Federal Practitioner

While bariatric surgery does nothing to directly improve the disease of patients with type 1 diabetes, it can work indirectly by moderating severe obesity and improving insulin sensitivity to cut the total insulin needs of patients with type 1 diabetes and obesity, based on a single-center, retrospective chart review of 38 U.S. patients.

Two years following their bariatric surgery, these 38 patients with confirmed type 1 diabetes and an average body mass index of 43 kg/m² before surgery saw their average daily insulin requirement nearly halved, dropping from 118 units/day to 60 units/day, a significant decrease, Brian J. Dessify, DO, said in a presentation at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

Another measure of this effect showed that the percentage of patients who required more than one drug for treating their hyperglycemia fell from 66% before surgery to 52% 2 years after surgery, a change that was not statistically significant, said Dr. Dessify, a bariatric surgeon at Geisinger Medical Center in Danville, Pa.
 

Appropriate for patients with ‘double diabetes’

These results “provide good evidence for [using] bariatric surgery” in people with both obesity and type 1 diabetes,” he concluded. This includes people with what Dr. Dessify called “double diabetes,” meaning that they do not make endogenous insulin, and are also resistant to the effects of exogenous insulin and hence have features of both type 2 and type 1 diabetes.

Patrice Wendling/MDedge News

“This is a really important study,” commented Ali Aminian, MD, director of the Bariatric and Metabolic Institute of the Cleveland Clinic. “For patients with type 1 diabetes, the primary goal of bariatric surgery is weight loss and improvement of obesity-related comorbidities. Patients with type 2 diabetes can be a candidate for bariatric surgery regardless of their weight,” Dr. Aminian said as designated discussant for the report.

“The goal of bariatric surgery in patients with type 1 diabetes is to promote sensitivity to the exogenous insulin they receive,” agreed Julie Kim, MD, a bariatric surgeon at Mount Auburn Hospital in Waltham, Mass., and a second discussant for the report. Patients with double diabetes “are probably a subclass of patients [with type 1 diabetes] who might benefit even more from bariatric surgery.”
 

Using gastric sleeves to avoid diabetic ketoacidosis

Dr. Aminian also noted that “at the Cleveland Clinic we consider a sleeve gastrectomy the procedure of choice” for patients with type 1 diabetes or type 2 diabetes with insulin insufficiency “unless the patient has an absolute contraindication” because of the increased risk for diabetic ketoacidosis in these patients “undergoing any surgery, including bariatric surgery.” Patients with insulin insufficiency “require intensive diabetes and insulin management preoperatively to reduce their risk for developing diabetic ketoacidosis,” and using a sleeve rather than bypass generally results in “more reliable absorption of carbohydrates and nutrients” while also reducing the risk for hypoglycemia, Dr. Aminian said.

In the series reported by Dr. Dessify, 33 patients underwent gastric bypass and 5 had sleeve gastrectomy. The decision to use bypass usually stemmed from its “marginal” improvement in weight loss, compared with a sleeve procedure, and an overall preference at Geisinger for bypass procedures. Dr. Dessify added that he had not yet run a comprehensive assessment of diabetic ketoacidosis complications among patients in his reported series.

Those 38 patients underwent their bariatric procedure during 2002-2019, constituting fewer than 1% of the 4,549 total bariatric surgeries done at Geisinger during that period. The 38 patients with type 1 diabetes averaged 41 years of age, 33 (87%) were women, and 37 (97%) were White. Dr. Dessify and associates undertook this review “to help provide supporting evidence for using bariatric surgery in people with obesity and type 1 diabetes,” he noted.

Dr. Dessify, Dr. Aminian, and Dr. Kim had no disclosures.

[email protected]

While bariatric surgery does nothing to directly improve the disease of patients with type 1 diabetes, it can work indirectly by moderating severe obesity and improving insulin sensitivity to cut the total insulin needs of patients with type 1 diabetes and obesity, based on a single-center, retrospective chart review of 38 U.S. patients.

Two years following their bariatric surgery, these 38 patients with confirmed type 1 diabetes and an average body mass index of 43 kg/m² before surgery saw their average daily insulin requirement nearly halved, dropping from 118 units/day to 60 units/day, a significant decrease, Brian J. Dessify, DO, said in a presentation at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

Another measure of this effect showed that the percentage of patients who required more than one drug for treating their hyperglycemia fell from 66% before surgery to 52% 2 years after surgery, a change that was not statistically significant, said Dr. Dessify, a bariatric surgeon at Geisinger Medical Center in Danville, Pa.
 

Appropriate for patients with ‘double diabetes’

These results “provide good evidence for [using] bariatric surgery” in people with both obesity and type 1 diabetes,” he concluded. This includes people with what Dr. Dessify called “double diabetes,” meaning that they do not make endogenous insulin, and are also resistant to the effects of exogenous insulin and hence have features of both type 2 and type 1 diabetes.

Patrice Wendling/MDedge News

“This is a really important study,” commented Ali Aminian, MD, director of the Bariatric and Metabolic Institute of the Cleveland Clinic. “For patients with type 1 diabetes, the primary goal of bariatric surgery is weight loss and improvement of obesity-related comorbidities. Patients with type 2 diabetes can be a candidate for bariatric surgery regardless of their weight,” Dr. Aminian said as designated discussant for the report.

“The goal of bariatric surgery in patients with type 1 diabetes is to promote sensitivity to the exogenous insulin they receive,” agreed Julie Kim, MD, a bariatric surgeon at Mount Auburn Hospital in Waltham, Mass., and a second discussant for the report. Patients with double diabetes “are probably a subclass of patients [with type 1 diabetes] who might benefit even more from bariatric surgery.”
 

Using gastric sleeves to avoid diabetic ketoacidosis

Dr. Aminian also noted that “at the Cleveland Clinic we consider a sleeve gastrectomy the procedure of choice” for patients with type 1 diabetes or type 2 diabetes with insulin insufficiency “unless the patient has an absolute contraindication” because of the increased risk for diabetic ketoacidosis in these patients “undergoing any surgery, including bariatric surgery.” Patients with insulin insufficiency “require intensive diabetes and insulin management preoperatively to reduce their risk for developing diabetic ketoacidosis,” and using a sleeve rather than bypass generally results in “more reliable absorption of carbohydrates and nutrients” while also reducing the risk for hypoglycemia, Dr. Aminian said.

In the series reported by Dr. Dessify, 33 patients underwent gastric bypass and 5 had sleeve gastrectomy. The decision to use bypass usually stemmed from its “marginal” improvement in weight loss, compared with a sleeve procedure, and an overall preference at Geisinger for bypass procedures. Dr. Dessify added that he had not yet run a comprehensive assessment of diabetic ketoacidosis complications among patients in his reported series.

Those 38 patients underwent their bariatric procedure during 2002-2019, constituting fewer than 1% of the 4,549 total bariatric surgeries done at Geisinger during that period. The 38 patients with type 1 diabetes averaged 41 years of age, 33 (87%) were women, and 37 (97%) were White. Dr. Dessify and associates undertook this review “to help provide supporting evidence for using bariatric surgery in people with obesity and type 1 diabetes,” he noted.

Dr. Dessify, Dr. Aminian, and Dr. Kim had no disclosures.

[email protected]

While bariatric surgery does nothing to directly improve the disease of patients with type 1 diabetes, it can work indirectly by moderating severe obesity and improving insulin sensitivity to cut the total insulin needs of patients with type 1 diabetes and obesity, based on a single-center, retrospective chart review of 38 U.S. patients.

Two years following their bariatric surgery, these 38 patients with confirmed type 1 diabetes and an average body mass index of 43 kg/m² before surgery saw their average daily insulin requirement nearly halved, dropping from 118 units/day to 60 units/day, a significant decrease, Brian J. Dessify, DO, said in a presentation at the annual meeting of the American Society for Metabolic and Bariatric Surgery.

Another measure of this effect showed that the percentage of patients who required more than one drug for treating their hyperglycemia fell from 66% before surgery to 52% 2 years after surgery, a change that was not statistically significant, said Dr. Dessify, a bariatric surgeon at Geisinger Medical Center in Danville, Pa.
 

Appropriate for patients with ‘double diabetes’

These results “provide good evidence for [using] bariatric surgery” in people with both obesity and type 1 diabetes,” he concluded. This includes people with what Dr. Dessify called “double diabetes,” meaning that they do not make endogenous insulin, and are also resistant to the effects of exogenous insulin and hence have features of both type 2 and type 1 diabetes.

Patrice Wendling/MDedge News

“This is a really important study,” commented Ali Aminian, MD, director of the Bariatric and Metabolic Institute of the Cleveland Clinic. “For patients with type 1 diabetes, the primary goal of bariatric surgery is weight loss and improvement of obesity-related comorbidities. Patients with type 2 diabetes can be a candidate for bariatric surgery regardless of their weight,” Dr. Aminian said as designated discussant for the report.

“The goal of bariatric surgery in patients with type 1 diabetes is to promote sensitivity to the exogenous insulin they receive,” agreed Julie Kim, MD, a bariatric surgeon at Mount Auburn Hospital in Waltham, Mass., and a second discussant for the report. Patients with double diabetes “are probably a subclass of patients [with type 1 diabetes] who might benefit even more from bariatric surgery.”
 

Using gastric sleeves to avoid diabetic ketoacidosis

Dr. Aminian also noted that “at the Cleveland Clinic we consider a sleeve gastrectomy the procedure of choice” for patients with type 1 diabetes or type 2 diabetes with insulin insufficiency “unless the patient has an absolute contraindication” because of the increased risk for diabetic ketoacidosis in these patients “undergoing any surgery, including bariatric surgery.” Patients with insulin insufficiency “require intensive diabetes and insulin management preoperatively to reduce their risk for developing diabetic ketoacidosis,” and using a sleeve rather than bypass generally results in “more reliable absorption of carbohydrates and nutrients” while also reducing the risk for hypoglycemia, Dr. Aminian said.

In the series reported by Dr. Dessify, 33 patients underwent gastric bypass and 5 had sleeve gastrectomy. The decision to use bypass usually stemmed from its “marginal” improvement in weight loss, compared with a sleeve procedure, and an overall preference at Geisinger for bypass procedures. Dr. Dessify added that he had not yet run a comprehensive assessment of diabetic ketoacidosis complications among patients in his reported series.

Those 38 patients underwent their bariatric procedure during 2002-2019, constituting fewer than 1% of the 4,549 total bariatric surgeries done at Geisinger during that period. The 38 patients with type 1 diabetes averaged 41 years of age, 33 (87%) were women, and 37 (97%) were White. Dr. Dessify and associates undertook this review “to help provide supporting evidence for using bariatric surgery in people with obesity and type 1 diabetes,” he noted.

Dr. Dessify, Dr. Aminian, and Dr. Kim had no disclosures.

[email protected]

A high-profile, Washington-based consumer advocacy group is calling for the removal of the U.S. Food and Drug Administration’s acting commissioner and two other top officials, saying that the agency’s approval of the Alzheimer’s drug aducanumab (Aduhelm, Biogen) was “reckless.”

In a letter to the U.S. Department of Health and Human Services Secretary Xavier Becerra, Michael A. Carome, MD, director of Public Citizen’s Health Research Group, said: “The FDA’s decision to approve aducanumab for anyone with Alzheimer’s disease, regardless of severity, showed a stunning disregard for science, eviscerated the agency’s standards for approving new drugs, and ranks as one of the most irresponsible and egregious decisions in the history of the agency.”

Public Citizen urged Mr. Becerra to seek the resignations or the removal of the three FDA officials it said were most responsible for the approval – Acting FDA Commissioner Janet Woodcock, MD; Center for Drug Evaluation and Research (CDER) Director Patrizia Cavazzoni, MD; and CDER’s Office of Neuroscience Director Billy Dunn, MD.

“This decision is a disastrous blow to the agency’s credibility, public health, and the financial sustainability of the Medicare program,” writes Dr. Carome, noting that Biogen said it would charge $56,000 annually for the infusion.

Aaron Kesselheim, MD, one of three FDA Peripheral and Central Nervous System Drugs advisory committee members who resigned in the wake of the approval, agreed with Public Citizen that the agency’s credibility is suffering.

“The aducanumab decision is the worst example yet of the FDA’s movement away from its high standards,” Dr. Kesselheim, a professor of medicine at Harvard Medical School, Boston, and Harvard colleague Jerry Avorn, MD, wrote in the New York Times on June 15.

“As physicians, we know well that Alzheimer’s disease is a terrible condition,” they wrote. However, they added, “approving a drug that has such poor evidence that it works and causes such worrisome side effects is not the solution.”

In his resignation letter, Dr. Kesselheim said he had also been dismayed by the agency’s 2016 approval of eteplirsen (Exondys 51, Sarepta Therapeutics) for Duchenne muscular dystrophy. In both the eteplirsen and aducanumab approvals, the agency went against its advisers’ recommendations, Dr. Kesselheim said.
 

Advocates who backed approval decry cost

Aducanumab had a rocky road to approval but had unwavering backing from the Alzheimer’s Association and at least one other organization, UsAgainstAlzheimer’s.

The Alzheimer’s Association was particularly outspoken in its support and, in March, was accused of potential conflict of interest by Public Citizen and several neurologists because the association accepted at least $1.4 million from Biogen and its partner Eisai since fiscal year 2018.

The association applauded the FDA approval but, a few days later, expressed outrage over the $56,000-a-year price tag.

“This price is simply unacceptable,” the Alzheimer’s Association said in the statement. “For many, this price will pose an insurmountable barrier to access, it complicates and jeopardizes sustainable access to this treatment, and may further deepen issues of health equity,” the association said, adding, “We call on Biogen to change this price.”

UsAgainstAlzheimer’s also expressed concerns about access, even before it knew aducanumab’s price.  

“Shockingly, Medicare does not reimburse patients for the expensive PET scans important to determine whether someone is appropriate for this drug,” noted George Vradenburg, chairman and cofounder of the group, in a June 7 statement. “We intend to work with Biogen and Medicare to make access to this drug affordable for every American who needs it,” Mr. Vradenburg said.

Dr. Carome said the advocates’ complaints were hard to fathom.

“This should not have come as a surprise to anyone,” Dr. Carome said, adding that “it’s essentially the ballpark figure the company threw out weeks ago.”

“Fifty-six-thousand-dollars is particularly egregiously overpriced for a drug that doesn’t work,” Dr. Carome said. “If the [Alzheimer’s Association] truly finds this objectionable, hopefully they’ll stop accepting money from Biogen and its partner Eisai,” he added.

“The Alzheimer’s Association is recognizing that the genie is out of the bottle and that they are going to have trouble reining in the inevitable run-away costs,” said Mike Greicius, MD, MPH, associate professor of neurology at Stanford University’s Wu Tsai Neurosciences Institute, Stanford, California.

“In addition to the eye-popping annual cost that Biogen has invented, I hope the Alzheimer’s Association is also concerned about the dangerously loose and broad FDA labeling which does not require screening for amyloid-positivity and does not restrict use to the milder forms of disease studied in the Phase 3 trials,” Dr. Greicius said.

Another advocacy group, Patients For Affordable Drugs, commended the Alzheimer’s Association. Its statement “was nothing short of courageous, especially in light of the Alzheimer’s Association’s reliance on funding from drug corporations, including Biogen,” said David Mitchell, a cancer patient and founder of Patients For Affordable Drugs, in a statement.

Mr. Mitchell said his members “stand with the Alzheimer’s Association in its denunciation of the price set by Biogen” and called for a new law that would allow Medicare to negotiate drug prices.

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

A high-profile, Washington-based consumer advocacy group is calling for the removal of the U.S. Food and Drug Administration’s acting commissioner and two other top officials, saying that the agency’s approval of the Alzheimer’s drug aducanumab (Aduhelm, Biogen) was “reckless.”

In a letter to the U.S. Department of Health and Human Services Secretary Xavier Becerra, Michael A. Carome, MD, director of Public Citizen’s Health Research Group, said: “The FDA’s decision to approve aducanumab for anyone with Alzheimer’s disease, regardless of severity, showed a stunning disregard for science, eviscerated the agency’s standards for approving new drugs, and ranks as one of the most irresponsible and egregious decisions in the history of the agency.”

Public Citizen urged Mr. Becerra to seek the resignations or the removal of the three FDA officials it said were most responsible for the approval – Acting FDA Commissioner Janet Woodcock, MD; Center for Drug Evaluation and Research (CDER) Director Patrizia Cavazzoni, MD; and CDER’s Office of Neuroscience Director Billy Dunn, MD.

“This decision is a disastrous blow to the agency’s credibility, public health, and the financial sustainability of the Medicare program,” writes Dr. Carome, noting that Biogen said it would charge $56,000 annually for the infusion.

Aaron Kesselheim, MD, one of three FDA Peripheral and Central Nervous System Drugs advisory committee members who resigned in the wake of the approval, agreed with Public Citizen that the agency’s credibility is suffering.

“The aducanumab decision is the worst example yet of the FDA’s movement away from its high standards,” Dr. Kesselheim, a professor of medicine at Harvard Medical School, Boston, and Harvard colleague Jerry Avorn, MD, wrote in the New York Times on June 15.

“As physicians, we know well that Alzheimer’s disease is a terrible condition,” they wrote. However, they added, “approving a drug that has such poor evidence that it works and causes such worrisome side effects is not the solution.”

In his resignation letter, Dr. Kesselheim said he had also been dismayed by the agency’s 2016 approval of eteplirsen (Exondys 51, Sarepta Therapeutics) for Duchenne muscular dystrophy. In both the eteplirsen and aducanumab approvals, the agency went against its advisers’ recommendations, Dr. Kesselheim said.
 

Advocates who backed approval decry cost

Aducanumab had a rocky road to approval but had unwavering backing from the Alzheimer’s Association and at least one other organization, UsAgainstAlzheimer’s.

The Alzheimer’s Association was particularly outspoken in its support and, in March, was accused of potential conflict of interest by Public Citizen and several neurologists because the association accepted at least $1.4 million from Biogen and its partner Eisai since fiscal year 2018.

The association applauded the FDA approval but, a few days later, expressed outrage over the $56,000-a-year price tag.

“This price is simply unacceptable,” the Alzheimer’s Association said in the statement. “For many, this price will pose an insurmountable barrier to access, it complicates and jeopardizes sustainable access to this treatment, and may further deepen issues of health equity,” the association said, adding, “We call on Biogen to change this price.”

UsAgainstAlzheimer’s also expressed concerns about access, even before it knew aducanumab’s price.  

“Shockingly, Medicare does not reimburse patients for the expensive PET scans important to determine whether someone is appropriate for this drug,” noted George Vradenburg, chairman and cofounder of the group, in a June 7 statement. “We intend to work with Biogen and Medicare to make access to this drug affordable for every American who needs it,” Mr. Vradenburg said.

Dr. Carome said the advocates’ complaints were hard to fathom.

“This should not have come as a surprise to anyone,” Dr. Carome said, adding that “it’s essentially the ballpark figure the company threw out weeks ago.”

“Fifty-six-thousand-dollars is particularly egregiously overpriced for a drug that doesn’t work,” Dr. Carome said. “If the [Alzheimer’s Association] truly finds this objectionable, hopefully they’ll stop accepting money from Biogen and its partner Eisai,” he added.

“The Alzheimer’s Association is recognizing that the genie is out of the bottle and that they are going to have trouble reining in the inevitable run-away costs,” said Mike Greicius, MD, MPH, associate professor of neurology at Stanford University’s Wu Tsai Neurosciences Institute, Stanford, California.

“In addition to the eye-popping annual cost that Biogen has invented, I hope the Alzheimer’s Association is also concerned about the dangerously loose and broad FDA labeling which does not require screening for amyloid-positivity and does not restrict use to the milder forms of disease studied in the Phase 3 trials,” Dr. Greicius said.

Another advocacy group, Patients For Affordable Drugs, commended the Alzheimer’s Association. Its statement “was nothing short of courageous, especially in light of the Alzheimer’s Association’s reliance on funding from drug corporations, including Biogen,” said David Mitchell, a cancer patient and founder of Patients For Affordable Drugs, in a statement.

Mr. Mitchell said his members “stand with the Alzheimer’s Association in its denunciation of the price set by Biogen” and called for a new law that would allow Medicare to negotiate drug prices.

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

A high-profile, Washington-based consumer advocacy group is calling for the removal of the U.S. Food and Drug Administration’s acting commissioner and two other top officials, saying that the agency’s approval of the Alzheimer’s drug aducanumab (Aduhelm, Biogen) was “reckless.”

In a letter to the U.S. Department of Health and Human Services Secretary Xavier Becerra, Michael A. Carome, MD, director of Public Citizen’s Health Research Group, said: “The FDA’s decision to approve aducanumab for anyone with Alzheimer’s disease, regardless of severity, showed a stunning disregard for science, eviscerated the agency’s standards for approving new drugs, and ranks as one of the most irresponsible and egregious decisions in the history of the agency.”

Public Citizen urged Mr. Becerra to seek the resignations or the removal of the three FDA officials it said were most responsible for the approval – Acting FDA Commissioner Janet Woodcock, MD; Center for Drug Evaluation and Research (CDER) Director Patrizia Cavazzoni, MD; and CDER’s Office of Neuroscience Director Billy Dunn, MD.

“This decision is a disastrous blow to the agency’s credibility, public health, and the financial sustainability of the Medicare program,” writes Dr. Carome, noting that Biogen said it would charge $56,000 annually for the infusion.

Aaron Kesselheim, MD, one of three FDA Peripheral and Central Nervous System Drugs advisory committee members who resigned in the wake of the approval, agreed with Public Citizen that the agency’s credibility is suffering.

“The aducanumab decision is the worst example yet of the FDA’s movement away from its high standards,” Dr. Kesselheim, a professor of medicine at Harvard Medical School, Boston, and Harvard colleague Jerry Avorn, MD, wrote in the New York Times on June 15.

“As physicians, we know well that Alzheimer’s disease is a terrible condition,” they wrote. However, they added, “approving a drug that has such poor evidence that it works and causes such worrisome side effects is not the solution.”

In his resignation letter, Dr. Kesselheim said he had also been dismayed by the agency’s 2016 approval of eteplirsen (Exondys 51, Sarepta Therapeutics) for Duchenne muscular dystrophy. In both the eteplirsen and aducanumab approvals, the agency went against its advisers’ recommendations, Dr. Kesselheim said.
 

Advocates who backed approval decry cost

Aducanumab had a rocky road to approval but had unwavering backing from the Alzheimer’s Association and at least one other organization, UsAgainstAlzheimer’s.

The Alzheimer’s Association was particularly outspoken in its support and, in March, was accused of potential conflict of interest by Public Citizen and several neurologists because the association accepted at least $1.4 million from Biogen and its partner Eisai since fiscal year 2018.

The association applauded the FDA approval but, a few days later, expressed outrage over the $56,000-a-year price tag.

“This price is simply unacceptable,” the Alzheimer’s Association said in the statement. “For many, this price will pose an insurmountable barrier to access, it complicates and jeopardizes sustainable access to this treatment, and may further deepen issues of health equity,” the association said, adding, “We call on Biogen to change this price.”

UsAgainstAlzheimer’s also expressed concerns about access, even before it knew aducanumab’s price.  

“Shockingly, Medicare does not reimburse patients for the expensive PET scans important to determine whether someone is appropriate for this drug,” noted George Vradenburg, chairman and cofounder of the group, in a June 7 statement. “We intend to work with Biogen and Medicare to make access to this drug affordable for every American who needs it,” Mr. Vradenburg said.

Dr. Carome said the advocates’ complaints were hard to fathom.

“This should not have come as a surprise to anyone,” Dr. Carome said, adding that “it’s essentially the ballpark figure the company threw out weeks ago.”

“Fifty-six-thousand-dollars is particularly egregiously overpriced for a drug that doesn’t work,” Dr. Carome said. “If the [Alzheimer’s Association] truly finds this objectionable, hopefully they’ll stop accepting money from Biogen and its partner Eisai,” he added.

“The Alzheimer’s Association is recognizing that the genie is out of the bottle and that they are going to have trouble reining in the inevitable run-away costs,” said Mike Greicius, MD, MPH, associate professor of neurology at Stanford University’s Wu Tsai Neurosciences Institute, Stanford, California.

“In addition to the eye-popping annual cost that Biogen has invented, I hope the Alzheimer’s Association is also concerned about the dangerously loose and broad FDA labeling which does not require screening for amyloid-positivity and does not restrict use to the milder forms of disease studied in the Phase 3 trials,” Dr. Greicius said.

Another advocacy group, Patients For Affordable Drugs, commended the Alzheimer’s Association. Its statement “was nothing short of courageous, especially in light of the Alzheimer’s Association’s reliance on funding from drug corporations, including Biogen,” said David Mitchell, a cancer patient and founder of Patients For Affordable Drugs, in a statement.

Mr. Mitchell said his members “stand with the Alzheimer’s Association in its denunciation of the price set by Biogen” and called for a new law that would allow Medicare to negotiate drug prices.

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

Gradually, we are emerging from the chaos, isolation, and anxiety of COVID-19. As the Centers for Disease Control and Prevention adjusts its recommendations and vaccinations become more widely available, our communities are beginning to return to normalcy. We are encouraged to put aside our masks if vaccinated and rejoin society, to venture out with less hesitancy and anxiety. As family and friends reunite, memories of confusion, frustration, and fear are beginning to fade to black. Despite the prevailing belief that we should move on, look forward, and remember the past to safeguard our future, remnants of the pandemic remain.

shironosov/Getty Images

Unvaccinated individuals, notably children under the age of 12, are quite significant in number. The use of telehealth is now standard practice.

For several years, we were warned about the looming “mental health crisis.” The past year has demonstrated that a crisis no longer looms – it has arrived. Our patients can reveal the vulnerability COVID-19 has wrought – from the devastation of lives lost, supply shortages, loss of employment and financial stability – to a lack of access to computers and thereby, the risk of educational decline. Those factors, coupled with isolation and uncertainty about the future, have led to an influx of individuals with anxiety, depression, and other mood disorders seeking mental health treatment.
 

Doctors, others suffering

As result of a medical culture guided by the sacred oath to which care, compassion, and dedication held as true in ancient Greece as it does today, the focus centers on those around us – while signs of our own weariness are waved away as “a bad day.” Even though several support groups are readily available to offer a listening ear and mental health physicians who focus on the treatment of health care professionals are becoming more ubiquitous, the vestiges of past doctrine remain.

In this modern age of medical training, there is often as much sacrifice as there is attainment of knowledge. This philosophy is so ingrained that throughout training and practice one may come across colleagues experiencing an abundance of guilt when leave is needed for personal reasons. We are quick to recommend such steps for our patients, family, and friends, but hesitant to consider such for ourselves. Yet, of all the lessons this past year has wrought, the importance of mental health and self-care cannot be overstated. This raises the question: How do we incorporate wellness into our routines while navigating the complexity of medicine?

It is vital to accept our humanity as something not to repair, treat, or overcome but to understand. There is strength and power in vulnerability. If we do not perceive and validate this process within ourselves, how can we do so for others? In other words, the oxygen mask must be placed on us first before we can place it on anyone else – patients or otherwise.

Chiefly and above all else, the importance of identifying individual signs of stress is essential. Where do you hold tension? Are you prone to GI distress or headaches when taxed? Do you tend toward irritability, apathy, or exhaustion?

Once this is determined, it is important to assess your stress on a numerical scale, such as those used for pain. Are you a 5 or an 8? Finally, are there identifiable triggers or reliable alleviators? Is there a time of day or day of the week that is most difficult to manage? Can you anticipate potential stressors? Understanding your triggers, listening to your body, and practicing the language of self is the first step toward wellness.

Following introspection and observation, the next step is inventory. Take stock of your reserves. What replenishes? What depletes? What brings joy? What brings dread? Are there certain activities that mitigate stress? If so, how much time do they entail? Identify your number on a scale and associate that number with specific strategies or techniques. Remember that decompression for a 6 might be excessive for a 4. Furthermore, what is the duration of these feelings? Chronic stressors may incur gradual change verses sudden impact if acute. Through identifying personal signs, devising and using a scale, as well as escalating or de-escalating factors, individuals become more in tune with their bodies and therefore, more likely to intervene before burnout takes hold.

With this process well integrated, one can now consider stylized approaches for stress management. For example, those inclined toward mindfulness practices may find yoga, meditation, and relaxation exercises beneficial. Others may thrive on positive affirmations, gratitude, and thankfulness. While some might find relief in physical activity, be it strenuous or casual, the creative arts might appeal to those who find joy in painting, writing, or doing crafts. In addition, baking, reading, dancing, and/or listening to music might help lift stress.

Along with those discoveries, or in some cases, rediscoveries, basic needs such as dietary habits and nutrition, hydration, and sleep are vital toward emotional regulation, physiological homeostasis, and stress modulation. Remember HALT: Hungry, Angry, Lonely, Tired, Too hot, Too cold, Sad or Stressed. Those strategies are meant to guide self-care and highlight the importance of allowing time for self-awareness. Imagine yourself as if you are meeting a new patient. Establish rapport, identify symptoms, and explore options for treatment. When we give time to ourselves, we can give time more freely to others. With this in mind, try following the 5-minute wellness check that I formulated:

1. How am I feeling? What am I feeling?

2. Assess HALTS.

3. Identify the number on your scale.

4. Methods of quick de-escalation:

• Designate and schedule personal time.
• Write down daily goals.
• Repeat positive affirmations or write down words of gratitude.
• Use deep breathing exercises.
• Stretch or take a brief walk.
• Engage in mindfulness practices, such as meditation.

Once we develop a habit of monitoring, assessing, and practicing self-care, the process becomes more efficient and effective. Think of the way a seasoned attending can manage workflow with ease, compared with an intern. Recognizing signs and using these strategies routinely can become a quick daily measure of well-being.
 

Dr. Thomas is a board-certified adult psychiatrist with interests in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. Dr. Thomas has no conflicts of interest.

Gradually, we are emerging from the chaos, isolation, and anxiety of COVID-19. As the Centers for Disease Control and Prevention adjusts its recommendations and vaccinations become more widely available, our communities are beginning to return to normalcy. We are encouraged to put aside our masks if vaccinated and rejoin society, to venture out with less hesitancy and anxiety. As family and friends reunite, memories of confusion, frustration, and fear are beginning to fade to black. Despite the prevailing belief that we should move on, look forward, and remember the past to safeguard our future, remnants of the pandemic remain.

shironosov/Getty Images

Unvaccinated individuals, notably children under the age of 12, are quite significant in number. The use of telehealth is now standard practice.

For several years, we were warned about the looming “mental health crisis.” The past year has demonstrated that a crisis no longer looms – it has arrived. Our patients can reveal the vulnerability COVID-19 has wrought – from the devastation of lives lost, supply shortages, loss of employment and financial stability – to a lack of access to computers and thereby, the risk of educational decline. Those factors, coupled with isolation and uncertainty about the future, have led to an influx of individuals with anxiety, depression, and other mood disorders seeking mental health treatment.
 

Doctors, others suffering

As result of a medical culture guided by the sacred oath to which care, compassion, and dedication held as true in ancient Greece as it does today, the focus centers on those around us – while signs of our own weariness are waved away as “a bad day.” Even though several support groups are readily available to offer a listening ear and mental health physicians who focus on the treatment of health care professionals are becoming more ubiquitous, the vestiges of past doctrine remain.

In this modern age of medical training, there is often as much sacrifice as there is attainment of knowledge. This philosophy is so ingrained that throughout training and practice one may come across colleagues experiencing an abundance of guilt when leave is needed for personal reasons. We are quick to recommend such steps for our patients, family, and friends, but hesitant to consider such for ourselves. Yet, of all the lessons this past year has wrought, the importance of mental health and self-care cannot be overstated. This raises the question: How do we incorporate wellness into our routines while navigating the complexity of medicine?

It is vital to accept our humanity as something not to repair, treat, or overcome but to understand. There is strength and power in vulnerability. If we do not perceive and validate this process within ourselves, how can we do so for others? In other words, the oxygen mask must be placed on us first before we can place it on anyone else – patients or otherwise.

Chiefly and above all else, the importance of identifying individual signs of stress is essential. Where do you hold tension? Are you prone to GI distress or headaches when taxed? Do you tend toward irritability, apathy, or exhaustion?

Once this is determined, it is important to assess your stress on a numerical scale, such as those used for pain. Are you a 5 or an 8? Finally, are there identifiable triggers or reliable alleviators? Is there a time of day or day of the week that is most difficult to manage? Can you anticipate potential stressors? Understanding your triggers, listening to your body, and practicing the language of self is the first step toward wellness.

Following introspection and observation, the next step is inventory. Take stock of your reserves. What replenishes? What depletes? What brings joy? What brings dread? Are there certain activities that mitigate stress? If so, how much time do they entail? Identify your number on a scale and associate that number with specific strategies or techniques. Remember that decompression for a 6 might be excessive for a 4. Furthermore, what is the duration of these feelings? Chronic stressors may incur gradual change verses sudden impact if acute. Through identifying personal signs, devising and using a scale, as well as escalating or de-escalating factors, individuals become more in tune with their bodies and therefore, more likely to intervene before burnout takes hold.

With this process well integrated, one can now consider stylized approaches for stress management. For example, those inclined toward mindfulness practices may find yoga, meditation, and relaxation exercises beneficial. Others may thrive on positive affirmations, gratitude, and thankfulness. While some might find relief in physical activity, be it strenuous or casual, the creative arts might appeal to those who find joy in painting, writing, or doing crafts. In addition, baking, reading, dancing, and/or listening to music might help lift stress.

Along with those discoveries, or in some cases, rediscoveries, basic needs such as dietary habits and nutrition, hydration, and sleep are vital toward emotional regulation, physiological homeostasis, and stress modulation. Remember HALT: Hungry, Angry, Lonely, Tired, Too hot, Too cold, Sad or Stressed. Those strategies are meant to guide self-care and highlight the importance of allowing time for self-awareness. Imagine yourself as if you are meeting a new patient. Establish rapport, identify symptoms, and explore options for treatment. When we give time to ourselves, we can give time more freely to others. With this in mind, try following the 5-minute wellness check that I formulated:

1. How am I feeling? What am I feeling?

2. Assess HALTS.

3. Identify the number on your scale.

4. Methods of quick de-escalation:

• Designate and schedule personal time.
• Write down daily goals.
• Repeat positive affirmations or write down words of gratitude.
• Use deep breathing exercises.
• Stretch or take a brief walk.
• Engage in mindfulness practices, such as meditation.

Once we develop a habit of monitoring, assessing, and practicing self-care, the process becomes more efficient and effective. Think of the way a seasoned attending can manage workflow with ease, compared with an intern. Recognizing signs and using these strategies routinely can become a quick daily measure of well-being.
 

Dr. Thomas is a board-certified adult psychiatrist with interests in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. Dr. Thomas has no conflicts of interest.

Gradually, we are emerging from the chaos, isolation, and anxiety of COVID-19. As the Centers for Disease Control and Prevention adjusts its recommendations and vaccinations become more widely available, our communities are beginning to return to normalcy. We are encouraged to put aside our masks if vaccinated and rejoin society, to venture out with less hesitancy and anxiety. As family and friends reunite, memories of confusion, frustration, and fear are beginning to fade to black. Despite the prevailing belief that we should move on, look forward, and remember the past to safeguard our future, remnants of the pandemic remain.

shironosov/Getty Images

Unvaccinated individuals, notably children under the age of 12, are quite significant in number. The use of telehealth is now standard practice.

For several years, we were warned about the looming “mental health crisis.” The past year has demonstrated that a crisis no longer looms – it has arrived. Our patients can reveal the vulnerability COVID-19 has wrought – from the devastation of lives lost, supply shortages, loss of employment and financial stability – to a lack of access to computers and thereby, the risk of educational decline. Those factors, coupled with isolation and uncertainty about the future, have led to an influx of individuals with anxiety, depression, and other mood disorders seeking mental health treatment.
 

Doctors, others suffering

As result of a medical culture guided by the sacred oath to which care, compassion, and dedication held as true in ancient Greece as it does today, the focus centers on those around us – while signs of our own weariness are waved away as “a bad day.” Even though several support groups are readily available to offer a listening ear and mental health physicians who focus on the treatment of health care professionals are becoming more ubiquitous, the vestiges of past doctrine remain.

In this modern age of medical training, there is often as much sacrifice as there is attainment of knowledge. This philosophy is so ingrained that throughout training and practice one may come across colleagues experiencing an abundance of guilt when leave is needed for personal reasons. We are quick to recommend such steps for our patients, family, and friends, but hesitant to consider such for ourselves. Yet, of all the lessons this past year has wrought, the importance of mental health and self-care cannot be overstated. This raises the question: How do we incorporate wellness into our routines while navigating the complexity of medicine?

It is vital to accept our humanity as something not to repair, treat, or overcome but to understand. There is strength and power in vulnerability. If we do not perceive and validate this process within ourselves, how can we do so for others? In other words, the oxygen mask must be placed on us first before we can place it on anyone else – patients or otherwise.

Chiefly and above all else, the importance of identifying individual signs of stress is essential. Where do you hold tension? Are you prone to GI distress or headaches when taxed? Do you tend toward irritability, apathy, or exhaustion?

Once this is determined, it is important to assess your stress on a numerical scale, such as those used for pain. Are you a 5 or an 8? Finally, are there identifiable triggers or reliable alleviators? Is there a time of day or day of the week that is most difficult to manage? Can you anticipate potential stressors? Understanding your triggers, listening to your body, and practicing the language of self is the first step toward wellness.

Following introspection and observation, the next step is inventory. Take stock of your reserves. What replenishes? What depletes? What brings joy? What brings dread? Are there certain activities that mitigate stress? If so, how much time do they entail? Identify your number on a scale and associate that number with specific strategies or techniques. Remember that decompression for a 6 might be excessive for a 4. Furthermore, what is the duration of these feelings? Chronic stressors may incur gradual change verses sudden impact if acute. Through identifying personal signs, devising and using a scale, as well as escalating or de-escalating factors, individuals become more in tune with their bodies and therefore, more likely to intervene before burnout takes hold.

With this process well integrated, one can now consider stylized approaches for stress management. For example, those inclined toward mindfulness practices may find yoga, meditation, and relaxation exercises beneficial. Others may thrive on positive affirmations, gratitude, and thankfulness. While some might find relief in physical activity, be it strenuous or casual, the creative arts might appeal to those who find joy in painting, writing, or doing crafts. In addition, baking, reading, dancing, and/or listening to music might help lift stress.

Along with those discoveries, or in some cases, rediscoveries, basic needs such as dietary habits and nutrition, hydration, and sleep are vital toward emotional regulation, physiological homeostasis, and stress modulation. Remember HALT: Hungry, Angry, Lonely, Tired, Too hot, Too cold, Sad or Stressed. Those strategies are meant to guide self-care and highlight the importance of allowing time for self-awareness. Imagine yourself as if you are meeting a new patient. Establish rapport, identify symptoms, and explore options for treatment. When we give time to ourselves, we can give time more freely to others. With this in mind, try following the 5-minute wellness check that I formulated:

1. How am I feeling? What am I feeling?

2. Assess HALTS.

3. Identify the number on your scale.

4. Methods of quick de-escalation:

• Designate and schedule personal time.
• Write down daily goals.
• Repeat positive affirmations or write down words of gratitude.
• Use deep breathing exercises.
• Stretch or take a brief walk.
• Engage in mindfulness practices, such as meditation.

Once we develop a habit of monitoring, assessing, and practicing self-care, the process becomes more efficient and effective. Think of the way a seasoned attending can manage workflow with ease, compared with an intern. Recognizing signs and using these strategies routinely can become a quick daily measure of well-being.
 

Dr. Thomas is a board-certified adult psychiatrist with interests in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. Dr. Thomas has no conflicts of interest.

A report by the American Medical Association’s medical education advisory body points to systemic racism or other systems of oppression as causing a lack of representation, exclusion, and marginalization in medical education and medicine.

The report received overwhelming support at the House of Delegates, the AMA’s legislative policy making body, during an online meeting held June 13.

The Council on Medical Education’s report recommends that the AMA acknowledge the harm caused by the Flexner Report, which was issued in 1910 and has since shaped medical education. The Flexner Report caused harm not only to historically Black medical schools, but also to physician workforce diversity and to the clinical outcomes of minority and marginalized patients, according to the medical education advisory body.

The council also recommended conducting a study on medical education with a focus on health equity and racial justice, improving diversity among healthcare workers, and fixing inequitable outcomes from minorities and marginalized patient populations.

The report comes on the heels of the resignation of JAMA editor-in-chief Howard Bauchner, MD, and another high-ranking editor following a February podcast on systemic racism in medicine. The AMA has since released a strategic plan addressing racism and health inequity that has divided membership.
 

Flexner Report’s effect on physician diversity

The Council on Medical Education’s report observed that as a result of the Flexner Report’s recommendations, 89 medical schools, including 5 of the 7 existing medical schools training Black physicians, were closed because they didn’t meet the report’s standards. In addition, the report created a limited role for Black physicians while “hint[ing] that Black physicians possessed less potential and ability than their White counterparts,” read the Council’s report.

In addition to consigning the role of the Black physician to “educating the [Black] race to know and to practice fundamental hygienic principles,” the Flexner Report also observed that “a well-taught negro sanitarian will be immensely useful,” per the Council’s report.

The impact of the closure of medical schools training Black physicians was dramatic. According to the Council’s report, in 1964, 93% of medical students in the United States were men and 97% of those students were non-Hispanic White.

Today, 56% of physicians identify as White, 17% as Asian, 6% as Hispanic, and 5% as Black or African American, per the Association of American Medical Colleges; nearly 14% of active physicians didn’t report their race in the survey. By means of contrast, the U.S. population in 2019 was 60% White, 19% Latino/Hispanic, 13% Black or African American, and 6% Asian American, according to the Brookings Institute.

Abraham Flexner, who wrote the Flexner Report, is often referred to as the “father of modern medical education,” according to the AAMC. In November, the AAMC observed that the Flexner Report contained racist and sexist ideas and that his work contributed to the closure of historically Black medical schools. Both statements were included in AAMC’s announcement about the removal of Flexner’s name from its most prestigious award. As of January, the award is now called the AAMC Award for Excellence in Medical Education.
 

Pathway programs can increase diversity

Pathway programs, which leverage targeted milestones along the journey to becoming a physician in order to increase diversity, were an area of focus in the council’s report. These programs “can exert a meaningful, positive effect on student outcomes and increase diversity across various levels of educational settings,” according to its report.

Centers of Excellence, which provides grants for mentorship and training programs, is one of many pathway programs. During the 2018-2019 academic year, Centers of Excellence supported more than 1,300 trainees – 99% of them were underrepresented minorities and 64% came from financially or educationally disadvantaged backgrounds. In 2006, federal funding was cut to these programs and the number of Centers of Excellence fell.

Still, the report cites the passage of federal funding in 2020 of $50 million for public institutions of higher education that train physicians; educational institutions in states with a projected primary care shortage in 2025 are given priority in the grant-funding process.
 

AMA council’s report garners support from delegates

Delegates voiced overwhelming support of the council’s report during the June 13 meeting. Lou Edje, MD, a Perrysburgh, Ohio–based family physician, voiced strong support for the council’s report, in particular its recommendations that recognize the harm caused by the Flexner Report. Dr. Edje observed that the Flexner Report, with its elimination of five of seven Black medical schools, “[set] back admissions of Black students into medicine by 50 years.”

“Empathy is what we are called to have as physicians. I implore you to simply substitute your ethnicity into these quotes to help understand the historic need for health equity in medicine today. This CME report is part of the antidote to Flexner. We support [it] fully,” concluded Dr. Edje, who spoke for the Great Lakes States Coalition of the AMA.

Rohan Khazanchi, a medical student at the University of Nebraska, Omaha, and a member of the council, said, “Our broad attempt with this report was twofold: to fill gaps in AMA policy with evidence-based recommendations which could improve diversity in our health workforce and, second, to enhance our organization’s vision for truth, reconciliation, and healing to redress the historic marginalization of minoritized physicians in medicine.”

According to an AMA spokesperson, the House of Delegates will vote on this and other policies this week, after which the policies are considered final.

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

A report by the American Medical Association’s medical education advisory body points to systemic racism or other systems of oppression as causing a lack of representation, exclusion, and marginalization in medical education and medicine.

The report received overwhelming support at the House of Delegates, the AMA’s legislative policy making body, during an online meeting held June 13.

The Council on Medical Education’s report recommends that the AMA acknowledge the harm caused by the Flexner Report, which was issued in 1910 and has since shaped medical education. The Flexner Report caused harm not only to historically Black medical schools, but also to physician workforce diversity and to the clinical outcomes of minority and marginalized patients, according to the medical education advisory body.

The council also recommended conducting a study on medical education with a focus on health equity and racial justice, improving diversity among healthcare workers, and fixing inequitable outcomes from minorities and marginalized patient populations.

The report comes on the heels of the resignation of JAMA editor-in-chief Howard Bauchner, MD, and another high-ranking editor following a February podcast on systemic racism in medicine. The AMA has since released a strategic plan addressing racism and health inequity that has divided membership.
 

Flexner Report’s effect on physician diversity

The Council on Medical Education’s report observed that as a result of the Flexner Report’s recommendations, 89 medical schools, including 5 of the 7 existing medical schools training Black physicians, were closed because they didn’t meet the report’s standards. In addition, the report created a limited role for Black physicians while “hint[ing] that Black physicians possessed less potential and ability than their White counterparts,” read the Council’s report.

In addition to consigning the role of the Black physician to “educating the [Black] race to know and to practice fundamental hygienic principles,” the Flexner Report also observed that “a well-taught negro sanitarian will be immensely useful,” per the Council’s report.

The impact of the closure of medical schools training Black physicians was dramatic. According to the Council’s report, in 1964, 93% of medical students in the United States were men and 97% of those students were non-Hispanic White.

Today, 56% of physicians identify as White, 17% as Asian, 6% as Hispanic, and 5% as Black or African American, per the Association of American Medical Colleges; nearly 14% of active physicians didn’t report their race in the survey. By means of contrast, the U.S. population in 2019 was 60% White, 19% Latino/Hispanic, 13% Black or African American, and 6% Asian American, according to the Brookings Institute.

Abraham Flexner, who wrote the Flexner Report, is often referred to as the “father of modern medical education,” according to the AAMC. In November, the AAMC observed that the Flexner Report contained racist and sexist ideas and that his work contributed to the closure of historically Black medical schools. Both statements were included in AAMC’s announcement about the removal of Flexner’s name from its most prestigious award. As of January, the award is now called the AAMC Award for Excellence in Medical Education.
 

Pathway programs can increase diversity

Pathway programs, which leverage targeted milestones along the journey to becoming a physician in order to increase diversity, were an area of focus in the council’s report. These programs “can exert a meaningful, positive effect on student outcomes and increase diversity across various levels of educational settings,” according to its report.

Centers of Excellence, which provides grants for mentorship and training programs, is one of many pathway programs. During the 2018-2019 academic year, Centers of Excellence supported more than 1,300 trainees – 99% of them were underrepresented minorities and 64% came from financially or educationally disadvantaged backgrounds. In 2006, federal funding was cut to these programs and the number of Centers of Excellence fell.

Still, the report cites the passage of federal funding in 2020 of $50 million for public institutions of higher education that train physicians; educational institutions in states with a projected primary care shortage in 2025 are given priority in the grant-funding process.
 

AMA council’s report garners support from delegates

Delegates voiced overwhelming support of the council’s report during the June 13 meeting. Lou Edje, MD, a Perrysburgh, Ohio–based family physician, voiced strong support for the council’s report, in particular its recommendations that recognize the harm caused by the Flexner Report. Dr. Edje observed that the Flexner Report, with its elimination of five of seven Black medical schools, “[set] back admissions of Black students into medicine by 50 years.”

“Empathy is what we are called to have as physicians. I implore you to simply substitute your ethnicity into these quotes to help understand the historic need for health equity in medicine today. This CME report is part of the antidote to Flexner. We support [it] fully,” concluded Dr. Edje, who spoke for the Great Lakes States Coalition of the AMA.

Rohan Khazanchi, a medical student at the University of Nebraska, Omaha, and a member of the council, said, “Our broad attempt with this report was twofold: to fill gaps in AMA policy with evidence-based recommendations which could improve diversity in our health workforce and, second, to enhance our organization’s vision for truth, reconciliation, and healing to redress the historic marginalization of minoritized physicians in medicine.”

According to an AMA spokesperson, the House of Delegates will vote on this and other policies this week, after which the policies are considered final.

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

A report by the American Medical Association’s medical education advisory body points to systemic racism or other systems of oppression as causing a lack of representation, exclusion, and marginalization in medical education and medicine.

The report received overwhelming support at the House of Delegates, the AMA’s legislative policy making body, during an online meeting held June 13.

The Council on Medical Education’s report recommends that the AMA acknowledge the harm caused by the Flexner Report, which was issued in 1910 and has since shaped medical education. The Flexner Report caused harm not only to historically Black medical schools, but also to physician workforce diversity and to the clinical outcomes of minority and marginalized patients, according to the medical education advisory body.

The council also recommended conducting a study on medical education with a focus on health equity and racial justice, improving diversity among healthcare workers, and fixing inequitable outcomes from minorities and marginalized patient populations.

The report comes on the heels of the resignation of JAMA editor-in-chief Howard Bauchner, MD, and another high-ranking editor following a February podcast on systemic racism in medicine. The AMA has since released a strategic plan addressing racism and health inequity that has divided membership.
 

Flexner Report’s effect on physician diversity

The Council on Medical Education’s report observed that as a result of the Flexner Report’s recommendations, 89 medical schools, including 5 of the 7 existing medical schools training Black physicians, were closed because they didn’t meet the report’s standards. In addition, the report created a limited role for Black physicians while “hint[ing] that Black physicians possessed less potential and ability than their White counterparts,” read the Council’s report.

In addition to consigning the role of the Black physician to “educating the [Black] race to know and to practice fundamental hygienic principles,” the Flexner Report also observed that “a well-taught negro sanitarian will be immensely useful,” per the Council’s report.

The impact of the closure of medical schools training Black physicians was dramatic. According to the Council’s report, in 1964, 93% of medical students in the United States were men and 97% of those students were non-Hispanic White.

Today, 56% of physicians identify as White, 17% as Asian, 6% as Hispanic, and 5% as Black or African American, per the Association of American Medical Colleges; nearly 14% of active physicians didn’t report their race in the survey. By means of contrast, the U.S. population in 2019 was 60% White, 19% Latino/Hispanic, 13% Black or African American, and 6% Asian American, according to the Brookings Institute.

Abraham Flexner, who wrote the Flexner Report, is often referred to as the “father of modern medical education,” according to the AAMC. In November, the AAMC observed that the Flexner Report contained racist and sexist ideas and that his work contributed to the closure of historically Black medical schools. Both statements were included in AAMC’s announcement about the removal of Flexner’s name from its most prestigious award. As of January, the award is now called the AAMC Award for Excellence in Medical Education.
 

Pathway programs can increase diversity

Pathway programs, which leverage targeted milestones along the journey to becoming a physician in order to increase diversity, were an area of focus in the council’s report. These programs “can exert a meaningful, positive effect on student outcomes and increase diversity across various levels of educational settings,” according to its report.

Centers of Excellence, which provides grants for mentorship and training programs, is one of many pathway programs. During the 2018-2019 academic year, Centers of Excellence supported more than 1,300 trainees – 99% of them were underrepresented minorities and 64% came from financially or educationally disadvantaged backgrounds. In 2006, federal funding was cut to these programs and the number of Centers of Excellence fell.

Still, the report cites the passage of federal funding in 2020 of $50 million for public institutions of higher education that train physicians; educational institutions in states with a projected primary care shortage in 2025 are given priority in the grant-funding process.
 

AMA council’s report garners support from delegates

Delegates voiced overwhelming support of the council’s report during the June 13 meeting. Lou Edje, MD, a Perrysburgh, Ohio–based family physician, voiced strong support for the council’s report, in particular its recommendations that recognize the harm caused by the Flexner Report. Dr. Edje observed that the Flexner Report, with its elimination of five of seven Black medical schools, “[set] back admissions of Black students into medicine by 50 years.”

“Empathy is what we are called to have as physicians. I implore you to simply substitute your ethnicity into these quotes to help understand the historic need for health equity in medicine today. This CME report is part of the antidote to Flexner. We support [it] fully,” concluded Dr. Edje, who spoke for the Great Lakes States Coalition of the AMA.

Rohan Khazanchi, a medical student at the University of Nebraska, Omaha, and a member of the council, said, “Our broad attempt with this report was twofold: to fill gaps in AMA policy with evidence-based recommendations which could improve diversity in our health workforce and, second, to enhance our organization’s vision for truth, reconciliation, and healing to redress the historic marginalization of minoritized physicians in medicine.”

According to an AMA spokesperson, the House of Delegates will vote on this and other policies this week, after which the policies are considered final.

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

In the United States, cryoablation or freezing tissue to death is a primary treatment option for a variety of cancers, including those originating in or spread to the bone, cervix, eye, kidney, liver, lung, pancreas, prostate, and skin.

Cryoablation for prostate cancer, one of the most common cancers in men, was first approved in the 1990s.

But unlike in Europe, this nonsurgical approach is not approved for breast cancer in the United States; it is one of the most common cancers in women.

So why is this approach still experimental for breast cancer?

“I don’t know,” answered cryoablation researcher Richard Fine, MD, of West Cancer Center in Germantown, Tenn., when asked by this news organization.

“It’s very interesting how slow the [Food and Drug Administration] is in approving devices for breast cancer [when compared with] other cancers,” he said.
 

New clinical data

Perhaps new clinical data will eventually lead to approval of this nonsurgical technique for use in low-risk breast cancer. However, the related trial had a controversial design that might discourage uptake by practitioners if it is approved, said an expert not involved in the study.

Nevertheless, the new data show that cryoablation can be an effective treatment for small, low-risk, early-stage breast cancers in older patients.

The findings come from ICE-3, a multicenter single-arm study of cryoablation in 194 such patients with mean follow-up of roughly 3 years.

It used liquid nitrogen-based cryoablation technology from IceCure Medical Ltd., an Israeli company and the study sponsor.

The results show that 2.06% (n = 4) of patients had a recurrence in the same breast, which is “basically the same” as lumpectomy, the surgical standard for this patient group, said Dr. Fine, the lead investigator on the trial.

These are interim data, Dr. Fine said at the American Society of Breast Surgeons annual meeting, held virtually.

The primary outcome is the 5-year recurrence rate, and this is the first-ever cryoablation trial that does not involve follow-up surgery, he said.

Cryoablation, which delivers a gas to a tumor via a thin needle-like probe that is guided by ultrasound, has multiple advantages over surgery, Dr. Fine said.

“The noninvasive procedure is fast, painless, and can be delivered under local anesthesia in a doctor’s office. Recovery time is minimal and cosmetic outcomes are excellent with little loss of breast tissue and no scarring,” he said in a meeting press statement.

The potential market for cryoablation in breast cancer is large, as it is intended for tumors ≤1.5 cm, which comprise approximately 60%-70% of stage 1 breast cancers that are hormone receptor–positive (HR+), and HER2-negative (HER2–), Dr. Fine said in an interview.

Cryoablation is part of a logical, de-escalation of breast cancer care, he added. “We have moved from radical mastectomy to modified mastectomy to lumpectomy – so the next step in that evolution is ablative technology, which is ‘nonsurgical.’ ”

There are other experimental ablative treatments for breast cancer including high-frequency ultrasound and laser, but cryoablation is the furthest along in development.

Cryoablation as a primary cancer treatment was first approved for coverage by the Centers for Medicare & Medicaid Services for localized prostate cancer in 1999.

But the concept extends back to 1845, when English physician James Arnott first used iced salt solutions (about –20 °C or – 4 °F) to induce tissue necrosis, reducing tumor size and ameliorating pain. Because the crude cryogen needed to be applied topically, the pioneering technique was limited to breast and cervical cancers because of their accessibility.
 

Not likely to show superiority

The new study’s population was composed of women aged 60 years or older (mean of 75 years) with unifocal invasive ductal cancers measuring ≤1.5 cm or less that were all low-grade, HR+, and HER2–, as noted.

The liquid nitrogen–based cryoablation consisted of a freeze-thaw-freeze cycle that totals 20-40 minutes, with freezing temperatures targeting the tumor area and turning it into an “ice ball.”

That ice ball eventually surrounds the tumor, creating a “lethal zone,” and thus a margin in which no cancer exists, akin to surgery, said Dr. Fine.

There were no significant device-related adverse events or complications reported, say the investigators. Most of the adverse events were minor and included bruising, localized edema, minor skin freeze burn, rash, minor bleeding from needle insertion, minor local hematoma, skin induration, minor infection, and pruritis.

Two of 15 patients who underwent sentinel lymph node biopsies had a positive sentinel node. At the discretion of their treating physician, 27 patients underwent adjuvant radiation, 1 patient received chemotherapy, and 148 began endocrine therapy. More than 95% of the patients and 98% of physicians reported satisfaction from the cosmetic results during follow-up visits.

Because not all patients underwent sentinel lymph node biopsy and adjuvant radiation, there is likely to be controversy about this approach, suggested Deanna J. Attai, MD, a breast surgeon at the University of California, Los Angeles, and past president of the American Society of Breast Surgeons, who was asked for comment.

“We have studies that [indicate that] these treatments don’t add significant benefit [in this patient population] but there still is this hesitation [to forgo them],” she told this news organization.

“The patients in this study were exceedingly low risk,” she emphasized.

“Is 5 years enough to assess recurrence rates? The answer is probably no. Recurrences or distant metastases are more likely to happen 10-20 years later.”

Thus, it will be difficult to show that cryoablation is superior to surgery, she said.

“You can show that cryoablation is not inferior to lumpectomy alone – which allows patients to avoid the operating room,” Dr. Attai summarized.
 

The surgical mindset and breast cancer

Dr. Attai, who was not involved in the current trial, was an investigator in an earlier single-arm cooperative group study of cryoablation for breast cancer, which had the rate of complete tumor ablation as the primary outcome. The study, known as the American College of Surgeons Oncology Group Z1072 trial, enrolled 99 patients, all of whom underwent ablation followed by surgery. The study reported results in 2014 but was very slow to develop, she observed.

“I did my first training in 2004 and I don’t think the study opened for several years after that. I think there’s been a lot of hesitation to change the mindset that every cancer needs to be removed surgically,” Dr. Attai stated.

“When you put breast cancer in the context of the other organs, we are lagging behind a bit [with cryoablation],” she added.

“I don’t want to go there but … the innovation for male diseases and procedures sometimes surpasses that of women’s diseases,” she said.

But she also defended her fellow practitioners. “There’s been tremendous changes in management over the 27 years I’ve been in practice,” she said, citing the movement from mastectomy to lumpectomy as one of multiple big changes.

The disparity between the development of cryoablation for breast and prostate cancer is a mystery when you contemplate the potential side effects, Dr. Fine observed. “There’s not a lot of vital structures inside the breast, so you don’t have risks that you have with the prostate, including urinary incontinence and impotence.”

As a next move, the American Society of Breast Surgeons is planning to establish a cryoablation registry and aims to enroll 50 sites and 500 patients who are aged 55-85 years; for those aged 65-70, radiation therapy will be required, said Dr. Fine.

Currently, cryoablation for breast cancer is allowed only in a clinical trial, so a registry would expand usage considerably, he said.

However, cryoablation, including from IceCure, has FDA clearance for ablating cancerous tissue in general (but not breast cancer specifically).  

Dr. Attai hopes the field is ready for the nonsurgical approach.

“Halsted died in 1922 and the Halsted radical mastectomy really didn’t start to fall out of favor until the 1950s, 1960,” said Dr. Attai, referring to Dr William Halsted, who pioneered the procedure in the 1890s. “I would hope we are better at speeding up our progress. Changing the surgical mindset takes time,” she said.

Dr. Fine was an investigator in the ICE3 trial, which is funded by IceCure Medical. Dr. Attai has disclosed no relevant financial relationships.

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

In the United States, cryoablation or freezing tissue to death is a primary treatment option for a variety of cancers, including those originating in or spread to the bone, cervix, eye, kidney, liver, lung, pancreas, prostate, and skin.

Cryoablation for prostate cancer, one of the most common cancers in men, was first approved in the 1990s.

But unlike in Europe, this nonsurgical approach is not approved for breast cancer in the United States; it is one of the most common cancers in women.

So why is this approach still experimental for breast cancer?

“I don’t know,” answered cryoablation researcher Richard Fine, MD, of West Cancer Center in Germantown, Tenn., when asked by this news organization.

“It’s very interesting how slow the [Food and Drug Administration] is in approving devices for breast cancer [when compared with] other cancers,” he said.
 

New clinical data

Perhaps new clinical data will eventually lead to approval of this nonsurgical technique for use in low-risk breast cancer. However, the related trial had a controversial design that might discourage uptake by practitioners if it is approved, said an expert not involved in the study.

Nevertheless, the new data show that cryoablation can be an effective treatment for small, low-risk, early-stage breast cancers in older patients.

The findings come from ICE-3, a multicenter single-arm study of cryoablation in 194 such patients with mean follow-up of roughly 3 years.

It used liquid nitrogen-based cryoablation technology from IceCure Medical Ltd., an Israeli company and the study sponsor.

The results show that 2.06% (n = 4) of patients had a recurrence in the same breast, which is “basically the same” as lumpectomy, the surgical standard for this patient group, said Dr. Fine, the lead investigator on the trial.

These are interim data, Dr. Fine said at the American Society of Breast Surgeons annual meeting, held virtually.

The primary outcome is the 5-year recurrence rate, and this is the first-ever cryoablation trial that does not involve follow-up surgery, he said.

Cryoablation, which delivers a gas to a tumor via a thin needle-like probe that is guided by ultrasound, has multiple advantages over surgery, Dr. Fine said.

“The noninvasive procedure is fast, painless, and can be delivered under local anesthesia in a doctor’s office. Recovery time is minimal and cosmetic outcomes are excellent with little loss of breast tissue and no scarring,” he said in a meeting press statement.

The potential market for cryoablation in breast cancer is large, as it is intended for tumors ≤1.5 cm, which comprise approximately 60%-70% of stage 1 breast cancers that are hormone receptor–positive (HR+), and HER2-negative (HER2–), Dr. Fine said in an interview.

Cryoablation is part of a logical, de-escalation of breast cancer care, he added. “We have moved from radical mastectomy to modified mastectomy to lumpectomy – so the next step in that evolution is ablative technology, which is ‘nonsurgical.’ ”

There are other experimental ablative treatments for breast cancer including high-frequency ultrasound and laser, but cryoablation is the furthest along in development.

Cryoablation as a primary cancer treatment was first approved for coverage by the Centers for Medicare & Medicaid Services for localized prostate cancer in 1999.

But the concept extends back to 1845, when English physician James Arnott first used iced salt solutions (about –20 °C or – 4 °F) to induce tissue necrosis, reducing tumor size and ameliorating pain. Because the crude cryogen needed to be applied topically, the pioneering technique was limited to breast and cervical cancers because of their accessibility.
 

Not likely to show superiority

The new study’s population was composed of women aged 60 years or older (mean of 75 years) with unifocal invasive ductal cancers measuring ≤1.5 cm or less that were all low-grade, HR+, and HER2–, as noted.

The liquid nitrogen–based cryoablation consisted of a freeze-thaw-freeze cycle that totals 20-40 minutes, with freezing temperatures targeting the tumor area and turning it into an “ice ball.”

That ice ball eventually surrounds the tumor, creating a “lethal zone,” and thus a margin in which no cancer exists, akin to surgery, said Dr. Fine.

There were no significant device-related adverse events or complications reported, say the investigators. Most of the adverse events were minor and included bruising, localized edema, minor skin freeze burn, rash, minor bleeding from needle insertion, minor local hematoma, skin induration, minor infection, and pruritis.

Two of 15 patients who underwent sentinel lymph node biopsies had a positive sentinel node. At the discretion of their treating physician, 27 patients underwent adjuvant radiation, 1 patient received chemotherapy, and 148 began endocrine therapy. More than 95% of the patients and 98% of physicians reported satisfaction from the cosmetic results during follow-up visits.

Because not all patients underwent sentinel lymph node biopsy and adjuvant radiation, there is likely to be controversy about this approach, suggested Deanna J. Attai, MD, a breast surgeon at the University of California, Los Angeles, and past president of the American Society of Breast Surgeons, who was asked for comment.

“We have studies that [indicate that] these treatments don’t add significant benefit [in this patient population] but there still is this hesitation [to forgo them],” she told this news organization.

“The patients in this study were exceedingly low risk,” she emphasized.

“Is 5 years enough to assess recurrence rates? The answer is probably no. Recurrences or distant metastases are more likely to happen 10-20 years later.”

Thus, it will be difficult to show that cryoablation is superior to surgery, she said.

“You can show that cryoablation is not inferior to lumpectomy alone – which allows patients to avoid the operating room,” Dr. Attai summarized.
 

The surgical mindset and breast cancer

Dr. Attai, who was not involved in the current trial, was an investigator in an earlier single-arm cooperative group study of cryoablation for breast cancer, which had the rate of complete tumor ablation as the primary outcome. The study, known as the American College of Surgeons Oncology Group Z1072 trial, enrolled 99 patients, all of whom underwent ablation followed by surgery. The study reported results in 2014 but was very slow to develop, she observed.

“I did my first training in 2004 and I don’t think the study opened for several years after that. I think there’s been a lot of hesitation to change the mindset that every cancer needs to be removed surgically,” Dr. Attai stated.

“When you put breast cancer in the context of the other organs, we are lagging behind a bit [with cryoablation],” she added.

“I don’t want to go there but … the innovation for male diseases and procedures sometimes surpasses that of women’s diseases,” she said.

But she also defended her fellow practitioners. “There’s been tremendous changes in management over the 27 years I’ve been in practice,” she said, citing the movement from mastectomy to lumpectomy as one of multiple big changes.

The disparity between the development of cryoablation for breast and prostate cancer is a mystery when you contemplate the potential side effects, Dr. Fine observed. “There’s not a lot of vital structures inside the breast, so you don’t have risks that you have with the prostate, including urinary incontinence and impotence.”

As a next move, the American Society of Breast Surgeons is planning to establish a cryoablation registry and aims to enroll 50 sites and 500 patients who are aged 55-85 years; for those aged 65-70, radiation therapy will be required, said Dr. Fine.

Currently, cryoablation for breast cancer is allowed only in a clinical trial, so a registry would expand usage considerably, he said.

However, cryoablation, including from IceCure, has FDA clearance for ablating cancerous tissue in general (but not breast cancer specifically).  

Dr. Attai hopes the field is ready for the nonsurgical approach.

“Halsted died in 1922 and the Halsted radical mastectomy really didn’t start to fall out of favor until the 1950s, 1960,” said Dr. Attai, referring to Dr William Halsted, who pioneered the procedure in the 1890s. “I would hope we are better at speeding up our progress. Changing the surgical mindset takes time,” she said.

Dr. Fine was an investigator in the ICE3 trial, which is funded by IceCure Medical. Dr. Attai has disclosed no relevant financial relationships.

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

In the United States, cryoablation or freezing tissue to death is a primary treatment option for a variety of cancers, including those originating in or spread to the bone, cervix, eye, kidney, liver, lung, pancreas, prostate, and skin.

Cryoablation for prostate cancer, one of the most common cancers in men, was first approved in the 1990s.

But unlike in Europe, this nonsurgical approach is not approved for breast cancer in the United States; it is one of the most common cancers in women.

So why is this approach still experimental for breast cancer?

“I don’t know,” answered cryoablation researcher Richard Fine, MD, of West Cancer Center in Germantown, Tenn., when asked by this news organization.

“It’s very interesting how slow the [Food and Drug Administration] is in approving devices for breast cancer [when compared with] other cancers,” he said.
 

New clinical data

Perhaps new clinical data will eventually lead to approval of this nonsurgical technique for use in low-risk breast cancer. However, the related trial had a controversial design that might discourage uptake by practitioners if it is approved, said an expert not involved in the study.

Nevertheless, the new data show that cryoablation can be an effective treatment for small, low-risk, early-stage breast cancers in older patients.

The findings come from ICE-3, a multicenter single-arm study of cryoablation in 194 such patients with mean follow-up of roughly 3 years.

It used liquid nitrogen-based cryoablation technology from IceCure Medical Ltd., an Israeli company and the study sponsor.

The results show that 2.06% (n = 4) of patients had a recurrence in the same breast, which is “basically the same” as lumpectomy, the surgical standard for this patient group, said Dr. Fine, the lead investigator on the trial.

These are interim data, Dr. Fine said at the American Society of Breast Surgeons annual meeting, held virtually.

The primary outcome is the 5-year recurrence rate, and this is the first-ever cryoablation trial that does not involve follow-up surgery, he said.

Cryoablation, which delivers a gas to a tumor via a thin needle-like probe that is guided by ultrasound, has multiple advantages over surgery, Dr. Fine said.

“The noninvasive procedure is fast, painless, and can be delivered under local anesthesia in a doctor’s office. Recovery time is minimal and cosmetic outcomes are excellent with little loss of breast tissue and no scarring,” he said in a meeting press statement.

The potential market for cryoablation in breast cancer is large, as it is intended for tumors ≤1.5 cm, which comprise approximately 60%-70% of stage 1 breast cancers that are hormone receptor–positive (HR+), and HER2-negative (HER2–), Dr. Fine said in an interview.

Cryoablation is part of a logical, de-escalation of breast cancer care, he added. “We have moved from radical mastectomy to modified mastectomy to lumpectomy – so the next step in that evolution is ablative technology, which is ‘nonsurgical.’ ”

There are other experimental ablative treatments for breast cancer including high-frequency ultrasound and laser, but cryoablation is the furthest along in development.

Cryoablation as a primary cancer treatment was first approved for coverage by the Centers for Medicare & Medicaid Services for localized prostate cancer in 1999.

But the concept extends back to 1845, when English physician James Arnott first used iced salt solutions (about –20 °C or – 4 °F) to induce tissue necrosis, reducing tumor size and ameliorating pain. Because the crude cryogen needed to be applied topically, the pioneering technique was limited to breast and cervical cancers because of their accessibility.
 

Not likely to show superiority

The new study’s population was composed of women aged 60 years or older (mean of 75 years) with unifocal invasive ductal cancers measuring ≤1.5 cm or less that were all low-grade, HR+, and HER2–, as noted.

The liquid nitrogen–based cryoablation consisted of a freeze-thaw-freeze cycle that totals 20-40 minutes, with freezing temperatures targeting the tumor area and turning it into an “ice ball.”

That ice ball eventually surrounds the tumor, creating a “lethal zone,” and thus a margin in which no cancer exists, akin to surgery, said Dr. Fine.

There were no significant device-related adverse events or complications reported, say the investigators. Most of the adverse events were minor and included bruising, localized edema, minor skin freeze burn, rash, minor bleeding from needle insertion, minor local hematoma, skin induration, minor infection, and pruritis.

Two of 15 patients who underwent sentinel lymph node biopsies had a positive sentinel node. At the discretion of their treating physician, 27 patients underwent adjuvant radiation, 1 patient received chemotherapy, and 148 began endocrine therapy. More than 95% of the patients and 98% of physicians reported satisfaction from the cosmetic results during follow-up visits.

Because not all patients underwent sentinel lymph node biopsy and adjuvant radiation, there is likely to be controversy about this approach, suggested Deanna J. Attai, MD, a breast surgeon at the University of California, Los Angeles, and past president of the American Society of Breast Surgeons, who was asked for comment.

“We have studies that [indicate that] these treatments don’t add significant benefit [in this patient population] but there still is this hesitation [to forgo them],” she told this news organization.

“The patients in this study were exceedingly low risk,” she emphasized.

“Is 5 years enough to assess recurrence rates? The answer is probably no. Recurrences or distant metastases are more likely to happen 10-20 years later.”

Thus, it will be difficult to show that cryoablation is superior to surgery, she said.

“You can show that cryoablation is not inferior to lumpectomy alone – which allows patients to avoid the operating room,” Dr. Attai summarized.
 

The surgical mindset and breast cancer

Dr. Attai, who was not involved in the current trial, was an investigator in an earlier single-arm cooperative group study of cryoablation for breast cancer, which had the rate of complete tumor ablation as the primary outcome. The study, known as the American College of Surgeons Oncology Group Z1072 trial, enrolled 99 patients, all of whom underwent ablation followed by surgery. The study reported results in 2014 but was very slow to develop, she observed.

“I did my first training in 2004 and I don’t think the study opened for several years after that. I think there’s been a lot of hesitation to change the mindset that every cancer needs to be removed surgically,” Dr. Attai stated.

“When you put breast cancer in the context of the other organs, we are lagging behind a bit [with cryoablation],” she added.

“I don’t want to go there but … the innovation for male diseases and procedures sometimes surpasses that of women’s diseases,” she said.

But she also defended her fellow practitioners. “There’s been tremendous changes in management over the 27 years I’ve been in practice,” she said, citing the movement from mastectomy to lumpectomy as one of multiple big changes.

The disparity between the development of cryoablation for breast and prostate cancer is a mystery when you contemplate the potential side effects, Dr. Fine observed. “There’s not a lot of vital structures inside the breast, so you don’t have risks that you have with the prostate, including urinary incontinence and impotence.”

As a next move, the American Society of Breast Surgeons is planning to establish a cryoablation registry and aims to enroll 50 sites and 500 patients who are aged 55-85 years; for those aged 65-70, radiation therapy will be required, said Dr. Fine.

Currently, cryoablation for breast cancer is allowed only in a clinical trial, so a registry would expand usage considerably, he said.

However, cryoablation, including from IceCure, has FDA clearance for ablating cancerous tissue in general (but not breast cancer specifically).  

Dr. Attai hopes the field is ready for the nonsurgical approach.

“Halsted died in 1922 and the Halsted radical mastectomy really didn’t start to fall out of favor until the 1950s, 1960,” said Dr. Attai, referring to Dr William Halsted, who pioneered the procedure in the 1890s. “I would hope we are better at speeding up our progress. Changing the surgical mindset takes time,” she said.

Dr. Fine was an investigator in the ICE3 trial, which is funded by IceCure Medical. Dr. Attai has disclosed no relevant financial relationships.

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

In early June the Food and Drug Administration – amid a storm of controversy – approved aducanumab, a monoclonal antibody developed to treat Alzheimer’s disease. The approval was hailed by advocacy groups and some practitioners as a victory for patients and families, as the drug – the first anti-Alzheimer’s agent to reach the market in 18 years – is a potentially disease-modifying therapy, which acts to clear amyloid plaques from the brain.

But several prominent Alzheimer’s researchers lambasted the agency’s decision, citing unclear evidence of benefit, trials that did not meet their primary endpoints, and reliance on a post hoc analysis of a high-dose subgroup of patients in a halted trial to argue that aducanumab (Aduhelm, Biogen, and Eisai), slowed cognitive and functional decline by 22% on one measure. In November 2020, 10 of 11 members of an independent FDA advisory committee voted against aducanumab’s approval, citing holes in the data and concerns about the quality of the evidence. After the agency went on to approve anyway, three members of that committee resigned in protest.

The FDA decision on aducanumab was made using the agency’s accelerated approval pathway, which allows for the use of a surrogate endpoint – in this case imaging that showed amyloid clearance from the brain – to predict clinical benefit. But amyloid clearance, which a number of experimental antiamyloid antibodies have been shown capable of, has not been definitively linked to clinical benefit. Aducanumab, which is delivered by monthly intravenous infusion, will be marketed pending results from a phase 4 clinical trial, which the manufacturer has nearly a decade to complete. The drug’s price was announced at $56,000 per year, underscoring concern over its modest-at-best benefits.

Clinicians prescribing aducanumab must obtain magnetic resonance imaging at baseline and repeatedly during the course of treatment to detect brain edema and microhemorrhages, which occurred in a third of high-dose patients in clinical trials. Beyond this, there are few restrictions. The FDA label allows for its use in any patient deemed to have Alzheimer’s disease, without stipulations as to disease stage or evidence of brain amyloid. Payers, of course, are likely to restrict use to certain patient groups, and to require evidence of amyloid positivity. The FDA offered no guidance on when treatment should be ceased, leaving payers to make that call as well. Whatever aducanumab’s value and role turns out to be, the first-in-class treatment for Alzheimer’s disease is likely to have a major impact on how patients are assessed and treated in the coming years, and embolden manufactures of similar agents to seek FDA approval.

This news organization reached out to researchers, advocates, and specialists in the community to learn how they see this change playing out.
 

Fielding broad interest

Maria C. Carrillo, PhD, chief science officer of the Alzheimer’s Association, which was a strong proponent of aducanumab’s approval, acknowledged in an interview that the months to come are likely to be confusing for practitioners and families alike as the drug makes its way into community practices.

“We understand that off the bat millions of Americans will not have access to this tomorrow, but over time that will build. And the physician community, the specialists most likely to be prescribing this, over the next few years will even expand further,” Dr. Carrillo said.

For now, those specialists are mostly just struggling to respond responsibly to a deluge of inquiries from patients and their families.

“I’ve gotten like 20 calls in the just the past 2 days,” said neurologist Philip R. Delio, MD, who practices in Santa Barbara, Calif. “This is a longstanding issue that physicians have with patients’ access to information. Patients are getting information about a drug which isn’t available yet. They don’t know that it’s not ready to be sold. They don’t necessarily realize that a biopharma company won’t go into production until the FDA approves the drug.”

The challenge of delivery

Intravenous infusions are new to Alzheimer’s disease and pose all sorts of logistical hurdles. The Alzheimer’s Association’s Dr. Carrillo described the situation as “manageable,” noting that infusions are standard of care for many diseases, and that neurologists now have more than 15 years’ experience with them for multiple sclerosis.

Still, most clinicians treating Alzheimer’s disease in the community – neurologists, geriatricians, psychiatrists, and primary care physicians – do not have infusion centers in their practices. Virtually none have experience with or access to PET-amyloid, or with screening for amyloid-related imaging abnormalities–edema (ARIA-e) on MRI, as required by the FDA.

“I contacted the hospital infusion center we use and said I could end up sending five or six patients a week, can you handle this? They only have so many chairs,” Dr. Delio said. “I am one neurologist in a local community, and I might have 50 candidates for this drug. That’s a lot for them.” Patients with cognitive impairment are also difficult to infuse and may need to be treated at home, he noted.

“MRIs are easy enough to do,” Dr. Delio said. “But do we know what ARIA-e looks like on imaging? You’d have to talk to the radiologists – this is another element of uncertainty. Do we even know what we’re looking for with these scans? Will we recognize this?”

Neurologist Jeffrey L. Cummings, MD, ScD, of the University of Nevada, Las Vegas, a vocal proponent of aducanumab and lead author of a May 2021 paper defending the evidence for it, acknowledged that the field was unprepared for a wide-scale adoption of infusions in dementia treatment, pointing to a Rand Corporation study from 2017 that warned that screening, diagnosis, and availability of infusion chairs would have to be drastically scaled up to meet demand.

“There are few clinicians who know how to identify MCI, too few imaging centers, too few radiologists who know how to identify ARIA-e on MRI, so all of these things will be required to be put into place. The label doesn’t specify any of this, but good clinical practice will require that, and getting this up and running will take 18 to 24 months,” Dr. Cummings said.

Neurologist David S. Knopman, MD, of the Mayo Clinic in Rochester, Minn., a leading critic of the evidence for aducanumab who recently resigned his position on the independent committee that advises the FDA on neurology drugs, said that for large research institutions like his that have served as trial sites, the transition to offering PET-amyloid, MRI, and infusions in clinical practice will be easier.

Uncertainty over costs

Aducanumab’s true costs, to patients and to taxpayers, remain unknown. The $56,000 per year currently cited by its manufacturer “doesn’t count the PET scans and MRIs,” Dr. Knopman noted. “We’re probably pushing $100,00 a year for the first year of treatment.”

Most of that expense will likely be borne by Medicare, he said, and if not, “that will exacerbate existing health care disparities. People who can pay out of pocket are a pretty limited group.”

Dr. Scharre agreed that the costs of treatment were concerning, and that “at least you should be able to narrow it down and hopefully just use health care dollars for people who might stand to benefit,” he said – namely patients in an earlier stage of disease.

The Alzheimer’s Association’s Dr. Carrillo declined to address the high price of aducanumab or its implications, saying only that the association is “very invested in all aspects of access including covering costs associated with the drug and the rest of treatment.”

Access also means “infrastructure, access to physicians to diagnose, access to diagnostics,” Dr. Carrillo said.

Dr. Cummings said aducanumab’s price would likely come down through negotiations with the Centers for Medicare & Medicaid Services, copayments, and bulk purchases.

The FDA has offered no guidance on how long treatment with aducanumab should last, or what should prompt withdrawal of treatment, meaning that patients could, in theory, stay on it to the end of their lives – raising costs further.

Critics have also noted that a built-in financial incentive under Medicare Part B, which covers infusion drugs, could result in overprescription of aducanumab. Under Medicare Part B, prescribing physicians are reimbursed 6% of a drug’s average sales price.
 

Geriatricians wary

On social media and in the lay press, geriatricians have been among the most outspoken opponents of the FDA decision and the Alzheimer’s Association’s advocacy of aducanumab.

Eric Widera, MD, a geriatrician at the University of California, San Francisco, said that the specialty might be less likely than others to embrace aducanumab. “I think part of the reasons geriatricians don’t make a lot of money is they have strong commitment to their values,” Dr. Widera said.

A fractured research community

Ever since October 2019, when Biogen and Eisai announced that despite two trials halted for futility, they would go ahead and seek FDA approval for aducanumab, the Alzheimer’s research community has been bitterly divided over the drug and the FDA’s accelerated approval process.

Top researchers published critical editorials in journals, with some eventually taking their case to major newspapers as well. The Alzheimer’s Association’s position on the drug has clashed with that of many researchers whose work it supports.

“The Alzheimer’s community has been wonderfully collegial – we all have a common purpose,” Dr. Cummings said. “Now we have people taking extreme positions and I’m hoping this will not result in a permanent fracturing of the community.”

Chief among the critics’ concerns is that the FDA decision ratified the use of antiamyloid therapies based on biomarker evidence, opening the door for makers of similar drugs – those still under development or even those whose development has been halted – to seek approval on weak evidence of clinical benefit.

Whether the approval will chill research into drugs targeting pathways other than amyloid is uncertain.

Dr. Cummings said he felt that while the aducanumab decision would spur other manufacturers of antiamyloid drugs to seek accelerated approval, other classes of Alzheimer’s therapies in development also stand to get a boost. Many Alzheimer’s experts believe that a combination of drugs targeting different elements of the disease pathway – not just amyloid – will be needed in the long run.

Dr. Scharre said that the buzz over aducanumab’s approval will have at least one concrete benefit: people getting into doctors’ offices sooner.

“The people who come into our memory centers represent only a fraction of people walking around with MCI – there are people out there who may have heard that it’s normal aging; they have decreased insight; there’s denial, there’s embarrassment – there’s hundreds of reasons people avoid getting seen,” he said.

“Perhaps they come in and learn that they don’t have any degenerative process but their thyroid is out of whack, or there’s something else causing cognitive impairment. And if they do have a degenerative process, they’ll have time to start [aducanumab], and hopefully get to see a reduction in the decline.”

Dr. Knopman was a site investigator for the Biogen aducanumab trials and has consulted for Samus Therapeutics, Third Rock, Roche, and Alzeca Biosciences. A former member of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee, he was recused from the Nov. 6, 2020, meeting that voted against aducanumab. Dr. Cummings has consulted for Biogen, Eisai, and other manufacturers. Dr. Scharre reports financial relationships with Biogen, Brain Test, Acadia, and Vascular Scientific. Dr. Widera has no disclosures. Dr. Delio is a speaker for Gore Medical, Allergan, and Biohaven Pharmaceuticals.

In early June the Food and Drug Administration – amid a storm of controversy – approved aducanumab, a monoclonal antibody developed to treat Alzheimer’s disease. The approval was hailed by advocacy groups and some practitioners as a victory for patients and families, as the drug – the first anti-Alzheimer’s agent to reach the market in 18 years – is a potentially disease-modifying therapy, which acts to clear amyloid plaques from the brain.

But several prominent Alzheimer’s researchers lambasted the agency’s decision, citing unclear evidence of benefit, trials that did not meet their primary endpoints, and reliance on a post hoc analysis of a high-dose subgroup of patients in a halted trial to argue that aducanumab (Aduhelm, Biogen, and Eisai), slowed cognitive and functional decline by 22% on one measure. In November 2020, 10 of 11 members of an independent FDA advisory committee voted against aducanumab’s approval, citing holes in the data and concerns about the quality of the evidence. After the agency went on to approve anyway, three members of that committee resigned in protest.

The FDA decision on aducanumab was made using the agency’s accelerated approval pathway, which allows for the use of a surrogate endpoint – in this case imaging that showed amyloid clearance from the brain – to predict clinical benefit. But amyloid clearance, which a number of experimental antiamyloid antibodies have been shown capable of, has not been definitively linked to clinical benefit. Aducanumab, which is delivered by monthly intravenous infusion, will be marketed pending results from a phase 4 clinical trial, which the manufacturer has nearly a decade to complete. The drug’s price was announced at $56,000 per year, underscoring concern over its modest-at-best benefits.

Clinicians prescribing aducanumab must obtain magnetic resonance imaging at baseline and repeatedly during the course of treatment to detect brain edema and microhemorrhages, which occurred in a third of high-dose patients in clinical trials. Beyond this, there are few restrictions. The FDA label allows for its use in any patient deemed to have Alzheimer’s disease, without stipulations as to disease stage or evidence of brain amyloid. Payers, of course, are likely to restrict use to certain patient groups, and to require evidence of amyloid positivity. The FDA offered no guidance on when treatment should be ceased, leaving payers to make that call as well. Whatever aducanumab’s value and role turns out to be, the first-in-class treatment for Alzheimer’s disease is likely to have a major impact on how patients are assessed and treated in the coming years, and embolden manufactures of similar agents to seek FDA approval.

This news organization reached out to researchers, advocates, and specialists in the community to learn how they see this change playing out.
 

Fielding broad interest

Maria C. Carrillo, PhD, chief science officer of the Alzheimer’s Association, which was a strong proponent of aducanumab’s approval, acknowledged in an interview that the months to come are likely to be confusing for practitioners and families alike as the drug makes its way into community practices.

“We understand that off the bat millions of Americans will not have access to this tomorrow, but over time that will build. And the physician community, the specialists most likely to be prescribing this, over the next few years will even expand further,” Dr. Carrillo said.

For now, those specialists are mostly just struggling to respond responsibly to a deluge of inquiries from patients and their families.

“I’ve gotten like 20 calls in the just the past 2 days,” said neurologist Philip R. Delio, MD, who practices in Santa Barbara, Calif. “This is a longstanding issue that physicians have with patients’ access to information. Patients are getting information about a drug which isn’t available yet. They don’t know that it’s not ready to be sold. They don’t necessarily realize that a biopharma company won’t go into production until the FDA approves the drug.”

The challenge of delivery

Intravenous infusions are new to Alzheimer’s disease and pose all sorts of logistical hurdles. The Alzheimer’s Association’s Dr. Carrillo described the situation as “manageable,” noting that infusions are standard of care for many diseases, and that neurologists now have more than 15 years’ experience with them for multiple sclerosis.

Still, most clinicians treating Alzheimer’s disease in the community – neurologists, geriatricians, psychiatrists, and primary care physicians – do not have infusion centers in their practices. Virtually none have experience with or access to PET-amyloid, or with screening for amyloid-related imaging abnormalities–edema (ARIA-e) on MRI, as required by the FDA.

“I contacted the hospital infusion center we use and said I could end up sending five or six patients a week, can you handle this? They only have so many chairs,” Dr. Delio said. “I am one neurologist in a local community, and I might have 50 candidates for this drug. That’s a lot for them.” Patients with cognitive impairment are also difficult to infuse and may need to be treated at home, he noted.

“MRIs are easy enough to do,” Dr. Delio said. “But do we know what ARIA-e looks like on imaging? You’d have to talk to the radiologists – this is another element of uncertainty. Do we even know what we’re looking for with these scans? Will we recognize this?”

Neurologist Jeffrey L. Cummings, MD, ScD, of the University of Nevada, Las Vegas, a vocal proponent of aducanumab and lead author of a May 2021 paper defending the evidence for it, acknowledged that the field was unprepared for a wide-scale adoption of infusions in dementia treatment, pointing to a Rand Corporation study from 2017 that warned that screening, diagnosis, and availability of infusion chairs would have to be drastically scaled up to meet demand.

“There are few clinicians who know how to identify MCI, too few imaging centers, too few radiologists who know how to identify ARIA-e on MRI, so all of these things will be required to be put into place. The label doesn’t specify any of this, but good clinical practice will require that, and getting this up and running will take 18 to 24 months,” Dr. Cummings said.

Neurologist David S. Knopman, MD, of the Mayo Clinic in Rochester, Minn., a leading critic of the evidence for aducanumab who recently resigned his position on the independent committee that advises the FDA on neurology drugs, said that for large research institutions like his that have served as trial sites, the transition to offering PET-amyloid, MRI, and infusions in clinical practice will be easier.

Uncertainty over costs

Aducanumab’s true costs, to patients and to taxpayers, remain unknown. The $56,000 per year currently cited by its manufacturer “doesn’t count the PET scans and MRIs,” Dr. Knopman noted. “We’re probably pushing $100,00 a year for the first year of treatment.”

Most of that expense will likely be borne by Medicare, he said, and if not, “that will exacerbate existing health care disparities. People who can pay out of pocket are a pretty limited group.”

Dr. Scharre agreed that the costs of treatment were concerning, and that “at least you should be able to narrow it down and hopefully just use health care dollars for people who might stand to benefit,” he said – namely patients in an earlier stage of disease.

The Alzheimer’s Association’s Dr. Carrillo declined to address the high price of aducanumab or its implications, saying only that the association is “very invested in all aspects of access including covering costs associated with the drug and the rest of treatment.”

Access also means “infrastructure, access to physicians to diagnose, access to diagnostics,” Dr. Carrillo said.

Dr. Cummings said aducanumab’s price would likely come down through negotiations with the Centers for Medicare & Medicaid Services, copayments, and bulk purchases.

The FDA has offered no guidance on how long treatment with aducanumab should last, or what should prompt withdrawal of treatment, meaning that patients could, in theory, stay on it to the end of their lives – raising costs further.

Critics have also noted that a built-in financial incentive under Medicare Part B, which covers infusion drugs, could result in overprescription of aducanumab. Under Medicare Part B, prescribing physicians are reimbursed 6% of a drug’s average sales price.
 

Geriatricians wary

On social media and in the lay press, geriatricians have been among the most outspoken opponents of the FDA decision and the Alzheimer’s Association’s advocacy of aducanumab.

Eric Widera, MD, a geriatrician at the University of California, San Francisco, said that the specialty might be less likely than others to embrace aducanumab. “I think part of the reasons geriatricians don’t make a lot of money is they have strong commitment to their values,” Dr. Widera said.

A fractured research community

Ever since October 2019, when Biogen and Eisai announced that despite two trials halted for futility, they would go ahead and seek FDA approval for aducanumab, the Alzheimer’s research community has been bitterly divided over the drug and the FDA’s accelerated approval process.

Top researchers published critical editorials in journals, with some eventually taking their case to major newspapers as well. The Alzheimer’s Association’s position on the drug has clashed with that of many researchers whose work it supports.

“The Alzheimer’s community has been wonderfully collegial – we all have a common purpose,” Dr. Cummings said. “Now we have people taking extreme positions and I’m hoping this will not result in a permanent fracturing of the community.”

Chief among the critics’ concerns is that the FDA decision ratified the use of antiamyloid therapies based on biomarker evidence, opening the door for makers of similar drugs – those still under development or even those whose development has been halted – to seek approval on weak evidence of clinical benefit.

Whether the approval will chill research into drugs targeting pathways other than amyloid is uncertain.

Dr. Cummings said he felt that while the aducanumab decision would spur other manufacturers of antiamyloid drugs to seek accelerated approval, other classes of Alzheimer’s therapies in development also stand to get a boost. Many Alzheimer’s experts believe that a combination of drugs targeting different elements of the disease pathway – not just amyloid – will be needed in the long run.

Dr. Scharre said that the buzz over aducanumab’s approval will have at least one concrete benefit: people getting into doctors’ offices sooner.

“The people who come into our memory centers represent only a fraction of people walking around with MCI – there are people out there who may have heard that it’s normal aging; they have decreased insight; there’s denial, there’s embarrassment – there’s hundreds of reasons people avoid getting seen,” he said.

“Perhaps they come in and learn that they don’t have any degenerative process but their thyroid is out of whack, or there’s something else causing cognitive impairment. And if they do have a degenerative process, they’ll have time to start [aducanumab], and hopefully get to see a reduction in the decline.”

Dr. Knopman was a site investigator for the Biogen aducanumab trials and has consulted for Samus Therapeutics, Third Rock, Roche, and Alzeca Biosciences. A former member of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee, he was recused from the Nov. 6, 2020, meeting that voted against aducanumab. Dr. Cummings has consulted for Biogen, Eisai, and other manufacturers. Dr. Scharre reports financial relationships with Biogen, Brain Test, Acadia, and Vascular Scientific. Dr. Widera has no disclosures. Dr. Delio is a speaker for Gore Medical, Allergan, and Biohaven Pharmaceuticals.

In early June the Food and Drug Administration – amid a storm of controversy – approved aducanumab, a monoclonal antibody developed to treat Alzheimer’s disease. The approval was hailed by advocacy groups and some practitioners as a victory for patients and families, as the drug – the first anti-Alzheimer’s agent to reach the market in 18 years – is a potentially disease-modifying therapy, which acts to clear amyloid plaques from the brain.

But several prominent Alzheimer’s researchers lambasted the agency’s decision, citing unclear evidence of benefit, trials that did not meet their primary endpoints, and reliance on a post hoc analysis of a high-dose subgroup of patients in a halted trial to argue that aducanumab (Aduhelm, Biogen, and Eisai), slowed cognitive and functional decline by 22% on one measure. In November 2020, 10 of 11 members of an independent FDA advisory committee voted against aducanumab’s approval, citing holes in the data and concerns about the quality of the evidence. After the agency went on to approve anyway, three members of that committee resigned in protest.

The FDA decision on aducanumab was made using the agency’s accelerated approval pathway, which allows for the use of a surrogate endpoint – in this case imaging that showed amyloid clearance from the brain – to predict clinical benefit. But amyloid clearance, which a number of experimental antiamyloid antibodies have been shown capable of, has not been definitively linked to clinical benefit. Aducanumab, which is delivered by monthly intravenous infusion, will be marketed pending results from a phase 4 clinical trial, which the manufacturer has nearly a decade to complete. The drug’s price was announced at $56,000 per year, underscoring concern over its modest-at-best benefits.

Clinicians prescribing aducanumab must obtain magnetic resonance imaging at baseline and repeatedly during the course of treatment to detect brain edema and microhemorrhages, which occurred in a third of high-dose patients in clinical trials. Beyond this, there are few restrictions. The FDA label allows for its use in any patient deemed to have Alzheimer’s disease, without stipulations as to disease stage or evidence of brain amyloid. Payers, of course, are likely to restrict use to certain patient groups, and to require evidence of amyloid positivity. The FDA offered no guidance on when treatment should be ceased, leaving payers to make that call as well. Whatever aducanumab’s value and role turns out to be, the first-in-class treatment for Alzheimer’s disease is likely to have a major impact on how patients are assessed and treated in the coming years, and embolden manufactures of similar agents to seek FDA approval.

This news organization reached out to researchers, advocates, and specialists in the community to learn how they see this change playing out.
 

Fielding broad interest

Maria C. Carrillo, PhD, chief science officer of the Alzheimer’s Association, which was a strong proponent of aducanumab’s approval, acknowledged in an interview that the months to come are likely to be confusing for practitioners and families alike as the drug makes its way into community practices.

“We understand that off the bat millions of Americans will not have access to this tomorrow, but over time that will build. And the physician community, the specialists most likely to be prescribing this, over the next few years will even expand further,” Dr. Carrillo said.

For now, those specialists are mostly just struggling to respond responsibly to a deluge of inquiries from patients and their families.

“I’ve gotten like 20 calls in the just the past 2 days,” said neurologist Philip R. Delio, MD, who practices in Santa Barbara, Calif. “This is a longstanding issue that physicians have with patients’ access to information. Patients are getting information about a drug which isn’t available yet. They don’t know that it’s not ready to be sold. They don’t necessarily realize that a biopharma company won’t go into production until the FDA approves the drug.”

The challenge of delivery

Intravenous infusions are new to Alzheimer’s disease and pose all sorts of logistical hurdles. The Alzheimer’s Association’s Dr. Carrillo described the situation as “manageable,” noting that infusions are standard of care for many diseases, and that neurologists now have more than 15 years’ experience with them for multiple sclerosis.

Still, most clinicians treating Alzheimer’s disease in the community – neurologists, geriatricians, psychiatrists, and primary care physicians – do not have infusion centers in their practices. Virtually none have experience with or access to PET-amyloid, or with screening for amyloid-related imaging abnormalities–edema (ARIA-e) on MRI, as required by the FDA.

“I contacted the hospital infusion center we use and said I could end up sending five or six patients a week, can you handle this? They only have so many chairs,” Dr. Delio said. “I am one neurologist in a local community, and I might have 50 candidates for this drug. That’s a lot for them.” Patients with cognitive impairment are also difficult to infuse and may need to be treated at home, he noted.

“MRIs are easy enough to do,” Dr. Delio said. “But do we know what ARIA-e looks like on imaging? You’d have to talk to the radiologists – this is another element of uncertainty. Do we even know what we’re looking for with these scans? Will we recognize this?”

Neurologist Jeffrey L. Cummings, MD, ScD, of the University of Nevada, Las Vegas, a vocal proponent of aducanumab and lead author of a May 2021 paper defending the evidence for it, acknowledged that the field was unprepared for a wide-scale adoption of infusions in dementia treatment, pointing to a Rand Corporation study from 2017 that warned that screening, diagnosis, and availability of infusion chairs would have to be drastically scaled up to meet demand.

“There are few clinicians who know how to identify MCI, too few imaging centers, too few radiologists who know how to identify ARIA-e on MRI, so all of these things will be required to be put into place. The label doesn’t specify any of this, but good clinical practice will require that, and getting this up and running will take 18 to 24 months,” Dr. Cummings said.

Neurologist David S. Knopman, MD, of the Mayo Clinic in Rochester, Minn., a leading critic of the evidence for aducanumab who recently resigned his position on the independent committee that advises the FDA on neurology drugs, said that for large research institutions like his that have served as trial sites, the transition to offering PET-amyloid, MRI, and infusions in clinical practice will be easier.

Uncertainty over costs

Aducanumab’s true costs, to patients and to taxpayers, remain unknown. The $56,000 per year currently cited by its manufacturer “doesn’t count the PET scans and MRIs,” Dr. Knopman noted. “We’re probably pushing $100,00 a year for the first year of treatment.”

Most of that expense will likely be borne by Medicare, he said, and if not, “that will exacerbate existing health care disparities. People who can pay out of pocket are a pretty limited group.”

Dr. Scharre agreed that the costs of treatment were concerning, and that “at least you should be able to narrow it down and hopefully just use health care dollars for people who might stand to benefit,” he said – namely patients in an earlier stage of disease.

The Alzheimer’s Association’s Dr. Carrillo declined to address the high price of aducanumab or its implications, saying only that the association is “very invested in all aspects of access including covering costs associated with the drug and the rest of treatment.”

Access also means “infrastructure, access to physicians to diagnose, access to diagnostics,” Dr. Carrillo said.

Dr. Cummings said aducanumab’s price would likely come down through negotiations with the Centers for Medicare & Medicaid Services, copayments, and bulk purchases.

The FDA has offered no guidance on how long treatment with aducanumab should last, or what should prompt withdrawal of treatment, meaning that patients could, in theory, stay on it to the end of their lives – raising costs further.

Critics have also noted that a built-in financial incentive under Medicare Part B, which covers infusion drugs, could result in overprescription of aducanumab. Under Medicare Part B, prescribing physicians are reimbursed 6% of a drug’s average sales price.
 

Geriatricians wary

On social media and in the lay press, geriatricians have been among the most outspoken opponents of the FDA decision and the Alzheimer’s Association’s advocacy of aducanumab.

Eric Widera, MD, a geriatrician at the University of California, San Francisco, said that the specialty might be less likely than others to embrace aducanumab. “I think part of the reasons geriatricians don’t make a lot of money is they have strong commitment to their values,” Dr. Widera said.

A fractured research community

Ever since October 2019, when Biogen and Eisai announced that despite two trials halted for futility, they would go ahead and seek FDA approval for aducanumab, the Alzheimer’s research community has been bitterly divided over the drug and the FDA’s accelerated approval process.

Top researchers published critical editorials in journals, with some eventually taking their case to major newspapers as well. The Alzheimer’s Association’s position on the drug has clashed with that of many researchers whose work it supports.

“The Alzheimer’s community has been wonderfully collegial – we all have a common purpose,” Dr. Cummings said. “Now we have people taking extreme positions and I’m hoping this will not result in a permanent fracturing of the community.”

Chief among the critics’ concerns is that the FDA decision ratified the use of antiamyloid therapies based on biomarker evidence, opening the door for makers of similar drugs – those still under development or even those whose development has been halted – to seek approval on weak evidence of clinical benefit.

Whether the approval will chill research into drugs targeting pathways other than amyloid is uncertain.

Dr. Cummings said he felt that while the aducanumab decision would spur other manufacturers of antiamyloid drugs to seek accelerated approval, other classes of Alzheimer’s therapies in development also stand to get a boost. Many Alzheimer’s experts believe that a combination of drugs targeting different elements of the disease pathway – not just amyloid – will be needed in the long run.

Dr. Scharre said that the buzz over aducanumab’s approval will have at least one concrete benefit: people getting into doctors’ offices sooner.

“The people who come into our memory centers represent only a fraction of people walking around with MCI – there are people out there who may have heard that it’s normal aging; they have decreased insight; there’s denial, there’s embarrassment – there’s hundreds of reasons people avoid getting seen,” he said.

“Perhaps they come in and learn that they don’t have any degenerative process but their thyroid is out of whack, or there’s something else causing cognitive impairment. And if they do have a degenerative process, they’ll have time to start [aducanumab], and hopefully get to see a reduction in the decline.”

Dr. Knopman was a site investigator for the Biogen aducanumab trials and has consulted for Samus Therapeutics, Third Rock, Roche, and Alzeca Biosciences. A former member of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee, he was recused from the Nov. 6, 2020, meeting that voted against aducanumab. Dr. Cummings has consulted for Biogen, Eisai, and other manufacturers. Dr. Scharre reports financial relationships with Biogen, Brain Test, Acadia, and Vascular Scientific. Dr. Widera has no disclosures. Dr. Delio is a speaker for Gore Medical, Allergan, and Biohaven Pharmaceuticals.

The results from three small studies of targeted therapy for rare brain tumors were “remarkable,” according to Jaishri Blakeley, MD, a neurology professor at Johns Hopkins Medicine, Baltimore, who discussed the studies after they were presented at the American Society of Clinical Oncology meeting.

Although most patients don’t have targetable mutations, molecular testing “is well worth the effort,” for those that do. “I think it’s fair to say that precision medicine” – well established in other tumor types – “is finally here in full force for neuro-oncology,” Dr. Blakeley said.
 

A promising start

Fifteen of 16 patients (94%) in one study had newly diagnosed and untreated papillary craniopharyngiomas (PCPs) that harbored BRAF V600E mutations, a common finding in PCPs, which have no effective medical treatment.

Tumors shrunk 68%-99% in 14 patients (93%) after treatment with the BRAF inhibitor vemurafenib plus the MEK inhibitor cobimetinib, which was included to stave off resistance to vemurafenib. The 24-month progression free survival was 93%.

The combination resulted in significant response in all patients who received at least one cycle of therapy, with a median 91% volume reduction. “Our study indicates that BRAF/MEK inhibitors could be a powerful tool in the treatment of previously untreated PCP, with the potential to avoid the morbidity associated with radiation and surgery,” concluded lead investigator and presenter Priscilla K. Brastianos, MD, associate professor of medicine at Mass General Cancer Center, Boston.

Thirty-three people in the second study had a mix of high and low grade gliomas or other CNS tumors positive for TRK gene fusions, a known oncogenic driver; the majority were children. They were treated with the TRK inhibitor larotrectinib after progressing on other systemic therapies.

The objective response rate was 30%, and the disease control rate was 73% at 24 weeks, with a median time to best response of 1.9 months. Tumors shrank in 82% of evaluable patients. Median progression-free survival was 18.3 months, and overall survival was not reached.

“These results support testing for TRK gene fusions for all patients with CNS tumors, especially if there is no known driver and especially in infants,” concluded lead investigator and presenter Sebastien Perreault, MD, a clinical assistant neurosciences professor at the University of Montreal.

The third study tested ALK inhibitors such as crizotinib in seven patients with adult-onset neuroblastoma, a rare and almost invariably fatal tumor known to be enriched for ALK mutations; the subjects were positive for them.

Their disease remained stable anywhere from 3.4 to 37.4 months. Median time to progression was 15.5 months, and median overall survival was 46.5 months.

ALK inhibitors “can be a well-tolerated options for treatment, improving time to progression. Development of resistance to one agent does not preclude use of other agents in the same drug class. ALK inhibitors should be considered when treating patients with this diagnosis,” said lead investigator and presenter Jessica Stiefel, MD, a pediatric hematology oncology fellow at Memorial Sloan Kettering Cancer Center, New York.
 

A ‘strong’ recommendation

The data “are great news” across the board. Targeted therapy applied to the right CNS tumor can have “dramatic” benefit for tumor control, Dr. Blakeley said.

But organizing molecular testing is not straightforward and requires strategies to balance “the use of precious resources, such as time money, and tissue,” with the potential benefit. Interpretation of testing results isn’t straightforward either, and is best handled by a molecular tumor board. Clinical pharmacists are also key to accessing expensive medications off label for CNS tumors.

Adverse events are also a consideration. Most of the subjects in the PCP study had grade 3/4 toxicity. Three patients in the ALK inhibitor study had to stop because of adverse events. Almost 40% on larotrectinib had grade 3 or 4 toxicity; nobody came off treatment, but a third had to skip doses.

Once an actionable mutation is identified, Dr. Blakeley’s “strong recommendation” is to enroll patients in a clinical trial that targets it, to take advantage the structure already in place to secure treatment, managed patients, and assess outcomes.

The National Cancer Institute’s MATCH trial is one of several options.

The BRAF/MEK inhibitor study was funded by Genentech and the National Institutes of Health. Dr. Brastianos had ties to numerous companies, including Pfizer, Lilly, and Merck. The TRK inhibitor study was funded by Bayer/Lilly. Dr. Perreault is a speaker and researcher for the company and has other ties. Dr. Blakeley is an adviser and/or researcher for a number of companies, including AbbVie, Astellas, BMS, and Exelixis. Dr. Stiefel didn’t have any disclosures, and didn’t report outside funding.

[email protected]

The results from three small studies of targeted therapy for rare brain tumors were “remarkable,” according to Jaishri Blakeley, MD, a neurology professor at Johns Hopkins Medicine, Baltimore, who discussed the studies after they were presented at the American Society of Clinical Oncology meeting.

Although most patients don’t have targetable mutations, molecular testing “is well worth the effort,” for those that do. “I think it’s fair to say that precision medicine” – well established in other tumor types – “is finally here in full force for neuro-oncology,” Dr. Blakeley said.
 

A promising start

Fifteen of 16 patients (94%) in one study had newly diagnosed and untreated papillary craniopharyngiomas (PCPs) that harbored BRAF V600E mutations, a common finding in PCPs, which have no effective medical treatment.

Tumors shrunk 68%-99% in 14 patients (93%) after treatment with the BRAF inhibitor vemurafenib plus the MEK inhibitor cobimetinib, which was included to stave off resistance to vemurafenib. The 24-month progression free survival was 93%.

The combination resulted in significant response in all patients who received at least one cycle of therapy, with a median 91% volume reduction. “Our study indicates that BRAF/MEK inhibitors could be a powerful tool in the treatment of previously untreated PCP, with the potential to avoid the morbidity associated with radiation and surgery,” concluded lead investigator and presenter Priscilla K. Brastianos, MD, associate professor of medicine at Mass General Cancer Center, Boston.

Thirty-three people in the second study had a mix of high and low grade gliomas or other CNS tumors positive for TRK gene fusions, a known oncogenic driver; the majority were children. They were treated with the TRK inhibitor larotrectinib after progressing on other systemic therapies.

The objective response rate was 30%, and the disease control rate was 73% at 24 weeks, with a median time to best response of 1.9 months. Tumors shrank in 82% of evaluable patients. Median progression-free survival was 18.3 months, and overall survival was not reached.

“These results support testing for TRK gene fusions for all patients with CNS tumors, especially if there is no known driver and especially in infants,” concluded lead investigator and presenter Sebastien Perreault, MD, a clinical assistant neurosciences professor at the University of Montreal.

The third study tested ALK inhibitors such as crizotinib in seven patients with adult-onset neuroblastoma, a rare and almost invariably fatal tumor known to be enriched for ALK mutations; the subjects were positive for them.

Their disease remained stable anywhere from 3.4 to 37.4 months. Median time to progression was 15.5 months, and median overall survival was 46.5 months.

ALK inhibitors “can be a well-tolerated options for treatment, improving time to progression. Development of resistance to one agent does not preclude use of other agents in the same drug class. ALK inhibitors should be considered when treating patients with this diagnosis,” said lead investigator and presenter Jessica Stiefel, MD, a pediatric hematology oncology fellow at Memorial Sloan Kettering Cancer Center, New York.
 

A ‘strong’ recommendation

The data “are great news” across the board. Targeted therapy applied to the right CNS tumor can have “dramatic” benefit for tumor control, Dr. Blakeley said.

But organizing molecular testing is not straightforward and requires strategies to balance “the use of precious resources, such as time money, and tissue,” with the potential benefit. Interpretation of testing results isn’t straightforward either, and is best handled by a molecular tumor board. Clinical pharmacists are also key to accessing expensive medications off label for CNS tumors.

Adverse events are also a consideration. Most of the subjects in the PCP study had grade 3/4 toxicity. Three patients in the ALK inhibitor study had to stop because of adverse events. Almost 40% on larotrectinib had grade 3 or 4 toxicity; nobody came off treatment, but a third had to skip doses.

Once an actionable mutation is identified, Dr. Blakeley’s “strong recommendation” is to enroll patients in a clinical trial that targets it, to take advantage the structure already in place to secure treatment, managed patients, and assess outcomes.

The National Cancer Institute’s MATCH trial is one of several options.

The BRAF/MEK inhibitor study was funded by Genentech and the National Institutes of Health. Dr. Brastianos had ties to numerous companies, including Pfizer, Lilly, and Merck. The TRK inhibitor study was funded by Bayer/Lilly. Dr. Perreault is a speaker and researcher for the company and has other ties. Dr. Blakeley is an adviser and/or researcher for a number of companies, including AbbVie, Astellas, BMS, and Exelixis. Dr. Stiefel didn’t have any disclosures, and didn’t report outside funding.

[email protected]

The results from three small studies of targeted therapy for rare brain tumors were “remarkable,” according to Jaishri Blakeley, MD, a neurology professor at Johns Hopkins Medicine, Baltimore, who discussed the studies after they were presented at the American Society of Clinical Oncology meeting.

Although most patients don’t have targetable mutations, molecular testing “is well worth the effort,” for those that do. “I think it’s fair to say that precision medicine” – well established in other tumor types – “is finally here in full force for neuro-oncology,” Dr. Blakeley said.
 

A promising start

Fifteen of 16 patients (94%) in one study had newly diagnosed and untreated papillary craniopharyngiomas (PCPs) that harbored BRAF V600E mutations, a common finding in PCPs, which have no effective medical treatment.

Tumors shrunk 68%-99% in 14 patients (93%) after treatment with the BRAF inhibitor vemurafenib plus the MEK inhibitor cobimetinib, which was included to stave off resistance to vemurafenib. The 24-month progression free survival was 93%.

The combination resulted in significant response in all patients who received at least one cycle of therapy, with a median 91% volume reduction. “Our study indicates that BRAF/MEK inhibitors could be a powerful tool in the treatment of previously untreated PCP, with the potential to avoid the morbidity associated with radiation and surgery,” concluded lead investigator and presenter Priscilla K. Brastianos, MD, associate professor of medicine at Mass General Cancer Center, Boston.

Thirty-three people in the second study had a mix of high and low grade gliomas or other CNS tumors positive for TRK gene fusions, a known oncogenic driver; the majority were children. They were treated with the TRK inhibitor larotrectinib after progressing on other systemic therapies.

The objective response rate was 30%, and the disease control rate was 73% at 24 weeks, with a median time to best response of 1.9 months. Tumors shrank in 82% of evaluable patients. Median progression-free survival was 18.3 months, and overall survival was not reached.

“These results support testing for TRK gene fusions for all patients with CNS tumors, especially if there is no known driver and especially in infants,” concluded lead investigator and presenter Sebastien Perreault, MD, a clinical assistant neurosciences professor at the University of Montreal.

The third study tested ALK inhibitors such as crizotinib in seven patients with adult-onset neuroblastoma, a rare and almost invariably fatal tumor known to be enriched for ALK mutations; the subjects were positive for them.

Their disease remained stable anywhere from 3.4 to 37.4 months. Median time to progression was 15.5 months, and median overall survival was 46.5 months.

ALK inhibitors “can be a well-tolerated options for treatment, improving time to progression. Development of resistance to one agent does not preclude use of other agents in the same drug class. ALK inhibitors should be considered when treating patients with this diagnosis,” said lead investigator and presenter Jessica Stiefel, MD, a pediatric hematology oncology fellow at Memorial Sloan Kettering Cancer Center, New York.
 

A ‘strong’ recommendation

The data “are great news” across the board. Targeted therapy applied to the right CNS tumor can have “dramatic” benefit for tumor control, Dr. Blakeley said.

But organizing molecular testing is not straightforward and requires strategies to balance “the use of precious resources, such as time money, and tissue,” with the potential benefit. Interpretation of testing results isn’t straightforward either, and is best handled by a molecular tumor board. Clinical pharmacists are also key to accessing expensive medications off label for CNS tumors.

Adverse events are also a consideration. Most of the subjects in the PCP study had grade 3/4 toxicity. Three patients in the ALK inhibitor study had to stop because of adverse events. Almost 40% on larotrectinib had grade 3 or 4 toxicity; nobody came off treatment, but a third had to skip doses.

Once an actionable mutation is identified, Dr. Blakeley’s “strong recommendation” is to enroll patients in a clinical trial that targets it, to take advantage the structure already in place to secure treatment, managed patients, and assess outcomes.

The National Cancer Institute’s MATCH trial is one of several options.

The BRAF/MEK inhibitor study was funded by Genentech and the National Institutes of Health. Dr. Brastianos had ties to numerous companies, including Pfizer, Lilly, and Merck. The TRK inhibitor study was funded by Bayer/Lilly. Dr. Perreault is a speaker and researcher for the company and has other ties. Dr. Blakeley is an adviser and/or researcher for a number of companies, including AbbVie, Astellas, BMS, and Exelixis. Dr. Stiefel didn’t have any disclosures, and didn’t report outside funding.

[email protected]

Patients with relapsed or refractory B-cell non-Hodgkin lymphomas who are not candidates for hematopoietic stem cell transplant have a generally poor prognosis and few treatment options, but an experimental combination of the antibody-drug conjugate naratuximab with rituximab showed promising efficacy and acceptable safety in these patients in a phase 2 trial.

Among patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) the combination was associated with a 44.7% overall response rate, including 31.6% complete responses, and two-thirds of patients had responses lasting more than 12 months, reported Moshe Yair Levy, MD, from Texas Oncology–Baylor Charles A Sammons Cancer Center in Dallas.

“This is, in my viewpoint, very exciting therapy,” he said in a question-and-answer session following his presentation of the data in a late-breaking abstract session during the European Hematology Association annual congress. (Abstract LB1903).

Naratuximab emtansine is an investigational antibody-drug conjugate (ADC) consisting of a humanized monoclonal antibody against CD37, a surface marker on B lymphocytes that is highly expressed in non-Hodgkin lymphoma (NHL), conjugated to a cytotoxic derivative of maitansine.

CD37 is also an internalizable cell-surface antigen, making it an attractive candidate for an ADC approach.

In a phase 1 trial, naratuximab monotherapy showed a good safety profile and a 22% overall response rate, Dr. Levy noted.

“What they found is that, if you coadminister this ADC with rituximab, you’re actually going to get more internalization of the CD37 monoclonal, therefore more payload delivered to your target cells,” he said.

He reported results of a multicenter, adaptive phase 2 study of the combination in patients with DLBCL and other relapsed/refractory NHL.
 

DLBCL and others

The trial was divided into two parts, with the first consisting of a safety run-in phase with expansion in patients with confirmed diagnoses of relapsed/refractory NHL, including DLBCL, follicular lymphoma, mantle cell lymphoma, and marginal zone lymphoma.

Patients with double- or triple-hit disease (with translocations in MYC plus either BCL2 and/or BCL6), bulky disease, or transformed lymphoma were eligible.

The second part consisted of two cohorts of patients with DLBCL treated with naratuximab and rituximab either weekly or every 3 weeks.

All patients in the study had received one to six prior lines of therapy, and had Eastern Cooperative Oncology Group performance status of 0-2. Patients with CNS lymphomas or prior anti-CD37 targeting therapy were excluded.

The safety population included 50 patients with DLBCL assigned to therapy every 3 weeks, 30 assigned to weekly therapy, and 20 patients with other NHL.