Clinical Endocrinology News

The Food and Drug Administration (FDA) has issued new draft guidance that does not require additional switching studies for biosimilars seeking interchangeability. These studies were previously recommended to demonstrate that switching between the biosimilar and its reference product showed no greater risk than using the reference product alone.

“The recommendations in today’s draft guidance, when finalized, will provide clarity and transparency about the FDA’s thinking and align the review and approval process with existing and emerging science,” said Sarah Yim, MD, director of the FDA’s Office of Therapeutic Biologics and Biosimilars in a statement on June 20. “We have gained valuable experience reviewing both biosimilar and interchangeable biosimilar medications over the past 10 years. Both biosimilars and interchangeable biosimilars meet the same high standard of biosimilarity for FDA approval and both are as safe and effective as the reference product.”

An interchangeable status allows a biosimilar product to be swapped with the reference product without involvement from the prescribing provider, depending on state law.

While switching studies were not required under previous FDA guidance, the 2019 document did state that the agency “expects that applications generally will include data from a switching study or studies in one or more appropriate conditions of use.”

However, of the 13 biosimilars that received interchangeability status, 9 did not include switching study data.

“Experience has shown that, for the products approved as biosimilars to date, the risk in terms of safety or diminished efficacy is insignificant following single or multiple switches between a reference product and a biosimilar product,” the FDA stated. The agency’s investigators also conducted a systematic review of switching studies, which found no differences in risk for death, serious adverse events, and treatment discontinuations in participants switched between biosimilars and reference products and those that remained on reference products.

“Additionally, today’s analytical tools can accurately evaluate the structure and effects [of] biologic products, both in the lab (in vitro) and in living organisms (in vivo) with more precision and sensitivity than switching studies,” the agency noted.

The FDA is now calling for commentary on these draft recommendations to be submitted by Aug. 20, 2024.

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

The Food and Drug Administration (FDA) has issued new draft guidance that does not require additional switching studies for biosimilars seeking interchangeability. These studies were previously recommended to demonstrate that switching between the biosimilar and its reference product showed no greater risk than using the reference product alone.

“The recommendations in today’s draft guidance, when finalized, will provide clarity and transparency about the FDA’s thinking and align the review and approval process with existing and emerging science,” said Sarah Yim, MD, director of the FDA’s Office of Therapeutic Biologics and Biosimilars in a statement on June 20. “We have gained valuable experience reviewing both biosimilar and interchangeable biosimilar medications over the past 10 years. Both biosimilars and interchangeable biosimilars meet the same high standard of biosimilarity for FDA approval and both are as safe and effective as the reference product.”

An interchangeable status allows a biosimilar product to be swapped with the reference product without involvement from the prescribing provider, depending on state law.

While switching studies were not required under previous FDA guidance, the 2019 document did state that the agency “expects that applications generally will include data from a switching study or studies in one or more appropriate conditions of use.”

However, of the 13 biosimilars that received interchangeability status, 9 did not include switching study data.

“Experience has shown that, for the products approved as biosimilars to date, the risk in terms of safety or diminished efficacy is insignificant following single or multiple switches between a reference product and a biosimilar product,” the FDA stated. The agency’s investigators also conducted a systematic review of switching studies, which found no differences in risk for death, serious adverse events, and treatment discontinuations in participants switched between biosimilars and reference products and those that remained on reference products.

“Additionally, today’s analytical tools can accurately evaluate the structure and effects [of] biologic products, both in the lab (in vitro) and in living organisms (in vivo) with more precision and sensitivity than switching studies,” the agency noted.

The FDA is now calling for commentary on these draft recommendations to be submitted by Aug. 20, 2024.

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

The Food and Drug Administration (FDA) has issued new draft guidance that does not require additional switching studies for biosimilars seeking interchangeability. These studies were previously recommended to demonstrate that switching between the biosimilar and its reference product showed no greater risk than using the reference product alone.

“The recommendations in today’s draft guidance, when finalized, will provide clarity and transparency about the FDA’s thinking and align the review and approval process with existing and emerging science,” said Sarah Yim, MD, director of the FDA’s Office of Therapeutic Biologics and Biosimilars in a statement on June 20. “We have gained valuable experience reviewing both biosimilar and interchangeable biosimilar medications over the past 10 years. Both biosimilars and interchangeable biosimilars meet the same high standard of biosimilarity for FDA approval and both are as safe and effective as the reference product.”

An interchangeable status allows a biosimilar product to be swapped with the reference product without involvement from the prescribing provider, depending on state law.

While switching studies were not required under previous FDA guidance, the 2019 document did state that the agency “expects that applications generally will include data from a switching study or studies in one or more appropriate conditions of use.”

However, of the 13 biosimilars that received interchangeability status, 9 did not include switching study data.

“Experience has shown that, for the products approved as biosimilars to date, the risk in terms of safety or diminished efficacy is insignificant following single or multiple switches between a reference product and a biosimilar product,” the FDA stated. The agency’s investigators also conducted a systematic review of switching studies, which found no differences in risk for death, serious adverse events, and treatment discontinuations in participants switched between biosimilars and reference products and those that remained on reference products.

“Additionally, today’s analytical tools can accurately evaluate the structure and effects [of] biologic products, both in the lab (in vitro) and in living organisms (in vivo) with more precision and sensitivity than switching studies,” the agency noted.

The FDA is now calling for commentary on these draft recommendations to be submitted by Aug. 20, 2024.

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

TOPLINE:

In men with type 2 diabetes (T2D), higher serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were associated with a lower risk for metabolic dysfunction–associated fatty liver disease (MAFLD), whereas higher progesterone levels were associated with a higher risk. In women with T2D, sex- or thyroid-related hormones were not independently associated with the risk for MAFLD.

METHODOLOGY:

• People with T2D may have FLD, and this study explored the link between sex-related and thyroid-related hormone levels and MAFLD to explore and confirm risk factors.
• The researchers used a 2020 definition of MAFLD, now defined in patients as both hepatic steatosis and the presence of overweight/obesity, T2D, or evidence of metabolic dysfunction in lean individuals.
• This cross-sectional study conducted in one hospital in China included 432 patients hospitalized because of T2D and its complications from January 2018 to April 2020 (median T2D duration, 6 years; mean age, 55.8 years; 247 men and 185 postmenopausal women).
• Researchers measured and later adjusted for potential confounding factors, including weight, height, waist circumference, arterial blood pressure, glycemic parameters, liver function, and lipid profiles.
• They assessed blood levels of sex and thyroid hormones by chemiluminescent immunoassays; MAFLD was diagnosed by either ultrasonography findings of hepatic steatosis or a high liver fat index score (fatty liver index > 60).

TAKEAWAY:

• Overall, 275 (63.7%) patients were diagnosed with MAFLD; after adjusting for potential confounding factors, none of the sex- and thyroid-related hormones were independently associated with the risk for MAFLD in all patients with T2D.
• In men with T2D, higher serum levels of FSH (adjusted odds ratio [aOR], 0.919; P = .019) and LH (aOR, 0.888; P = .022) were associated with a reduced risk for MAFLD.
• Higher serum levels of progesterone were associated with an increased risk for MAFLD in men with T2D (aOR, 8.069; P = .003).
• In women with T2D, sex hormones and thyroid hormones were not significantly linked to the risk of developing MAFLD.

IN PRACTICE:

“Our findings could be used to imply that screening for MAFLD and monitoring sex-related hormones are important for T2D patients, especially in men,” the authors wrote.

SOURCE:

This study was led by Weihong Lu, Xiamen Clinical Research Center for Cancer Therapy, Xiamen, China; Shangjian Li, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China; and Yuhua Li, China University of Mining & Technology-Beijing, Beijing, and was published online in BMC Endocrine Disorders.

LIMITATIONS:

Temporal sequences of the associations between sex-related and thyroid-related hormones and MAFLD were not evaluated because of the cross-sectional nature of the study. The small sample size from a single institution may have introduced selection bias. Serum levels of sex hormone-binding globulin and free testosterone were not assessed. The postmenopausal status of women in the study may have affected the ability to find sex-hormone related associations. The findings can only be limitedly extrapolated to similar patients with T2D but not the general population.

DISCLOSURES:

The study was supported by the Fujian Province Nature Science Foundations, China, and the Guiding Project on Medicine and Health in Xiamen, China. The authors declared no conflicts of interest.

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

TOPLINE:

In men with type 2 diabetes (T2D), higher serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were associated with a lower risk for metabolic dysfunction–associated fatty liver disease (MAFLD), whereas higher progesterone levels were associated with a higher risk. In women with T2D, sex- or thyroid-related hormones were not independently associated with the risk for MAFLD.

METHODOLOGY:

• People with T2D may have FLD, and this study explored the link between sex-related and thyroid-related hormone levels and MAFLD to explore and confirm risk factors.
• The researchers used a 2020 definition of MAFLD, now defined in patients as both hepatic steatosis and the presence of overweight/obesity, T2D, or evidence of metabolic dysfunction in lean individuals.
• This cross-sectional study conducted in one hospital in China included 432 patients hospitalized because of T2D and its complications from January 2018 to April 2020 (median T2D duration, 6 years; mean age, 55.8 years; 247 men and 185 postmenopausal women).
• Researchers measured and later adjusted for potential confounding factors, including weight, height, waist circumference, arterial blood pressure, glycemic parameters, liver function, and lipid profiles.
• They assessed blood levels of sex and thyroid hormones by chemiluminescent immunoassays; MAFLD was diagnosed by either ultrasonography findings of hepatic steatosis or a high liver fat index score (fatty liver index > 60).

TAKEAWAY:

• Overall, 275 (63.7%) patients were diagnosed with MAFLD; after adjusting for potential confounding factors, none of the sex- and thyroid-related hormones were independently associated with the risk for MAFLD in all patients with T2D.
• In men with T2D, higher serum levels of FSH (adjusted odds ratio [aOR], 0.919; P = .019) and LH (aOR, 0.888; P = .022) were associated with a reduced risk for MAFLD.
• Higher serum levels of progesterone were associated with an increased risk for MAFLD in men with T2D (aOR, 8.069; P = .003).
• In women with T2D, sex hormones and thyroid hormones were not significantly linked to the risk of developing MAFLD.

IN PRACTICE:

“Our findings could be used to imply that screening for MAFLD and monitoring sex-related hormones are important for T2D patients, especially in men,” the authors wrote.

SOURCE:

This study was led by Weihong Lu, Xiamen Clinical Research Center for Cancer Therapy, Xiamen, China; Shangjian Li, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China; and Yuhua Li, China University of Mining & Technology-Beijing, Beijing, and was published online in BMC Endocrine Disorders.

LIMITATIONS:

Temporal sequences of the associations between sex-related and thyroid-related hormones and MAFLD were not evaluated because of the cross-sectional nature of the study. The small sample size from a single institution may have introduced selection bias. Serum levels of sex hormone-binding globulin and free testosterone were not assessed. The postmenopausal status of women in the study may have affected the ability to find sex-hormone related associations. The findings can only be limitedly extrapolated to similar patients with T2D but not the general population.

DISCLOSURES:

The study was supported by the Fujian Province Nature Science Foundations, China, and the Guiding Project on Medicine and Health in Xiamen, China. The authors declared no conflicts of interest.

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

TOPLINE:

In men with type 2 diabetes (T2D), higher serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were associated with a lower risk for metabolic dysfunction–associated fatty liver disease (MAFLD), whereas higher progesterone levels were associated with a higher risk. In women with T2D, sex- or thyroid-related hormones were not independently associated with the risk for MAFLD.

METHODOLOGY:

• People with T2D may have FLD, and this study explored the link between sex-related and thyroid-related hormone levels and MAFLD to explore and confirm risk factors.
• The researchers used a 2020 definition of MAFLD, now defined in patients as both hepatic steatosis and the presence of overweight/obesity, T2D, or evidence of metabolic dysfunction in lean individuals.
• This cross-sectional study conducted in one hospital in China included 432 patients hospitalized because of T2D and its complications from January 2018 to April 2020 (median T2D duration, 6 years; mean age, 55.8 years; 247 men and 185 postmenopausal women).
• Researchers measured and later adjusted for potential confounding factors, including weight, height, waist circumference, arterial blood pressure, glycemic parameters, liver function, and lipid profiles.
• They assessed blood levels of sex and thyroid hormones by chemiluminescent immunoassays; MAFLD was diagnosed by either ultrasonography findings of hepatic steatosis or a high liver fat index score (fatty liver index > 60).

TAKEAWAY:

• Overall, 275 (63.7%) patients were diagnosed with MAFLD; after adjusting for potential confounding factors, none of the sex- and thyroid-related hormones were independently associated with the risk for MAFLD in all patients with T2D.
• In men with T2D, higher serum levels of FSH (adjusted odds ratio [aOR], 0.919; P = .019) and LH (aOR, 0.888; P = .022) were associated with a reduced risk for MAFLD.
• Higher serum levels of progesterone were associated with an increased risk for MAFLD in men with T2D (aOR, 8.069; P = .003).
• In women with T2D, sex hormones and thyroid hormones were not significantly linked to the risk of developing MAFLD.

IN PRACTICE:

“Our findings could be used to imply that screening for MAFLD and monitoring sex-related hormones are important for T2D patients, especially in men,” the authors wrote.

SOURCE:

This study was led by Weihong Lu, Xiamen Clinical Research Center for Cancer Therapy, Xiamen, China; Shangjian Li, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China; and Yuhua Li, China University of Mining & Technology-Beijing, Beijing, and was published online in BMC Endocrine Disorders.

LIMITATIONS:

Temporal sequences of the associations between sex-related and thyroid-related hormones and MAFLD were not evaluated because of the cross-sectional nature of the study. The small sample size from a single institution may have introduced selection bias. Serum levels of sex hormone-binding globulin and free testosterone were not assessed. The postmenopausal status of women in the study may have affected the ability to find sex-hormone related associations. The findings can only be limitedly extrapolated to similar patients with T2D but not the general population.

DISCLOSURES:

The study was supported by the Fujian Province Nature Science Foundations, China, and the Guiding Project on Medicine and Health in Xiamen, China. The authors declared no conflicts of interest.

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

TOPLINE:

An experimental pancreatic gene therapy given to a mouse model of obesity as a one-time, single-dose treatment showed improvements in body composition and fasting glucose comparable with those achieved with the glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide, without the reversal of fat-loss and glycemia improvements that are a key concern with the withdrawal of GLP-1 receptor agonist drugs.

METHODOLOGY:

• The adeno-associated virus–based GLP-1 pancreatic gene therapy is designed to induce durable islet production of GLP-1 peptides that could, in theory, negate the need for regular injections or dosing of conventional GLP-1 receptor agonist drugs.
• With initial preclinical research showing benefits in Yucatan pigs, the authors tested the pancreatic gene therapy in mice representing a validated model of diet-induced obesity.
• The mice were randomized to receive either a single-dose administration of the pancreatic gene therapy (n = 10), daily subcutaneous semaglutide injections (n = 10; 10 nmol/kg/d for 4 weeks), pancreatic gene therapy placebo (n = 8), or a semaglutide placebo (n = 8).
• The gene therapy is designed to be delivered directly to the pancreas with a needle puncture, using a proprietary endoscopic delivery method that is similar to procedures commonly performed by gastrointestinal endoscopists, limiting systemic exposure.
• At 4 weeks, semaglutide was discontinued, and 5 of the 10 mice in that group were randomized to the gene therapy, while the other 5 received placebo.

TAKEAWAY:

• At week 4, the pancreatic gene therapy arm had a reduction in fat mass of 21%, compared with 16% with semaglutide (P < .05; both P < .0001 vs placebo)
• The pancreatic gene therapy and semaglutide groups each preserved lean mass, with a loss of only 5% of body weight (both P < .0001 vs placebo).
• At week 8, mice withdrawn from semaglutide had nearly a full reversal of the fat and lean mass losses observed at 4 weeks, returning to within 1% and 2% below baseline, respectively, while the semaglutide-withdrawn mice treated with gene therapy maintained a fat reduction of 17% (P < .01) and lean mass of 5% (P < .0001).
• Significant improvements in fasting glucose were observed in the gene therapy and semaglutide-treated mice at week 4 (both 18%; P < .0001).
• While semaglutide-withdrawal resulted in a rebound of fasting glucose to baseline at week 8, those who had initially received gene therapy or were switched over to the therapy maintained fasting glucose reductions of 21% and 22% at 8 weeks (P < .0001 and P < .001), respectively.
• No indications of pancreatic inflammation or injury were observed in any of the groups.

IN PRACTICE:

The results suggest the therapy could represent “a reliable, ‘off ramp’ from chronic GLP-1 drugs that allows people to maintain the weight loss and blood sugar benefits, even as they stop taking these medicines,” said first author Harith Rajagopalan, MD, PhD, cofounder and chief executive officer of Fractyl Health, which is developing the gene therapy, in a press statement issued by the company.

The therapy is being developed as a candidate for the treatment of type 2 diabetes and plans are underway for the first in-human study in type 2 diabetes in 2025, Dr. Rajagopalan noted while presenting the results at the American Diabetes Association (ADA)’s 84th scientific sessions.
 

SOURCE:

The study was presented on June 23, 2024, at the annual meeting of the ADA’s 84th scientific sessions (Abstract #261-OR).

LIMITATIONS:

The pancreatic gene therapy is in early development and has not been assessed by any regulatory body for investigational or commercial use.

Asked by an audience member at the ADA presentation if the therapy would be reversible if complications were to arise, Dr. Rajagopalan responded that “there are ways to tune this effect in order to prevent complications from occurring, which we will discuss in due course.”

Also asked about the potential for a positive feedback loop with GLP-1 signaling and insulin signaling, Dr. Rajagopalan noted that “I don’t believe that we have seen any evidence of that risk so far. One could hypothesize, but we have not seen anything [in that regard] that would be a cause for concern.”
 

DISCLOSURES:

The study was funded by Fractyl Health, and Dr. Rajagopalan and the authors declared being employees and stockholders/shareholders of the company.

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

TOPLINE:

An experimental pancreatic gene therapy given to a mouse model of obesity as a one-time, single-dose treatment showed improvements in body composition and fasting glucose comparable with those achieved with the glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide, without the reversal of fat-loss and glycemia improvements that are a key concern with the withdrawal of GLP-1 receptor agonist drugs.

METHODOLOGY:

• The adeno-associated virus–based GLP-1 pancreatic gene therapy is designed to induce durable islet production of GLP-1 peptides that could, in theory, negate the need for regular injections or dosing of conventional GLP-1 receptor agonist drugs.
• With initial preclinical research showing benefits in Yucatan pigs, the authors tested the pancreatic gene therapy in mice representing a validated model of diet-induced obesity.
• The mice were randomized to receive either a single-dose administration of the pancreatic gene therapy (n = 10), daily subcutaneous semaglutide injections (n = 10; 10 nmol/kg/d for 4 weeks), pancreatic gene therapy placebo (n = 8), or a semaglutide placebo (n = 8).
• The gene therapy is designed to be delivered directly to the pancreas with a needle puncture, using a proprietary endoscopic delivery method that is similar to procedures commonly performed by gastrointestinal endoscopists, limiting systemic exposure.
• At 4 weeks, semaglutide was discontinued, and 5 of the 10 mice in that group were randomized to the gene therapy, while the other 5 received placebo.

TAKEAWAY:

• At week 4, the pancreatic gene therapy arm had a reduction in fat mass of 21%, compared with 16% with semaglutide (P < .05; both P < .0001 vs placebo)
• The pancreatic gene therapy and semaglutide groups each preserved lean mass, with a loss of only 5% of body weight (both P < .0001 vs placebo).
• At week 8, mice withdrawn from semaglutide had nearly a full reversal of the fat and lean mass losses observed at 4 weeks, returning to within 1% and 2% below baseline, respectively, while the semaglutide-withdrawn mice treated with gene therapy maintained a fat reduction of 17% (P < .01) and lean mass of 5% (P < .0001).
• Significant improvements in fasting glucose were observed in the gene therapy and semaglutide-treated mice at week 4 (both 18%; P < .0001).
• While semaglutide-withdrawal resulted in a rebound of fasting glucose to baseline at week 8, those who had initially received gene therapy or were switched over to the therapy maintained fasting glucose reductions of 21% and 22% at 8 weeks (P < .0001 and P < .001), respectively.
• No indications of pancreatic inflammation or injury were observed in any of the groups.

IN PRACTICE:

The results suggest the therapy could represent “a reliable, ‘off ramp’ from chronic GLP-1 drugs that allows people to maintain the weight loss and blood sugar benefits, even as they stop taking these medicines,” said first author Harith Rajagopalan, MD, PhD, cofounder and chief executive officer of Fractyl Health, which is developing the gene therapy, in a press statement issued by the company.

The therapy is being developed as a candidate for the treatment of type 2 diabetes and plans are underway for the first in-human study in type 2 diabetes in 2025, Dr. Rajagopalan noted while presenting the results at the American Diabetes Association (ADA)’s 84th scientific sessions.
 

SOURCE:

The study was presented on June 23, 2024, at the annual meeting of the ADA’s 84th scientific sessions (Abstract #261-OR).

LIMITATIONS:

The pancreatic gene therapy is in early development and has not been assessed by any regulatory body for investigational or commercial use.

Asked by an audience member at the ADA presentation if the therapy would be reversible if complications were to arise, Dr. Rajagopalan responded that “there are ways to tune this effect in order to prevent complications from occurring, which we will discuss in due course.”

Also asked about the potential for a positive feedback loop with GLP-1 signaling and insulin signaling, Dr. Rajagopalan noted that “I don’t believe that we have seen any evidence of that risk so far. One could hypothesize, but we have not seen anything [in that regard] that would be a cause for concern.”
 

DISCLOSURES:

The study was funded by Fractyl Health, and Dr. Rajagopalan and the authors declared being employees and stockholders/shareholders of the company.

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

TOPLINE:

An experimental pancreatic gene therapy given to a mouse model of obesity as a one-time, single-dose treatment showed improvements in body composition and fasting glucose comparable with those achieved with the glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide, without the reversal of fat-loss and glycemia improvements that are a key concern with the withdrawal of GLP-1 receptor agonist drugs.

METHODOLOGY:

• The adeno-associated virus–based GLP-1 pancreatic gene therapy is designed to induce durable islet production of GLP-1 peptides that could, in theory, negate the need for regular injections or dosing of conventional GLP-1 receptor agonist drugs.
• With initial preclinical research showing benefits in Yucatan pigs, the authors tested the pancreatic gene therapy in mice representing a validated model of diet-induced obesity.
• The mice were randomized to receive either a single-dose administration of the pancreatic gene therapy (n = 10), daily subcutaneous semaglutide injections (n = 10; 10 nmol/kg/d for 4 weeks), pancreatic gene therapy placebo (n = 8), or a semaglutide placebo (n = 8).
• The gene therapy is designed to be delivered directly to the pancreas with a needle puncture, using a proprietary endoscopic delivery method that is similar to procedures commonly performed by gastrointestinal endoscopists, limiting systemic exposure.
• At 4 weeks, semaglutide was discontinued, and 5 of the 10 mice in that group were randomized to the gene therapy, while the other 5 received placebo.

TAKEAWAY:

• At week 4, the pancreatic gene therapy arm had a reduction in fat mass of 21%, compared with 16% with semaglutide (P < .05; both P < .0001 vs placebo)
• The pancreatic gene therapy and semaglutide groups each preserved lean mass, with a loss of only 5% of body weight (both P < .0001 vs placebo).
• At week 8, mice withdrawn from semaglutide had nearly a full reversal of the fat and lean mass losses observed at 4 weeks, returning to within 1% and 2% below baseline, respectively, while the semaglutide-withdrawn mice treated with gene therapy maintained a fat reduction of 17% (P < .01) and lean mass of 5% (P < .0001).
• Significant improvements in fasting glucose were observed in the gene therapy and semaglutide-treated mice at week 4 (both 18%; P < .0001).
• While semaglutide-withdrawal resulted in a rebound of fasting glucose to baseline at week 8, those who had initially received gene therapy or were switched over to the therapy maintained fasting glucose reductions of 21% and 22% at 8 weeks (P < .0001 and P < .001), respectively.
• No indications of pancreatic inflammation or injury were observed in any of the groups.

IN PRACTICE:

The results suggest the therapy could represent “a reliable, ‘off ramp’ from chronic GLP-1 drugs that allows people to maintain the weight loss and blood sugar benefits, even as they stop taking these medicines,” said first author Harith Rajagopalan, MD, PhD, cofounder and chief executive officer of Fractyl Health, which is developing the gene therapy, in a press statement issued by the company.

The therapy is being developed as a candidate for the treatment of type 2 diabetes and plans are underway for the first in-human study in type 2 diabetes in 2025, Dr. Rajagopalan noted while presenting the results at the American Diabetes Association (ADA)’s 84th scientific sessions.
 

SOURCE:

The study was presented on June 23, 2024, at the annual meeting of the ADA’s 84th scientific sessions (Abstract #261-OR).

LIMITATIONS:

The pancreatic gene therapy is in early development and has not been assessed by any regulatory body for investigational or commercial use.

Asked by an audience member at the ADA presentation if the therapy would be reversible if complications were to arise, Dr. Rajagopalan responded that “there are ways to tune this effect in order to prevent complications from occurring, which we will discuss in due course.”

Also asked about the potential for a positive feedback loop with GLP-1 signaling and insulin signaling, Dr. Rajagopalan noted that “I don’t believe that we have seen any evidence of that risk so far. One could hypothesize, but we have not seen anything [in that regard] that would be a cause for concern.”
 

DISCLOSURES:

The study was funded by Fractyl Health, and Dr. Rajagopalan and the authors declared being employees and stockholders/shareholders of the company.

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

Halifax, Nova Scotia; American Samoa; Queens, New York; Lansing, Michigan; Gurugram, India. I often ask patients where they’re from. Practicing in San Diego, the answers are a geography lesson. People from around the world come here. I sometimes add the more interesting question: How’d you end up here? Many took the three highways to San Diego: the Navy, the defense industry (like General Dynamics), or followed a partner. My Queens patient had a better answer: Super Bowl XXII. On Sunday, Jan. 31st, 1988, the Redskins played the Broncos in San Diego. John Elway and the Broncos lost, but it didn’t matter. “I was scrapin’ the ice off my windshield that Monday morning when I thought, that’s it. I’m done! I drove to the garage where I worked and quit on the spot. Then I drove home and packed my bags.”

In a paper on how to make life decisions, this guy would be Exhibit A: “Don’t overthink it.” That approach might not be suitable for everyone, or for every decision. It might actually be an example of how not to make life decisions (more on that later). But, is there a best way to go about making big life decisions?

The first treatise on this subject was a paper by one Franklin, Ben in 1772. Providing advice to a friend on how to make a career decision, Franklin argued: “My way is to divide half a sheet of paper by a line into two columns; writing over the one Pro and over the other Con.” This “moral algebra” as he called it was a framework to put rigor to a messy, organic problem.

wrawecihokilospeslofriphohobuchibiletutawrospepehophastephechewrubrelopadrocosleswobislimimumesoclupiuiposwocihistithophabru

The flaw in this method is that in the end you have two lists. Then what? Do the length of the lists decide? What if some factors are more important? Well, let’s add tools to help. You could use a spreadsheet and assign weights to each variable. Then sum the values and choose based on that. So if “not scraping ice off your windshield” is twice as important as “doubling your rent,” then you’ve got your answer. But what if you aren’t good at estimating how important things are? Actually, most of us are pretty awful at assigning weights to life variables – having bags of money is the consummate example. Seems important, but because of habituation, it turns out to not be sustainable. Note Exhibit B, our wealthy neighbor who owns a Lambo and G-Wagen (AMG squared, of course), who just parked a Cybertruck in his driveway. Realizing the risk of depending on peoples’ flawed judgment, companies instead use statistical modeling called bootstrap aggregating to “vote” on the weights for variables in a prediction. If you aren’t sure how important a new Rivian or walking to the beach would be, a model can answer that for you! It’s a bit disconcerting, I know. I mean, how can a model know what we’d like? Wait, isn’t that how Netflix picks stuff for you? Exactly.

Ok, so why don’t we just ask our friendly personal AI? “OK, ChatGPT, given what you know about me, where can I have it all?” Alas, here we slam into a glass wall. It seems the answer is out there but even our life-changing magical AI tools fail us. Mathematically, it is impossible to have it all. An illustrative example of this is called the economic “impossible trinity problem.” Even the most sophisticated algorithm cannot find an optional solution to some trinities such as fixed foreign exchange rate, free capital movement, and an independent monetary policy. Economists have concluded you must trade off one to have the other two. Impossible trinities are common in economics and in life. Armistead Maupin in his “Tales of the City” codifies it as Mona’s Law, the essence of which is: You cannot have the perfect job, the perfect partner, and the perfect house at the same time. (See Exhibit C, one Tom Brady).

[embed:render:related:node:267456]

This brings me to my final point, hard decisions are matters of the heart and experiencing life is the best way to understand its beautiful chaos. If making rash judgments is ill-advised and using technology cannot solve all problems (try asking your AI buddy for the square root of 2 as a fraction) what tools can we use? Maybe try reading more novels. They allow us to experience multiple lifetimes in a short time, which is what we need to learn what matters. Reading Dorothea’s choice at the end of “Middlemarch” is a nice example. Should she give up Lowick Manor and marry the penniless Ladislaw or keep it and use her wealth to help others? Seeing her struggle helps us understand how to answer questions like: Should I give up my academic practice or marry that guy or move to Texas? These cannot be reduced to arithmetic. The only way to know is to know as much of life as possible.

My last visit with my Queens patient was our last together. He’s divorced and moving from San Diego to Gallatin, Tennessee. “I’ve paid my last taxes to California, Doc. I decided that’s it, I’m done!” Perhaps he should have read “The Grapes of Wrath” before he set out for California in the first place.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

Halifax, Nova Scotia; American Samoa; Queens, New York; Lansing, Michigan; Gurugram, India. I often ask patients where they’re from. Practicing in San Diego, the answers are a geography lesson. People from around the world come here. I sometimes add the more interesting question: How’d you end up here? Many took the three highways to San Diego: the Navy, the defense industry (like General Dynamics), or followed a partner. My Queens patient had a better answer: Super Bowl XXII. On Sunday, Jan. 31st, 1988, the Redskins played the Broncos in San Diego. John Elway and the Broncos lost, but it didn’t matter. “I was scrapin’ the ice off my windshield that Monday morning when I thought, that’s it. I’m done! I drove to the garage where I worked and quit on the spot. Then I drove home and packed my bags.”

In a paper on how to make life decisions, this guy would be Exhibit A: “Don’t overthink it.” That approach might not be suitable for everyone, or for every decision. It might actually be an example of how not to make life decisions (more on that later). But, is there a best way to go about making big life decisions?

The first treatise on this subject was a paper by one Franklin, Ben in 1772. Providing advice to a friend on how to make a career decision, Franklin argued: “My way is to divide half a sheet of paper by a line into two columns; writing over the one Pro and over the other Con.” This “moral algebra” as he called it was a framework to put rigor to a messy, organic problem.

wrawecihokilospeslofriphohobuchibiletutawrospepehophastephechewrubrelopadrocosleswobislimimumesoclupiuiposwocihistithophabru

The flaw in this method is that in the end you have two lists. Then what? Do the length of the lists decide? What if some factors are more important? Well, let’s add tools to help. You could use a spreadsheet and assign weights to each variable. Then sum the values and choose based on that. So if “not scraping ice off your windshield” is twice as important as “doubling your rent,” then you’ve got your answer. But what if you aren’t good at estimating how important things are? Actually, most of us are pretty awful at assigning weights to life variables – having bags of money is the consummate example. Seems important, but because of habituation, it turns out to not be sustainable. Note Exhibit B, our wealthy neighbor who owns a Lambo and G-Wagen (AMG squared, of course), who just parked a Cybertruck in his driveway. Realizing the risk of depending on peoples’ flawed judgment, companies instead use statistical modeling called bootstrap aggregating to “vote” on the weights for variables in a prediction. If you aren’t sure how important a new Rivian or walking to the beach would be, a model can answer that for you! It’s a bit disconcerting, I know. I mean, how can a model know what we’d like? Wait, isn’t that how Netflix picks stuff for you? Exactly.

Ok, so why don’t we just ask our friendly personal AI? “OK, ChatGPT, given what you know about me, where can I have it all?” Alas, here we slam into a glass wall. It seems the answer is out there but even our life-changing magical AI tools fail us. Mathematically, it is impossible to have it all. An illustrative example of this is called the economic “impossible trinity problem.” Even the most sophisticated algorithm cannot find an optional solution to some trinities such as fixed foreign exchange rate, free capital movement, and an independent monetary policy. Economists have concluded you must trade off one to have the other two. Impossible trinities are common in economics and in life. Armistead Maupin in his “Tales of the City” codifies it as Mona’s Law, the essence of which is: You cannot have the perfect job, the perfect partner, and the perfect house at the same time. (See Exhibit C, one Tom Brady).

[embed:render:related:node:267456]

This brings me to my final point, hard decisions are matters of the heart and experiencing life is the best way to understand its beautiful chaos. If making rash judgments is ill-advised and using technology cannot solve all problems (try asking your AI buddy for the square root of 2 as a fraction) what tools can we use? Maybe try reading more novels. They allow us to experience multiple lifetimes in a short time, which is what we need to learn what matters. Reading Dorothea’s choice at the end of “Middlemarch” is a nice example. Should she give up Lowick Manor and marry the penniless Ladislaw or keep it and use her wealth to help others? Seeing her struggle helps us understand how to answer questions like: Should I give up my academic practice or marry that guy or move to Texas? These cannot be reduced to arithmetic. The only way to know is to know as much of life as possible.

My last visit with my Queens patient was our last together. He’s divorced and moving from San Diego to Gallatin, Tennessee. “I’ve paid my last taxes to California, Doc. I decided that’s it, I’m done!” Perhaps he should have read “The Grapes of Wrath” before he set out for California in the first place.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

Halifax, Nova Scotia; American Samoa; Queens, New York; Lansing, Michigan; Gurugram, India. I often ask patients where they’re from. Practicing in San Diego, the answers are a geography lesson. People from around the world come here. I sometimes add the more interesting question: How’d you end up here? Many took the three highways to San Diego: the Navy, the defense industry (like General Dynamics), or followed a partner. My Queens patient had a better answer: Super Bowl XXII. On Sunday, Jan. 31st, 1988, the Redskins played the Broncos in San Diego. John Elway and the Broncos lost, but it didn’t matter. “I was scrapin’ the ice off my windshield that Monday morning when I thought, that’s it. I’m done! I drove to the garage where I worked and quit on the spot. Then I drove home and packed my bags.”

In a paper on how to make life decisions, this guy would be Exhibit A: “Don’t overthink it.” That approach might not be suitable for everyone, or for every decision. It might actually be an example of how not to make life decisions (more on that later). But, is there a best way to go about making big life decisions?

The first treatise on this subject was a paper by one Franklin, Ben in 1772. Providing advice to a friend on how to make a career decision, Franklin argued: “My way is to divide half a sheet of paper by a line into two columns; writing over the one Pro and over the other Con.” This “moral algebra” as he called it was a framework to put rigor to a messy, organic problem.

wrawecihokilospeslofriphohobuchibiletutawrospepehophastephechewrubrelopadrocosleswobislimimumesoclupiuiposwocihistithophabru

The flaw in this method is that in the end you have two lists. Then what? Do the length of the lists decide? What if some factors are more important? Well, let’s add tools to help. You could use a spreadsheet and assign weights to each variable. Then sum the values and choose based on that. So if “not scraping ice off your windshield” is twice as important as “doubling your rent,” then you’ve got your answer. But what if you aren’t good at estimating how important things are? Actually, most of us are pretty awful at assigning weights to life variables – having bags of money is the consummate example. Seems important, but because of habituation, it turns out to not be sustainable. Note Exhibit B, our wealthy neighbor who owns a Lambo and G-Wagen (AMG squared, of course), who just parked a Cybertruck in his driveway. Realizing the risk of depending on peoples’ flawed judgment, companies instead use statistical modeling called bootstrap aggregating to “vote” on the weights for variables in a prediction. If you aren’t sure how important a new Rivian or walking to the beach would be, a model can answer that for you! It’s a bit disconcerting, I know. I mean, how can a model know what we’d like? Wait, isn’t that how Netflix picks stuff for you? Exactly.

Ok, so why don’t we just ask our friendly personal AI? “OK, ChatGPT, given what you know about me, where can I have it all?” Alas, here we slam into a glass wall. It seems the answer is out there but even our life-changing magical AI tools fail us. Mathematically, it is impossible to have it all. An illustrative example of this is called the economic “impossible trinity problem.” Even the most sophisticated algorithm cannot find an optional solution to some trinities such as fixed foreign exchange rate, free capital movement, and an independent monetary policy. Economists have concluded you must trade off one to have the other two. Impossible trinities are common in economics and in life. Armistead Maupin in his “Tales of the City” codifies it as Mona’s Law, the essence of which is: You cannot have the perfect job, the perfect partner, and the perfect house at the same time. (See Exhibit C, one Tom Brady).

[embed:render:related:node:267456]

This brings me to my final point, hard decisions are matters of the heart and experiencing life is the best way to understand its beautiful chaos. If making rash judgments is ill-advised and using technology cannot solve all problems (try asking your AI buddy for the square root of 2 as a fraction) what tools can we use? Maybe try reading more novels. They allow us to experience multiple lifetimes in a short time, which is what we need to learn what matters. Reading Dorothea’s choice at the end of “Middlemarch” is a nice example. Should she give up Lowick Manor and marry the penniless Ladislaw or keep it and use her wealth to help others? Seeing her struggle helps us understand how to answer questions like: Should I give up my academic practice or marry that guy or move to Texas? These cannot be reduced to arithmetic. The only way to know is to know as much of life as possible.

My last visit with my Queens patient was our last together. He’s divorced and moving from San Diego to Gallatin, Tennessee. “I’ve paid my last taxes to California, Doc. I decided that’s it, I’m done!” Perhaps he should have read “The Grapes of Wrath” before he set out for California in the first place.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

MONTREAL – Levels of neurofilament light chain (Nfl) may be a biomarker of chemotherapy-induced peripheral neurotoxicity (CIPN), new research suggests.

Investigators found Nfl levels increased in cancer patients following a first infusion of the medication paclitaxel and corresponded to neuropathy severity 6-12 months post-treatment, suggesting the blood protein may provide an early CIPN biomarker.

“Nfl after a single cycle could detect axonal degeneration,” said lead investigator Masarra Joda, a researcher and PhD candidate at the University of Sydney in Australia. She added that “quantification of Nfl may provide a clinically useful marker of emerging neurotoxicity in patients vulnerable to CIPN.”

The findings were presented at the Peripheral Nerve Society (PNS) 2024 annual meeting.
 

Common, Burdensome Side Effect

A common side effect of chemotherapy, CIPN manifests as sensory neuropathy and causes degeneration of the peripheral axons. A protein biomarker of axonal degeneration, Nfl has previously been investigated as a way of identifying patients at risk of CIPN.

The goal of the current study was to identify the potential link between Nfl with neurophysiological markers of axon degeneration in patients receiving the neurotoxin chemotherapy paclitaxel.

The study included 93 cancer patients. All were assessed at the beginning, middle, and end of treatment. CIPN was assessed using blood samples of Nfl and the Total Neuropathy Score (TNS), the Common Terminology Criteria for Adverse Events (CTCAE) neuropathy scale, and patient-reported measures using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Chemotherapy-Induced Peripheral Neuropathy Module (EORTC-CIPN20).

Axonal degeneration was measured with neurophysiological tests including sural nerve compound sensory action potential (CSAP) for the lower limbs, and sensory median nerve CSAP, as well as stimulus threshold testing, for the upper limbs. 

Almost all of study participants (97%) were female. The majority (66%) had breast cancer and 30% had gynecological cancer. Most (73%) were receiving a weekly regimen of paclitaxel, and the remainder were treated with taxanes plus platinum once every 3 weeks. By the end of treatment, 82% of the patients had developed CIPN, which was mild in 44% and moderate/severe in 38%. 

Nfl levels increased significantly from baseline to after the first dose of chemotherapy (P < .001), “highlighting that nerve damage occurs from the very beginning of treatment,” senior investigator Susanna Park, PhD, told this news organization. 

In addition, “patients with higher Nfl levels after a single paclitaxel treatment had greater neuropathy at the end of treatment (higher EORTC scores [P ≤ .026], and higher TNS scores [P ≤ .00]),” added Dr. Park, who is associate professor at the University of Sydney.

“Importantly, we also looked at long-term outcomes beyond the end of chemotherapy, because chronic neuropathy produces a significant burden in cancer survivors,” said Dr. Park. 

“Among a total of 44 patients who completed the 6- to 12-month post-treatment follow-up, NfL levels after a single treatment were linked to severity of nerve damage quantified with neurophysiological tests, and greater Nfl levels at mid-treatment were correlated with worse patient and neurologically graded neuropathy at 6-12 months.”

Dr. Park said the results suggest that NfL may provide a biomarker of long-term axon damage and that Nfl assays “may enable clinicians to evaluate the risk of long-term toxicity early during paclitaxel treatment to hopefully provide clinically significant information to guide better treatment titration.” 

Currently, she said, CIPN is a prominent cause of dose reduction and early chemotherapy cessation. 

“For example, in early breast cancer around 25% of patients experience a dose reduction due to the severity of neuropathy symptoms.” But, she said, “there is no standardized way of identifying which patients are at risk of long-term neuropathy and therefore, may benefit more from dose reduction. In this setting, a biomarker such as Nfl could provide oncologists with more information about the risk of long-term toxicity and take that into account in dose decision-making.” 

For some cancers, she added, there are multiple potential therapy options.

“A biomarker such as NfL could assist in determining risk-benefit profile in terms of switching to alternate therapies. However, further studies will be needed to fully define the utility of NfL as a biomarker of paclitaxel neuropathy.” 
 

Promising Research

Commenting on the research for this news organization, Maryam Lustberg, MD, associate professor, director of the Center for Breast Cancer at Smilow Cancer Hospital and Yale Cancer Center, and chief of Breast Medical Oncology at Yale Cancer Center, in New Haven, Connecticut, said the study “builds on a body of work previously reported by others showing that neurofilament light chains as detected in the blood can be associated with early signs of neurotoxic injury.” 

She added that the research “is promising, since existing clinical and patient-reported measures tend to under-detect chemotherapy-induced neuropathy until more permanent injury might have occurred.” 

Dr. Lustberg, who is immediate past president of the Multinational Association of Supportive Care in Cancer, said future studies are needed before Nfl testing can be implemented in routine practice, but that “early detection will allow earlier initiation of supportive care strategies such as physical therapy and exercise, as well as dose modifications, which may be helpful for preventing permanent damage and improving quality of life.” 

The investigators and Dr. Lustberg report no relevant financial relationships.

A version of this article appeared on Medscape.com.

MONTREAL – Levels of neurofilament light chain (Nfl) may be a biomarker of chemotherapy-induced peripheral neurotoxicity (CIPN), new research suggests.

Investigators found Nfl levels increased in cancer patients following a first infusion of the medication paclitaxel and corresponded to neuropathy severity 6-12 months post-treatment, suggesting the blood protein may provide an early CIPN biomarker.

“Nfl after a single cycle could detect axonal degeneration,” said lead investigator Masarra Joda, a researcher and PhD candidate at the University of Sydney in Australia. She added that “quantification of Nfl may provide a clinically useful marker of emerging neurotoxicity in patients vulnerable to CIPN.”

The findings were presented at the Peripheral Nerve Society (PNS) 2024 annual meeting.
 

Common, Burdensome Side Effect

A common side effect of chemotherapy, CIPN manifests as sensory neuropathy and causes degeneration of the peripheral axons. A protein biomarker of axonal degeneration, Nfl has previously been investigated as a way of identifying patients at risk of CIPN.

The goal of the current study was to identify the potential link between Nfl with neurophysiological markers of axon degeneration in patients receiving the neurotoxin chemotherapy paclitaxel.

The study included 93 cancer patients. All were assessed at the beginning, middle, and end of treatment. CIPN was assessed using blood samples of Nfl and the Total Neuropathy Score (TNS), the Common Terminology Criteria for Adverse Events (CTCAE) neuropathy scale, and patient-reported measures using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Chemotherapy-Induced Peripheral Neuropathy Module (EORTC-CIPN20).

Axonal degeneration was measured with neurophysiological tests including sural nerve compound sensory action potential (CSAP) for the lower limbs, and sensory median nerve CSAP, as well as stimulus threshold testing, for the upper limbs. 

Almost all of study participants (97%) were female. The majority (66%) had breast cancer and 30% had gynecological cancer. Most (73%) were receiving a weekly regimen of paclitaxel, and the remainder were treated with taxanes plus platinum once every 3 weeks. By the end of treatment, 82% of the patients had developed CIPN, which was mild in 44% and moderate/severe in 38%. 

Nfl levels increased significantly from baseline to after the first dose of chemotherapy (P < .001), “highlighting that nerve damage occurs from the very beginning of treatment,” senior investigator Susanna Park, PhD, told this news organization. 

In addition, “patients with higher Nfl levels after a single paclitaxel treatment had greater neuropathy at the end of treatment (higher EORTC scores [P ≤ .026], and higher TNS scores [P ≤ .00]),” added Dr. Park, who is associate professor at the University of Sydney.

“Importantly, we also looked at long-term outcomes beyond the end of chemotherapy, because chronic neuropathy produces a significant burden in cancer survivors,” said Dr. Park. 

“Among a total of 44 patients who completed the 6- to 12-month post-treatment follow-up, NfL levels after a single treatment were linked to severity of nerve damage quantified with neurophysiological tests, and greater Nfl levels at mid-treatment were correlated with worse patient and neurologically graded neuropathy at 6-12 months.”

Dr. Park said the results suggest that NfL may provide a biomarker of long-term axon damage and that Nfl assays “may enable clinicians to evaluate the risk of long-term toxicity early during paclitaxel treatment to hopefully provide clinically significant information to guide better treatment titration.” 

Currently, she said, CIPN is a prominent cause of dose reduction and early chemotherapy cessation. 

“For example, in early breast cancer around 25% of patients experience a dose reduction due to the severity of neuropathy symptoms.” But, she said, “there is no standardized way of identifying which patients are at risk of long-term neuropathy and therefore, may benefit more from dose reduction. In this setting, a biomarker such as Nfl could provide oncologists with more information about the risk of long-term toxicity and take that into account in dose decision-making.” 

For some cancers, she added, there are multiple potential therapy options.

“A biomarker such as NfL could assist in determining risk-benefit profile in terms of switching to alternate therapies. However, further studies will be needed to fully define the utility of NfL as a biomarker of paclitaxel neuropathy.” 
 

Promising Research

Commenting on the research for this news organization, Maryam Lustberg, MD, associate professor, director of the Center for Breast Cancer at Smilow Cancer Hospital and Yale Cancer Center, and chief of Breast Medical Oncology at Yale Cancer Center, in New Haven, Connecticut, said the study “builds on a body of work previously reported by others showing that neurofilament light chains as detected in the blood can be associated with early signs of neurotoxic injury.” 

She added that the research “is promising, since existing clinical and patient-reported measures tend to under-detect chemotherapy-induced neuropathy until more permanent injury might have occurred.” 

Dr. Lustberg, who is immediate past president of the Multinational Association of Supportive Care in Cancer, said future studies are needed before Nfl testing can be implemented in routine practice, but that “early detection will allow earlier initiation of supportive care strategies such as physical therapy and exercise, as well as dose modifications, which may be helpful for preventing permanent damage and improving quality of life.” 

The investigators and Dr. Lustberg report no relevant financial relationships.

A version of this article appeared on Medscape.com.

MONTREAL – Levels of neurofilament light chain (Nfl) may be a biomarker of chemotherapy-induced peripheral neurotoxicity (CIPN), new research suggests.

Investigators found Nfl levels increased in cancer patients following a first infusion of the medication paclitaxel and corresponded to neuropathy severity 6-12 months post-treatment, suggesting the blood protein may provide an early CIPN biomarker.

“Nfl after a single cycle could detect axonal degeneration,” said lead investigator Masarra Joda, a researcher and PhD candidate at the University of Sydney in Australia. She added that “quantification of Nfl may provide a clinically useful marker of emerging neurotoxicity in patients vulnerable to CIPN.”

The findings were presented at the Peripheral Nerve Society (PNS) 2024 annual meeting.
 

Common, Burdensome Side Effect

A common side effect of chemotherapy, CIPN manifests as sensory neuropathy and causes degeneration of the peripheral axons. A protein biomarker of axonal degeneration, Nfl has previously been investigated as a way of identifying patients at risk of CIPN.

The goal of the current study was to identify the potential link between Nfl with neurophysiological markers of axon degeneration in patients receiving the neurotoxin chemotherapy paclitaxel.

The study included 93 cancer patients. All were assessed at the beginning, middle, and end of treatment. CIPN was assessed using blood samples of Nfl and the Total Neuropathy Score (TNS), the Common Terminology Criteria for Adverse Events (CTCAE) neuropathy scale, and patient-reported measures using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Chemotherapy-Induced Peripheral Neuropathy Module (EORTC-CIPN20).

Axonal degeneration was measured with neurophysiological tests including sural nerve compound sensory action potential (CSAP) for the lower limbs, and sensory median nerve CSAP, as well as stimulus threshold testing, for the upper limbs. 

Almost all of study participants (97%) were female. The majority (66%) had breast cancer and 30% had gynecological cancer. Most (73%) were receiving a weekly regimen of paclitaxel, and the remainder were treated with taxanes plus platinum once every 3 weeks. By the end of treatment, 82% of the patients had developed CIPN, which was mild in 44% and moderate/severe in 38%. 

Nfl levels increased significantly from baseline to after the first dose of chemotherapy (P < .001), “highlighting that nerve damage occurs from the very beginning of treatment,” senior investigator Susanna Park, PhD, told this news organization. 

In addition, “patients with higher Nfl levels after a single paclitaxel treatment had greater neuropathy at the end of treatment (higher EORTC scores [P ≤ .026], and higher TNS scores [P ≤ .00]),” added Dr. Park, who is associate professor at the University of Sydney.

“Importantly, we also looked at long-term outcomes beyond the end of chemotherapy, because chronic neuropathy produces a significant burden in cancer survivors,” said Dr. Park. 

“Among a total of 44 patients who completed the 6- to 12-month post-treatment follow-up, NfL levels after a single treatment were linked to severity of nerve damage quantified with neurophysiological tests, and greater Nfl levels at mid-treatment were correlated with worse patient and neurologically graded neuropathy at 6-12 months.”

Dr. Park said the results suggest that NfL may provide a biomarker of long-term axon damage and that Nfl assays “may enable clinicians to evaluate the risk of long-term toxicity early during paclitaxel treatment to hopefully provide clinically significant information to guide better treatment titration.” 

Currently, she said, CIPN is a prominent cause of dose reduction and early chemotherapy cessation. 

“For example, in early breast cancer around 25% of patients experience a dose reduction due to the severity of neuropathy symptoms.” But, she said, “there is no standardized way of identifying which patients are at risk of long-term neuropathy and therefore, may benefit more from dose reduction. In this setting, a biomarker such as Nfl could provide oncologists with more information about the risk of long-term toxicity and take that into account in dose decision-making.” 

For some cancers, she added, there are multiple potential therapy options.

“A biomarker such as NfL could assist in determining risk-benefit profile in terms of switching to alternate therapies. However, further studies will be needed to fully define the utility of NfL as a biomarker of paclitaxel neuropathy.” 
 

Promising Research

Commenting on the research for this news organization, Maryam Lustberg, MD, associate professor, director of the Center for Breast Cancer at Smilow Cancer Hospital and Yale Cancer Center, and chief of Breast Medical Oncology at Yale Cancer Center, in New Haven, Connecticut, said the study “builds on a body of work previously reported by others showing that neurofilament light chains as detected in the blood can be associated with early signs of neurotoxic injury.” 

She added that the research “is promising, since existing clinical and patient-reported measures tend to under-detect chemotherapy-induced neuropathy until more permanent injury might have occurred.” 

Dr. Lustberg, who is immediate past president of the Multinational Association of Supportive Care in Cancer, said future studies are needed before Nfl testing can be implemented in routine practice, but that “early detection will allow earlier initiation of supportive care strategies such as physical therapy and exercise, as well as dose modifications, which may be helpful for preventing permanent damage and improving quality of life.” 

The investigators and Dr. Lustberg report no relevant financial relationships.

A version of this article appeared on Medscape.com.

The Centers for Medicare & Medicaid Services (CMS) has announced the conclusion of a program that provided billions in early Medicare payments to those affected by the Change Healthcare/UnitedHealth Group cyberattack last winter. The Accelerated and Advance Payment program, which began in early March to assist hospitals and practices facing significant reimbursement delays, will stop accepting applications after July 12, 2024.

CMS reported that the program advanced more than $2.55 billion in Medicare payments to > 4200 Part A providers, including hospitals, and more than $717.18 million in payments to Part B suppliers such as physicians, nonphysician practitioners, and durable medical equipment suppliers.

According to CMS, the Medicare billing system is now functioning properly, and 96% of the early payments have been recovered. The advances were to represent ≤ 30 days of typical claims payments in a 3-month period of 2023, with full repayment expected within 90 days through “automatic recoupment from Medicare claims” — no extensions allowed.

The agency took a victory lap regarding its response. “In the face of one of the most widespread cyberattacks on the US health care industry, CMS promptly took action to get providers and suppliers access to the funds they needed to continue providing patients with vital care,” CMS Administrator Chiquita Brooks-LaSure said in a statement. “Our efforts helped minimize the disruptive fallout from this incident, and we will remain vigilant to be ready to address future events.”

Ongoing Concerns from Health Care Organizations

Ben Teicher, an American Hospital Association spokesman, said that the organization hopes that CMS will be responsive if there’s more need for action after the advance payment program expires. The organization represents about 5000 hospitals, health care systems, and other providers.

“Our members report that the aftereffects of this event will likely be felt throughout the remainder of the year,” he said. According to Teicher, hospitals remain concerned about their ability to process claims and appeal denials, the safety of reconnecting to cyber services, and access to information needed to bill patients and reconcile payments.

In addition, hospitals are concerned about “financial support to mitigate the considerable costs incurred as a result of the cyberattack,” he said.

Charlene MacDonald, executive vice-president of public affairs at the Federation of American Hospitals, which represents more than 1000 for-profit hospitals, sent a statement to this news organization that said some providers “are still feeling the effects of care denials and delays caused by insurer inaction.

“We appreciate that the Administration acted within its authority to support providers during this unprecedented crisis and blunt these devastating impacts, especially because a vast majority of managed care companies failed to step up to the plate,” she said. “It is now time to shift our focus to holding plans accountable for using tactics to delay and deny needed patient care.”

Cyberattack Impact and Response

The ransom-based cyberattack against Change Healthcare/UnitedHealth Group targeted an electronic data interchange clearing house processing payer reimbursement systems, disrupting cash flows at hospitals and medical practices, and affecting patient access to prescriptions and life-saving therapy.

Change Healthcare — part of the UnitedHealth Group subsidiary Optum — processes half of all medical claims, according to a Department of Justice lawsuit. The American Hospital Association described the cyberattack as “the most significant and consequential incident of its kind” in US history.

By late March, UnitedHealth Group said nearly all medical and pharmacy claims were processing properly, while a deputy secretary of the US Department of Health & Human Services told clinicians that officials were focusing on the last group of clinicians who were facing cash-flow problems.

Still, a senior advisor with CMS told providers at that time that “we have heard from so many providers over the last several weeks who are really struggling to make ends meet right now or who are worried that they will not be able to make payroll in the weeks to come.”

Randy Dotinga is a freelance health/medical reporter and board member of the Association of Health Care Journalists.

A version of this article appeared on Medscape.com.

The Centers for Medicare & Medicaid Services (CMS) has announced the conclusion of a program that provided billions in early Medicare payments to those affected by the Change Healthcare/UnitedHealth Group cyberattack last winter. The Accelerated and Advance Payment program, which began in early March to assist hospitals and practices facing significant reimbursement delays, will stop accepting applications after July 12, 2024.

CMS reported that the program advanced more than $2.55 billion in Medicare payments to > 4200 Part A providers, including hospitals, and more than $717.18 million in payments to Part B suppliers such as physicians, nonphysician practitioners, and durable medical equipment suppliers.

According to CMS, the Medicare billing system is now functioning properly, and 96% of the early payments have been recovered. The advances were to represent ≤ 30 days of typical claims payments in a 3-month period of 2023, with full repayment expected within 90 days through “automatic recoupment from Medicare claims” — no extensions allowed.

The agency took a victory lap regarding its response. “In the face of one of the most widespread cyberattacks on the US health care industry, CMS promptly took action to get providers and suppliers access to the funds they needed to continue providing patients with vital care,” CMS Administrator Chiquita Brooks-LaSure said in a statement. “Our efforts helped minimize the disruptive fallout from this incident, and we will remain vigilant to be ready to address future events.”

Ongoing Concerns from Health Care Organizations

Ben Teicher, an American Hospital Association spokesman, said that the organization hopes that CMS will be responsive if there’s more need for action after the advance payment program expires. The organization represents about 5000 hospitals, health care systems, and other providers.

“Our members report that the aftereffects of this event will likely be felt throughout the remainder of the year,” he said. According to Teicher, hospitals remain concerned about their ability to process claims and appeal denials, the safety of reconnecting to cyber services, and access to information needed to bill patients and reconcile payments.

In addition, hospitals are concerned about “financial support to mitigate the considerable costs incurred as a result of the cyberattack,” he said.

Charlene MacDonald, executive vice-president of public affairs at the Federation of American Hospitals, which represents more than 1000 for-profit hospitals, sent a statement to this news organization that said some providers “are still feeling the effects of care denials and delays caused by insurer inaction.

“We appreciate that the Administration acted within its authority to support providers during this unprecedented crisis and blunt these devastating impacts, especially because a vast majority of managed care companies failed to step up to the plate,” she said. “It is now time to shift our focus to holding plans accountable for using tactics to delay and deny needed patient care.”

Cyberattack Impact and Response

The ransom-based cyberattack against Change Healthcare/UnitedHealth Group targeted an electronic data interchange clearing house processing payer reimbursement systems, disrupting cash flows at hospitals and medical practices, and affecting patient access to prescriptions and life-saving therapy.

Change Healthcare — part of the UnitedHealth Group subsidiary Optum — processes half of all medical claims, according to a Department of Justice lawsuit. The American Hospital Association described the cyberattack as “the most significant and consequential incident of its kind” in US history.

By late March, UnitedHealth Group said nearly all medical and pharmacy claims were processing properly, while a deputy secretary of the US Department of Health & Human Services told clinicians that officials were focusing on the last group of clinicians who were facing cash-flow problems.

Still, a senior advisor with CMS told providers at that time that “we have heard from so many providers over the last several weeks who are really struggling to make ends meet right now or who are worried that they will not be able to make payroll in the weeks to come.”

Randy Dotinga is a freelance health/medical reporter and board member of the Association of Health Care Journalists.

A version of this article appeared on Medscape.com.

The Centers for Medicare & Medicaid Services (CMS) has announced the conclusion of a program that provided billions in early Medicare payments to those affected by the Change Healthcare/UnitedHealth Group cyberattack last winter. The Accelerated and Advance Payment program, which began in early March to assist hospitals and practices facing significant reimbursement delays, will stop accepting applications after July 12, 2024.

CMS reported that the program advanced more than $2.55 billion in Medicare payments to > 4200 Part A providers, including hospitals, and more than $717.18 million in payments to Part B suppliers such as physicians, nonphysician practitioners, and durable medical equipment suppliers.

According to CMS, the Medicare billing system is now functioning properly, and 96% of the early payments have been recovered. The advances were to represent ≤ 30 days of typical claims payments in a 3-month period of 2023, with full repayment expected within 90 days through “automatic recoupment from Medicare claims” — no extensions allowed.

The agency took a victory lap regarding its response. “In the face of one of the most widespread cyberattacks on the US health care industry, CMS promptly took action to get providers and suppliers access to the funds they needed to continue providing patients with vital care,” CMS Administrator Chiquita Brooks-LaSure said in a statement. “Our efforts helped minimize the disruptive fallout from this incident, and we will remain vigilant to be ready to address future events.”

Ongoing Concerns from Health Care Organizations

Ben Teicher, an American Hospital Association spokesman, said that the organization hopes that CMS will be responsive if there’s more need for action after the advance payment program expires. The organization represents about 5000 hospitals, health care systems, and other providers.

“Our members report that the aftereffects of this event will likely be felt throughout the remainder of the year,” he said. According to Teicher, hospitals remain concerned about their ability to process claims and appeal denials, the safety of reconnecting to cyber services, and access to information needed to bill patients and reconcile payments.

In addition, hospitals are concerned about “financial support to mitigate the considerable costs incurred as a result of the cyberattack,” he said.

Charlene MacDonald, executive vice-president of public affairs at the Federation of American Hospitals, which represents more than 1000 for-profit hospitals, sent a statement to this news organization that said some providers “are still feeling the effects of care denials and delays caused by insurer inaction.

“We appreciate that the Administration acted within its authority to support providers during this unprecedented crisis and blunt these devastating impacts, especially because a vast majority of managed care companies failed to step up to the plate,” she said. “It is now time to shift our focus to holding plans accountable for using tactics to delay and deny needed patient care.”

Cyberattack Impact and Response

The ransom-based cyberattack against Change Healthcare/UnitedHealth Group targeted an electronic data interchange clearing house processing payer reimbursement systems, disrupting cash flows at hospitals and medical practices, and affecting patient access to prescriptions and life-saving therapy.

Change Healthcare — part of the UnitedHealth Group subsidiary Optum — processes half of all medical claims, according to a Department of Justice lawsuit. The American Hospital Association described the cyberattack as “the most significant and consequential incident of its kind” in US history.

By late March, UnitedHealth Group said nearly all medical and pharmacy claims were processing properly, while a deputy secretary of the US Department of Health & Human Services told clinicians that officials were focusing on the last group of clinicians who were facing cash-flow problems.

Still, a senior advisor with CMS told providers at that time that “we have heard from so many providers over the last several weeks who are really struggling to make ends meet right now or who are worried that they will not be able to make payroll in the weeks to come.”

Randy Dotinga is a freelance health/medical reporter and board member of the Association of Health Care Journalists.

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 (GLP-1) receptor agonists such as semaglutide (marketed as Ozempic and Rybelsus for type 2 diabetes and as Wegovy for obesity) slow down digestion and curb hunger by working on the brain’s dopamine reward center. They are prescribed to promote weight loss, metabolic health in type 2 diabetes, and heart health in coronary artery disease.

Semaglutide can be prescribed in two forms: the brand-name version, which is approved and confirmed as safe and effective by the US Food and Drug Administration (FDA), and the versions that can be obtained from a compounding pharmacy. Compounding pharmacies are permitted by the FDA to produce what is “ essentially a copy” of approved medications when there’s an official shortage, which is currently the case with semaglutide and other GLP-1 receptor agonists.

Patients are often drawn to compounding pharmacies for pricing-related reasons. If semaglutide is prescribed for a clear indication like diabetes and is covered by insurance, the brand-name version is commonly dispensed. However, if it’s not covered, patients need to pay out of pocket for branded versions, which carry a monthly cost of $1000 or more. Alternatively, their doctors can prescribe compounded semaglutide, which some telehealth companies advertise at costs of approximately $150-$300 per month.
 

Potential Issues With Compounded Semaglutide 

Compounding pharmacies produce drugs from raw materials containing active pharmaceutical ingredients (APIs). Although compounders use many of the same ingredients found in brand-name medications, for drugs like semaglutide, they may opt for specific salts that are not identical to those involved in the production of the standard versions. These salts are typically reserved for research purposes and may not be suitable for general use.

In late 2023, the FDA issued a letter asking the public to exercise caution when using compounded products containing semaglutide or semaglutide salts. This was followed in January 2024 by an FDA communication citing adverse events reported with the use of compounded semaglutide and advising patients to avoid these versions if an approved form of the drug is available.
 

Compound Pharmacies: A Closer Look 

Compounding pharmacies have exploded in popularity in the past several decades. The compounding pharmacy market is expected to grow at 7.8% per year over the next decade. 

Historically, compounding pharmacies have filled a niche for specialty vitamins for intravenous administration as well as chemotherapy medications. They also offer controlled substances, such as ketamine lozenges and nasal sprays, which are unavailable or are in short supply from traditional manufacturers.

Compounding pharmacies fall into two categories. First are compounding pharmacies covered under Section 503A of the Federal Food, Drug and Cosmetic Act; these drugs are neither tested nor monitored. Such facilities do not have to report adverse events to the FDA. The second category is Section 503B outsourcing facilities. These pharmacies choose to be tested by, to be inspected by, and to report adverse events to the FDA. 
 

The FDA’s Latest Update on This Issue

This news organization contacted the FDA for an update on the adverse events reported about compounded semaglutide. From August 8, 2021, to March 31, 2024, they received more than 20,000 adverse events reports for FDA-approved semaglutide. Comparatively, there were 210 adverse events reported on compounded semaglutide products. 

The FDA went on to describe that many of the adverse events reported were consistent with known reactions in the labeling, like nausea, diarrhea, and headache. Yet, they added that, “the FDA is unable to determine how, or if, other factors may have contributed to these adverse events, such as differences in ingredients and formulation between FDA-approved and compounded semaglutide products.” They also noted there was variation in the data quality in the reports they have received, which came only from 503B compounding pharmacies.

In conclusion, given the concerns about compounded semaglutide, it is prudent for the prescribing physicians as well as the patients taking the medication to know that risks are “higher” according to the FDA. We eagerly await more specific information from the FDA to better understand reported adverse events. 
 

How to Help Patients Receive Safe Compounded Semaglutide 

For clinicians considering prescribing semaglutide from compounding pharmacies, there are several questions worth asking, according to the Alliance for Pharmacy Compounding. First, find out whether the pharmacy complies with United States Pharmacopeia compounding standards and whether they source their APIs from FDA-registered facilities, the latter being required by federal law. It’s also important to ensure that these facilities undergo periodic third-party testing to verify medication purity and dosing. 

Ask whether the pharmacy is accredited by the Pharmacy Compounding Accreditation Board (PCAB). Accreditation from the PCAB means that pharmacies have been assessed for processes related to continuous quality improvement. In addition, ask whether the pharmacy is designated as a 503B compounder and if not, why.

Finally, interviewing the pharmacist themselves can provide useful information about staffing, training, and their methods of preparing medications. For example, if they are preparing a sterile eye drop, it is important to ask about sterility testing.

Jesse M. Pines, MD, MBA, MSCE, is a clinical professor of emergency medicine at George Washington University in Washington, and a professor in the department of emergency medicine at Drexel University College of Medicine in Philadelphia, Pennsylvania. Dr. Pines is also the chief of clinical innovation at US Acute Care Solutions in Canton, Ohio. Robert D. Glatter, MD, is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. Dr. Pines reported conflicts of interest with CSL Behring and Abbott Point-of-Care. Dr. Glatter reported no relevant conflicts of interest.
 

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

Glucagon-like peptide 1 (GLP-1) receptor agonists such as semaglutide (marketed as Ozempic and Rybelsus for type 2 diabetes and as Wegovy for obesity) slow down digestion and curb hunger by working on the brain’s dopamine reward center. They are prescribed to promote weight loss, metabolic health in type 2 diabetes, and heart health in coronary artery disease.

Semaglutide can be prescribed in two forms: the brand-name version, which is approved and confirmed as safe and effective by the US Food and Drug Administration (FDA), and the versions that can be obtained from a compounding pharmacy. Compounding pharmacies are permitted by the FDA to produce what is “ essentially a copy” of approved medications when there’s an official shortage, which is currently the case with semaglutide and other GLP-1 receptor agonists.

Patients are often drawn to compounding pharmacies for pricing-related reasons. If semaglutide is prescribed for a clear indication like diabetes and is covered by insurance, the brand-name version is commonly dispensed. However, if it’s not covered, patients need to pay out of pocket for branded versions, which carry a monthly cost of $1000 or more. Alternatively, their doctors can prescribe compounded semaglutide, which some telehealth companies advertise at costs of approximately $150-$300 per month.
 

Potential Issues With Compounded Semaglutide 

Compounding pharmacies produce drugs from raw materials containing active pharmaceutical ingredients (APIs). Although compounders use many of the same ingredients found in brand-name medications, for drugs like semaglutide, they may opt for specific salts that are not identical to those involved in the production of the standard versions. These salts are typically reserved for research purposes and may not be suitable for general use.

In late 2023, the FDA issued a letter asking the public to exercise caution when using compounded products containing semaglutide or semaglutide salts. This was followed in January 2024 by an FDA communication citing adverse events reported with the use of compounded semaglutide and advising patients to avoid these versions if an approved form of the drug is available.
 

Compound Pharmacies: A Closer Look 

Compounding pharmacies have exploded in popularity in the past several decades. The compounding pharmacy market is expected to grow at 7.8% per year over the next decade. 

Historically, compounding pharmacies have filled a niche for specialty vitamins for intravenous administration as well as chemotherapy medications. They also offer controlled substances, such as ketamine lozenges and nasal sprays, which are unavailable or are in short supply from traditional manufacturers.

Compounding pharmacies fall into two categories. First are compounding pharmacies covered under Section 503A of the Federal Food, Drug and Cosmetic Act; these drugs are neither tested nor monitored. Such facilities do not have to report adverse events to the FDA. The second category is Section 503B outsourcing facilities. These pharmacies choose to be tested by, to be inspected by, and to report adverse events to the FDA. 
 

The FDA’s Latest Update on This Issue

This news organization contacted the FDA for an update on the adverse events reported about compounded semaglutide. From August 8, 2021, to March 31, 2024, they received more than 20,000 adverse events reports for FDA-approved semaglutide. Comparatively, there were 210 adverse events reported on compounded semaglutide products. 

The FDA went on to describe that many of the adverse events reported were consistent with known reactions in the labeling, like nausea, diarrhea, and headache. Yet, they added that, “the FDA is unable to determine how, or if, other factors may have contributed to these adverse events, such as differences in ingredients and formulation between FDA-approved and compounded semaglutide products.” They also noted there was variation in the data quality in the reports they have received, which came only from 503B compounding pharmacies.

In conclusion, given the concerns about compounded semaglutide, it is prudent for the prescribing physicians as well as the patients taking the medication to know that risks are “higher” according to the FDA. We eagerly await more specific information from the FDA to better understand reported adverse events. 
 

How to Help Patients Receive Safe Compounded Semaglutide 

For clinicians considering prescribing semaglutide from compounding pharmacies, there are several questions worth asking, according to the Alliance for Pharmacy Compounding. First, find out whether the pharmacy complies with United States Pharmacopeia compounding standards and whether they source their APIs from FDA-registered facilities, the latter being required by federal law. It’s also important to ensure that these facilities undergo periodic third-party testing to verify medication purity and dosing. 

Ask whether the pharmacy is accredited by the Pharmacy Compounding Accreditation Board (PCAB). Accreditation from the PCAB means that pharmacies have been assessed for processes related to continuous quality improvement. In addition, ask whether the pharmacy is designated as a 503B compounder and if not, why.

Finally, interviewing the pharmacist themselves can provide useful information about staffing, training, and their methods of preparing medications. For example, if they are preparing a sterile eye drop, it is important to ask about sterility testing.

Jesse M. Pines, MD, MBA, MSCE, is a clinical professor of emergency medicine at George Washington University in Washington, and a professor in the department of emergency medicine at Drexel University College of Medicine in Philadelphia, Pennsylvania. Dr. Pines is also the chief of clinical innovation at US Acute Care Solutions in Canton, Ohio. Robert D. Glatter, MD, is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. Dr. Pines reported conflicts of interest with CSL Behring and Abbott Point-of-Care. Dr. Glatter reported no relevant conflicts of interest.
 

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

Glucagon-like peptide 1 (GLP-1) receptor agonists such as semaglutide (marketed as Ozempic and Rybelsus for type 2 diabetes and as Wegovy for obesity) slow down digestion and curb hunger by working on the brain’s dopamine reward center. They are prescribed to promote weight loss, metabolic health in type 2 diabetes, and heart health in coronary artery disease.

Semaglutide can be prescribed in two forms: the brand-name version, which is approved and confirmed as safe and effective by the US Food and Drug Administration (FDA), and the versions that can be obtained from a compounding pharmacy. Compounding pharmacies are permitted by the FDA to produce what is “ essentially a copy” of approved medications when there’s an official shortage, which is currently the case with semaglutide and other GLP-1 receptor agonists.

Patients are often drawn to compounding pharmacies for pricing-related reasons. If semaglutide is prescribed for a clear indication like diabetes and is covered by insurance, the brand-name version is commonly dispensed. However, if it’s not covered, patients need to pay out of pocket for branded versions, which carry a monthly cost of $1000 or more. Alternatively, their doctors can prescribe compounded semaglutide, which some telehealth companies advertise at costs of approximately $150-$300 per month.
 

Potential Issues With Compounded Semaglutide 

Compounding pharmacies produce drugs from raw materials containing active pharmaceutical ingredients (APIs). Although compounders use many of the same ingredients found in brand-name medications, for drugs like semaglutide, they may opt for specific salts that are not identical to those involved in the production of the standard versions. These salts are typically reserved for research purposes and may not be suitable for general use.

In late 2023, the FDA issued a letter asking the public to exercise caution when using compounded products containing semaglutide or semaglutide salts. This was followed in January 2024 by an FDA communication citing adverse events reported with the use of compounded semaglutide and advising patients to avoid these versions if an approved form of the drug is available.
 

Compound Pharmacies: A Closer Look 

Compounding pharmacies have exploded in popularity in the past several decades. The compounding pharmacy market is expected to grow at 7.8% per year over the next decade. 

Historically, compounding pharmacies have filled a niche for specialty vitamins for intravenous administration as well as chemotherapy medications. They also offer controlled substances, such as ketamine lozenges and nasal sprays, which are unavailable or are in short supply from traditional manufacturers.

Compounding pharmacies fall into two categories. First are compounding pharmacies covered under Section 503A of the Federal Food, Drug and Cosmetic Act; these drugs are neither tested nor monitored. Such facilities do not have to report adverse events to the FDA. The second category is Section 503B outsourcing facilities. These pharmacies choose to be tested by, to be inspected by, and to report adverse events to the FDA. 
 

The FDA’s Latest Update on This Issue

This news organization contacted the FDA for an update on the adverse events reported about compounded semaglutide. From August 8, 2021, to March 31, 2024, they received more than 20,000 adverse events reports for FDA-approved semaglutide. Comparatively, there were 210 adverse events reported on compounded semaglutide products. 

The FDA went on to describe that many of the adverse events reported were consistent with known reactions in the labeling, like nausea, diarrhea, and headache. Yet, they added that, “the FDA is unable to determine how, or if, other factors may have contributed to these adverse events, such as differences in ingredients and formulation between FDA-approved and compounded semaglutide products.” They also noted there was variation in the data quality in the reports they have received, which came only from 503B compounding pharmacies.

In conclusion, given the concerns about compounded semaglutide, it is prudent for the prescribing physicians as well as the patients taking the medication to know that risks are “higher” according to the FDA. We eagerly await more specific information from the FDA to better understand reported adverse events. 
 

How to Help Patients Receive Safe Compounded Semaglutide 

For clinicians considering prescribing semaglutide from compounding pharmacies, there are several questions worth asking, according to the Alliance for Pharmacy Compounding. First, find out whether the pharmacy complies with United States Pharmacopeia compounding standards and whether they source their APIs from FDA-registered facilities, the latter being required by federal law. It’s also important to ensure that these facilities undergo periodic third-party testing to verify medication purity and dosing. 

Ask whether the pharmacy is accredited by the Pharmacy Compounding Accreditation Board (PCAB). Accreditation from the PCAB means that pharmacies have been assessed for processes related to continuous quality improvement. In addition, ask whether the pharmacy is designated as a 503B compounder and if not, why.

Finally, interviewing the pharmacist themselves can provide useful information about staffing, training, and their methods of preparing medications. For example, if they are preparing a sterile eye drop, it is important to ask about sterility testing.

Jesse M. Pines, MD, MBA, MSCE, is a clinical professor of emergency medicine at George Washington University in Washington, and a professor in the department of emergency medicine at Drexel University College of Medicine in Philadelphia, Pennsylvania. Dr. Pines is also the chief of clinical innovation at US Acute Care Solutions in Canton, Ohio. Robert D. Glatter, MD, is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. Dr. Pines reported conflicts of interest with CSL Behring and Abbott Point-of-Care. Dr. Glatter reported no relevant conflicts of interest.
 

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

This transcript has been edited for clarity. 

Andrew N. Wilner, MD: My guest today is Dr. Jose Merino, editor in chief of the Neurology family of journals and professor of neurology and co-vice chair of education at Georgetown University in Washington, DC.

Our program today is a follow-up of Dr. Merino’s presentation at the recent American Academy of Neurology meeting in Denver, Colorado. Along with two other panelists, Dr. Merino discussed the role of open-access publication and the dangers of predatory journals. 

Jose G. Merino, MD, MPhil: Thank you for having me here. It’s a pleasure.
 

Open Access Defined

Dr. Wilner: I remember when publication in neurology was pretty straightforward. It was either the green journal or the blue journal, but things have certainly changed. I think one topic that is not clear to everyone is this concept of open access. Could you define that for us? 

Dr. Merino: Sure. Open access is a mode of publication that fosters more open or accessible science. The idea of open access is that it combines two main elements. One is that the papers that are published become immediately available to anybody with an internet connection anywhere in the world without any restrictions. 

The second important element from open access, which makes it different from other models we can talk about, is the fact that the authors retain the copyright of their work, but they give the journal and readers a license to use, reproduce, and modify the content.

This is different, for example, from instances where we have funder mandates. For example, NIH papers have to become available 6 months after publication, so they’re available to everybody but not immediately. 

Then copyright is retained, in the case of NIH employees, for example, by the government or by the journals themselves. The two elements of open access, I think, are immediate access to the material and the fact that it’s published with a Creative Commons license. 

Dr. Wilner: I remember that when a journal article was published, say, in Neurology, if you didn’t have a subscription to Neurology, you went to the library that hopefully had a subscription.

If they didn’t have it, you would write to the author and say, “Hey, I heard you have this great paper because the abstract was out there. Could you send me a reprint?” Has that whole universe evaporated? 

Dr. Merino: It depends on how the paper is published. For example, in Neurology, some of the research we publish is open access. Basically, if you have an internet connection, you can access the paper.

That’s the case for papers published in our wholly open-access journals in the Neurology family like Neurology Neuroimmunology & Neuroinflammation, Neurology Genetics, or Neurology Education. 

For other papers that are published in Neurology, not under open access, there is a paywall. For some of them, the paywall comes down after a few months based on funder mandates and so on. As I was mentioning, the NIH-funded papers are available 6 months later. 

In the first 6 months, you may have to go to your library, and if your library has a subscription, you can download it directly. [This is also true for] those that always stay behind the paywall, where you have to have a subscription or your library has to have a subscription.
 

Is Pay to Publish a Red Flag?

Dr. Wilner: I’m a professional writer. With any luck, when I write something, I get paid to write it. There’s been a long tradition in academic medicine that when you submit an article to, say, Neurology, you don’t get paid as an author for the publication. Your reward is the honor of it being published. 

Neurology supports itself in various ways, including advertising and so on. That’s been the contract: free publication for work that merits it, and the journal survives on its own. 

With open access, one of the things that’s happened is that — and I’ve published open access myself — is that I get a notification that I need to pay to have my article that I’ve slaved over published. Explain that, please. 

Dr. Merino: This is the issue with open access. As I mentioned, the paper gets published. You’re giving the journal a license to publish it. You’re retaining the copyright of your work. That means that the journal cannot make money or support itself by just publishing open access because they belong to you. 

Typically, open-access journals are not in print and don’t have much in terms of advertising. The contract is you’re giving me a license to publish it, but it’s your journal, so you’re paying a fee for the journal expenses to basically produce your paper. That’s what’s happening with open access. 

That’s been recognized with many funders, for example, with NIH funding or many of the European funders, they’re including open-access fees as part of their funding for research. Now, of course, this doesn’t help if you’re not a funded researcher or if you’re a fellow who’s doing work and so on. 

Typically, most journals will have waived fees or lower fees for these situations. The reason for the open-access fee is the fact that you’re retaining the copyright. You’re not giving it to the journal who can then use it to generate its revenue for supporting itself, the editorial staff, and so on. 

Dr. Wilner: This idea of charging for publication has created a satellite business of what are called predatory journals. How does one know if the open-access journal that I’m submitting to is really just in the business of wanting my $300 or my $900 to get published? How do I know if that’s a reasonable place to publish? 
 

Predatory Journals

Dr. Merino: That’s a big challenge that has come with this whole idea of open access and the fact that now, many journals are online only, so you’re no longer seeing a physical copy. That has given rise to the predatory journals. 

The predatory journal, by definition, is a journal that claims to be open access. They’ll take your paper and publish it, but they don’t provide all the other services that you would typically expect from the fact that you’re paying an open-access fee. This includes getting appropriate peer review, production of the manuscript, and long-term curation and storage of the manuscript. 

Many predatory journals will take your open-access fee, accept any paper that you submit, regardless of the quality, because they’re charging the fees for that. They don’t send it to real peer review, and then in a few months, the journal disappears so there’s no way for anybody to actually find your paper anymore. 

There are certain checklists. Dr. David Moher at the University of Toronto has produced some work trying to help us identify predatory journals. 

One thing I typically suggest to people who ask me this question is: Have you ever heard of this journal before? Does the journal have a track record? How far back does the story of the journal go? Is it supported by a publisher that you know? Do you know anybody who has published there? Is it something you can easily access?

If in doubt, always ask your friendly medical librarian. There used to be lists that were kept in terms of predatory journals that were being constantly updated, but those had to be shut down. As far as I understand, there were legal issues in terms of how things got on that list. 

I think that overall, if you’ve heard of it, if it’s relevant, if it’s known in your field, and if your librarian knows it, it’s probably a good legitimate open-access journal. There are many very good legitimate open-access journals. 

I mentioned the two that we have in our family, but all the other major journals have their own open-access journal within their family. There are some, like BMC or PLOS, that are completely open-access and legitimate journals. 
 

Impact Factor

Dr. Wilner: What about impact factor? Many journals boast about their impact factor. I’m not sure how to interpret that number. 

Dr. Merino: Impact factor is very interesting. The impact factor was developed by medical librarians to try to identify the journals they should be subscribing to. It’s a measure of the average citations to an average paper in the journal. 

It doesn’t tell you about specific papers. It tells you, on average, how many of the papers in this journal get cited so many times. It’s calculated by the number of articles that were cited divided by the number of articles that were published. Journals that publish many papers, like Neurology, have a hard time bringing up their impact factor beyond a certain level. 

Similarly, very small journals with one or two very highly cited papers have a very high impact factor. It’s being used as a measure, perhaps inappropriately, of how good or how reputable a journal is. We all say we don’t care about journal impact factors, but we all know our journal impact factor and we used to know it to three decimals. Now, they changed the system, and there’s only one decimal point, which makes more sense. 

This is more important, for example, for authors when deciding where to submit papers. I know that in some countries, particularly in Europe, the impact factor of the journal where you publish has an impact on your promotion decisions. 

I would say what’s even more important than the impact factor, is to say, “Well, is this the journal that fits the scope of my paper? Is this the journal that reaches the audience that I want to reach when I write my paper?” 

There are some papers, for example, that are very influential. The impact factor just captures citations. There are some papers that are very influential that may not get cited very often. There may be papers that change clinical practice. 

If you read a paper that tells you that you should be changing how you treat your patients with myasthenia based on this paper, that may not get cited. It’s a very clinically focused paper, but it’s probably more impactful than one that gets cited very much in some respect, or they make it to public policy decisions, and so on. 

I think it’s important to look more at the audience and the journal scope when you submit your papers. 

Dr. Wilner: One other technical question. The journals also say they’re indexed in PubMed or Google Scholar. If I want to publish my paper and I want it indexed where the right people are going to find it, where does it need to be indexed? 

Dr. Merino: I grew up using Index Medicus, MedlinePlus, and the Library of Science. I still do. If I need to find something, I go to PubMed. Ideally, papers are listed in MedlinePlus or can be found in PubMed. They’re not the same thing, but you can find them through them. 

That would be an important thing. Nowadays, a lot more people are using Google Scholar or Google just to identify papers. It may be a little bit less relevant, but it’s still a measure of the quality of the journal before they get indexed in some of these. For example, if you get listed in MedlinePlus, it has gone through certain quality checks by the index itself to see whether they would accept the journal or not. That’s something you want to check.

Typically, most of the large journals or the journals you and I know about are listed in more than one place, right? They’re listed in Scopus and Web of Science. They’re listed in MedlinePlus and so on. Again, if you’re submitting your paper, go somewhere where you know the journal and you’ve heard about it. 

Dr. Wilner: I’m not going to ask you about artificial intelligence. We can do that another time. I want to ask something closer to me, which is this question of publish or perish. 

There seems to be, in academics, more emphasis on the number of papers that one has published rather than their quality. How does a younger academician or one who really needs to publish cope with that? 

Dr. Merino: Many people are writing up research that may not be relevant or that may not be high quality just because you need to have a long list of papers to get promoted, for example, if you’re an academician. 

Doug Altman, who was a very influential person in the field quality of not only medical statistics but also medical publishing, had the idea that we need less research, but we need better research. 

We often receive papers where you say, well, what’s the rationale behind the question in this paper? It’s like they had a large amount of data and were trying to squeeze as much as they could out of that. I think, as a young academician, the important thing to think about is whether it is an important question that matters to you and to the field, from whatever perspective, whether it’s going to advance research, advance clinical care, or have public policy implications. 

Is this one where the answer will be important no matter what the answer is? If you’re thinking of that, your work will be well recognized, people will know you, and you’ll get invited to collaborate. I think that’s the most important thing rather than just churning out a large number of papers. 

The productivity will come from the fact that you start by saying, let me ask something that’s really meaningful to me and to the field, with a good question and using strong research methodology. 

Dr. Wilner: Thanks for that, Dr. Merino. I think that’s very valuable for all of us. This has been a great discussion. Do you have any final comments before we wrap up? 

Dr. Merino: I want to encourage people to continue reading medical journals all the time and submitting to us, again, good research and important questions with robust methodology. That’s what we’re looking for in Neurology and most serious medical journals.
 

Dr. Wilner is an associate professor of neurology at the University of Tennessee Health Science Center, Memphis. Dr. Merino is a professor in the department of neurology at Georgetown University Medical Center, Washington, DC. Dr. Wilner reported conflicts of interest with Accordant Health Services and Lulu Publishing. Dr. Merino reported no relevant conflicts of interest.

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

This transcript has been edited for clarity. 

Andrew N. Wilner, MD: My guest today is Dr. Jose Merino, editor in chief of the Neurology family of journals and professor of neurology and co-vice chair of education at Georgetown University in Washington, DC.

Our program today is a follow-up of Dr. Merino’s presentation at the recent American Academy of Neurology meeting in Denver, Colorado. Along with two other panelists, Dr. Merino discussed the role of open-access publication and the dangers of predatory journals. 

Jose G. Merino, MD, MPhil: Thank you for having me here. It’s a pleasure.
 

Open Access Defined

Dr. Wilner: I remember when publication in neurology was pretty straightforward. It was either the green journal or the blue journal, but things have certainly changed. I think one topic that is not clear to everyone is this concept of open access. Could you define that for us? 

Dr. Merino: Sure. Open access is a mode of publication that fosters more open or accessible science. The idea of open access is that it combines two main elements. One is that the papers that are published become immediately available to anybody with an internet connection anywhere in the world without any restrictions. 

The second important element from open access, which makes it different from other models we can talk about, is the fact that the authors retain the copyright of their work, but they give the journal and readers a license to use, reproduce, and modify the content.

This is different, for example, from instances where we have funder mandates. For example, NIH papers have to become available 6 months after publication, so they’re available to everybody but not immediately. 

Then copyright is retained, in the case of NIH employees, for example, by the government or by the journals themselves. The two elements of open access, I think, are immediate access to the material and the fact that it’s published with a Creative Commons license. 

Dr. Wilner: I remember that when a journal article was published, say, in Neurology, if you didn’t have a subscription to Neurology, you went to the library that hopefully had a subscription.

If they didn’t have it, you would write to the author and say, “Hey, I heard you have this great paper because the abstract was out there. Could you send me a reprint?” Has that whole universe evaporated? 

Dr. Merino: It depends on how the paper is published. For example, in Neurology, some of the research we publish is open access. Basically, if you have an internet connection, you can access the paper.

That’s the case for papers published in our wholly open-access journals in the Neurology family like Neurology Neuroimmunology & Neuroinflammation, Neurology Genetics, or Neurology Education. 

For other papers that are published in Neurology, not under open access, there is a paywall. For some of them, the paywall comes down after a few months based on funder mandates and so on. As I was mentioning, the NIH-funded papers are available 6 months later. 

In the first 6 months, you may have to go to your library, and if your library has a subscription, you can download it directly. [This is also true for] those that always stay behind the paywall, where you have to have a subscription or your library has to have a subscription.
 

Is Pay to Publish a Red Flag?

Dr. Wilner: I’m a professional writer. With any luck, when I write something, I get paid to write it. There’s been a long tradition in academic medicine that when you submit an article to, say, Neurology, you don’t get paid as an author for the publication. Your reward is the honor of it being published. 

Neurology supports itself in various ways, including advertising and so on. That’s been the contract: free publication for work that merits it, and the journal survives on its own. 

With open access, one of the things that’s happened is that — and I’ve published open access myself — is that I get a notification that I need to pay to have my article that I’ve slaved over published. Explain that, please. 

Dr. Merino: This is the issue with open access. As I mentioned, the paper gets published. You’re giving the journal a license to publish it. You’re retaining the copyright of your work. That means that the journal cannot make money or support itself by just publishing open access because they belong to you. 

Typically, open-access journals are not in print and don’t have much in terms of advertising. The contract is you’re giving me a license to publish it, but it’s your journal, so you’re paying a fee for the journal expenses to basically produce your paper. That’s what’s happening with open access. 

That’s been recognized with many funders, for example, with NIH funding or many of the European funders, they’re including open-access fees as part of their funding for research. Now, of course, this doesn’t help if you’re not a funded researcher or if you’re a fellow who’s doing work and so on. 

Typically, most journals will have waived fees or lower fees for these situations. The reason for the open-access fee is the fact that you’re retaining the copyright. You’re not giving it to the journal who can then use it to generate its revenue for supporting itself, the editorial staff, and so on. 

Dr. Wilner: This idea of charging for publication has created a satellite business of what are called predatory journals. How does one know if the open-access journal that I’m submitting to is really just in the business of wanting my $300 or my $900 to get published? How do I know if that’s a reasonable place to publish? 
 

Predatory Journals

Dr. Merino: That’s a big challenge that has come with this whole idea of open access and the fact that now, many journals are online only, so you’re no longer seeing a physical copy. That has given rise to the predatory journals. 

The predatory journal, by definition, is a journal that claims to be open access. They’ll take your paper and publish it, but they don’t provide all the other services that you would typically expect from the fact that you’re paying an open-access fee. This includes getting appropriate peer review, production of the manuscript, and long-term curation and storage of the manuscript. 

Many predatory journals will take your open-access fee, accept any paper that you submit, regardless of the quality, because they’re charging the fees for that. They don’t send it to real peer review, and then in a few months, the journal disappears so there’s no way for anybody to actually find your paper anymore. 

There are certain checklists. Dr. David Moher at the University of Toronto has produced some work trying to help us identify predatory journals. 

One thing I typically suggest to people who ask me this question is: Have you ever heard of this journal before? Does the journal have a track record? How far back does the story of the journal go? Is it supported by a publisher that you know? Do you know anybody who has published there? Is it something you can easily access?

If in doubt, always ask your friendly medical librarian. There used to be lists that were kept in terms of predatory journals that were being constantly updated, but those had to be shut down. As far as I understand, there were legal issues in terms of how things got on that list. 

I think that overall, if you’ve heard of it, if it’s relevant, if it’s known in your field, and if your librarian knows it, it’s probably a good legitimate open-access journal. There are many very good legitimate open-access journals. 

I mentioned the two that we have in our family, but all the other major journals have their own open-access journal within their family. There are some, like BMC or PLOS, that are completely open-access and legitimate journals. 
 

Impact Factor

Dr. Wilner: What about impact factor? Many journals boast about their impact factor. I’m not sure how to interpret that number. 

Dr. Merino: Impact factor is very interesting. The impact factor was developed by medical librarians to try to identify the journals they should be subscribing to. It’s a measure of the average citations to an average paper in the journal. 

It doesn’t tell you about specific papers. It tells you, on average, how many of the papers in this journal get cited so many times. It’s calculated by the number of articles that were cited divided by the number of articles that were published. Journals that publish many papers, like Neurology, have a hard time bringing up their impact factor beyond a certain level. 

Similarly, very small journals with one or two very highly cited papers have a very high impact factor. It’s being used as a measure, perhaps inappropriately, of how good or how reputable a journal is. We all say we don’t care about journal impact factors, but we all know our journal impact factor and we used to know it to three decimals. Now, they changed the system, and there’s only one decimal point, which makes more sense. 

This is more important, for example, for authors when deciding where to submit papers. I know that in some countries, particularly in Europe, the impact factor of the journal where you publish has an impact on your promotion decisions. 

I would say what’s even more important than the impact factor, is to say, “Well, is this the journal that fits the scope of my paper? Is this the journal that reaches the audience that I want to reach when I write my paper?” 

There are some papers, for example, that are very influential. The impact factor just captures citations. There are some papers that are very influential that may not get cited very often. There may be papers that change clinical practice. 

If you read a paper that tells you that you should be changing how you treat your patients with myasthenia based on this paper, that may not get cited. It’s a very clinically focused paper, but it’s probably more impactful than one that gets cited very much in some respect, or they make it to public policy decisions, and so on. 

I think it’s important to look more at the audience and the journal scope when you submit your papers. 

Dr. Wilner: One other technical question. The journals also say they’re indexed in PubMed or Google Scholar. If I want to publish my paper and I want it indexed where the right people are going to find it, where does it need to be indexed? 

Dr. Merino: I grew up using Index Medicus, MedlinePlus, and the Library of Science. I still do. If I need to find something, I go to PubMed. Ideally, papers are listed in MedlinePlus or can be found in PubMed. They’re not the same thing, but you can find them through them. 

That would be an important thing. Nowadays, a lot more people are using Google Scholar or Google just to identify papers. It may be a little bit less relevant, but it’s still a measure of the quality of the journal before they get indexed in some of these. For example, if you get listed in MedlinePlus, it has gone through certain quality checks by the index itself to see whether they would accept the journal or not. That’s something you want to check.

Typically, most of the large journals or the journals you and I know about are listed in more than one place, right? They’re listed in Scopus and Web of Science. They’re listed in MedlinePlus and so on. Again, if you’re submitting your paper, go somewhere where you know the journal and you’ve heard about it. 

Dr. Wilner: I’m not going to ask you about artificial intelligence. We can do that another time. I want to ask something closer to me, which is this question of publish or perish. 

There seems to be, in academics, more emphasis on the number of papers that one has published rather than their quality. How does a younger academician or one who really needs to publish cope with that? 

Dr. Merino: Many people are writing up research that may not be relevant or that may not be high quality just because you need to have a long list of papers to get promoted, for example, if you’re an academician. 

Doug Altman, who was a very influential person in the field quality of not only medical statistics but also medical publishing, had the idea that we need less research, but we need better research. 

We often receive papers where you say, well, what’s the rationale behind the question in this paper? It’s like they had a large amount of data and were trying to squeeze as much as they could out of that. I think, as a young academician, the important thing to think about is whether it is an important question that matters to you and to the field, from whatever perspective, whether it’s going to advance research, advance clinical care, or have public policy implications. 

Is this one where the answer will be important no matter what the answer is? If you’re thinking of that, your work will be well recognized, people will know you, and you’ll get invited to collaborate. I think that’s the most important thing rather than just churning out a large number of papers. 

The productivity will come from the fact that you start by saying, let me ask something that’s really meaningful to me and to the field, with a good question and using strong research methodology. 

Dr. Wilner: Thanks for that, Dr. Merino. I think that’s very valuable for all of us. This has been a great discussion. Do you have any final comments before we wrap up? 

Dr. Merino: I want to encourage people to continue reading medical journals all the time and submitting to us, again, good research and important questions with robust methodology. That’s what we’re looking for in Neurology and most serious medical journals.
 

Dr. Wilner is an associate professor of neurology at the University of Tennessee Health Science Center, Memphis. Dr. Merino is a professor in the department of neurology at Georgetown University Medical Center, Washington, DC. Dr. Wilner reported conflicts of interest with Accordant Health Services and Lulu Publishing. Dr. Merino reported no relevant conflicts of interest.

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

This transcript has been edited for clarity. 

Andrew N. Wilner, MD: My guest today is Dr. Jose Merino, editor in chief of the Neurology family of journals and professor of neurology and co-vice chair of education at Georgetown University in Washington, DC.

Our program today is a follow-up of Dr. Merino’s presentation at the recent American Academy of Neurology meeting in Denver, Colorado. Along with two other panelists, Dr. Merino discussed the role of open-access publication and the dangers of predatory journals. 

Jose G. Merino, MD, MPhil: Thank you for having me here. It’s a pleasure.
 

Open Access Defined

Dr. Wilner: I remember when publication in neurology was pretty straightforward. It was either the green journal or the blue journal, but things have certainly changed. I think one topic that is not clear to everyone is this concept of open access. Could you define that for us? 

Dr. Merino: Sure. Open access is a mode of publication that fosters more open or accessible science. The idea of open access is that it combines two main elements. One is that the papers that are published become immediately available to anybody with an internet connection anywhere in the world without any restrictions. 

The second important element from open access, which makes it different from other models we can talk about, is the fact that the authors retain the copyright of their work, but they give the journal and readers a license to use, reproduce, and modify the content.

This is different, for example, from instances where we have funder mandates. For example, NIH papers have to become available 6 months after publication, so they’re available to everybody but not immediately. 

Then copyright is retained, in the case of NIH employees, for example, by the government or by the journals themselves. The two elements of open access, I think, are immediate access to the material and the fact that it’s published with a Creative Commons license. 

Dr. Wilner: I remember that when a journal article was published, say, in Neurology, if you didn’t have a subscription to Neurology, you went to the library that hopefully had a subscription.

If they didn’t have it, you would write to the author and say, “Hey, I heard you have this great paper because the abstract was out there. Could you send me a reprint?” Has that whole universe evaporated? 

Dr. Merino: It depends on how the paper is published. For example, in Neurology, some of the research we publish is open access. Basically, if you have an internet connection, you can access the paper.

That’s the case for papers published in our wholly open-access journals in the Neurology family like Neurology Neuroimmunology & Neuroinflammation, Neurology Genetics, or Neurology Education. 

For other papers that are published in Neurology, not under open access, there is a paywall. For some of them, the paywall comes down after a few months based on funder mandates and so on. As I was mentioning, the NIH-funded papers are available 6 months later. 

In the first 6 months, you may have to go to your library, and if your library has a subscription, you can download it directly. [This is also true for] those that always stay behind the paywall, where you have to have a subscription or your library has to have a subscription.
 

Is Pay to Publish a Red Flag?

Dr. Wilner: I’m a professional writer. With any luck, when I write something, I get paid to write it. There’s been a long tradition in academic medicine that when you submit an article to, say, Neurology, you don’t get paid as an author for the publication. Your reward is the honor of it being published. 

Neurology supports itself in various ways, including advertising and so on. That’s been the contract: free publication for work that merits it, and the journal survives on its own. 

With open access, one of the things that’s happened is that — and I’ve published open access myself — is that I get a notification that I need to pay to have my article that I’ve slaved over published. Explain that, please. 

Dr. Merino: This is the issue with open access. As I mentioned, the paper gets published. You’re giving the journal a license to publish it. You’re retaining the copyright of your work. That means that the journal cannot make money or support itself by just publishing open access because they belong to you. 

Typically, open-access journals are not in print and don’t have much in terms of advertising. The contract is you’re giving me a license to publish it, but it’s your journal, so you’re paying a fee for the journal expenses to basically produce your paper. That’s what’s happening with open access. 

That’s been recognized with many funders, for example, with NIH funding or many of the European funders, they’re including open-access fees as part of their funding for research. Now, of course, this doesn’t help if you’re not a funded researcher or if you’re a fellow who’s doing work and so on. 

Typically, most journals will have waived fees or lower fees for these situations. The reason for the open-access fee is the fact that you’re retaining the copyright. You’re not giving it to the journal who can then use it to generate its revenue for supporting itself, the editorial staff, and so on. 

Dr. Wilner: This idea of charging for publication has created a satellite business of what are called predatory journals. How does one know if the open-access journal that I’m submitting to is really just in the business of wanting my $300 or my $900 to get published? How do I know if that’s a reasonable place to publish? 
 

Predatory Journals

Dr. Merino: That’s a big challenge that has come with this whole idea of open access and the fact that now, many journals are online only, so you’re no longer seeing a physical copy. That has given rise to the predatory journals. 

The predatory journal, by definition, is a journal that claims to be open access. They’ll take your paper and publish it, but they don’t provide all the other services that you would typically expect from the fact that you’re paying an open-access fee. This includes getting appropriate peer review, production of the manuscript, and long-term curation and storage of the manuscript. 

Many predatory journals will take your open-access fee, accept any paper that you submit, regardless of the quality, because they’re charging the fees for that. They don’t send it to real peer review, and then in a few months, the journal disappears so there’s no way for anybody to actually find your paper anymore. 

There are certain checklists. Dr. David Moher at the University of Toronto has produced some work trying to help us identify predatory journals. 

One thing I typically suggest to people who ask me this question is: Have you ever heard of this journal before? Does the journal have a track record? How far back does the story of the journal go? Is it supported by a publisher that you know? Do you know anybody who has published there? Is it something you can easily access?

If in doubt, always ask your friendly medical librarian. There used to be lists that were kept in terms of predatory journals that were being constantly updated, but those had to be shut down. As far as I understand, there were legal issues in terms of how things got on that list. 

I think that overall, if you’ve heard of it, if it’s relevant, if it’s known in your field, and if your librarian knows it, it’s probably a good legitimate open-access journal. There are many very good legitimate open-access journals. 

I mentioned the two that we have in our family, but all the other major journals have their own open-access journal within their family. There are some, like BMC or PLOS, that are completely open-access and legitimate journals. 
 

Impact Factor

Dr. Wilner: What about impact factor? Many journals boast about their impact factor. I’m not sure how to interpret that number. 

Dr. Merino: Impact factor is very interesting. The impact factor was developed by medical librarians to try to identify the journals they should be subscribing to. It’s a measure of the average citations to an average paper in the journal. 

It doesn’t tell you about specific papers. It tells you, on average, how many of the papers in this journal get cited so many times. It’s calculated by the number of articles that were cited divided by the number of articles that were published. Journals that publish many papers, like Neurology, have a hard time bringing up their impact factor beyond a certain level. 

Similarly, very small journals with one or two very highly cited papers have a very high impact factor. It’s being used as a measure, perhaps inappropriately, of how good or how reputable a journal is. We all say we don’t care about journal impact factors, but we all know our journal impact factor and we used to know it to three decimals. Now, they changed the system, and there’s only one decimal point, which makes more sense. 

This is more important, for example, for authors when deciding where to submit papers. I know that in some countries, particularly in Europe, the impact factor of the journal where you publish has an impact on your promotion decisions. 

I would say what’s even more important than the impact factor, is to say, “Well, is this the journal that fits the scope of my paper? Is this the journal that reaches the audience that I want to reach when I write my paper?” 

There are some papers, for example, that are very influential. The impact factor just captures citations. There are some papers that are very influential that may not get cited very often. There may be papers that change clinical practice. 

If you read a paper that tells you that you should be changing how you treat your patients with myasthenia based on this paper, that may not get cited. It’s a very clinically focused paper, but it’s probably more impactful than one that gets cited very much in some respect, or they make it to public policy decisions, and so on. 

I think it’s important to look more at the audience and the journal scope when you submit your papers. 

Dr. Wilner: One other technical question. The journals also say they’re indexed in PubMed or Google Scholar. If I want to publish my paper and I want it indexed where the right people are going to find it, where does it need to be indexed? 

Dr. Merino: I grew up using Index Medicus, MedlinePlus, and the Library of Science. I still do. If I need to find something, I go to PubMed. Ideally, papers are listed in MedlinePlus or can be found in PubMed. They’re not the same thing, but you can find them through them. 

That would be an important thing. Nowadays, a lot more people are using Google Scholar or Google just to identify papers. It may be a little bit less relevant, but it’s still a measure of the quality of the journal before they get indexed in some of these. For example, if you get listed in MedlinePlus, it has gone through certain quality checks by the index itself to see whether they would accept the journal or not. That’s something you want to check.

Typically, most of the large journals or the journals you and I know about are listed in more than one place, right? They’re listed in Scopus and Web of Science. They’re listed in MedlinePlus and so on. Again, if you’re submitting your paper, go somewhere where you know the journal and you’ve heard about it. 

Dr. Wilner: I’m not going to ask you about artificial intelligence. We can do that another time. I want to ask something closer to me, which is this question of publish or perish. 

There seems to be, in academics, more emphasis on the number of papers that one has published rather than their quality. How does a younger academician or one who really needs to publish cope with that? 

Dr. Merino: Many people are writing up research that may not be relevant or that may not be high quality just because you need to have a long list of papers to get promoted, for example, if you’re an academician. 

Doug Altman, who was a very influential person in the field quality of not only medical statistics but also medical publishing, had the idea that we need less research, but we need better research. 

We often receive papers where you say, well, what’s the rationale behind the question in this paper? It’s like they had a large amount of data and were trying to squeeze as much as they could out of that. I think, as a young academician, the important thing to think about is whether it is an important question that matters to you and to the field, from whatever perspective, whether it’s going to advance research, advance clinical care, or have public policy implications. 

Is this one where the answer will be important no matter what the answer is? If you’re thinking of that, your work will be well recognized, people will know you, and you’ll get invited to collaborate. I think that’s the most important thing rather than just churning out a large number of papers. 

The productivity will come from the fact that you start by saying, let me ask something that’s really meaningful to me and to the field, with a good question and using strong research methodology. 

Dr. Wilner: Thanks for that, Dr. Merino. I think that’s very valuable for all of us. This has been a great discussion. Do you have any final comments before we wrap up? 

Dr. Merino: I want to encourage people to continue reading medical journals all the time and submitting to us, again, good research and important questions with robust methodology. That’s what we’re looking for in Neurology and most serious medical journals.
 

Dr. Wilner is an associate professor of neurology at the University of Tennessee Health Science Center, Memphis. Dr. Merino is a professor in the department of neurology at Georgetown University Medical Center, Washington, DC. Dr. Wilner reported conflicts of interest with Accordant Health Services and Lulu Publishing. Dr. Merino reported no relevant conflicts of interest.

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

When he completed his fellowship at Fox Chase Cancer Center in Philadelphia, Moshe Chasky, MD, joined a small five-person practice that rented space from the city’s Jefferson Hospital in Philadelphia. The arrangement seemed to work well for the hospital and the small practice, which remained independent.

Within 10 years, the hospital sought to buy the practice, Alliance Cancer Specialists.

But the oncologists at Alliance did not want to join Jefferson.

The hospital eventually entered into an exclusive agreement with its own medical group to provide inpatient oncology/hematology services at three Jefferson Health–Northeast hospitals and stripped Dr. Chasky and his colleagues of their privileges at those facilities, Medscape Medical News reported last year.

The Alliance story is a familiar one for independent community oncology practices, said Jeff Patton, MD, CEO of OneOncology, a management services organization.

A 2020 report from the Community Oncology Alliance (COA), for instance, tracked mergers, acquisitions, and closures in the community oncology setting and found the number of practices acquired by hospitals, known as vertical integration, nearly tripled from 2010 to 2020.

“Some hospitals are pretty predatory in their approach,” Dr. Patton said. If hospitals have their own oncology program, “they’ll employ the referring doctors and then discourage them or prevent them from referring patients to our independent practices that are not owned by the hospital.”

Still, in the face of growing pressure to join hospitals, some community oncology practices are finding ways to survive and maintain their independence.
 

A Growing Trend

The latest data continue to show a clear trend: Consolidation in oncology is on the rise.

A 2024 study revealed that the pace of consolidation seems to be increasing.

The analysis found that, between 2015 and 2022, the number of medical oncologists increased by 14% and the number of medical oncologists per practice increased by 40%, while the number of practices decreased by 18%.

While about 44% of practices remain independent, the percentage of medical oncologists working in practices with more than 25 clinicians has increased from 34% in 2015 to 44% in 2022. By 2022, the largest 102 practices in the United States employed more than 40% of all medical oncologists.

“The rate of consolidation seems to be rapid,” study coauthor Parsa Erfani, MD, an internal medicine resident at Brigham & Women’s Hospital, Boston, explained.

Consolidation appears to breed more consolidation. The researchers found, for instance, that markets with greater hospital consolidation and more hospital beds per capita were more likely to undergo consolidation in oncology.

Consolidation may be higher in these markets “because hospitals or health systems are buying up oncology practices or conversely because oncology practices are merging to compete more effectively with larger hospitals in the area,” Dr. Erfani told this news organization.

Mergers among independent practices, known as horizontal integration, have also been on the rise, according to the 2020 COA report. These mergers can help counter pressures from hospitals seeking to acquire community practices as well as prevent practices and their clinics from closing.

Although Dr. Erfani’s research wasn’t designed to determine the factors behind consolidation, he and his colleagues point to the Affordable Care Act (ACA) and the federal 340B Drug Pricing Program as potential drivers of this trend.

The ACA encouraged consolidation as a way to improve efficiency and created the need for ever-larger information systems to collect and report quality data. But these data collection and reporting requirements have become increasingly difficult for smaller practices to take on.

The 340B Program, however, may be a bigger contributing factor to consolidation. Created in 1992, the 340B Program allows qualifying hospitals and clinics that treat low-income and uninsured patients to buy outpatient prescription drugs at a 25%-50% discount.

Hospitals seeking to capitalize on the margins possible under the 340B Program will “buy all the referring physicians in a market so that the medical oncology group is left with little choice but to sell to the hospital,” said Dr. Patton.

“Those 340B dollars are worth a lot to hospitals,” said David A. Eagle, MD, a hematologist/oncologist with New York Cancer & Blood Specialists and past president of COA. The program “creates an appetite for nonprofit hospitals to want to grow their medical oncology programs,” he told this news organization.

Declining Medicare reimbursement has also hit independent practices hard.

Over the past 15 years, compared with inflation, physicians have gotten “a pay rate decrease from Medicare,” said Dr. Patton. Payers have followed that lead and tried to cut pay for clinicians, especially those who do not have market share, he said. Paying them less is “disingenuous knowing that our costs of providing care are going up,” he said.
 

Less Access, Higher Costs, Worse Care?

Many studies have demonstrated that, when hospitals become behemoths in a given market, healthcare costs go up.

“There are robust data showing that consolidation increases healthcare costs by reducing competition, including in oncology,” wrote Dr. Erfani and colleagues.

Oncology practices that are owned by hospitals bill facility fees for outpatient chemotherapy treatment, adding another layer of cost, the researchers explained, citing a 2019 Health Economics study.

Another analysis, published in 2020, found that hospital prices for the top 37 infused cancer drugs averaged 86% more per unit than the price charged by physician offices. Hospital outpatient departments charged even more, on average, for drugs — 128% more for nivolumab and 428% more for fluorouracil, for instance.

In their 2024 analysis, Dr. Erfani and colleagues also found that increased hospital market concentration was associated with worse quality of care, across all assessed patient satisfaction measures, and may result in worse access to care as well.

Overall, these consolidation “trends have important implications for cancer care cost, quality, and access,” the authors concluded.
 

Navigating the Consolidation Trend

In the face of mounting pressure to join hospitals, community oncology practices have typically relied on horizontal mergers to maintain their independence. An increasing number of practices, however, are now turning to another strategy: Management services organizations.

According to some oncologists, a core benefit of joining a management services organization is their community practices can maintain autonomy, hold on to referrals, and benefit from access to a wider network of peers and recently approved treatments such as chimeric antigen receptor T-cell therapies.

In these arrangements, the management company also provides business assistance to practices, including help with billing and collection, payer negotiations, supply chain issues, and credentialing, as well as recruiting, hiring, and marketing.

These management organizations, which include American Oncology Network, Integrated Oncology Network, OneOncology, and Verdi Oncology, are, however, backed by private equity. According to a 2022 report, private equity–backed management organizations have ramped up arrangements with community oncology practices over the past few years — a trend that has concerned some experts.

The authors of a recent analysis in JAMA Internal Medicine explained that, although private equity involvement in physician practices may enable operational efficiencies, “critics point to potential conflicts of interest” and highlight concerns that patients “may face additional barriers to both accessibility and affordability of care.”

The difference, according to some oncologists, is their practices are not owned by the management services organization; instead, the practices enter contracts that outline the boundaries of the relationship and stipulate fees to the management organizations.

In 2020, Dr. Chasky’s practice, Alliance Cancer Specialists, joined The US Oncology Network, a management services organization wholly owned by McKesson. The organization provides the practice with capital and other resources, as well as access to the Sarah Cannon Research Institute, so patients can participate in clinical trials.

“We totally function as an independent practice,” said Dr. Chasky. “We make our own management decisions,” he said. For instance, if Alliance wants to hire a new clinician, US Oncology helps with the recruitment. “But at the end of the day, it’s our practice,” he said.

Davey Daniel, MD — whose community practice joined the management services organization OneOncology — has seen the benefits of being part of a larger network. For instance, bispecific therapies for leukemias, lymphomas, and multiple myeloma are typically administered at academic centers because of the risk for cytokine release syndrome.

However, physician leaders in the OneOncology network “came up with a playbook on how to do it safely” in the community setting, said Dr. Daniel. “It meant that we were adopting FDA newly approved therapies in a very short course.”

Being able to draw from a wider pool of expertise has had other advantages. Dr. Daniel can lean on pathologists and research scientists in the network for advice on targeted therapy use. “We’re actually bringing precision medicine expertise to the community,” Dr. Daniel said.

Dr. Chasky and Dr. Eagle, whose practice is also part of OneOncology, said that continuing to work in the community setting has allowed them greater flexibility.

Dr. Eagle explained that New York Cancer & Blood Specialists tries to offer patients an appointment within 2 days of a referral, and it allows walk-in visits.

Dr. Chasky leans into the flexibility by having staff stay late, when needed, to ensure that all patients are seen. “We’re there for our patients at all hours,” Dr. Chasky said, adding that often “you don’t have that flexibility when you work for a big hospital system.”

The bottom line is community oncology can still thrive, said Nick Ferreyros, managing director of COA, “as long as we have a healthy competitive ecosystem where [we] are valued and seen as an important part of our cancer care system.”

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

When he completed his fellowship at Fox Chase Cancer Center in Philadelphia, Moshe Chasky, MD, joined a small five-person practice that rented space from the city’s Jefferson Hospital in Philadelphia. The arrangement seemed to work well for the hospital and the small practice, which remained independent.

Within 10 years, the hospital sought to buy the practice, Alliance Cancer Specialists.

But the oncologists at Alliance did not want to join Jefferson.

The hospital eventually entered into an exclusive agreement with its own medical group to provide inpatient oncology/hematology services at three Jefferson Health–Northeast hospitals and stripped Dr. Chasky and his colleagues of their privileges at those facilities, Medscape Medical News reported last year.

The Alliance story is a familiar one for independent community oncology practices, said Jeff Patton, MD, CEO of OneOncology, a management services organization.

A 2020 report from the Community Oncology Alliance (COA), for instance, tracked mergers, acquisitions, and closures in the community oncology setting and found the number of practices acquired by hospitals, known as vertical integration, nearly tripled from 2010 to 2020.

“Some hospitals are pretty predatory in their approach,” Dr. Patton said. If hospitals have their own oncology program, “they’ll employ the referring doctors and then discourage them or prevent them from referring patients to our independent practices that are not owned by the hospital.”

Still, in the face of growing pressure to join hospitals, some community oncology practices are finding ways to survive and maintain their independence.
 

A Growing Trend

The latest data continue to show a clear trend: Consolidation in oncology is on the rise.

A 2024 study revealed that the pace of consolidation seems to be increasing.

The analysis found that, between 2015 and 2022, the number of medical oncologists increased by 14% and the number of medical oncologists per practice increased by 40%, while the number of practices decreased by 18%.

While about 44% of practices remain independent, the percentage of medical oncologists working in practices with more than 25 clinicians has increased from 34% in 2015 to 44% in 2022. By 2022, the largest 102 practices in the United States employed more than 40% of all medical oncologists.

“The rate of consolidation seems to be rapid,” study coauthor Parsa Erfani, MD, an internal medicine resident at Brigham & Women’s Hospital, Boston, explained.

Consolidation appears to breed more consolidation. The researchers found, for instance, that markets with greater hospital consolidation and more hospital beds per capita were more likely to undergo consolidation in oncology.

Consolidation may be higher in these markets “because hospitals or health systems are buying up oncology practices or conversely because oncology practices are merging to compete more effectively with larger hospitals in the area,” Dr. Erfani told this news organization.

Mergers among independent practices, known as horizontal integration, have also been on the rise, according to the 2020 COA report. These mergers can help counter pressures from hospitals seeking to acquire community practices as well as prevent practices and their clinics from closing.

Although Dr. Erfani’s research wasn’t designed to determine the factors behind consolidation, he and his colleagues point to the Affordable Care Act (ACA) and the federal 340B Drug Pricing Program as potential drivers of this trend.

The ACA encouraged consolidation as a way to improve efficiency and created the need for ever-larger information systems to collect and report quality data. But these data collection and reporting requirements have become increasingly difficult for smaller practices to take on.

The 340B Program, however, may be a bigger contributing factor to consolidation. Created in 1992, the 340B Program allows qualifying hospitals and clinics that treat low-income and uninsured patients to buy outpatient prescription drugs at a 25%-50% discount.

Hospitals seeking to capitalize on the margins possible under the 340B Program will “buy all the referring physicians in a market so that the medical oncology group is left with little choice but to sell to the hospital,” said Dr. Patton.

“Those 340B dollars are worth a lot to hospitals,” said David A. Eagle, MD, a hematologist/oncologist with New York Cancer & Blood Specialists and past president of COA. The program “creates an appetite for nonprofit hospitals to want to grow their medical oncology programs,” he told this news organization.

Declining Medicare reimbursement has also hit independent practices hard.

Over the past 15 years, compared with inflation, physicians have gotten “a pay rate decrease from Medicare,” said Dr. Patton. Payers have followed that lead and tried to cut pay for clinicians, especially those who do not have market share, he said. Paying them less is “disingenuous knowing that our costs of providing care are going up,” he said.
 

Less Access, Higher Costs, Worse Care?

Many studies have demonstrated that, when hospitals become behemoths in a given market, healthcare costs go up.

“There are robust data showing that consolidation increases healthcare costs by reducing competition, including in oncology,” wrote Dr. Erfani and colleagues.

Oncology practices that are owned by hospitals bill facility fees for outpatient chemotherapy treatment, adding another layer of cost, the researchers explained, citing a 2019 Health Economics study.

Another analysis, published in 2020, found that hospital prices for the top 37 infused cancer drugs averaged 86% more per unit than the price charged by physician offices. Hospital outpatient departments charged even more, on average, for drugs — 128% more for nivolumab and 428% more for fluorouracil, for instance.

In their 2024 analysis, Dr. Erfani and colleagues also found that increased hospital market concentration was associated with worse quality of care, across all assessed patient satisfaction measures, and may result in worse access to care as well.

Overall, these consolidation “trends have important implications for cancer care cost, quality, and access,” the authors concluded.
 

Navigating the Consolidation Trend

In the face of mounting pressure to join hospitals, community oncology practices have typically relied on horizontal mergers to maintain their independence. An increasing number of practices, however, are now turning to another strategy: Management services organizations.

According to some oncologists, a core benefit of joining a management services organization is their community practices can maintain autonomy, hold on to referrals, and benefit from access to a wider network of peers and recently approved treatments such as chimeric antigen receptor T-cell therapies.

In these arrangements, the management company also provides business assistance to practices, including help with billing and collection, payer negotiations, supply chain issues, and credentialing, as well as recruiting, hiring, and marketing.

These management organizations, which include American Oncology Network, Integrated Oncology Network, OneOncology, and Verdi Oncology, are, however, backed by private equity. According to a 2022 report, private equity–backed management organizations have ramped up arrangements with community oncology practices over the past few years — a trend that has concerned some experts.

The authors of a recent analysis in JAMA Internal Medicine explained that, although private equity involvement in physician practices may enable operational efficiencies, “critics point to potential conflicts of interest” and highlight concerns that patients “may face additional barriers to both accessibility and affordability of care.”

The difference, according to some oncologists, is their practices are not owned by the management services organization; instead, the practices enter contracts that outline the boundaries of the relationship and stipulate fees to the management organizations.

In 2020, Dr. Chasky’s practice, Alliance Cancer Specialists, joined The US Oncology Network, a management services organization wholly owned by McKesson. The organization provides the practice with capital and other resources, as well as access to the Sarah Cannon Research Institute, so patients can participate in clinical trials.

“We totally function as an independent practice,” said Dr. Chasky. “We make our own management decisions,” he said. For instance, if Alliance wants to hire a new clinician, US Oncology helps with the recruitment. “But at the end of the day, it’s our practice,” he said.

Davey Daniel, MD — whose community practice joined the management services organization OneOncology — has seen the benefits of being part of a larger network. For instance, bispecific therapies for leukemias, lymphomas, and multiple myeloma are typically administered at academic centers because of the risk for cytokine release syndrome.

However, physician leaders in the OneOncology network “came up with a playbook on how to do it safely” in the community setting, said Dr. Daniel. “It meant that we were adopting FDA newly approved therapies in a very short course.”

Being able to draw from a wider pool of expertise has had other advantages. Dr. Daniel can lean on pathologists and research scientists in the network for advice on targeted therapy use. “We’re actually bringing precision medicine expertise to the community,” Dr. Daniel said.

Dr. Chasky and Dr. Eagle, whose practice is also part of OneOncology, said that continuing to work in the community setting has allowed them greater flexibility.

Dr. Eagle explained that New York Cancer & Blood Specialists tries to offer patients an appointment within 2 days of a referral, and it allows walk-in visits.

Dr. Chasky leans into the flexibility by having staff stay late, when needed, to ensure that all patients are seen. “We’re there for our patients at all hours,” Dr. Chasky said, adding that often “you don’t have that flexibility when you work for a big hospital system.”

The bottom line is community oncology can still thrive, said Nick Ferreyros, managing director of COA, “as long as we have a healthy competitive ecosystem where [we] are valued and seen as an important part of our cancer care system.”

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

When he completed his fellowship at Fox Chase Cancer Center in Philadelphia, Moshe Chasky, MD, joined a small five-person practice that rented space from the city’s Jefferson Hospital in Philadelphia. The arrangement seemed to work well for the hospital and the small practice, which remained independent.

Within 10 years, the hospital sought to buy the practice, Alliance Cancer Specialists.

But the oncologists at Alliance did not want to join Jefferson.

The hospital eventually entered into an exclusive agreement with its own medical group to provide inpatient oncology/hematology services at three Jefferson Health–Northeast hospitals and stripped Dr. Chasky and his colleagues of their privileges at those facilities, Medscape Medical News reported last year.

The Alliance story is a familiar one for independent community oncology practices, said Jeff Patton, MD, CEO of OneOncology, a management services organization.

A 2020 report from the Community Oncology Alliance (COA), for instance, tracked mergers, acquisitions, and closures in the community oncology setting and found the number of practices acquired by hospitals, known as vertical integration, nearly tripled from 2010 to 2020.

“Some hospitals are pretty predatory in their approach,” Dr. Patton said. If hospitals have their own oncology program, “they’ll employ the referring doctors and then discourage them or prevent them from referring patients to our independent practices that are not owned by the hospital.”

Still, in the face of growing pressure to join hospitals, some community oncology practices are finding ways to survive and maintain their independence.
 

A Growing Trend

The latest data continue to show a clear trend: Consolidation in oncology is on the rise.

A 2024 study revealed that the pace of consolidation seems to be increasing.

The analysis found that, between 2015 and 2022, the number of medical oncologists increased by 14% and the number of medical oncologists per practice increased by 40%, while the number of practices decreased by 18%.

While about 44% of practices remain independent, the percentage of medical oncologists working in practices with more than 25 clinicians has increased from 34% in 2015 to 44% in 2022. By 2022, the largest 102 practices in the United States employed more than 40% of all medical oncologists.

“The rate of consolidation seems to be rapid,” study coauthor Parsa Erfani, MD, an internal medicine resident at Brigham & Women’s Hospital, Boston, explained.

Consolidation appears to breed more consolidation. The researchers found, for instance, that markets with greater hospital consolidation and more hospital beds per capita were more likely to undergo consolidation in oncology.

Consolidation may be higher in these markets “because hospitals or health systems are buying up oncology practices or conversely because oncology practices are merging to compete more effectively with larger hospitals in the area,” Dr. Erfani told this news organization.

Mergers among independent practices, known as horizontal integration, have also been on the rise, according to the 2020 COA report. These mergers can help counter pressures from hospitals seeking to acquire community practices as well as prevent practices and their clinics from closing.

Although Dr. Erfani’s research wasn’t designed to determine the factors behind consolidation, he and his colleagues point to the Affordable Care Act (ACA) and the federal 340B Drug Pricing Program as potential drivers of this trend.

The ACA encouraged consolidation as a way to improve efficiency and created the need for ever-larger information systems to collect and report quality data. But these data collection and reporting requirements have become increasingly difficult for smaller practices to take on.

The 340B Program, however, may be a bigger contributing factor to consolidation. Created in 1992, the 340B Program allows qualifying hospitals and clinics that treat low-income and uninsured patients to buy outpatient prescription drugs at a 25%-50% discount.

Hospitals seeking to capitalize on the margins possible under the 340B Program will “buy all the referring physicians in a market so that the medical oncology group is left with little choice but to sell to the hospital,” said Dr. Patton.

“Those 340B dollars are worth a lot to hospitals,” said David A. Eagle, MD, a hematologist/oncologist with New York Cancer & Blood Specialists and past president of COA. The program “creates an appetite for nonprofit hospitals to want to grow their medical oncology programs,” he told this news organization.

Declining Medicare reimbursement has also hit independent practices hard.

Over the past 15 years, compared with inflation, physicians have gotten “a pay rate decrease from Medicare,” said Dr. Patton. Payers have followed that lead and tried to cut pay for clinicians, especially those who do not have market share, he said. Paying them less is “disingenuous knowing that our costs of providing care are going up,” he said.
 

Less Access, Higher Costs, Worse Care?

Many studies have demonstrated that, when hospitals become behemoths in a given market, healthcare costs go up.

“There are robust data showing that consolidation increases healthcare costs by reducing competition, including in oncology,” wrote Dr. Erfani and colleagues.

Oncology practices that are owned by hospitals bill facility fees for outpatient chemotherapy treatment, adding another layer of cost, the researchers explained, citing a 2019 Health Economics study.

Another analysis, published in 2020, found that hospital prices for the top 37 infused cancer drugs averaged 86% more per unit than the price charged by physician offices. Hospital outpatient departments charged even more, on average, for drugs — 128% more for nivolumab and 428% more for fluorouracil, for instance.

In their 2024 analysis, Dr. Erfani and colleagues also found that increased hospital market concentration was associated with worse quality of care, across all assessed patient satisfaction measures, and may result in worse access to care as well.

Overall, these consolidation “trends have important implications for cancer care cost, quality, and access,” the authors concluded.
 

Navigating the Consolidation Trend

In the face of mounting pressure to join hospitals, community oncology practices have typically relied on horizontal mergers to maintain their independence. An increasing number of practices, however, are now turning to another strategy: Management services organizations.

According to some oncologists, a core benefit of joining a management services organization is their community practices can maintain autonomy, hold on to referrals, and benefit from access to a wider network of peers and recently approved treatments such as chimeric antigen receptor T-cell therapies.

In these arrangements, the management company also provides business assistance to practices, including help with billing and collection, payer negotiations, supply chain issues, and credentialing, as well as recruiting, hiring, and marketing.

These management organizations, which include American Oncology Network, Integrated Oncology Network, OneOncology, and Verdi Oncology, are, however, backed by private equity. According to a 2022 report, private equity–backed management organizations have ramped up arrangements with community oncology practices over the past few years — a trend that has concerned some experts.

The authors of a recent analysis in JAMA Internal Medicine explained that, although private equity involvement in physician practices may enable operational efficiencies, “critics point to potential conflicts of interest” and highlight concerns that patients “may face additional barriers to both accessibility and affordability of care.”

The difference, according to some oncologists, is their practices are not owned by the management services organization; instead, the practices enter contracts that outline the boundaries of the relationship and stipulate fees to the management organizations.

In 2020, Dr. Chasky’s practice, Alliance Cancer Specialists, joined The US Oncology Network, a management services organization wholly owned by McKesson. The organization provides the practice with capital and other resources, as well as access to the Sarah Cannon Research Institute, so patients can participate in clinical trials.

“We totally function as an independent practice,” said Dr. Chasky. “We make our own management decisions,” he said. For instance, if Alliance wants to hire a new clinician, US Oncology helps with the recruitment. “But at the end of the day, it’s our practice,” he said.

Davey Daniel, MD — whose community practice joined the management services organization OneOncology — has seen the benefits of being part of a larger network. For instance, bispecific therapies for leukemias, lymphomas, and multiple myeloma are typically administered at academic centers because of the risk for cytokine release syndrome.

However, physician leaders in the OneOncology network “came up with a playbook on how to do it safely” in the community setting, said Dr. Daniel. “It meant that we were adopting FDA newly approved therapies in a very short course.”

Being able to draw from a wider pool of expertise has had other advantages. Dr. Daniel can lean on pathologists and research scientists in the network for advice on targeted therapy use. “We’re actually bringing precision medicine expertise to the community,” Dr. Daniel said.

Dr. Chasky and Dr. Eagle, whose practice is also part of OneOncology, said that continuing to work in the community setting has allowed them greater flexibility.

Dr. Eagle explained that New York Cancer & Blood Specialists tries to offer patients an appointment within 2 days of a referral, and it allows walk-in visits.

Dr. Chasky leans into the flexibility by having staff stay late, when needed, to ensure that all patients are seen. “We’re there for our patients at all hours,” Dr. Chasky said, adding that often “you don’t have that flexibility when you work for a big hospital system.”

The bottom line is community oncology can still thrive, said Nick Ferreyros, managing director of COA, “as long as we have a healthy competitive ecosystem where [we] are valued and seen as an important part of our cancer care system.”

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

At the recent American Diabetes Association (ADA) Scientific Sessions, researchers unveiled promising data on a novel antimicrobial peptide PL-5 spray. This innovative treatment shows significant promise for managing mild to moderate infected diabetic foot ulcers. 

Of the 1.6 million people with diabetes in the United States and the tens of millions of similar people worldwide, 50% will require antimicrobials at some time during their life cycle. Diabetic foot infections are difficult to treat because of their resistance to conventional therapies, often leading to severe complications, including amputations. 

To address this issue, the antimicrobial peptide PL-5 spray was developed with a novel mechanism of action to potentially improve treatment outcomes. The study aimed to assess the clinical efficacy and safety of the PL-5 spray combined with standard debridement procedures in treating mild to moderate diabetic foot ulcers.

This multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted in four hospitals across China. Participants with mild to moderate diabetic foot ulcers were randomly assigned in a 2:1 ratio to either the PL-5 group or the placebo group, both receiving standard debridement. The primary endpoint was clinical efficacy at day 1 after the end of treatment (EOT1). Secondary endpoints included clinical efficacy at day 7 (EOT7), microbiological efficacy, drug-resistant bacteria clearance rate, wound healing rate, and safety outcomes evaluated at both EOT1 and EOT7.

The study included 47 participants, with 32 in the PL-5 group and 15 in the placebo group. Both groups had statistically comparable demographic and clinical characteristics. The primary endpoint showed a higher clinical efficacy (cure/improvement ratio) in the PL-5 group, compared with the control group (1.33 vs 0.55; P =.0764), suggesting a positive trend but not reaching statistical significance in this population.

Among the secondary endpoints, clinical efficacy at EOT7 was significantly higher in the PL-5 group than in the control group (1.6 vs 0.86). Microbial eradication rates were notably better in the PL-5 group at both EOT1 (57.89% vs 33.33%) and EOT7 (64.71% vs 40.00%). The clearance rates of drug-resistant bacteria were also higher in the PL-5 group at EOT1 (71.43% vs 50%).

Of importance, safety parameters showed no significant differences between the two groups (24.24% vs 33.33%), highlighting the favorable safety profile of PL-5 spray.

The study presented at the ADA Scientific Sessions provides a glint of promising evidence supporting the potential efficacy and safety of PL-5 spray in treating mild to moderate diabetic foot infections. Despite the limited sample size, the results suggest that PL-5 spray may enhance the recovery speed of diabetic foot wounds, particularly in clearing drug-resistant bacterial infections. These findings justify further investigation with larger sample sizes to confirm or refute the efficacy and potentially establish PL-5 spray as a standard treatment option in diabetic foot care.

The novel antimicrobial peptide PL-5 spray shows potential in addressing the challenging issue of diabetic foot infections. This recent ADA presentation sparked significant interest and discussions about the future of diabetic foot ulcer treatments, emphasizing the importance of innovative approaches in managing complex diabetic complications.

Dr. Armstrong is a professor of surgery and director of limb preservation at the University of Southern California, Los Angeles. He reported no relevant conflicts of interest.

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

At the recent American Diabetes Association (ADA) Scientific Sessions, researchers unveiled promising data on a novel antimicrobial peptide PL-5 spray. This innovative treatment shows significant promise for managing mild to moderate infected diabetic foot ulcers. 

Of the 1.6 million people with diabetes in the United States and the tens of millions of similar people worldwide, 50% will require antimicrobials at some time during their life cycle. Diabetic foot infections are difficult to treat because of their resistance to conventional therapies, often leading to severe complications, including amputations. 

To address this issue, the antimicrobial peptide PL-5 spray was developed with a novel mechanism of action to potentially improve treatment outcomes. The study aimed to assess the clinical efficacy and safety of the PL-5 spray combined with standard debridement procedures in treating mild to moderate diabetic foot ulcers.

This multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted in four hospitals across China. Participants with mild to moderate diabetic foot ulcers were randomly assigned in a 2:1 ratio to either the PL-5 group or the placebo group, both receiving standard debridement. The primary endpoint was clinical efficacy at day 1 after the end of treatment (EOT1). Secondary endpoints included clinical efficacy at day 7 (EOT7), microbiological efficacy, drug-resistant bacteria clearance rate, wound healing rate, and safety outcomes evaluated at both EOT1 and EOT7.

The study included 47 participants, with 32 in the PL-5 group and 15 in the placebo group. Both groups had statistically comparable demographic and clinical characteristics. The primary endpoint showed a higher clinical efficacy (cure/improvement ratio) in the PL-5 group, compared with the control group (1.33 vs 0.55; P =.0764), suggesting a positive trend but not reaching statistical significance in this population.

Among the secondary endpoints, clinical efficacy at EOT7 was significantly higher in the PL-5 group than in the control group (1.6 vs 0.86). Microbial eradication rates were notably better in the PL-5 group at both EOT1 (57.89% vs 33.33%) and EOT7 (64.71% vs 40.00%). The clearance rates of drug-resistant bacteria were also higher in the PL-5 group at EOT1 (71.43% vs 50%).

Of importance, safety parameters showed no significant differences between the two groups (24.24% vs 33.33%), highlighting the favorable safety profile of PL-5 spray.

The study presented at the ADA Scientific Sessions provides a glint of promising evidence supporting the potential efficacy and safety of PL-5 spray in treating mild to moderate diabetic foot infections. Despite the limited sample size, the results suggest that PL-5 spray may enhance the recovery speed of diabetic foot wounds, particularly in clearing drug-resistant bacterial infections. These findings justify further investigation with larger sample sizes to confirm or refute the efficacy and potentially establish PL-5 spray as a standard treatment option in diabetic foot care.

The novel antimicrobial peptide PL-5 spray shows potential in addressing the challenging issue of diabetic foot infections. This recent ADA presentation sparked significant interest and discussions about the future of diabetic foot ulcer treatments, emphasizing the importance of innovative approaches in managing complex diabetic complications.

Dr. Armstrong is a professor of surgery and director of limb preservation at the University of Southern California, Los Angeles. He reported no relevant conflicts of interest.

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

At the recent American Diabetes Association (ADA) Scientific Sessions, researchers unveiled promising data on a novel antimicrobial peptide PL-5 spray. This innovative treatment shows significant promise for managing mild to moderate infected diabetic foot ulcers. 

Of the 1.6 million people with diabetes in the United States and the tens of millions of similar people worldwide, 50% will require antimicrobials at some time during their life cycle. Diabetic foot infections are difficult to treat because of their resistance to conventional therapies, often leading to severe complications, including amputations. 

To address this issue, the antimicrobial peptide PL-5 spray was developed with a novel mechanism of action to potentially improve treatment outcomes. The study aimed to assess the clinical efficacy and safety of the PL-5 spray combined with standard debridement procedures in treating mild to moderate diabetic foot ulcers.

This multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted in four hospitals across China. Participants with mild to moderate diabetic foot ulcers were randomly assigned in a 2:1 ratio to either the PL-5 group or the placebo group, both receiving standard debridement. The primary endpoint was clinical efficacy at day 1 after the end of treatment (EOT1). Secondary endpoints included clinical efficacy at day 7 (EOT7), microbiological efficacy, drug-resistant bacteria clearance rate, wound healing rate, and safety outcomes evaluated at both EOT1 and EOT7.

The study included 47 participants, with 32 in the PL-5 group and 15 in the placebo group. Both groups had statistically comparable demographic and clinical characteristics. The primary endpoint showed a higher clinical efficacy (cure/improvement ratio) in the PL-5 group, compared with the control group (1.33 vs 0.55; P =.0764), suggesting a positive trend but not reaching statistical significance in this population.

Among the secondary endpoints, clinical efficacy at EOT7 was significantly higher in the PL-5 group than in the control group (1.6 vs 0.86). Microbial eradication rates were notably better in the PL-5 group at both EOT1 (57.89% vs 33.33%) and EOT7 (64.71% vs 40.00%). The clearance rates of drug-resistant bacteria were also higher in the PL-5 group at EOT1 (71.43% vs 50%).

Of importance, safety parameters showed no significant differences between the two groups (24.24% vs 33.33%), highlighting the favorable safety profile of PL-5 spray.

The study presented at the ADA Scientific Sessions provides a glint of promising evidence supporting the potential efficacy and safety of PL-5 spray in treating mild to moderate diabetic foot infections. Despite the limited sample size, the results suggest that PL-5 spray may enhance the recovery speed of diabetic foot wounds, particularly in clearing drug-resistant bacterial infections. These findings justify further investigation with larger sample sizes to confirm or refute the efficacy and potentially establish PL-5 spray as a standard treatment option in diabetic foot care.

The novel antimicrobial peptide PL-5 spray shows potential in addressing the challenging issue of diabetic foot infections. This recent ADA presentation sparked significant interest and discussions about the future of diabetic foot ulcer treatments, emphasizing the importance of innovative approaches in managing complex diabetic complications.

Dr. Armstrong is a professor of surgery and director of limb preservation at the University of Southern California, Los Angeles. He reported no relevant conflicts of interest.

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