclosed ties with Novartis, Afimmune, the American Society of Hematology, and the National Institutes of Health. Thompson reported relationships with bluebird bio, Beam, Editas, Novartis, and Novo Nordisk.
 

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

Demand for new weight loss drugs has surged over the past few years. 

Led by the antiobesity drugs semaglutide (Wegovy) and tirzepatide (Zepbound), these popular medications — more commonly known as glucagon-like peptide 1 (GLP-1) agonists — have become game changers for shedding excess pounds.

Aside from obesity indications, both drugs have been approved to treat type 2 diabetes under different brand names and have a growing list of other potential benefits, such as reducing inflammation and depression. 

These antiobesity drugs could even have a place in cancer care.

While there’s limited data to support the use of GLP-1 agonists for weight loss in cancer, some oncologists have begun carefully integrating the antiobesity agents into care and studying their effects in this patient population.

The reason: Research suggests that obesity can reduce the effectiveness of cancer therapies, especially in patients with breast cancer, and can increase the risk for treatment-related side effects. 

The idea is that managing patients’ weight will improve their cancer outcomes, explained Lajos Pusztai, MD, PhD, a breast cancer specialist and professor of medicine at Yale School of Medicine in New Haven, Connecticut. 

Although Dr. Pusztai and his oncology peers at Yale don’t yet use GPL-1 agonists, Neil Iyengar, MD, and colleagues have begun doing so to help some patients with breast cancer manage their weight. Dr. Iyengar estimates that a few hundred — almost 40% — of his patients are on the antiobesity drugs.

“For a patient who has really tried to reduce their weight and who is in the obese range, that’s where I think the use of these medications can be considered,” said Dr. Iyengar, a breast cancer oncologist at Memorial Sloan Kettering Cancer Center in New York City. 

Why GLP-1s in Cancer?

GLP-1 is a hormone that the small intestine releases after eating. GLP-1 agonists work by mimicking GLP-1 to trigger the release of insulin and reduce the production of glucagon — two processes that help regulate blood sugar. 

These agents, such as Wegovy (or Ozempic when prescribed for diabetes), also slow gastric emptying and can make people feel fuller longer. 

Zebound (or Mounjaro for type 2 diabetes) is considered a dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, which may enhance its weight loss benefits.

In practice, however, these drugs can increase nausea and vomiting from chemotherapy, so Dr. Iyengar typically has patients use them afterwards, during maintenance treatment.

Oncologists don’t prescribe the drugs themselves but instead refer patients to endocrinologists or weight management centers that then write the prescriptions. Taking these drugs involves weekly subcutaneous injections patients can administer themselves.

Endocrinologist Emily Gallagher, MD, PhD, of Mount Sinai Hospital in New York City, estimates she has prescribed the antiobesity drugs to a few hundred patients with cancer and, like Dr. Iyengar, uses the drugs during maintenance treatment with hormone therapy for breast cancer. She also has used these agents in patients with prostate and endometrial cancers and has found the drugs can help counter steroid weight gain in multiple myeloma. 

But, to date, the evidence for using GPL-1 agonists in cancer remains limited and the practice has not yet become widespread.

Research largely comes down to a few small retrospective studies in patients with breast cancer receiving aromatase inhibitors. Although no safety issues have emerged so far, these initial reports suggest that the drugs lead to significantly less weight loss in patients with cancer compared to the general population. 

Dr. Iyengar led one recent study, presented at the 2024 annual meeting of the American Society of Clinical Oncology, in which he and his team assessed outcomes in 75 women with breast cancer who received a GLP-1 agonist. Almost 80% of patients had diabetes, and 60% received hormone therapy, most commonly an aromatase inhibitor. Patients’ median body mass index (BMI) at baseline was 34 kg/m² (range, 23-50 kg/m²).

From baseline, patients lost 6.2 kg, on average, or about 5% of their total body weight, 12 months after initiating GLP-1 therapy. 

In contrast, phase 3 trials show much higher mean weight loss — about two times — in patients without cancer. 

Another recent study also reported modest weight loss results in patients with breast cancer undergoing endocrine therapy. The researchers reported that, at 12 months, Wegovy led to 4.34% reduction in BMI, compared with a 14% change reported in the general population. Zebound, however, was associated with a 2.31% BMI increase overall — though some patients did experience a decrease — compared with a 15% reduction in the general population. 

“These findings indicate a substantially reduced weight loss efficacy in breast cancer patients on endocrine therapy compared to the general population,” the authors concluded.

It’s unclear why the drugs appear to not work as well in patients with cancer. It’s possible that hormone therapy or metabolic changes interfere with their effectiveness, given that some cancer therapies lead to weight gain. Steroids and hormone therapies, for instance, often increase appetite, and some treatments can slow patients’ metabolism or lead to fatigue, which can make it harder to exercise.

Patients with cancer may need a higher dose of GLP-1 agonists to achieve similar weight loss to the general population, Dr. Iyengar noted.

However, Dr. Gallagher said, in her own experience, she hasn’t found the drugs to be less effective in patients with cancer, especially the newer agents, like Wegovy and Zepbound. 

As for safety, Wegovy and Zepbound both carry a black box warning for thyroid C-cell tumors, including medullary thyroid carcinoma. (Recent research, however, has found that GLP-1 agonists do not increase thyroid cancer risk). 

These antiobesity agents are also contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients who have multiple endocrine neoplasia syndrome type 2, which is associated with medullary thyroid carcinoma.

Dr. Gallagher hasn’t seen any secondary tumors — thyroid or otherwise — in her patients with cancer, but she follows the labeling contraindications. Dr. Iyengar also noted that more recent and larger data sets have shown no impact on this risk, which may not actually exist, he said

Dr. Gallagher remains cautious about using GPL-1 agonists in patients who have had bariatric surgery because these agents can compound the slower gastric emptying and intestinal transit from surgery, potentially leading to gastrointestinal obstructions. 

Looking ahead, GPL-1 manufacturers are interested in adding cancer indications to the drug labeling. Both Dr. Iyengar and Dr. Gallagher said their institutions are in talks with companies to participate in large, multicenter, global phase 3 trials.

Dr. Iyengar welcomes the efforts, not only to test the effectiveness of GPL-1 agonists in oncology but also to “nail down” their safety in cancer. 

“I don’t think that there’s mechanistically anything that’s particularly worrisome,” and current observations suggest that these drugs are likely to be safe, Dr. Iyengar said. Even so, “GLP-1 agonists do a lot of things that we don’t fully understand yet.”

The bigger challenge, Dr. Iyengar noted, is that companies will have to show a sizable benefit to using these drugs in patients with cancer to get the Food and Drug Administration’s approval. And to move the needle on cancer-specific outcomes, these antiobesity drugs will need to demonstrate significant, durable weight loss in patients with cancer. 

But if these drugs can do that, “I think it’s going to be one of the biggest advances in medicine and oncology given the obesity and cancer epidemic,” Dr. Iyengar said. 

Dr. Iyengar has adviser and/or researcher ties with companies that make or are developing GPL-1 agonists, including AstraZeneca, Novartis, Gilead, and Pfizer. Dr. Gallagher is a consultant for Novartis, Flare Therapeutics, Reactive Biosciences, and Seagen.

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

Demand for new weight loss drugs has surged over the past few years. 

Led by the antiobesity drugs semaglutide (Wegovy) and tirzepatide (Zepbound), these popular medications — more commonly known as glucagon-like peptide 1 (GLP-1) agonists — have become game changers for shedding excess pounds.

Aside from obesity indications, both drugs have been approved to treat type 2 diabetes under different brand names and have a growing list of other potential benefits, such as reducing inflammation and depression. 

These antiobesity drugs could even have a place in cancer care.

While there’s limited data to support the use of GLP-1 agonists for weight loss in cancer, some oncologists have begun carefully integrating the antiobesity agents into care and studying their effects in this patient population.

The reason: Research suggests that obesity can reduce the effectiveness of cancer therapies, especially in patients with breast cancer, and can increase the risk for treatment-related side effects. 

The idea is that managing patients’ weight will improve their cancer outcomes, explained Lajos Pusztai, MD, PhD, a breast cancer specialist and professor of medicine at Yale School of Medicine in New Haven, Connecticut. 

Although Dr. Pusztai and his oncology peers at Yale don’t yet use GPL-1 agonists, Neil Iyengar, MD, and colleagues have begun doing so to help some patients with breast cancer manage their weight. Dr. Iyengar estimates that a few hundred — almost 40% — of his patients are on the antiobesity drugs.

“For a patient who has really tried to reduce their weight and who is in the obese range, that’s where I think the use of these medications can be considered,” said Dr. Iyengar, a breast cancer oncologist at Memorial Sloan Kettering Cancer Center in New York City. 

Why GLP-1s in Cancer?

GLP-1 is a hormone that the small intestine releases after eating. GLP-1 agonists work by mimicking GLP-1 to trigger the release of insulin and reduce the production of glucagon — two processes that help regulate blood sugar. 

These agents, such as Wegovy (or Ozempic when prescribed for diabetes), also slow gastric emptying and can make people feel fuller longer. 

Zebound (or Mounjaro for type 2 diabetes) is considered a dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, which may enhance its weight loss benefits.

In practice, however, these drugs can increase nausea and vomiting from chemotherapy, so Dr. Iyengar typically has patients use them afterwards, during maintenance treatment.

Oncologists don’t prescribe the drugs themselves but instead refer patients to endocrinologists or weight management centers that then write the prescriptions. Taking these drugs involves weekly subcutaneous injections patients can administer themselves.

Endocrinologist Emily Gallagher, MD, PhD, of Mount Sinai Hospital in New York City, estimates she has prescribed the antiobesity drugs to a few hundred patients with cancer and, like Dr. Iyengar, uses the drugs during maintenance treatment with hormone therapy for breast cancer. She also has used these agents in patients with prostate and endometrial cancers and has found the drugs can help counter steroid weight gain in multiple myeloma. 

But, to date, the evidence for using GPL-1 agonists in cancer remains limited and the practice has not yet become widespread.

Research largely comes down to a few small retrospective studies in patients with breast cancer receiving aromatase inhibitors. Although no safety issues have emerged so far, these initial reports suggest that the drugs lead to significantly less weight loss in patients with cancer compared to the general population. 

Dr. Iyengar led one recent study, presented at the 2024 annual meeting of the American Society of Clinical Oncology, in which he and his team assessed outcomes in 75 women with breast cancer who received a GLP-1 agonist. Almost 80% of patients had diabetes, and 60% received hormone therapy, most commonly an aromatase inhibitor. Patients’ median body mass index (BMI) at baseline was 34 kg/m² (range, 23-50 kg/m²).

From baseline, patients lost 6.2 kg, on average, or about 5% of their total body weight, 12 months after initiating GLP-1 therapy. 

In contrast, phase 3 trials show much higher mean weight loss — about two times — in patients without cancer. 

Another recent study also reported modest weight loss results in patients with breast cancer undergoing endocrine therapy. The researchers reported that, at 12 months, Wegovy led to 4.34% reduction in BMI, compared with a 14% change reported in the general population. Zebound, however, was associated with a 2.31% BMI increase overall — though some patients did experience a decrease — compared with a 15% reduction in the general population. 

“These findings indicate a substantially reduced weight loss efficacy in breast cancer patients on endocrine therapy compared to the general population,” the authors concluded.

It’s unclear why the drugs appear to not work as well in patients with cancer. It’s possible that hormone therapy or metabolic changes interfere with their effectiveness, given that some cancer therapies lead to weight gain. Steroids and hormone therapies, for instance, often increase appetite, and some treatments can slow patients’ metabolism or lead to fatigue, which can make it harder to exercise.

Patients with cancer may need a higher dose of GLP-1 agonists to achieve similar weight loss to the general population, Dr. Iyengar noted.

However, Dr. Gallagher said, in her own experience, she hasn’t found the drugs to be less effective in patients with cancer, especially the newer agents, like Wegovy and Zepbound. 

As for safety, Wegovy and Zepbound both carry a black box warning for thyroid C-cell tumors, including medullary thyroid carcinoma. (Recent research, however, has found that GLP-1 agonists do not increase thyroid cancer risk). 

These antiobesity agents are also contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients who have multiple endocrine neoplasia syndrome type 2, which is associated with medullary thyroid carcinoma.

Dr. Gallagher hasn’t seen any secondary tumors — thyroid or otherwise — in her patients with cancer, but she follows the labeling contraindications. Dr. Iyengar also noted that more recent and larger data sets have shown no impact on this risk, which may not actually exist, he said

Dr. Gallagher remains cautious about using GPL-1 agonists in patients who have had bariatric surgery because these agents can compound the slower gastric emptying and intestinal transit from surgery, potentially leading to gastrointestinal obstructions. 

Looking ahead, GPL-1 manufacturers are interested in adding cancer indications to the drug labeling. Both Dr. Iyengar and Dr. Gallagher said their institutions are in talks with companies to participate in large, multicenter, global phase 3 trials.

Dr. Iyengar welcomes the efforts, not only to test the effectiveness of GPL-1 agonists in oncology but also to “nail down” their safety in cancer. 

“I don’t think that there’s mechanistically anything that’s particularly worrisome,” and current observations suggest that these drugs are likely to be safe, Dr. Iyengar said. Even so, “GLP-1 agonists do a lot of things that we don’t fully understand yet.”

The bigger challenge, Dr. Iyengar noted, is that companies will have to show a sizable benefit to using these drugs in patients with cancer to get the Food and Drug Administration’s approval. And to move the needle on cancer-specific outcomes, these antiobesity drugs will need to demonstrate significant, durable weight loss in patients with cancer. 

But if these drugs can do that, “I think it’s going to be one of the biggest advances in medicine and oncology given the obesity and cancer epidemic,” Dr. Iyengar said. 

Dr. Iyengar has adviser and/or researcher ties with companies that make or are developing GPL-1 agonists, including AstraZeneca, Novartis, Gilead, and Pfizer. Dr. Gallagher is a consultant for Novartis, Flare Therapeutics, Reactive Biosciences, and Seagen.

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

Demand for new weight loss drugs has surged over the past few years. 

Led by the antiobesity drugs semaglutide (Wegovy) and tirzepatide (Zepbound), these popular medications — more commonly known as glucagon-like peptide 1 (GLP-1) agonists — have become game changers for shedding excess pounds.

Aside from obesity indications, both drugs have been approved to treat type 2 diabetes under different brand names and have a growing list of other potential benefits, such as reducing inflammation and depression. 

These antiobesity drugs could even have a place in cancer care.

While there’s limited data to support the use of GLP-1 agonists for weight loss in cancer, some oncologists have begun carefully integrating the antiobesity agents into care and studying their effects in this patient population.

The reason: Research suggests that obesity can reduce the effectiveness of cancer therapies, especially in patients with breast cancer, and can increase the risk for treatment-related side effects. 

The idea is that managing patients’ weight will improve their cancer outcomes, explained Lajos Pusztai, MD, PhD, a breast cancer specialist and professor of medicine at Yale School of Medicine in New Haven, Connecticut. 

Although Dr. Pusztai and his oncology peers at Yale don’t yet use GPL-1 agonists, Neil Iyengar, MD, and colleagues have begun doing so to help some patients with breast cancer manage their weight. Dr. Iyengar estimates that a few hundred — almost 40% — of his patients are on the antiobesity drugs.

“For a patient who has really tried to reduce their weight and who is in the obese range, that’s where I think the use of these medications can be considered,” said Dr. Iyengar, a breast cancer oncologist at Memorial Sloan Kettering Cancer Center in New York City. 

Why GLP-1s in Cancer?

GLP-1 is a hormone that the small intestine releases after eating. GLP-1 agonists work by mimicking GLP-1 to trigger the release of insulin and reduce the production of glucagon — two processes that help regulate blood sugar. 

These agents, such as Wegovy (or Ozempic when prescribed for diabetes), also slow gastric emptying and can make people feel fuller longer. 

Zebound (or Mounjaro for type 2 diabetes) is considered a dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, which may enhance its weight loss benefits.

In practice, however, these drugs can increase nausea and vomiting from chemotherapy, so Dr. Iyengar typically has patients use them afterwards, during maintenance treatment.

Oncologists don’t prescribe the drugs themselves but instead refer patients to endocrinologists or weight management centers that then write the prescriptions. Taking these drugs involves weekly subcutaneous injections patients can administer themselves.

Endocrinologist Emily Gallagher, MD, PhD, of Mount Sinai Hospital in New York City, estimates she has prescribed the antiobesity drugs to a few hundred patients with cancer and, like Dr. Iyengar, uses the drugs during maintenance treatment with hormone therapy for breast cancer. She also has used these agents in patients with prostate and endometrial cancers and has found the drugs can help counter steroid weight gain in multiple myeloma. 

But, to date, the evidence for using GPL-1 agonists in cancer remains limited and the practice has not yet become widespread.

Research largely comes down to a few small retrospective studies in patients with breast cancer receiving aromatase inhibitors. Although no safety issues have emerged so far, these initial reports suggest that the drugs lead to significantly less weight loss in patients with cancer compared to the general population. 

Dr. Iyengar led one recent study, presented at the 2024 annual meeting of the American Society of Clinical Oncology, in which he and his team assessed outcomes in 75 women with breast cancer who received a GLP-1 agonist. Almost 80% of patients had diabetes, and 60% received hormone therapy, most commonly an aromatase inhibitor. Patients’ median body mass index (BMI) at baseline was 34 kg/m² (range, 23-50 kg/m²).

From baseline, patients lost 6.2 kg, on average, or about 5% of their total body weight, 12 months after initiating GLP-1 therapy. 

In contrast, phase 3 trials show much higher mean weight loss — about two times — in patients without cancer. 

Another recent study also reported modest weight loss results in patients with breast cancer undergoing endocrine therapy. The researchers reported that, at 12 months, Wegovy led to 4.34% reduction in BMI, compared with a 14% change reported in the general population. Zebound, however, was associated with a 2.31% BMI increase overall — though some patients did experience a decrease — compared with a 15% reduction in the general population. 

“These findings indicate a substantially reduced weight loss efficacy in breast cancer patients on endocrine therapy compared to the general population,” the authors concluded.

It’s unclear why the drugs appear to not work as well in patients with cancer. It’s possible that hormone therapy or metabolic changes interfere with their effectiveness, given that some cancer therapies lead to weight gain. Steroids and hormone therapies, for instance, often increase appetite, and some treatments can slow patients’ metabolism or lead to fatigue, which can make it harder to exercise.

Patients with cancer may need a higher dose of GLP-1 agonists to achieve similar weight loss to the general population, Dr. Iyengar noted.

However, Dr. Gallagher said, in her own experience, she hasn’t found the drugs to be less effective in patients with cancer, especially the newer agents, like Wegovy and Zepbound. 

As for safety, Wegovy and Zepbound both carry a black box warning for thyroid C-cell tumors, including medullary thyroid carcinoma. (Recent research, however, has found that GLP-1 agonists do not increase thyroid cancer risk). 

These antiobesity agents are also contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients who have multiple endocrine neoplasia syndrome type 2, which is associated with medullary thyroid carcinoma.

Dr. Gallagher hasn’t seen any secondary tumors — thyroid or otherwise — in her patients with cancer, but she follows the labeling contraindications. Dr. Iyengar also noted that more recent and larger data sets have shown no impact on this risk, which may not actually exist, he said

Dr. Gallagher remains cautious about using GPL-1 agonists in patients who have had bariatric surgery because these agents can compound the slower gastric emptying and intestinal transit from surgery, potentially leading to gastrointestinal obstructions. 

Looking ahead, GPL-1 manufacturers are interested in adding cancer indications to the drug labeling. Both Dr. Iyengar and Dr. Gallagher said their institutions are in talks with companies to participate in large, multicenter, global phase 3 trials.

Dr. Iyengar welcomes the efforts, not only to test the effectiveness of GPL-1 agonists in oncology but also to “nail down” their safety in cancer. 

“I don’t think that there’s mechanistically anything that’s particularly worrisome,” and current observations suggest that these drugs are likely to be safe, Dr. Iyengar said. Even so, “GLP-1 agonists do a lot of things that we don’t fully understand yet.”

The bigger challenge, Dr. Iyengar noted, is that companies will have to show a sizable benefit to using these drugs in patients with cancer to get the Food and Drug Administration’s approval. And to move the needle on cancer-specific outcomes, these antiobesity drugs will need to demonstrate significant, durable weight loss in patients with cancer. 

But if these drugs can do that, “I think it’s going to be one of the biggest advances in medicine and oncology given the obesity and cancer epidemic,” Dr. Iyengar said. 

Dr. Iyengar has adviser and/or researcher ties with companies that make or are developing GPL-1 agonists, including AstraZeneca, Novartis, Gilead, and Pfizer. Dr. Gallagher is a consultant for Novartis, Flare Therapeutics, Reactive Biosciences, and Seagen.

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

Late last week, a US Food and Drug Administration (FDA) panel met to discuss whether to limit the use of nivolumab (Opdivo) and pembrolizumab (Keytruda) in patients with unresectable or metastatic esophageal squamous cell carcinoma and human epidermal growth factor receptor 2 (HER2)–negative, microsatellite stable gastric/gastroesophageal adenocarcinoma.

During the meeting, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted in favor of restricting the use of these immunotherapy agents to patients with programmed death-ligand 1 (PD-L1) expression of 1% or higher. 

The agency usually follows the ODAC’s advice.

The FDA had originally approved the two immune checkpoint inhibitors for both indications in combination with chemotherapy, regardless of patients’ PD-L1 status. The FDA had also approved nivolumab in combination with ipilimumab for esophageal cancer, regardless of PD-L1 expression. The approvals were based on overall benefit in intent-to-treat populations, not on specific PD-L1 expression subgroups.

Since then, additional studies — including the agency’s own pooled analyses of the approval trials — have found that overall survival benefits are limited to patients with PD-L1 expression of 1% or higher.

These findings have raised concerns that patients with no or low PD-L1 expression face the risks associated with immunotherapy, which include death, but minimal to no benefits.

In response, the FDA has considered changing the labeling for these indications to require a PD-L1 cutoff point of 1% or higher. The move would mirror guidelines from the American Society of Clinical Oncology and the National Comprehensive Cancer Network that already recommend use with chemotherapy only at certain PD-L1 cutoffs.

Before the agency acts, however, the FDA wanted the advice of the ODAC. It asked the 14-member panel whether the risk-benefit assessment is “favorable for the use of PD-1 inhibitors in first line” for the two indications among patients with PD-L1 expression below 1%.

In two nearly unanimous decisions for each indication, the panel voted that risk-benefit assessment was not favorable. In other words, the risks do outweigh the benefits for this patient population with no or low PD-L1 expression.

The determination also applies to tislelizumab (Tevimbra), an immune checkpoint inhibitor under review by the FDA for the same indications.

Voting came after hours of testimony from FDA scientists and the three drug companies involved in the decisions.

Merck, maker of pembrolizumab, was against any labeling change. Nivolumab’s maker, Bristol Myers Squibb (BMS), also wanted to stick with the current PD-L1 agnostic indications but said that any indication change should be class-wide to avoid confusion. BeiGene USA, maker of tislelizumab, had no problem with a PD-L1 cutoff of 1% because its approval trial showed benefit only in patients at that level or higher.

In general, Merck and BMS said the drug benefits correspond with higher PD-L1 expression but noted that patients with low or no PD-L1 expression can sometimes benefit from treatment. The companies had several patients testify to the benefits of the agents and noted patients like this would likely lose access. But an ODAC panelist noted that patients who died from immunotherapy complications weren’t there to respond.

The companies also expressed concern about taking treatment decisions out of the hands of oncologists as well as the need for additional biopsies to determine if tumors cross the proposed PD-L1 threshold at some point during treatment. With this potential new restriction, the companies were worried that insurance companies would be even less likely to pay for their checkpoint inhibitors in low or no PD-L1 expressors.

ODAC wasn’t moved. With consistent findings across multiple trials, the strength of the FDA’s data carried the day.

In a pooled analysis of the three companies’ unresectable or metastatic HER2–negative, microsatellite-stable gastric/gastroesophageal adenocarcinoma approval trials across almost 4000 patients, those with PD-L1 levels below 1% did not demonstrate a significant overall survival benefit (hazard ratio [HR], 0.91; 95% CI, 0.75-1.09). The median overall survival with immunotherapy plus chemotherapy was only 1 month more — 13.4 months vs 12.4 months with chemotherapy alone.

FDA’s pooled analysis for unresectable or metastatic esophageal squamous cell carcinoma also showed no overall survival benefit (HR, 1.1; 95% CI, 0.76-1.58), with a trend suggesting harm. Median overall survival with immunotherapy plus chemotherapy was 14.6 months vs 9.8 months with chemotherapy alone.

Despite the vote on esophageal squamous cell carcinoma, panelists had reservations about making decisions based on just over 160 patients with PD-L1 levels below 1% in the three esophageal squamous cell carcinoma trials.

Still, one panelist said, it’s likely “the best dataset we will get.”

The companies all used different methods to test PD-L1 levels, and attendees called for a single standardized PD-L1 test. Richard Pazdur, MD, head of the FDA’s Oncology Center of Excellence, said the agency has been working with companies for years to get them to agree to such a test, with no luck.

If the FDA ultimately decides to restrict immunotherapy use in this patient population based on PD-L1 levels, insurance company coverage may become more limited. Pazdur asked the companies if they would be willing to expand their patient assistance programs to provide free coverage of immune checkpoint blockers to patients with low or no PD-L1 expression.

BeiGene and BMS seemed open to the idea. Merck said, “We’ll have to ... think about it.”
 

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

Late last week, a US Food and Drug Administration (FDA) panel met to discuss whether to limit the use of nivolumab (Opdivo) and pembrolizumab (Keytruda) in patients with unresectable or metastatic esophageal squamous cell carcinoma and human epidermal growth factor receptor 2 (HER2)–negative, microsatellite stable gastric/gastroesophageal adenocarcinoma.

During the meeting, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted in favor of restricting the use of these immunotherapy agents to patients with programmed death-ligand 1 (PD-L1) expression of 1% or higher. 

The agency usually follows the ODAC’s advice.

The FDA had originally approved the two immune checkpoint inhibitors for both indications in combination with chemotherapy, regardless of patients’ PD-L1 status. The FDA had also approved nivolumab in combination with ipilimumab for esophageal cancer, regardless of PD-L1 expression. The approvals were based on overall benefit in intent-to-treat populations, not on specific PD-L1 expression subgroups.

Since then, additional studies — including the agency’s own pooled analyses of the approval trials — have found that overall survival benefits are limited to patients with PD-L1 expression of 1% or higher.

These findings have raised concerns that patients with no or low PD-L1 expression face the risks associated with immunotherapy, which include death, but minimal to no benefits.

In response, the FDA has considered changing the labeling for these indications to require a PD-L1 cutoff point of 1% or higher. The move would mirror guidelines from the American Society of Clinical Oncology and the National Comprehensive Cancer Network that already recommend use with chemotherapy only at certain PD-L1 cutoffs.

Before the agency acts, however, the FDA wanted the advice of the ODAC. It asked the 14-member panel whether the risk-benefit assessment is “favorable for the use of PD-1 inhibitors in first line” for the two indications among patients with PD-L1 expression below 1%.

In two nearly unanimous decisions for each indication, the panel voted that risk-benefit assessment was not favorable. In other words, the risks do outweigh the benefits for this patient population with no or low PD-L1 expression.

The determination also applies to tislelizumab (Tevimbra), an immune checkpoint inhibitor under review by the FDA for the same indications.

Voting came after hours of testimony from FDA scientists and the three drug companies involved in the decisions.

Merck, maker of pembrolizumab, was against any labeling change. Nivolumab’s maker, Bristol Myers Squibb (BMS), also wanted to stick with the current PD-L1 agnostic indications but said that any indication change should be class-wide to avoid confusion. BeiGene USA, maker of tislelizumab, had no problem with a PD-L1 cutoff of 1% because its approval trial showed benefit only in patients at that level or higher.

In general, Merck and BMS said the drug benefits correspond with higher PD-L1 expression but noted that patients with low or no PD-L1 expression can sometimes benefit from treatment. The companies had several patients testify to the benefits of the agents and noted patients like this would likely lose access. But an ODAC panelist noted that patients who died from immunotherapy complications weren’t there to respond.

The companies also expressed concern about taking treatment decisions out of the hands of oncologists as well as the need for additional biopsies to determine if tumors cross the proposed PD-L1 threshold at some point during treatment. With this potential new restriction, the companies were worried that insurance companies would be even less likely to pay for their checkpoint inhibitors in low or no PD-L1 expressors.

ODAC wasn’t moved. With consistent findings across multiple trials, the strength of the FDA’s data carried the day.

In a pooled analysis of the three companies’ unresectable or metastatic HER2–negative, microsatellite-stable gastric/gastroesophageal adenocarcinoma approval trials across almost 4000 patients, those with PD-L1 levels below 1% did not demonstrate a significant overall survival benefit (hazard ratio [HR], 0.91; 95% CI, 0.75-1.09). The median overall survival with immunotherapy plus chemotherapy was only 1 month more — 13.4 months vs 12.4 months with chemotherapy alone.

FDA’s pooled analysis for unresectable or metastatic esophageal squamous cell carcinoma also showed no overall survival benefit (HR, 1.1; 95% CI, 0.76-1.58), with a trend suggesting harm. Median overall survival with immunotherapy plus chemotherapy was 14.6 months vs 9.8 months with chemotherapy alone.

Despite the vote on esophageal squamous cell carcinoma, panelists had reservations about making decisions based on just over 160 patients with PD-L1 levels below 1% in the three esophageal squamous cell carcinoma trials.

Still, one panelist said, it’s likely “the best dataset we will get.”

The companies all used different methods to test PD-L1 levels, and attendees called for a single standardized PD-L1 test. Richard Pazdur, MD, head of the FDA’s Oncology Center of Excellence, said the agency has been working with companies for years to get them to agree to such a test, with no luck.

If the FDA ultimately decides to restrict immunotherapy use in this patient population based on PD-L1 levels, insurance company coverage may become more limited. Pazdur asked the companies if they would be willing to expand their patient assistance programs to provide free coverage of immune checkpoint blockers to patients with low or no PD-L1 expression.

BeiGene and BMS seemed open to the idea. Merck said, “We’ll have to ... think about it.”
 

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

Late last week, a US Food and Drug Administration (FDA) panel met to discuss whether to limit the use of nivolumab (Opdivo) and pembrolizumab (Keytruda) in patients with unresectable or metastatic esophageal squamous cell carcinoma and human epidermal growth factor receptor 2 (HER2)–negative, microsatellite stable gastric/gastroesophageal adenocarcinoma.

During the meeting, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted in favor of restricting the use of these immunotherapy agents to patients with programmed death-ligand 1 (PD-L1) expression of 1% or higher. 

The agency usually follows the ODAC’s advice.

The FDA had originally approved the two immune checkpoint inhibitors for both indications in combination with chemotherapy, regardless of patients’ PD-L1 status. The FDA had also approved nivolumab in combination with ipilimumab for esophageal cancer, regardless of PD-L1 expression. The approvals were based on overall benefit in intent-to-treat populations, not on specific PD-L1 expression subgroups.

Since then, additional studies — including the agency’s own pooled analyses of the approval trials — have found that overall survival benefits are limited to patients with PD-L1 expression of 1% or higher.

These findings have raised concerns that patients with no or low PD-L1 expression face the risks associated with immunotherapy, which include death, but minimal to no benefits.

In response, the FDA has considered changing the labeling for these indications to require a PD-L1 cutoff point of 1% or higher. The move would mirror guidelines from the American Society of Clinical Oncology and the National Comprehensive Cancer Network that already recommend use with chemotherapy only at certain PD-L1 cutoffs.

Before the agency acts, however, the FDA wanted the advice of the ODAC. It asked the 14-member panel whether the risk-benefit assessment is “favorable for the use of PD-1 inhibitors in first line” for the two indications among patients with PD-L1 expression below 1%.

In two nearly unanimous decisions for each indication, the panel voted that risk-benefit assessment was not favorable. In other words, the risks do outweigh the benefits for this patient population with no or low PD-L1 expression.

The determination also applies to tislelizumab (Tevimbra), an immune checkpoint inhibitor under review by the FDA for the same indications.

Voting came after hours of testimony from FDA scientists and the three drug companies involved in the decisions.

Merck, maker of pembrolizumab, was against any labeling change. Nivolumab’s maker, Bristol Myers Squibb (BMS), also wanted to stick with the current PD-L1 agnostic indications but said that any indication change should be class-wide to avoid confusion. BeiGene USA, maker of tislelizumab, had no problem with a PD-L1 cutoff of 1% because its approval trial showed benefit only in patients at that level or higher.

In general, Merck and BMS said the drug benefits correspond with higher PD-L1 expression but noted that patients with low or no PD-L1 expression can sometimes benefit from treatment. The companies had several patients testify to the benefits of the agents and noted patients like this would likely lose access. But an ODAC panelist noted that patients who died from immunotherapy complications weren’t there to respond.

The companies also expressed concern about taking treatment decisions out of the hands of oncologists as well as the need for additional biopsies to determine if tumors cross the proposed PD-L1 threshold at some point during treatment. With this potential new restriction, the companies were worried that insurance companies would be even less likely to pay for their checkpoint inhibitors in low or no PD-L1 expressors.

ODAC wasn’t moved. With consistent findings across multiple trials, the strength of the FDA’s data carried the day.

In a pooled analysis of the three companies’ unresectable or metastatic HER2–negative, microsatellite-stable gastric/gastroesophageal adenocarcinoma approval trials across almost 4000 patients, those with PD-L1 levels below 1% did not demonstrate a significant overall survival benefit (hazard ratio [HR], 0.91; 95% CI, 0.75-1.09). The median overall survival with immunotherapy plus chemotherapy was only 1 month more — 13.4 months vs 12.4 months with chemotherapy alone.

FDA’s pooled analysis for unresectable or metastatic esophageal squamous cell carcinoma also showed no overall survival benefit (HR, 1.1; 95% CI, 0.76-1.58), with a trend suggesting harm. Median overall survival with immunotherapy plus chemotherapy was 14.6 months vs 9.8 months with chemotherapy alone.

Despite the vote on esophageal squamous cell carcinoma, panelists had reservations about making decisions based on just over 160 patients with PD-L1 levels below 1% in the three esophageal squamous cell carcinoma trials.

Still, one panelist said, it’s likely “the best dataset we will get.”

The companies all used different methods to test PD-L1 levels, and attendees called for a single standardized PD-L1 test. Richard Pazdur, MD, head of the FDA’s Oncology Center of Excellence, said the agency has been working with companies for years to get them to agree to such a test, with no luck.

If the FDA ultimately decides to restrict immunotherapy use in this patient population based on PD-L1 levels, insurance company coverage may become more limited. Pazdur asked the companies if they would be willing to expand their patient assistance programs to provide free coverage of immune checkpoint blockers to patients with low or no PD-L1 expression.

BeiGene and BMS seemed open to the idea. Merck said, “We’ll have to ... think about it.”
 

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