Skin symptoms, like systemic symptoms, differ by COVID-19 variant, according to a large retrospective study that compared clinical data from more than 300,000 participants in the United Kingdom during the Omicron and Delta waves.

Among the key findings, the study shows that skin involvement during the Omicron wave was less frequent than during the Delta wave (11.4% vs. 17.6%), skin symptoms generally resolved more quickly, and that the risk for skin symptoms was similar whether patients had or had not been vaccinated, according to a team led by Alessia Visconti, PhD, a research fellow in the department of twin research and genetic epidemiology, King’s College, London.

These data are consistent with the experience of those dermatologists who have been following this area closely, according to Esther Freeman, MD, PhD, associate professor of dermatology at Harvard Medical School and director of MGH Global Health Dermatology at Massachusetts General Hospital, both in Boston.

“Anecdotally, we thought we were seeing fewer skin symptoms with Omicron versus Delta and the ancestral strains, and now this study shows it is true,” said Dr. Freeman, who is also principal investigator of the American Academy of Dermatology’s International Dermatology COVID-19 Registry.

The data also confirm that the skin is less likely to be involved than in past waves of COVID-19 infections.

“Up to this point, it was hard to know if we were seeing fewer referrals for COVID-related skin rashes or if clinicians had just become more comfortable with these rashes and were not referring them as often,” added Dr. Freeman, who was among the study coauthors.

Data captured from 348,691 patients

The data from the study was generated by 348,691 users in the United Kingdom of the ZOE COVID study app, a smartphone-based tool introduced relatively early in the pandemic. It asked users to provide demographic data, information on COVID-19 symptoms, including those involving the skin, and treatments. Of 33 COVID-related symptoms included in the app, five related to the skin (acral rash, burning rash, erythematopapular rash, urticarial rash, and unusual hair loss).

While the focus of this study was to compare skin manifestations during the Omicron wave with the Delta wave of COVID-19, the investigators also had data on the experience in 2020 with wild-type COVID-19 that preceded both variants. Overall, this showed a stepwise decline in skin symptoms overall, as well in as skin symptoms that occurred in the absence of systemic symptoms.

“The shift in the skin manifestations makes sense when you think about the change that is also being seen in the systemic symptoms,” said Dr. Freeman, referring to lower rates of cough and loss of smell but higher rates of sore throat and fatigue. “Omicron is achieving immune escape, which is why there is a shift in involved tissues,” she said in an interview.

Previous data collected during the wild-type COVID-19 stage of the pandemic by the same group of investigators showed that 17% of patients reported skin rash as the first symptom of COVID-19 infection, and 21% reported skin rash as the only clinical sign of infection.

In the Delta and Omicron waves, skin rash was an isolated initial symptom in only 0.8% and 0.5% of patients, respectively. (The authors noted that, in the United Kingdom, the first documented samples of the Delta variant were detected in October 2020, and the first documented samples of the Omicron variant were detected in November 2021.)

During the early stages of wild-type COVID, an acral rash was characteristic, occurring in 3.1% of patients, according to the U.K. data. In the Delta wave, acral rashes, at an incidence of 1.1% remained positively correlated with a diagnosis of COVID-19 infection. In the Omicron wave, acral rashes were observed in only 0.7% of patients and were no longer statistically correlated with a positive COVID diagnosis.


 

Characteristic cutaneous symptoms are evolving

Early in the course of the COVID-19 epidemic, more than 30 types of rashes were observed in patients with COVID-19 infection. Cutaneous symptoms continue to be diverse, but some, such as acral rash, are being seen less frequently. For example, the odds ratio of a positive COVID-19 diagnosis among those with an erythematopapular rash fell from 1.76 to 1.08 between the Delta and Omicron waves.

While specific cutaneous symptoms are less predictive of a diagnosis of COVID-19, clinicians should not discount cutaneous symptoms as a sign of disease, according to Veronique Bataille, MD, PhD, a consultant dermatologist at King’s College.

“You need to keep an open mind” regarding cutaneous signs and a diagnosis of COVID-19, Dr. Bataille, one of the coauthors of the U.K. report, said in an interview. In general, she considers a low threshold of suspicion appropriate. “If the patient has no past history of skin disease and no other triggers for a rash, then, in a high prevalence area, COVID must be suspected.”

In most cases, the rash resolves on its own, but Dr. Bataille emphasized the need for individualized care. Even as the risk of life-threatening COVID-19 infections appears to be diminishing with current variants, cutaneous manifestations can be severe.

“There are cases of long COVID affecting the skin, such as urticaria or a lichenoid erythematopapular rash, both of which can be very pruritic and difficult to control,” she said.

Dr. Freeman echoed the importance of an individualized approach. She agreed that most cutaneous symptoms are self-limited, but there are exceptions and treatments vary for the different types of skin involvement. “I think another point to consider when examining skin lesions is monkey pox. The fact that these are overlapping outbreaks should not be ignored. You need to be alert for both.”

Dr. Visconti, Dr. Freeman, and Dr. Bataille reported no potential conflicts of interest.

Skin symptoms, like systemic symptoms, differ by COVID-19 variant, according to a large retrospective study that compared clinical data from more than 300,000 participants in the United Kingdom during the Omicron and Delta waves.

Among the key findings, the study shows that skin involvement during the Omicron wave was less frequent than during the Delta wave (11.4% vs. 17.6%), skin symptoms generally resolved more quickly, and that the risk for skin symptoms was similar whether patients had or had not been vaccinated, according to a team led by Alessia Visconti, PhD, a research fellow in the department of twin research and genetic epidemiology, King’s College, London.

These data are consistent with the experience of those dermatologists who have been following this area closely, according to Esther Freeman, MD, PhD, associate professor of dermatology at Harvard Medical School and director of MGH Global Health Dermatology at Massachusetts General Hospital, both in Boston.

“Anecdotally, we thought we were seeing fewer skin symptoms with Omicron versus Delta and the ancestral strains, and now this study shows it is true,” said Dr. Freeman, who is also principal investigator of the American Academy of Dermatology’s International Dermatology COVID-19 Registry.

The data also confirm that the skin is less likely to be involved than in past waves of COVID-19 infections.

“Up to this point, it was hard to know if we were seeing fewer referrals for COVID-related skin rashes or if clinicians had just become more comfortable with these rashes and were not referring them as often,” added Dr. Freeman, who was among the study coauthors.

Data captured from 348,691 patients

The data from the study was generated by 348,691 users in the United Kingdom of the ZOE COVID study app, a smartphone-based tool introduced relatively early in the pandemic. It asked users to provide demographic data, information on COVID-19 symptoms, including those involving the skin, and treatments. Of 33 COVID-related symptoms included in the app, five related to the skin (acral rash, burning rash, erythematopapular rash, urticarial rash, and unusual hair loss).

While the focus of this study was to compare skin manifestations during the Omicron wave with the Delta wave of COVID-19, the investigators also had data on the experience in 2020 with wild-type COVID-19 that preceded both variants. Overall, this showed a stepwise decline in skin symptoms overall, as well in as skin symptoms that occurred in the absence of systemic symptoms.

“The shift in the skin manifestations makes sense when you think about the change that is also being seen in the systemic symptoms,” said Dr. Freeman, referring to lower rates of cough and loss of smell but higher rates of sore throat and fatigue. “Omicron is achieving immune escape, which is why there is a shift in involved tissues,” she said in an interview.

Previous data collected during the wild-type COVID-19 stage of the pandemic by the same group of investigators showed that 17% of patients reported skin rash as the first symptom of COVID-19 infection, and 21% reported skin rash as the only clinical sign of infection.

In the Delta and Omicron waves, skin rash was an isolated initial symptom in only 0.8% and 0.5% of patients, respectively. (The authors noted that, in the United Kingdom, the first documented samples of the Delta variant were detected in October 2020, and the first documented samples of the Omicron variant were detected in November 2021.)

During the early stages of wild-type COVID, an acral rash was characteristic, occurring in 3.1% of patients, according to the U.K. data. In the Delta wave, acral rashes, at an incidence of 1.1% remained positively correlated with a diagnosis of COVID-19 infection. In the Omicron wave, acral rashes were observed in only 0.7% of patients and were no longer statistically correlated with a positive COVID diagnosis.


 

Characteristic cutaneous symptoms are evolving

Early in the course of the COVID-19 epidemic, more than 30 types of rashes were observed in patients with COVID-19 infection. Cutaneous symptoms continue to be diverse, but some, such as acral rash, are being seen less frequently. For example, the odds ratio of a positive COVID-19 diagnosis among those with an erythematopapular rash fell from 1.76 to 1.08 between the Delta and Omicron waves.

While specific cutaneous symptoms are less predictive of a diagnosis of COVID-19, clinicians should not discount cutaneous symptoms as a sign of disease, according to Veronique Bataille, MD, PhD, a consultant dermatologist at King’s College.

“You need to keep an open mind” regarding cutaneous signs and a diagnosis of COVID-19, Dr. Bataille, one of the coauthors of the U.K. report, said in an interview. In general, she considers a low threshold of suspicion appropriate. “If the patient has no past history of skin disease and no other triggers for a rash, then, in a high prevalence area, COVID must be suspected.”

In most cases, the rash resolves on its own, but Dr. Bataille emphasized the need for individualized care. Even as the risk of life-threatening COVID-19 infections appears to be diminishing with current variants, cutaneous manifestations can be severe.

“There are cases of long COVID affecting the skin, such as urticaria or a lichenoid erythematopapular rash, both of which can be very pruritic and difficult to control,” she said.

Dr. Freeman echoed the importance of an individualized approach. She agreed that most cutaneous symptoms are self-limited, but there are exceptions and treatments vary for the different types of skin involvement. “I think another point to consider when examining skin lesions is monkey pox. The fact that these are overlapping outbreaks should not be ignored. You need to be alert for both.”

Dr. Visconti, Dr. Freeman, and Dr. Bataille reported no potential conflicts of interest.

Skin symptoms, like systemic symptoms, differ by COVID-19 variant, according to a large retrospective study that compared clinical data from more than 300,000 participants in the United Kingdom during the Omicron and Delta waves.

Among the key findings, the study shows that skin involvement during the Omicron wave was less frequent than during the Delta wave (11.4% vs. 17.6%), skin symptoms generally resolved more quickly, and that the risk for skin symptoms was similar whether patients had or had not been vaccinated, according to a team led by Alessia Visconti, PhD, a research fellow in the department of twin research and genetic epidemiology, King’s College, London.

These data are consistent with the experience of those dermatologists who have been following this area closely, according to Esther Freeman, MD, PhD, associate professor of dermatology at Harvard Medical School and director of MGH Global Health Dermatology at Massachusetts General Hospital, both in Boston.

“Anecdotally, we thought we were seeing fewer skin symptoms with Omicron versus Delta and the ancestral strains, and now this study shows it is true,” said Dr. Freeman, who is also principal investigator of the American Academy of Dermatology’s International Dermatology COVID-19 Registry.

The data also confirm that the skin is less likely to be involved than in past waves of COVID-19 infections.

“Up to this point, it was hard to know if we were seeing fewer referrals for COVID-related skin rashes or if clinicians had just become more comfortable with these rashes and were not referring them as often,” added Dr. Freeman, who was among the study coauthors.

Data captured from 348,691 patients

The data from the study was generated by 348,691 users in the United Kingdom of the ZOE COVID study app, a smartphone-based tool introduced relatively early in the pandemic. It asked users to provide demographic data, information on COVID-19 symptoms, including those involving the skin, and treatments. Of 33 COVID-related symptoms included in the app, five related to the skin (acral rash, burning rash, erythematopapular rash, urticarial rash, and unusual hair loss).

While the focus of this study was to compare skin manifestations during the Omicron wave with the Delta wave of COVID-19, the investigators also had data on the experience in 2020 with wild-type COVID-19 that preceded both variants. Overall, this showed a stepwise decline in skin symptoms overall, as well in as skin symptoms that occurred in the absence of systemic symptoms.

“The shift in the skin manifestations makes sense when you think about the change that is also being seen in the systemic symptoms,” said Dr. Freeman, referring to lower rates of cough and loss of smell but higher rates of sore throat and fatigue. “Omicron is achieving immune escape, which is why there is a shift in involved tissues,” she said in an interview.

Previous data collected during the wild-type COVID-19 stage of the pandemic by the same group of investigators showed that 17% of patients reported skin rash as the first symptom of COVID-19 infection, and 21% reported skin rash as the only clinical sign of infection.

In the Delta and Omicron waves, skin rash was an isolated initial symptom in only 0.8% and 0.5% of patients, respectively. (The authors noted that, in the United Kingdom, the first documented samples of the Delta variant were detected in October 2020, and the first documented samples of the Omicron variant were detected in November 2021.)

During the early stages of wild-type COVID, an acral rash was characteristic, occurring in 3.1% of patients, according to the U.K. data. In the Delta wave, acral rashes, at an incidence of 1.1% remained positively correlated with a diagnosis of COVID-19 infection. In the Omicron wave, acral rashes were observed in only 0.7% of patients and were no longer statistically correlated with a positive COVID diagnosis.


 

Characteristic cutaneous symptoms are evolving

Early in the course of the COVID-19 epidemic, more than 30 types of rashes were observed in patients with COVID-19 infection. Cutaneous symptoms continue to be diverse, but some, such as acral rash, are being seen less frequently. For example, the odds ratio of a positive COVID-19 diagnosis among those with an erythematopapular rash fell from 1.76 to 1.08 between the Delta and Omicron waves.

While specific cutaneous symptoms are less predictive of a diagnosis of COVID-19, clinicians should not discount cutaneous symptoms as a sign of disease, according to Veronique Bataille, MD, PhD, a consultant dermatologist at King’s College.

“You need to keep an open mind” regarding cutaneous signs and a diagnosis of COVID-19, Dr. Bataille, one of the coauthors of the U.K. report, said in an interview. In general, she considers a low threshold of suspicion appropriate. “If the patient has no past history of skin disease and no other triggers for a rash, then, in a high prevalence area, COVID must be suspected.”

In most cases, the rash resolves on its own, but Dr. Bataille emphasized the need for individualized care. Even as the risk of life-threatening COVID-19 infections appears to be diminishing with current variants, cutaneous manifestations can be severe.

“There are cases of long COVID affecting the skin, such as urticaria or a lichenoid erythematopapular rash, both of which can be very pruritic and difficult to control,” she said.

Dr. Freeman echoed the importance of an individualized approach. She agreed that most cutaneous symptoms are self-limited, but there are exceptions and treatments vary for the different types of skin involvement. “I think another point to consider when examining skin lesions is monkey pox. The fact that these are overlapping outbreaks should not be ignored. You need to be alert for both.”

Dr. Visconti, Dr. Freeman, and Dr. Bataille reported no potential conflicts of interest.

New devices that use artificial intelligence (AI) to diagnose skin cancer – such as smartphone apps – have been popping up over the past few years, but there is some concern over the accuracy of these tools.

So far, the U.S. Food and Drug Administration has cleared two devices. Both are computer-aided skin lesion classification devices meant to help clinicians assess cases of suspected melanoma.

Both were given a class III designation. That classification is intended for products that are considered to have a high risk of harm because of flawed design or implementation. Many such devices are under development, and there has been a proposal to include these devices in class II, which is less restrictive.

The FDA turned to one of its expert panels for advice. At a meeting held on Aug. 29, experts on the panel offered differing views and expressed concerns about the accuracy of these devices.

This was the second day of meetings of the general and plastic surgery devices panel of the FDA’s Medical Devices Advisory Committee. On the previous day, the panel held a wide-ranging discussion about expanding use of skin lesion analyzer devices.

The FDA sought the expert panel’s advice concerning a field that appears to be heating up quickly after relatively quiet times.

Two devices have been approved by the FDA so far, but only one is still being promoted – SciBase AB’s Nevisense. The Swedish company announced in May 2020 that it had received FDA approval for Nevisense 3.0, the third generation of their Nevisense system for early melanoma detection, an AI-based point-of-care system for the noninvasive evaluation of irregular moles.

The other device, known as MelaFind, was acquired by Strata Skin Sciences, but the company said in 2017 that it discontinued research and development, sales, and support activity related to the device, according to a filing with the Securities and Exchange Commission.

But there’s been a swell in recent years in the number of publications related to the use of AI and machine learning, which could give rise to new tools for aiding in the diagnosis of skin conditions, including cancer. Google is among the companies that are involved in these efforts.

So, the FDA asked the expert panel to discuss a series of questions related to how the agency should weigh the risks of computer-aided devices for melanoma diagnosis. The agency also asked the panel to provide feedback about how well risks associated with such devices and tools might be managed and to offer suggestions.

The discussion at the July 29 meeting spun beyond narrow questions about reclassification of the current class III devices to topics involving emerging technology, such as efforts to apply AI to dermatology.

“Innovation continues. Medical device developers are anxious to plan how they might be able to develop the level of evidence that would meet your expectations” for future products, Binita Ashar, MD, a senior official in FDA’s Center for Devices and Radiological Health, told the panel.


 

Company CEO backs tougher regulation

Simon Grant, the chief executive of SciBase, which markets Nevisense, the first and only skin cancer–detecting device currently on the U.S. market, sought to make a case for sticking with the tougher class III regulations.

Speaking during the public comment session, Mr. Grant said switching to class II designations would weaken the standards used in clearing products that analyze skin lesions so as to put patients at risk.

Under the FDA’s rules, the agency designates as class III devices that present potential unreasonable risk of illness or injury. Only about 10% of devices fall into this category. Such devices include implantable pacemakers and breast implants, as well as SciBase’s Nevisense.

About 43% of medical devices fall into the class II category, which includes powered wheelchairs and some pregnancy test kits, the FDA website says.

Class I medical devices pose minimal potential for harm and tend to be simpler in design. These include enema kits and elastic bandages, the FDA says.

Mr. Grant told the meeting that in his career he has worked on two class III products and about 20 class II products. (He had previously worked at medical startups Synectics Medical and Neoventa, as well as established multinationals such as Medtronic.)

“I can tell you that – practically – the FDA has many fewer sticks and much less control when it comes to class II devices,” he said. He offered an example of a manufacturer of a class II device having more latitude in making small changes to products without notifying the FDA.

In his hypothetical example, such a change could have unintended consequences, and “with AI systems, small changes can result in large and nonlinear or even random effects,” Mr. Grant said. “But it’s too late if the product is on the market and the harm has already occurred,” he said.

The American Society for Dermatologic Surgery Association also protested the reclassifying of approved computer-aided melanoma detection class III devices.

In a statement posted on the FDA website as part of the materials for the meeting, the ASDSA raised a series of concerns about the prospects of expanded U.S. use of tools for assisting in diagnosing melanoma, including ones that would be marketed to consumers.

“To the extent that algorithms and devices for patient self-diagnosis of skin lesions are already widely available, they should be required to include detailed disclaimers that include that they are for entertainment and educational purposes and not a diagnostic device, that they are not approved by dermatologists or a recognized medical regulatory authority for self-diagnosis,” the ASDSA said.

Devices and algorithms in screening tools “are not highly regulated and remain unproven. They may result in wrong diagnoses, missed diagnoses, or over- or underdiagnosis,” the ASDSA added. “Both patients at low risk and those at high risk are better served by scheduling an in-person examination with a board-certified dermatologist, who can also help them determine the appropriate future skin screening schedule that is most appropriate for them.”

 

‘Stepping stone’

However, there is strong consumer demand for better information about skin conditions, and many patients face hurdles in going to dermatologists.

Google research has shown that consumers are seeking “a stepping stone” between the information they can easily find online and what they could get from a medical professional, said Lily Peng, MD, PhD, a director of product management for the health AI team at Google. Dr. Peng was a scheduled presenter at the July 29 meeting.

Consumers often are looking for more information on common conditions such as acne and poison ivy, and they sometimes face challenges in getting access to clinicians, she said.

“There are many unmet needs for consumers experiencing skin issues, many of which are lower-acuity conditions. There’s a big opportunity to increase accessibility and relevance of health journeys for consumers,” Dr. Peng said. “We have heard from consumers that they would like to have a self-help tool for nonserious conditions so they can decide when to seek medical attention.”

Dr. Peng’s presentation was not directly related to the question of class II or class III designation for existing products. Instead, her talk served as a glimpse into the work already underway in creating apps and tools for consumers.

Google researchers have published a number of studies in recent years about the use of AI to improve dermatology diagnosis.

A 2020 article reported on Google’s test of a form of AI known as deep learning system (DLS) to provide a differential diagnosis of skin conditions. On 963 validation cases, where a rotating panel of three board-certified dermatologists defined the reference standard, the DLS was noninferior to six other dermatologists and was superior to six primary care physicians (PCPs) and six nurse practitioners (NPs), according to a summary of the article.

A 2021 report published in JAMA Network Open said that use of an AI tool was associated with a higher agreement rate with dermatologists’ reference diagnoses for both PCPs and NPs.

In a 2021 blog post, Google scientists wrote that their AI model that powers a tool for checking skin conditions had earned European clearance, known as a CE mark, as a class I medical device.

SkinVision has an app that the company says “is available worldwide (with the exception of the USA and Canada).” The firm’s website includes a link where people in the United States and Canada can sign up for notifications about when SkinVision will be available in these nations. 


 

‘Not ready for prime time’

The FDA panel did not cast formal votes at the July 29 meeting. Rather, the members engaged in broad discussions about risks and potential benefits of new tools for aiding in the detection of skin cancer.

Among the key issues discussed was a question of whether the FDA could impose requirements and restrictions, known as special controls, to provide “reasonable assurance of safety and effectiveness” for computer-aided devices that provide adjunctive diagnostic information to dermatologists about lesions suspicious for melanoma.

Among the potential special controls would be clinical performance testing in regards to rates of the sensitivity (true-positive rate) and specificity (true-negative rate).

The FDA could also look at requirements on software validation and verification and cybersecurity testing, as well as directions on labeling so as to mitigate risk.

Dermatologists serving on the panel called for caution in proceeding with steps that would make it easier for companies to market tools for aiding in melanoma diagnosis than it would be within the class III framework used for MelaFind and Nevisense.

Many expressed concerns about the need to design studies that would answer questions about how well new tools could accurately identify concerning lesions.

The phrase “not ready for prime time” was used at least three times during the discussion.

FDA panelist Maral Skelsey, MD, a skin cancer specialist from Chevy Chase, Maryland, said that over the years, she had used both Nevisense and MelaFind.

She said she had found MelaFind “unusable,” owing in large part to the high number of false positives it generated. The device also was limited as to where on patients’ bodies it could be used.

However, she spoke with enthusiasm about the prospects for better devices to aid in diagnosis of skin lesions. “It’s an area where we’re on the verge, and we really need these devices. There’s a need for patients to be able to examine themselves, for nondermatologists to be able to assess lesions,” Dr. Skelsey said.

But this field is “just not ready for prime time” yet, even with special controls, Dr. Skelsey said. To loosen approval standards too quickly could be a “detriment to what’s coming down the pipeline,” she said.

“It’s harmful to things that are likely to be around the corner,” she said.

FDA panelist Renata Block, PA-C, who works in a Chicago dermatology practice, pressed for maintaining a class III designation. “We are not ready for prime time yet, though the data that is coming down the pipeline on what we have is quite exciting,” Ms. Block said.

FDA panelist Karla V. Ballman, PhD, a statistician from Weill Cornell Medicine, New York, said there would need to be a clear standard for clinical performance before proceeding toward reclassification of devices for aid in detecting melanoma. “I just don’t think it’s ready for prime time at this point and should remain in class III,” she said.

But there was support from some panelists for the idea of a lower bar for clearance, combined with special controls to ensure patient safety.

In expressing her view, FDA panelist Katalin Roth, MD, JD, professor of medicine, George Washington University, Washington, said she was an outlier in her support for the agency’s view that these risks could be managed and that future tools could allow more patients to take a step on the pathway toward critical diagnoses.

“I deal with a lot of people with cancer as a palliative care physician,” Dr. Roth said. “I think what we’re missing here is the issue of time. Melanoma is a terrible disease, and missing the diagnosis is a terrible thing, but I think special controls would be sufficient to counter the concerns of my colleagues on the committee.”

The FDA’s Dr. Ashar ended the meeting with questions posed to one panelist, Veronica Rotemberg, MD, PhD, a dermatologist at Memorial Sloan Kettering Cancer Center in New York.

Dr. Rotemberg has for years been working in the field of research on developing AI and other computer-based tools for detecting and diagnosing melanoma, the deadliest form of skin cancer.

She has been publicly skeptical of the performance of commercial apps that scan moles and other lesions and that claim to identify which are cancerous. A May blog post on the Memorial Sloan Kettering website highlighted a recent British Journal of Dermatology article in which Dr. Rotemberg and coauthors reported on their evaluations of commercial apps. They judged them to be on average only 59% accurate, the blog post said.

However, during an earlier discussion at the meeting, she had spoken more positively about the prospects for using special controls in the near term to mitigate risk, although she said she would have a “very long list” of these requirements.

In the closing exchange with Dr. Ashar, Dr. Rotemberg outlined steps that could potentially ensure the safe use of tools to aid in melanoma screening. These included a need for postmarketing surveillance, which would require evaluation over time of algorithms used in tools meant to detect skin cancer.

“We need to have a mechanism for sampling,” Dr. Rotemberg said. “Most of our data is electronic now anyway, so comparing an algorithm and performance with biopsy results should not be that challenging.”

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

New devices that use artificial intelligence (AI) to diagnose skin cancer – such as smartphone apps – have been popping up over the past few years, but there is some concern over the accuracy of these tools.

So far, the U.S. Food and Drug Administration has cleared two devices. Both are computer-aided skin lesion classification devices meant to help clinicians assess cases of suspected melanoma.

Both were given a class III designation. That classification is intended for products that are considered to have a high risk of harm because of flawed design or implementation. Many such devices are under development, and there has been a proposal to include these devices in class II, which is less restrictive.

The FDA turned to one of its expert panels for advice. At a meeting held on Aug. 29, experts on the panel offered differing views and expressed concerns about the accuracy of these devices.

This was the second day of meetings of the general and plastic surgery devices panel of the FDA’s Medical Devices Advisory Committee. On the previous day, the panel held a wide-ranging discussion about expanding use of skin lesion analyzer devices.

The FDA sought the expert panel’s advice concerning a field that appears to be heating up quickly after relatively quiet times.

Two devices have been approved by the FDA so far, but only one is still being promoted – SciBase AB’s Nevisense. The Swedish company announced in May 2020 that it had received FDA approval for Nevisense 3.0, the third generation of their Nevisense system for early melanoma detection, an AI-based point-of-care system for the noninvasive evaluation of irregular moles.

The other device, known as MelaFind, was acquired by Strata Skin Sciences, but the company said in 2017 that it discontinued research and development, sales, and support activity related to the device, according to a filing with the Securities and Exchange Commission.

But there’s been a swell in recent years in the number of publications related to the use of AI and machine learning, which could give rise to new tools for aiding in the diagnosis of skin conditions, including cancer. Google is among the companies that are involved in these efforts.

So, the FDA asked the expert panel to discuss a series of questions related to how the agency should weigh the risks of computer-aided devices for melanoma diagnosis. The agency also asked the panel to provide feedback about how well risks associated with such devices and tools might be managed and to offer suggestions.

The discussion at the July 29 meeting spun beyond narrow questions about reclassification of the current class III devices to topics involving emerging technology, such as efforts to apply AI to dermatology.

“Innovation continues. Medical device developers are anxious to plan how they might be able to develop the level of evidence that would meet your expectations” for future products, Binita Ashar, MD, a senior official in FDA’s Center for Devices and Radiological Health, told the panel.


 

Company CEO backs tougher regulation

Simon Grant, the chief executive of SciBase, which markets Nevisense, the first and only skin cancer–detecting device currently on the U.S. market, sought to make a case for sticking with the tougher class III regulations.

Speaking during the public comment session, Mr. Grant said switching to class II designations would weaken the standards used in clearing products that analyze skin lesions so as to put patients at risk.

Under the FDA’s rules, the agency designates as class III devices that present potential unreasonable risk of illness or injury. Only about 10% of devices fall into this category. Such devices include implantable pacemakers and breast implants, as well as SciBase’s Nevisense.

About 43% of medical devices fall into the class II category, which includes powered wheelchairs and some pregnancy test kits, the FDA website says.

Class I medical devices pose minimal potential for harm and tend to be simpler in design. These include enema kits and elastic bandages, the FDA says.

Mr. Grant told the meeting that in his career he has worked on two class III products and about 20 class II products. (He had previously worked at medical startups Synectics Medical and Neoventa, as well as established multinationals such as Medtronic.)

“I can tell you that – practically – the FDA has many fewer sticks and much less control when it comes to class II devices,” he said. He offered an example of a manufacturer of a class II device having more latitude in making small changes to products without notifying the FDA.

In his hypothetical example, such a change could have unintended consequences, and “with AI systems, small changes can result in large and nonlinear or even random effects,” Mr. Grant said. “But it’s too late if the product is on the market and the harm has already occurred,” he said.

The American Society for Dermatologic Surgery Association also protested the reclassifying of approved computer-aided melanoma detection class III devices.

In a statement posted on the FDA website as part of the materials for the meeting, the ASDSA raised a series of concerns about the prospects of expanded U.S. use of tools for assisting in diagnosing melanoma, including ones that would be marketed to consumers.

“To the extent that algorithms and devices for patient self-diagnosis of skin lesions are already widely available, they should be required to include detailed disclaimers that include that they are for entertainment and educational purposes and not a diagnostic device, that they are not approved by dermatologists or a recognized medical regulatory authority for self-diagnosis,” the ASDSA said.

Devices and algorithms in screening tools “are not highly regulated and remain unproven. They may result in wrong diagnoses, missed diagnoses, or over- or underdiagnosis,” the ASDSA added. “Both patients at low risk and those at high risk are better served by scheduling an in-person examination with a board-certified dermatologist, who can also help them determine the appropriate future skin screening schedule that is most appropriate for them.”

 

‘Stepping stone’

However, there is strong consumer demand for better information about skin conditions, and many patients face hurdles in going to dermatologists.

Google research has shown that consumers are seeking “a stepping stone” between the information they can easily find online and what they could get from a medical professional, said Lily Peng, MD, PhD, a director of product management for the health AI team at Google. Dr. Peng was a scheduled presenter at the July 29 meeting.

Consumers often are looking for more information on common conditions such as acne and poison ivy, and they sometimes face challenges in getting access to clinicians, she said.

“There are many unmet needs for consumers experiencing skin issues, many of which are lower-acuity conditions. There’s a big opportunity to increase accessibility and relevance of health journeys for consumers,” Dr. Peng said. “We have heard from consumers that they would like to have a self-help tool for nonserious conditions so they can decide when to seek medical attention.”

Dr. Peng’s presentation was not directly related to the question of class II or class III designation for existing products. Instead, her talk served as a glimpse into the work already underway in creating apps and tools for consumers.

Google researchers have published a number of studies in recent years about the use of AI to improve dermatology diagnosis.

A 2020 article reported on Google’s test of a form of AI known as deep learning system (DLS) to provide a differential diagnosis of skin conditions. On 963 validation cases, where a rotating panel of three board-certified dermatologists defined the reference standard, the DLS was noninferior to six other dermatologists and was superior to six primary care physicians (PCPs) and six nurse practitioners (NPs), according to a summary of the article.

A 2021 report published in JAMA Network Open said that use of an AI tool was associated with a higher agreement rate with dermatologists’ reference diagnoses for both PCPs and NPs.

In a 2021 blog post, Google scientists wrote that their AI model that powers a tool for checking skin conditions had earned European clearance, known as a CE mark, as a class I medical device.

SkinVision has an app that the company says “is available worldwide (with the exception of the USA and Canada).” The firm’s website includes a link where people in the United States and Canada can sign up for notifications about when SkinVision will be available in these nations. 


 

‘Not ready for prime time’

The FDA panel did not cast formal votes at the July 29 meeting. Rather, the members engaged in broad discussions about risks and potential benefits of new tools for aiding in the detection of skin cancer.

Among the key issues discussed was a question of whether the FDA could impose requirements and restrictions, known as special controls, to provide “reasonable assurance of safety and effectiveness” for computer-aided devices that provide adjunctive diagnostic information to dermatologists about lesions suspicious for melanoma.

Among the potential special controls would be clinical performance testing in regards to rates of the sensitivity (true-positive rate) and specificity (true-negative rate).

The FDA could also look at requirements on software validation and verification and cybersecurity testing, as well as directions on labeling so as to mitigate risk.

Dermatologists serving on the panel called for caution in proceeding with steps that would make it easier for companies to market tools for aiding in melanoma diagnosis than it would be within the class III framework used for MelaFind and Nevisense.

Many expressed concerns about the need to design studies that would answer questions about how well new tools could accurately identify concerning lesions.

The phrase “not ready for prime time” was used at least three times during the discussion.

FDA panelist Maral Skelsey, MD, a skin cancer specialist from Chevy Chase, Maryland, said that over the years, she had used both Nevisense and MelaFind.

She said she had found MelaFind “unusable,” owing in large part to the high number of false positives it generated. The device also was limited as to where on patients’ bodies it could be used.

However, she spoke with enthusiasm about the prospects for better devices to aid in diagnosis of skin lesions. “It’s an area where we’re on the verge, and we really need these devices. There’s a need for patients to be able to examine themselves, for nondermatologists to be able to assess lesions,” Dr. Skelsey said.

But this field is “just not ready for prime time” yet, even with special controls, Dr. Skelsey said. To loosen approval standards too quickly could be a “detriment to what’s coming down the pipeline,” she said.

“It’s harmful to things that are likely to be around the corner,” she said.

FDA panelist Renata Block, PA-C, who works in a Chicago dermatology practice, pressed for maintaining a class III designation. “We are not ready for prime time yet, though the data that is coming down the pipeline on what we have is quite exciting,” Ms. Block said.

FDA panelist Karla V. Ballman, PhD, a statistician from Weill Cornell Medicine, New York, said there would need to be a clear standard for clinical performance before proceeding toward reclassification of devices for aid in detecting melanoma. “I just don’t think it’s ready for prime time at this point and should remain in class III,” she said.

But there was support from some panelists for the idea of a lower bar for clearance, combined with special controls to ensure patient safety.

In expressing her view, FDA panelist Katalin Roth, MD, JD, professor of medicine, George Washington University, Washington, said she was an outlier in her support for the agency’s view that these risks could be managed and that future tools could allow more patients to take a step on the pathway toward critical diagnoses.

“I deal with a lot of people with cancer as a palliative care physician,” Dr. Roth said. “I think what we’re missing here is the issue of time. Melanoma is a terrible disease, and missing the diagnosis is a terrible thing, but I think special controls would be sufficient to counter the concerns of my colleagues on the committee.”

The FDA’s Dr. Ashar ended the meeting with questions posed to one panelist, Veronica Rotemberg, MD, PhD, a dermatologist at Memorial Sloan Kettering Cancer Center in New York.

Dr. Rotemberg has for years been working in the field of research on developing AI and other computer-based tools for detecting and diagnosing melanoma, the deadliest form of skin cancer.

She has been publicly skeptical of the performance of commercial apps that scan moles and other lesions and that claim to identify which are cancerous. A May blog post on the Memorial Sloan Kettering website highlighted a recent British Journal of Dermatology article in which Dr. Rotemberg and coauthors reported on their evaluations of commercial apps. They judged them to be on average only 59% accurate, the blog post said.

However, during an earlier discussion at the meeting, she had spoken more positively about the prospects for using special controls in the near term to mitigate risk, although she said she would have a “very long list” of these requirements.

In the closing exchange with Dr. Ashar, Dr. Rotemberg outlined steps that could potentially ensure the safe use of tools to aid in melanoma screening. These included a need for postmarketing surveillance, which would require evaluation over time of algorithms used in tools meant to detect skin cancer.

“We need to have a mechanism for sampling,” Dr. Rotemberg said. “Most of our data is electronic now anyway, so comparing an algorithm and performance with biopsy results should not be that challenging.”

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

New devices that use artificial intelligence (AI) to diagnose skin cancer – such as smartphone apps – have been popping up over the past few years, but there is some concern over the accuracy of these tools.

So far, the U.S. Food and Drug Administration has cleared two devices. Both are computer-aided skin lesion classification devices meant to help clinicians assess cases of suspected melanoma.

Both were given a class III designation. That classification is intended for products that are considered to have a high risk of harm because of flawed design or implementation. Many such devices are under development, and there has been a proposal to include these devices in class II, which is less restrictive.

The FDA turned to one of its expert panels for advice. At a meeting held on Aug. 29, experts on the panel offered differing views and expressed concerns about the accuracy of these devices.

This was the second day of meetings of the general and plastic surgery devices panel of the FDA’s Medical Devices Advisory Committee. On the previous day, the panel held a wide-ranging discussion about expanding use of skin lesion analyzer devices.

The FDA sought the expert panel’s advice concerning a field that appears to be heating up quickly after relatively quiet times.

Two devices have been approved by the FDA so far, but only one is still being promoted – SciBase AB’s Nevisense. The Swedish company announced in May 2020 that it had received FDA approval for Nevisense 3.0, the third generation of their Nevisense system for early melanoma detection, an AI-based point-of-care system for the noninvasive evaluation of irregular moles.

The other device, known as MelaFind, was acquired by Strata Skin Sciences, but the company said in 2017 that it discontinued research and development, sales, and support activity related to the device, according to a filing with the Securities and Exchange Commission.

But there’s been a swell in recent years in the number of publications related to the use of AI and machine learning, which could give rise to new tools for aiding in the diagnosis of skin conditions, including cancer. Google is among the companies that are involved in these efforts.

So, the FDA asked the expert panel to discuss a series of questions related to how the agency should weigh the risks of computer-aided devices for melanoma diagnosis. The agency also asked the panel to provide feedback about how well risks associated with such devices and tools might be managed and to offer suggestions.

The discussion at the July 29 meeting spun beyond narrow questions about reclassification of the current class III devices to topics involving emerging technology, such as efforts to apply AI to dermatology.

“Innovation continues. Medical device developers are anxious to plan how they might be able to develop the level of evidence that would meet your expectations” for future products, Binita Ashar, MD, a senior official in FDA’s Center for Devices and Radiological Health, told the panel.


 

Company CEO backs tougher regulation

Simon Grant, the chief executive of SciBase, which markets Nevisense, the first and only skin cancer–detecting device currently on the U.S. market, sought to make a case for sticking with the tougher class III regulations.

Speaking during the public comment session, Mr. Grant said switching to class II designations would weaken the standards used in clearing products that analyze skin lesions so as to put patients at risk.

Under the FDA’s rules, the agency designates as class III devices that present potential unreasonable risk of illness or injury. Only about 10% of devices fall into this category. Such devices include implantable pacemakers and breast implants, as well as SciBase’s Nevisense.

About 43% of medical devices fall into the class II category, which includes powered wheelchairs and some pregnancy test kits, the FDA website says.

Class I medical devices pose minimal potential for harm and tend to be simpler in design. These include enema kits and elastic bandages, the FDA says.

Mr. Grant told the meeting that in his career he has worked on two class III products and about 20 class II products. (He had previously worked at medical startups Synectics Medical and Neoventa, as well as established multinationals such as Medtronic.)

“I can tell you that – practically – the FDA has many fewer sticks and much less control when it comes to class II devices,” he said. He offered an example of a manufacturer of a class II device having more latitude in making small changes to products without notifying the FDA.

In his hypothetical example, such a change could have unintended consequences, and “with AI systems, small changes can result in large and nonlinear or even random effects,” Mr. Grant said. “But it’s too late if the product is on the market and the harm has already occurred,” he said.

The American Society for Dermatologic Surgery Association also protested the reclassifying of approved computer-aided melanoma detection class III devices.

In a statement posted on the FDA website as part of the materials for the meeting, the ASDSA raised a series of concerns about the prospects of expanded U.S. use of tools for assisting in diagnosing melanoma, including ones that would be marketed to consumers.

“To the extent that algorithms and devices for patient self-diagnosis of skin lesions are already widely available, they should be required to include detailed disclaimers that include that they are for entertainment and educational purposes and not a diagnostic device, that they are not approved by dermatologists or a recognized medical regulatory authority for self-diagnosis,” the ASDSA said.

Devices and algorithms in screening tools “are not highly regulated and remain unproven. They may result in wrong diagnoses, missed diagnoses, or over- or underdiagnosis,” the ASDSA added. “Both patients at low risk and those at high risk are better served by scheduling an in-person examination with a board-certified dermatologist, who can also help them determine the appropriate future skin screening schedule that is most appropriate for them.”

 

‘Stepping stone’

However, there is strong consumer demand for better information about skin conditions, and many patients face hurdles in going to dermatologists.

Google research has shown that consumers are seeking “a stepping stone” between the information they can easily find online and what they could get from a medical professional, said Lily Peng, MD, PhD, a director of product management for the health AI team at Google. Dr. Peng was a scheduled presenter at the July 29 meeting.

Consumers often are looking for more information on common conditions such as acne and poison ivy, and they sometimes face challenges in getting access to clinicians, she said.

“There are many unmet needs for consumers experiencing skin issues, many of which are lower-acuity conditions. There’s a big opportunity to increase accessibility and relevance of health journeys for consumers,” Dr. Peng said. “We have heard from consumers that they would like to have a self-help tool for nonserious conditions so they can decide when to seek medical attention.”

Dr. Peng’s presentation was not directly related to the question of class II or class III designation for existing products. Instead, her talk served as a glimpse into the work already underway in creating apps and tools for consumers.

Google researchers have published a number of studies in recent years about the use of AI to improve dermatology diagnosis.

A 2020 article reported on Google’s test of a form of AI known as deep learning system (DLS) to provide a differential diagnosis of skin conditions. On 963 validation cases, where a rotating panel of three board-certified dermatologists defined the reference standard, the DLS was noninferior to six other dermatologists and was superior to six primary care physicians (PCPs) and six nurse practitioners (NPs), according to a summary of the article.

A 2021 report published in JAMA Network Open said that use of an AI tool was associated with a higher agreement rate with dermatologists’ reference diagnoses for both PCPs and NPs.

In a 2021 blog post, Google scientists wrote that their AI model that powers a tool for checking skin conditions had earned European clearance, known as a CE mark, as a class I medical device.

SkinVision has an app that the company says “is available worldwide (with the exception of the USA and Canada).” The firm’s website includes a link where people in the United States and Canada can sign up for notifications about when SkinVision will be available in these nations. 


 

‘Not ready for prime time’

The FDA panel did not cast formal votes at the July 29 meeting. Rather, the members engaged in broad discussions about risks and potential benefits of new tools for aiding in the detection of skin cancer.

Among the key issues discussed was a question of whether the FDA could impose requirements and restrictions, known as special controls, to provide “reasonable assurance of safety and effectiveness” for computer-aided devices that provide adjunctive diagnostic information to dermatologists about lesions suspicious for melanoma.

Among the potential special controls would be clinical performance testing in regards to rates of the sensitivity (true-positive rate) and specificity (true-negative rate).

The FDA could also look at requirements on software validation and verification and cybersecurity testing, as well as directions on labeling so as to mitigate risk.

Dermatologists serving on the panel called for caution in proceeding with steps that would make it easier for companies to market tools for aiding in melanoma diagnosis than it would be within the class III framework used for MelaFind and Nevisense.

Many expressed concerns about the need to design studies that would answer questions about how well new tools could accurately identify concerning lesions.

The phrase “not ready for prime time” was used at least three times during the discussion.

FDA panelist Maral Skelsey, MD, a skin cancer specialist from Chevy Chase, Maryland, said that over the years, she had used both Nevisense and MelaFind.

She said she had found MelaFind “unusable,” owing in large part to the high number of false positives it generated. The device also was limited as to where on patients’ bodies it could be used.

However, she spoke with enthusiasm about the prospects for better devices to aid in diagnosis of skin lesions. “It’s an area where we’re on the verge, and we really need these devices. There’s a need for patients to be able to examine themselves, for nondermatologists to be able to assess lesions,” Dr. Skelsey said.

But this field is “just not ready for prime time” yet, even with special controls, Dr. Skelsey said. To loosen approval standards too quickly could be a “detriment to what’s coming down the pipeline,” she said.

“It’s harmful to things that are likely to be around the corner,” she said.

FDA panelist Renata Block, PA-C, who works in a Chicago dermatology practice, pressed for maintaining a class III designation. “We are not ready for prime time yet, though the data that is coming down the pipeline on what we have is quite exciting,” Ms. Block said.

FDA panelist Karla V. Ballman, PhD, a statistician from Weill Cornell Medicine, New York, said there would need to be a clear standard for clinical performance before proceeding toward reclassification of devices for aid in detecting melanoma. “I just don’t think it’s ready for prime time at this point and should remain in class III,” she said.

But there was support from some panelists for the idea of a lower bar for clearance, combined with special controls to ensure patient safety.

In expressing her view, FDA panelist Katalin Roth, MD, JD, professor of medicine, George Washington University, Washington, said she was an outlier in her support for the agency’s view that these risks could be managed and that future tools could allow more patients to take a step on the pathway toward critical diagnoses.

“I deal with a lot of people with cancer as a palliative care physician,” Dr. Roth said. “I think what we’re missing here is the issue of time. Melanoma is a terrible disease, and missing the diagnosis is a terrible thing, but I think special controls would be sufficient to counter the concerns of my colleagues on the committee.”

The FDA’s Dr. Ashar ended the meeting with questions posed to one panelist, Veronica Rotemberg, MD, PhD, a dermatologist at Memorial Sloan Kettering Cancer Center in New York.

Dr. Rotemberg has for years been working in the field of research on developing AI and other computer-based tools for detecting and diagnosing melanoma, the deadliest form of skin cancer.

She has been publicly skeptical of the performance of commercial apps that scan moles and other lesions and that claim to identify which are cancerous. A May blog post on the Memorial Sloan Kettering website highlighted a recent British Journal of Dermatology article in which Dr. Rotemberg and coauthors reported on their evaluations of commercial apps. They judged them to be on average only 59% accurate, the blog post said.

However, during an earlier discussion at the meeting, she had spoken more positively about the prospects for using special controls in the near term to mitigate risk, although she said she would have a “very long list” of these requirements.

In the closing exchange with Dr. Ashar, Dr. Rotemberg outlined steps that could potentially ensure the safe use of tools to aid in melanoma screening. These included a need for postmarketing surveillance, which would require evaluation over time of algorithms used in tools meant to detect skin cancer.

“We need to have a mechanism for sampling,” Dr. Rotemberg said. “Most of our data is electronic now anyway, so comparing an algorithm and performance with biopsy results should not be that challenging.”

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

MONTREAL – Interim results of ALLIANCE, the first head-to-head trial comparing two different tenofovir-containing antiretroviral regimens for the treatment of HIV and hepatitis B (HBV) coinfection, demonstrate the superiority of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) over dolutegravir plus tenofovir disoproxil fumarate (DTG + F/TDF), researchers reported at a meeting of the International AIDS Society.

While both regimens showed similar efficacy for HIV control, the B/F/TAF regimen produced better HBV results, with more HBV DNA suppression and significantly more seroconversion, reported lead investigator Anchalee Avihingsanon, MD, PhD, at a press conference during the meeting. Dr. Avihingsanon heads the medical department of the HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) at the Thai Red Cross AIDS Research Centre, Bangkok.

The ongoing phase 3, multicountry study has 48-week results for 243 participants, who were HIV/HBV coinfected and treatment naive. All subjects received three pills of ART per day, with blinded randomization to (active B/F/TAF + placebo DTG + placebo TDF/FTC or placebo B/F/TAF + active DTG + active TDF/FTC). The primary endpoints at 48 weeks were proportion of participants with HIV-1 RNA less than 50 copies/mL and plasma HBV DNA less than 29 IU/mL.

For the HIV endpoint, results showed both the B/F/TAF and DTG + F/TDF arms had high rates of suppression (95% and 91%, respectively, P = .21), but the B/F/TAF group had significantly higher rates of HBV DNA suppression (63% vs 43.4%, P = .0023) and HBeAg seroconversion (23.3% vs. 11.3%), with numerically higher, but not statistically significant differences in HBsAg loss/seroconversion (12.6% vs. 5.8% and 8.4% vs. 3.3%), HBeAg loss (25.6% vs 14.4%), and ALT normalization (73.3% vs 55.3%).

No participant developed treatment-emergent HIV-1 drug resistance while on B/F/TAF, and there were few study-drug–related AEs or discontinuations, she reported.

“There is hardly any good reason to give the two-pill DTG regimen over single-tablet BTG/TAF/FTC in HBV-coinfected people living with HIV [PLWH],” commented Babafemi Taiwo, MD, chief of infectious diseases and professor of medicine at Northwestern University in Evanston, Ill., who was not involved in the research. “This gives me confidence to prescribe bictegravir/TAF/FTC, which has the added advantage of being a single-tablet formulation, to HBV coinfected PLWH,” he said in an interview. However, he added, the results “call for some head-scratching since TAF is not known to be better than TDF for HBV treatment in persons without HIV.”

“The lower response rate of the TDF group is still poorly understood,” agreed Dr. Avihingsanon, emphasizing that “HBV and HIV/HBV are not the same, and TDF and TAF are also different. TAF has slightly more drug-drug interactions than TDF. I guess its end product in the liver might be higher. What is exciting to me is that there was such a high rate of HBsAg loss and HBs seroconversion in HIV/HBV coinfection, which is totally different from HBV monoinfection [< 1% at 48 weeks]. For me as an investigator, this important finding has additional benefit to further explore the immunologic outcome for possible HBV cure strategy.” She said the study remains blinded until week 96, at which time further data may shed light on this question. 

“Perhaps a larger study would help clarify impact of TAF versus TDF on measures that did not achieve statistical significance in this study. Long-term follow up to better understand the clinical implications of these results could be helpful as well,” Dr. Taiwo added.

The study was funded by Gilead. Dr. Avihingsanon reported no relevant disclosures. Dr. Taiwo disclosed that he has served as consultant to ViiV/GlaxoSmithKline, Johnson & Johnson, and Merck, and consulted for Gilead on COVID.

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

MONTREAL – Interim results of ALLIANCE, the first head-to-head trial comparing two different tenofovir-containing antiretroviral regimens for the treatment of HIV and hepatitis B (HBV) coinfection, demonstrate the superiority of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) over dolutegravir plus tenofovir disoproxil fumarate (DTG + F/TDF), researchers reported at a meeting of the International AIDS Society.

While both regimens showed similar efficacy for HIV control, the B/F/TAF regimen produced better HBV results, with more HBV DNA suppression and significantly more seroconversion, reported lead investigator Anchalee Avihingsanon, MD, PhD, at a press conference during the meeting. Dr. Avihingsanon heads the medical department of the HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) at the Thai Red Cross AIDS Research Centre, Bangkok.

The ongoing phase 3, multicountry study has 48-week results for 243 participants, who were HIV/HBV coinfected and treatment naive. All subjects received three pills of ART per day, with blinded randomization to (active B/F/TAF + placebo DTG + placebo TDF/FTC or placebo B/F/TAF + active DTG + active TDF/FTC). The primary endpoints at 48 weeks were proportion of participants with HIV-1 RNA less than 50 copies/mL and plasma HBV DNA less than 29 IU/mL.

For the HIV endpoint, results showed both the B/F/TAF and DTG + F/TDF arms had high rates of suppression (95% and 91%, respectively, P = .21), but the B/F/TAF group had significantly higher rates of HBV DNA suppression (63% vs 43.4%, P = .0023) and HBeAg seroconversion (23.3% vs. 11.3%), with numerically higher, but not statistically significant differences in HBsAg loss/seroconversion (12.6% vs. 5.8% and 8.4% vs. 3.3%), HBeAg loss (25.6% vs 14.4%), and ALT normalization (73.3% vs 55.3%).

No participant developed treatment-emergent HIV-1 drug resistance while on B/F/TAF, and there were few study-drug–related AEs or discontinuations, she reported.

“There is hardly any good reason to give the two-pill DTG regimen over single-tablet BTG/TAF/FTC in HBV-coinfected people living with HIV [PLWH],” commented Babafemi Taiwo, MD, chief of infectious diseases and professor of medicine at Northwestern University in Evanston, Ill., who was not involved in the research. “This gives me confidence to prescribe bictegravir/TAF/FTC, which has the added advantage of being a single-tablet formulation, to HBV coinfected PLWH,” he said in an interview. However, he added, the results “call for some head-scratching since TAF is not known to be better than TDF for HBV treatment in persons without HIV.”

“The lower response rate of the TDF group is still poorly understood,” agreed Dr. Avihingsanon, emphasizing that “HBV and HIV/HBV are not the same, and TDF and TAF are also different. TAF has slightly more drug-drug interactions than TDF. I guess its end product in the liver might be higher. What is exciting to me is that there was such a high rate of HBsAg loss and HBs seroconversion in HIV/HBV coinfection, which is totally different from HBV monoinfection [< 1% at 48 weeks]. For me as an investigator, this important finding has additional benefit to further explore the immunologic outcome for possible HBV cure strategy.” She said the study remains blinded until week 96, at which time further data may shed light on this question. 

“Perhaps a larger study would help clarify impact of TAF versus TDF on measures that did not achieve statistical significance in this study. Long-term follow up to better understand the clinical implications of these results could be helpful as well,” Dr. Taiwo added.

The study was funded by Gilead. Dr. Avihingsanon reported no relevant disclosures. Dr. Taiwo disclosed that he has served as consultant to ViiV/GlaxoSmithKline, Johnson & Johnson, and Merck, and consulted for Gilead on COVID.

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

MONTREAL – Interim results of ALLIANCE, the first head-to-head trial comparing two different tenofovir-containing antiretroviral regimens for the treatment of HIV and hepatitis B (HBV) coinfection, demonstrate the superiority of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) over dolutegravir plus tenofovir disoproxil fumarate (DTG + F/TDF), researchers reported at a meeting of the International AIDS Society.

While both regimens showed similar efficacy for HIV control, the B/F/TAF regimen produced better HBV results, with more HBV DNA suppression and significantly more seroconversion, reported lead investigator Anchalee Avihingsanon, MD, PhD, at a press conference during the meeting. Dr. Avihingsanon heads the medical department of the HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) at the Thai Red Cross AIDS Research Centre, Bangkok.

The ongoing phase 3, multicountry study has 48-week results for 243 participants, who were HIV/HBV coinfected and treatment naive. All subjects received three pills of ART per day, with blinded randomization to (active B/F/TAF + placebo DTG + placebo TDF/FTC or placebo B/F/TAF + active DTG + active TDF/FTC). The primary endpoints at 48 weeks were proportion of participants with HIV-1 RNA less than 50 copies/mL and plasma HBV DNA less than 29 IU/mL.

For the HIV endpoint, results showed both the B/F/TAF and DTG + F/TDF arms had high rates of suppression (95% and 91%, respectively, P = .21), but the B/F/TAF group had significantly higher rates of HBV DNA suppression (63% vs 43.4%, P = .0023) and HBeAg seroconversion (23.3% vs. 11.3%), with numerically higher, but not statistically significant differences in HBsAg loss/seroconversion (12.6% vs. 5.8% and 8.4% vs. 3.3%), HBeAg loss (25.6% vs 14.4%), and ALT normalization (73.3% vs 55.3%).

No participant developed treatment-emergent HIV-1 drug resistance while on B/F/TAF, and there were few study-drug–related AEs or discontinuations, she reported.

“There is hardly any good reason to give the two-pill DTG regimen over single-tablet BTG/TAF/FTC in HBV-coinfected people living with HIV [PLWH],” commented Babafemi Taiwo, MD, chief of infectious diseases and professor of medicine at Northwestern University in Evanston, Ill., who was not involved in the research. “This gives me confidence to prescribe bictegravir/TAF/FTC, which has the added advantage of being a single-tablet formulation, to HBV coinfected PLWH,” he said in an interview. However, he added, the results “call for some head-scratching since TAF is not known to be better than TDF for HBV treatment in persons without HIV.”

“The lower response rate of the TDF group is still poorly understood,” agreed Dr. Avihingsanon, emphasizing that “HBV and HIV/HBV are not the same, and TDF and TAF are also different. TAF has slightly more drug-drug interactions than TDF. I guess its end product in the liver might be higher. What is exciting to me is that there was such a high rate of HBsAg loss and HBs seroconversion in HIV/HBV coinfection, which is totally different from HBV monoinfection [< 1% at 48 weeks]. For me as an investigator, this important finding has additional benefit to further explore the immunologic outcome for possible HBV cure strategy.” She said the study remains blinded until week 96, at which time further data may shed light on this question. 

“Perhaps a larger study would help clarify impact of TAF versus TDF on measures that did not achieve statistical significance in this study. Long-term follow up to better understand the clinical implications of these results could be helpful as well,” Dr. Taiwo added.

The study was funded by Gilead. Dr. Avihingsanon reported no relevant disclosures. Dr. Taiwo disclosed that he has served as consultant to ViiV/GlaxoSmithKline, Johnson & Johnson, and Merck, and consulted for Gilead on COVID.

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

A new study sheds light on some of the risk factors for the development of psychosis, including the potentially causative role of sexual assault.

Investigators conducted an exposome-wide association analysis on more than 155,000 individuals. Of more than 140 correlates of psychotic experiences that they identified, they narrowed it down to 36 variables, which they further explored using Mendelian randomization analysis.

The analysis found that having been the victim of a sexual assault might be a potential causal risk factor for psychotic experiences. On the other hand, having experienced a physical violent crime, cannabis use, and prolonged worry after embarrassment showed a pleiotropic association and appeared to be an aftereffect of psychotic experience.

“From a public health perspective, we need more investment in comprehensive strategies to prevent traumatic experiences at the population level to decrease the burden of psychosis,” senior author Sinan Gülöksüz, MD, PhD, associate professor in the department of psychiatry and neuropsychiatry, Maastricht University Medical Center, the Netherlands, said in an interview.

“From a clinical perspective, clinicians should be aware of the harmful influence of traumatic experiences on mental health and address this through interventions such as trauma-informed care,” he said.

The study was published online in JAMA Psychiatry.

‘Disentangling’ cause and effect

“Previous research has shown associations between psychosis and a few environmental factors, such as substance use, urbanicity, pregnancy complications, and traumatic experiences, but research has so far investigated only a few specific environmental factors by singling them out in individual studies,” Dr. Gülöksüz said.

“Yet, environment is a much more complex and interactive network that includes many factors shaping our health – where we live, what we eat, our lifestyle preferences and habits such as exercise and smoking, and our social surrounding,” he continued. “Rarely has it been possible to understand whether these environmental factors have causal roles in developing psychosis.”

To investigate the question, the researchers turned to the UK Biobank, one of the largest population-based datasets in the world. The current study focused on individuals with completed data on mental questionnaires that assessed psychotic experiences (n = 155,247; mean [SD] age, 55.94 [7.74] years; 57% female).

They began by conducting an exposome-wide association study, using logistic regression analyses with psychotic experiences as the outcome and adjusting all analyses for age and sex.

“Initially, we identified many associations between environmental factors and psychotic experiences in this large cohort,” Dr. Gülöksüz reported.

In the final multivariable model, variables associated with psychotic experiences were further analyzed using “genetically informed approaches to probe potential associations.”

The researchers utilized Mendelian randomization (MR) methodology “to disentangle cause and effect in this observational study,” Dr. Gülöksüz said. “This method reduces confounding and reverse causation in observational studies by using genetic variants that have been passed on from generation to generation randomly as instruments.”

MR analysis “has allowed us to assess whether these associations reflect potentially causal influences of environmental factors on psychotic experiences,” he added.
 

Well-studied and unexplored risk factors

The researchers identified 162 variables associated with psychotic experiences in the discovery dataset and were able to replicate 148. When these 148 variables were subjected to multivariable analyses, 36 were found to be statistically significantly associated with psychotic experiences. Of these variables, 28 had “significant genetic overlap” with psychotic experiences.

When the researchers conducted one-sample MR analyses, they found forward associations with three variables and reverse associations with three variables.

Forward associations were found with ever having experienced sexual assault (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.14-1.52; P = 2.67), and forward associations (with pleiotropy) were found with ever having experienced a physically violent crime and risk-taking behavior (OR, 1.25, 95% CI, 1.11-1.41; P = 3.28 and OR, 1.21, 95% CI, 1.08-1.35; P = 1.34, respectively).

“The allele scores for these 3 variables explained 0.03% to 0.23% variance of the corresponding variable” and the F statistics “ranged from 21.53 to 181.84, indicating that the results did not suffer from a weak-instrument bias,” the authors reported.

The researchers calculated an instrument based on increasing psychotic experiences risk allele scores and found that these scores explained 0.14% variance of psychotic experiences (F statistic, 19.26).

Using that calculation, they found a reverse association with having experienced a physically violent crime (OR, 1.08; 95% CI, 1.04-1.13; P = 3.92 × 10-4), cannabis use (OR, 1.11; 95% CI, 1.06-1.15; P = 2.64 × 10-6), and worrying too long after embarrassment (OR, 1.06; 95% CI, 1.03-1.10; P = 3.96 × 10-4). They then validated these associations.

The presence of all five correlates was associated with tenfold increased odds of psychotic experiences (OR, 10.63; 95% CI, 8.27-13.65, P = 1.2 × 10-114).

“Associations with psychotic experiences were found with both well-studied and unexplored multiple correlated variables,” the authors stated.
 

Era of ‘big data’

In a comment, Chirag Patel, PhD, associate professor of biomedical informatics at Harvard Medical School, Boston, who was not involved with the study, said he thought the study was “a nice example of a data-driven and comprehensive study of the environment coupled with attempts to triangulate evidence from genetics, made possible by biobank data.

“To guide public health policies and implementation of prevention strategies for psychosis, we need more systematic analyses and triangulate evidence with genetically informed methods to identify potentially modifiable risk factors in the era of ‘big data,’ ” he said.

“For instance, traumatic experiences contribute to poor mental and physical health, including psychosis,” Dr. Gülöksüz added.

The Kootstra Talent Fellowship, the Ophelia Research Project, and the Vidi Award from the Netherlands Scientific Organization provided funding to individual investigators. Dr. Gülöksüz and coauthors declared no relevant financial conflicts. Dr. Patel served as a reviewer on the study.

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

A new study sheds light on some of the risk factors for the development of psychosis, including the potentially causative role of sexual assault.

Investigators conducted an exposome-wide association analysis on more than 155,000 individuals. Of more than 140 correlates of psychotic experiences that they identified, they narrowed it down to 36 variables, which they further explored using Mendelian randomization analysis.

The analysis found that having been the victim of a sexual assault might be a potential causal risk factor for psychotic experiences. On the other hand, having experienced a physical violent crime, cannabis use, and prolonged worry after embarrassment showed a pleiotropic association and appeared to be an aftereffect of psychotic experience.

“From a public health perspective, we need more investment in comprehensive strategies to prevent traumatic experiences at the population level to decrease the burden of psychosis,” senior author Sinan Gülöksüz, MD, PhD, associate professor in the department of psychiatry and neuropsychiatry, Maastricht University Medical Center, the Netherlands, said in an interview.

“From a clinical perspective, clinicians should be aware of the harmful influence of traumatic experiences on mental health and address this through interventions such as trauma-informed care,” he said.

The study was published online in JAMA Psychiatry.

‘Disentangling’ cause and effect

“Previous research has shown associations between psychosis and a few environmental factors, such as substance use, urbanicity, pregnancy complications, and traumatic experiences, but research has so far investigated only a few specific environmental factors by singling them out in individual studies,” Dr. Gülöksüz said.

“Yet, environment is a much more complex and interactive network that includes many factors shaping our health – where we live, what we eat, our lifestyle preferences and habits such as exercise and smoking, and our social surrounding,” he continued. “Rarely has it been possible to understand whether these environmental factors have causal roles in developing psychosis.”

To investigate the question, the researchers turned to the UK Biobank, one of the largest population-based datasets in the world. The current study focused on individuals with completed data on mental questionnaires that assessed psychotic experiences (n = 155,247; mean [SD] age, 55.94 [7.74] years; 57% female).

They began by conducting an exposome-wide association study, using logistic regression analyses with psychotic experiences as the outcome and adjusting all analyses for age and sex.

“Initially, we identified many associations between environmental factors and psychotic experiences in this large cohort,” Dr. Gülöksüz reported.

In the final multivariable model, variables associated with psychotic experiences were further analyzed using “genetically informed approaches to probe potential associations.”

The researchers utilized Mendelian randomization (MR) methodology “to disentangle cause and effect in this observational study,” Dr. Gülöksüz said. “This method reduces confounding and reverse causation in observational studies by using genetic variants that have been passed on from generation to generation randomly as instruments.”

MR analysis “has allowed us to assess whether these associations reflect potentially causal influences of environmental factors on psychotic experiences,” he added.
 

Well-studied and unexplored risk factors

The researchers identified 162 variables associated with psychotic experiences in the discovery dataset and were able to replicate 148. When these 148 variables were subjected to multivariable analyses, 36 were found to be statistically significantly associated with psychotic experiences. Of these variables, 28 had “significant genetic overlap” with psychotic experiences.

When the researchers conducted one-sample MR analyses, they found forward associations with three variables and reverse associations with three variables.

Forward associations were found with ever having experienced sexual assault (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.14-1.52; P = 2.67), and forward associations (with pleiotropy) were found with ever having experienced a physically violent crime and risk-taking behavior (OR, 1.25, 95% CI, 1.11-1.41; P = 3.28 and OR, 1.21, 95% CI, 1.08-1.35; P = 1.34, respectively).

“The allele scores for these 3 variables explained 0.03% to 0.23% variance of the corresponding variable” and the F statistics “ranged from 21.53 to 181.84, indicating that the results did not suffer from a weak-instrument bias,” the authors reported.

The researchers calculated an instrument based on increasing psychotic experiences risk allele scores and found that these scores explained 0.14% variance of psychotic experiences (F statistic, 19.26).

Using that calculation, they found a reverse association with having experienced a physically violent crime (OR, 1.08; 95% CI, 1.04-1.13; P = 3.92 × 10-4), cannabis use (OR, 1.11; 95% CI, 1.06-1.15; P = 2.64 × 10-6), and worrying too long after embarrassment (OR, 1.06; 95% CI, 1.03-1.10; P = 3.96 × 10-4). They then validated these associations.

The presence of all five correlates was associated with tenfold increased odds of psychotic experiences (OR, 10.63; 95% CI, 8.27-13.65, P = 1.2 × 10-114).

“Associations with psychotic experiences were found with both well-studied and unexplored multiple correlated variables,” the authors stated.
 

Era of ‘big data’

In a comment, Chirag Patel, PhD, associate professor of biomedical informatics at Harvard Medical School, Boston, who was not involved with the study, said he thought the study was “a nice example of a data-driven and comprehensive study of the environment coupled with attempts to triangulate evidence from genetics, made possible by biobank data.

“To guide public health policies and implementation of prevention strategies for psychosis, we need more systematic analyses and triangulate evidence with genetically informed methods to identify potentially modifiable risk factors in the era of ‘big data,’ ” he said.

“For instance, traumatic experiences contribute to poor mental and physical health, including psychosis,” Dr. Gülöksüz added.

The Kootstra Talent Fellowship, the Ophelia Research Project, and the Vidi Award from the Netherlands Scientific Organization provided funding to individual investigators. Dr. Gülöksüz and coauthors declared no relevant financial conflicts. Dr. Patel served as a reviewer on the study.

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

A new study sheds light on some of the risk factors for the development of psychosis, including the potentially causative role of sexual assault.

Investigators conducted an exposome-wide association analysis on more than 155,000 individuals. Of more than 140 correlates of psychotic experiences that they identified, they narrowed it down to 36 variables, which they further explored using Mendelian randomization analysis.

The analysis found that having been the victim of a sexual assault might be a potential causal risk factor for psychotic experiences. On the other hand, having experienced a physical violent crime, cannabis use, and prolonged worry after embarrassment showed a pleiotropic association and appeared to be an aftereffect of psychotic experience.

“From a public health perspective, we need more investment in comprehensive strategies to prevent traumatic experiences at the population level to decrease the burden of psychosis,” senior author Sinan Gülöksüz, MD, PhD, associate professor in the department of psychiatry and neuropsychiatry, Maastricht University Medical Center, the Netherlands, said in an interview.

“From a clinical perspective, clinicians should be aware of the harmful influence of traumatic experiences on mental health and address this through interventions such as trauma-informed care,” he said.

The study was published online in JAMA Psychiatry.

‘Disentangling’ cause and effect

“Previous research has shown associations between psychosis and a few environmental factors, such as substance use, urbanicity, pregnancy complications, and traumatic experiences, but research has so far investigated only a few specific environmental factors by singling them out in individual studies,” Dr. Gülöksüz said.

“Yet, environment is a much more complex and interactive network that includes many factors shaping our health – where we live, what we eat, our lifestyle preferences and habits such as exercise and smoking, and our social surrounding,” he continued. “Rarely has it been possible to understand whether these environmental factors have causal roles in developing psychosis.”

To investigate the question, the researchers turned to the UK Biobank, one of the largest population-based datasets in the world. The current study focused on individuals with completed data on mental questionnaires that assessed psychotic experiences (n = 155,247; mean [SD] age, 55.94 [7.74] years; 57% female).

They began by conducting an exposome-wide association study, using logistic regression analyses with psychotic experiences as the outcome and adjusting all analyses for age and sex.

“Initially, we identified many associations between environmental factors and psychotic experiences in this large cohort,” Dr. Gülöksüz reported.

In the final multivariable model, variables associated with psychotic experiences were further analyzed using “genetically informed approaches to probe potential associations.”

The researchers utilized Mendelian randomization (MR) methodology “to disentangle cause and effect in this observational study,” Dr. Gülöksüz said. “This method reduces confounding and reverse causation in observational studies by using genetic variants that have been passed on from generation to generation randomly as instruments.”

MR analysis “has allowed us to assess whether these associations reflect potentially causal influences of environmental factors on psychotic experiences,” he added.
 

Well-studied and unexplored risk factors

The researchers identified 162 variables associated with psychotic experiences in the discovery dataset and were able to replicate 148. When these 148 variables were subjected to multivariable analyses, 36 were found to be statistically significantly associated with psychotic experiences. Of these variables, 28 had “significant genetic overlap” with psychotic experiences.

When the researchers conducted one-sample MR analyses, they found forward associations with three variables and reverse associations with three variables.

Forward associations were found with ever having experienced sexual assault (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.14-1.52; P = 2.67), and forward associations (with pleiotropy) were found with ever having experienced a physically violent crime and risk-taking behavior (OR, 1.25, 95% CI, 1.11-1.41; P = 3.28 and OR, 1.21, 95% CI, 1.08-1.35; P = 1.34, respectively).

“The allele scores for these 3 variables explained 0.03% to 0.23% variance of the corresponding variable” and the F statistics “ranged from 21.53 to 181.84, indicating that the results did not suffer from a weak-instrument bias,” the authors reported.

The researchers calculated an instrument based on increasing psychotic experiences risk allele scores and found that these scores explained 0.14% variance of psychotic experiences (F statistic, 19.26).

Using that calculation, they found a reverse association with having experienced a physically violent crime (OR, 1.08; 95% CI, 1.04-1.13; P = 3.92 × 10-4), cannabis use (OR, 1.11; 95% CI, 1.06-1.15; P = 2.64 × 10-6), and worrying too long after embarrassment (OR, 1.06; 95% CI, 1.03-1.10; P = 3.96 × 10-4). They then validated these associations.

The presence of all five correlates was associated with tenfold increased odds of psychotic experiences (OR, 10.63; 95% CI, 8.27-13.65, P = 1.2 × 10-114).

“Associations with psychotic experiences were found with both well-studied and unexplored multiple correlated variables,” the authors stated.
 

Era of ‘big data’

In a comment, Chirag Patel, PhD, associate professor of biomedical informatics at Harvard Medical School, Boston, who was not involved with the study, said he thought the study was “a nice example of a data-driven and comprehensive study of the environment coupled with attempts to triangulate evidence from genetics, made possible by biobank data.

“To guide public health policies and implementation of prevention strategies for psychosis, we need more systematic analyses and triangulate evidence with genetically informed methods to identify potentially modifiable risk factors in the era of ‘big data,’ ” he said.

“For instance, traumatic experiences contribute to poor mental and physical health, including psychosis,” Dr. Gülöksüz added.

The Kootstra Talent Fellowship, the Ophelia Research Project, and the Vidi Award from the Netherlands Scientific Organization provided funding to individual investigators. Dr. Gülöksüz and coauthors declared no relevant financial conflicts. Dr. Patel served as a reviewer on the study.

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

Some patients with blood cancers for whom all other therapeutic options have been exhausted have one final chance of getting rid of their disease: treatment with chimeric antigen-receptor (CAR) T cells.

Described as a “living drug,” the treatment involves genetically engineering the patient’s own blood cells and reinfusing them back into their system. These CAR T cells then hunt down and destroy cancer cells; in some cases, they manage to eradicate the disease completely.

About half of patients with leukemia or lymphoma and about a third of those with multiple myeloma who receive this treatment have a complete remission and achieve a functional “cure.”

But not all patients who could benefit from this therapy are able to get it. Some are spending months on waiting lists, often deteriorating while they wait. These patients have exhausted all other therapeutic options, and many are facing hospice and death.

The scope of this problem was illustrated by a recent survey of the centers that are certified to deliver this complex therapy.

The survey was led by Yi Lin, MD, PhD, associate professor of medicine at the Mayo Clinic, Rochester, Minn., and medical director for the cellular therapy program. It was published as an abstract at the annual meeting of the American Society of Clinical Oncology recently, although it was not presented there.

“We wanted to find out just how widespread this problem is,” Dr. Lin said, adding: “There had been nothing in the literature thus far about it.”

The team contacted 20 centers across the United States and received responses from 17. Results showed that the median time on the waiting list was 6 months and that only 25% of patients eventually received CAR T-cell therapy. An additional 25% were able to enter a CAR T clinical trial. The remaining 50% of patients either were enrolled in a different type of trial, entered hospice, or died.

For patient selection, all centers reported using a committee of experienced physicians to ensure consistency. They employed different ethical principles for selection. Some centers sought to maximize the total benefit, such as selecting the patients most likely to achieve leukapheresis or a clinical response, while others based their decisions on the time patients spent on waiting list or gave priority to the patients who were the “worst off” with the most limited therapeutic options.
 

Shortage affecting mostly myeloma patients

The shortages in CAR T-cell therapies primarily involve the products used for patients with multiple myeloma.

The problem has not, as yet, noticeably spilled over to lymphoma and leukemia treatments, which use a slightly different type of CAR T-cell therapy (it targets CD19, whereas the cell therapies used for myeloma target BCMA).

“We have backlog of myeloma patients who don’t have access,” said Nina Shah, MD, a hematologist and professor of medicine at the University of California, San Francisco. “We have only four slots for the two myeloma products but about 50-60 eligible patients.”

Long waiting times for CAR T cells for myeloma have been an issue ever since the first of these products appeared on the market: idecabtagene vicleucel (ide-cel; Abecma), developed by Bluebird Bio and Bristol-Myers Squibb. “As soon as it became available in March 2021, we had people waiting and limits on our access to it,” Dr. Shah said.

A second CAR T-cell therapy for myeloma, ciltacabtagene autoleucel (cilta-cel, Carvykti), developed by Janssen and Legend Biotech, received approval in February 2022. While that helped provide centers with a few more slots, it wasn’t sufficient to cut waiting times, and the demand for these myeloma therapies continues to outstrip the capacity to produce CAR-T products in a timely manner.

“For myeloma, the demand is very high, as most patients are not cured from any other existing myeloma therapies, and most patients will make it to fifth-line therapy where the two CAR T-cell products are approved right now,” said Krina K. Patel, MD, medical director of the department of lymphoma/myeloma in the division of cancer medicine at the University of Texas MD Anderson Cancer Center, Houston.

“We likely have 10 eligible CAR-T myeloma patients each month at our center,” she said, “but were getting two slots per month for the past 8 months, and now are getting four slots a month.”

“Our clinic has also experienced the impact of the low number of manufacturing slots offered to each cancer center for some CAR T-cell products,” said David Maloney, MD, PhD, medical director, Cellular Immunotherapy and Bezos Family Immunotherapy Clinic, Seattle Cancer Care Alliance.

He noted that, as with other cancer centers, for multiple myeloma they are provided a specific number of manufacturing slots for each treatment. “Our providers discuss which patients are most appropriate for available slots for that month,” said Dr. Maloney.

“Additionally, juggling patient schedules may be required to address the extended manufacturing time for some products. In some cases, clinical trials may be available in a more timely fashion for appropriate patients, and in some cases, switching to an alternative product is possible,” he commented.
 

Complex causes behind bottleneck

The cause of the current bottleneck for myeloma patients is complex. It stems from a shortage of raw materials and supply chain restraints, among other things.

While the biggest impact of shortages has been on patients with multiple myeloma, Dr. Patel pointed out that these constraints are also affecting patients with lymphoma at her institution, but to a lesser degree.

“This is multifactorial as to why, but most of the issues arise from manufacturing,” Dr. Patel said in an interview. “Initially, the FDA limited how many slots each new product could have per month, then there was a viral vector shortage, and then the quality-control process the FDA requires takes longer than the manufacturing of the cells actually do.”

On top of that, “we have about a 5% manufacturing fail rate so far,” she added. Such failures occur when the cells taken from a patient cannot be converted into CAR T cells for therapy.

Matthew J. Frigault, MD, from the Center for Cellular Therapies, Mass General Cancer Center, Boston, explained that the growing excitement about the potential for cellular therapy and recent approvals for these products for use in earlier lines of treatment have increased demand for them.

There are also problems regarding supply. Manufacture and delivery of CAR T is complicated and takes time to scale up, Dr. Frigault pointed out. “Therefore, we are seeing limited access, more so for the BCMA-directed therapies [which are used for myeloma].”

The shortages and delays likely involve two main factors. “For the newer indications, there is a significant backlog of patients who have been waiting for these therapies and have not been able to access them in the clinical trial setting, and manufacturing is extremely complicated and not easily scaled up,” he said.

“That being said, manufacturers are trying to increase the number of available manufacturing slots and decrease the time needed to manufacture cells,” Dr. Frigault commented.

Delays in access to myeloma CAR T-cell therapy are also affecting patient care at Fox Chase Cancer Center in Philadelphia. “We have had about one slot every 2 months for Abecma,” noted Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase. “For Carvykti, there are only 32 certified centers in [the] U.S., and access is very limited.”

Dr. Fung explained that they have had to offer alternative treatments to many of their patients. “There are rumors that there’s shortage in obtaining raw materials, such as the virus used for transduction, although we have not encountered any problems in other CAR T products used for lymphomas.”
 

Pharma companies trying to meet the demand

This news organization reached out to the manufacturers of CAR T products. All have reported that they are doing what they feasibly can to ramp up production.

“The complexity of delivering CAR T-cell therapies is unlike any other traditional biologic or small-molecule medicine, using a patient’s own cells to start a highly sophisticated and personalized manufacturing process,” commented a spokesperson for BMS, which has two CAR T-cell products currently on the market.

“In this nascent field of cell therapy, we continue to evolve every day, addressing supply and manufacturing challenges head on by applying key learnings across our three state-of-the-art cell therapy facilities and two new facilities in progress.

“We have been encouraged by a steady increase in our manufacturing capacity, and we continue efforts to ramp up further to meet the demand for our cell therapies,” the BMS spokesperson commented. “We have already seen improvements in the stabilization of vector supply and expect additional improvements in capacity in the second half of 2022.”

Novartis said much the same thing. They have a “comprehensive, integrated global CAR-T manufacturing footprint that strengthens the flexibility, resilience, and sustainability of the Novartis manufacturing and supply chain. Together with an improved manufacturing process, we are confident in our ability to meet patient demand with timely delivery,” according to a Novartis spokesperson.

The spokesperson also pointed out that the company has continuously incorporated process improvements that have significantly increased manufacturing capacity and success rates for patients in need of CAR T cells.

“Data presented at [the] American Society of Hematology annual meeting in 2021 showed the Novartis Morris Plains facility, our flagship CAR T manufacturing site, had commercial manufacturing and shipping success rates of 96% and 99%, respectively, between January and August 2021,” according to the spokesperson.

Legend and Janssen, the companies behind Carvykti, one of the two approved cell products for myeloma, which launched earlier in 2022, said that they have continued to activate certified treatment centers in a phased approach that will enable them to expand availability throughout 2022 and beyond.

“This phased approach was designed to ensure the highest level of predictability and reliability for the patient and the certified treatment centers,” the spokesperson said. “We understand the urgency for patients in need of Carvyki and are committed to doing everything we can to accelerate our ability to deliver this important cell therapy in a reliable and timely manner.”

With regard to the industry-wide supply shortage of lentivirus, Legend and Janssen say they have put in place multiple processes to address the shortage, “including enhancing our own internal manufacturing capabilities of this essential drug substance, to ensure sufficient and sustained supply.”
 

Incredibly exciting potential

Given the immense potential of CAR T-cell therapy, the supply shortage that myeloma patients are experiencing is all the more poignant and distressing. While not everyone benefits, some patients for whom every other therapy failed and who were facing hospice have had dramatic results.

“Incredibly exciting with unbelievable potential” was how one expert described these new therapies when the first product was about to enter the marketplace. Since then, six CAR T-cell therapies have received regulatory approval for an ever-increasing range of hematologic malignancies.

But these CAR T-cell therapies have their own set of adverse events, which can be serious and even life-threatening. In addition, not all patients become cancer free, although long-term data are impressive.

A study that included one of the longest follow-ups to date was reported at the 2020 annual meeting of the American Society of Clinical Oncology. The researchers reported that remissions lasted over 9 years for patients with relapsed/refractory B-cell lymphoma or chronic lymphocytic leukemia who underwent treatment with Kite’s axicaptagene cilleucel (Yescarta). This review included 43 patients and showed an overall remission rate of 76%. Complete remission was achieved for 54% of patients, and partial remission was achieved for 22%.

The results with CAR T-cell therapy in multiple myeloma are not quite as impressive, but even so, the clinical data that supported the approval of Abecma showed that a third of patients, who had previously received a median of six prior therapies, achieved a complete response.

At the time of the Abecma approval, the lead investigator of the study, Nikhil Munshi, MD, of Dana-Farber Cancer Institute, Boston, commented: “The results of this trial represent a true turning point in the treatment of this disease. In my 30 years of treating myeloma, I have not seen any other therapy as effective in this group of patients.”

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

Some patients with blood cancers for whom all other therapeutic options have been exhausted have one final chance of getting rid of their disease: treatment with chimeric antigen-receptor (CAR) T cells.

Described as a “living drug,” the treatment involves genetically engineering the patient’s own blood cells and reinfusing them back into their system. These CAR T cells then hunt down and destroy cancer cells; in some cases, they manage to eradicate the disease completely.

About half of patients with leukemia or lymphoma and about a third of those with multiple myeloma who receive this treatment have a complete remission and achieve a functional “cure.”

But not all patients who could benefit from this therapy are able to get it. Some are spending months on waiting lists, often deteriorating while they wait. These patients have exhausted all other therapeutic options, and many are facing hospice and death.

The scope of this problem was illustrated by a recent survey of the centers that are certified to deliver this complex therapy.

The survey was led by Yi Lin, MD, PhD, associate professor of medicine at the Mayo Clinic, Rochester, Minn., and medical director for the cellular therapy program. It was published as an abstract at the annual meeting of the American Society of Clinical Oncology recently, although it was not presented there.

“We wanted to find out just how widespread this problem is,” Dr. Lin said, adding: “There had been nothing in the literature thus far about it.”

The team contacted 20 centers across the United States and received responses from 17. Results showed that the median time on the waiting list was 6 months and that only 25% of patients eventually received CAR T-cell therapy. An additional 25% were able to enter a CAR T clinical trial. The remaining 50% of patients either were enrolled in a different type of trial, entered hospice, or died.

For patient selection, all centers reported using a committee of experienced physicians to ensure consistency. They employed different ethical principles for selection. Some centers sought to maximize the total benefit, such as selecting the patients most likely to achieve leukapheresis or a clinical response, while others based their decisions on the time patients spent on waiting list or gave priority to the patients who were the “worst off” with the most limited therapeutic options.
 

Shortage affecting mostly myeloma patients

The shortages in CAR T-cell therapies primarily involve the products used for patients with multiple myeloma.

The problem has not, as yet, noticeably spilled over to lymphoma and leukemia treatments, which use a slightly different type of CAR T-cell therapy (it targets CD19, whereas the cell therapies used for myeloma target BCMA).

“We have backlog of myeloma patients who don’t have access,” said Nina Shah, MD, a hematologist and professor of medicine at the University of California, San Francisco. “We have only four slots for the two myeloma products but about 50-60 eligible patients.”

Long waiting times for CAR T cells for myeloma have been an issue ever since the first of these products appeared on the market: idecabtagene vicleucel (ide-cel; Abecma), developed by Bluebird Bio and Bristol-Myers Squibb. “As soon as it became available in March 2021, we had people waiting and limits on our access to it,” Dr. Shah said.

A second CAR T-cell therapy for myeloma, ciltacabtagene autoleucel (cilta-cel, Carvykti), developed by Janssen and Legend Biotech, received approval in February 2022. While that helped provide centers with a few more slots, it wasn’t sufficient to cut waiting times, and the demand for these myeloma therapies continues to outstrip the capacity to produce CAR-T products in a timely manner.

“For myeloma, the demand is very high, as most patients are not cured from any other existing myeloma therapies, and most patients will make it to fifth-line therapy where the two CAR T-cell products are approved right now,” said Krina K. Patel, MD, medical director of the department of lymphoma/myeloma in the division of cancer medicine at the University of Texas MD Anderson Cancer Center, Houston.

“We likely have 10 eligible CAR-T myeloma patients each month at our center,” she said, “but were getting two slots per month for the past 8 months, and now are getting four slots a month.”

“Our clinic has also experienced the impact of the low number of manufacturing slots offered to each cancer center for some CAR T-cell products,” said David Maloney, MD, PhD, medical director, Cellular Immunotherapy and Bezos Family Immunotherapy Clinic, Seattle Cancer Care Alliance.

He noted that, as with other cancer centers, for multiple myeloma they are provided a specific number of manufacturing slots for each treatment. “Our providers discuss which patients are most appropriate for available slots for that month,” said Dr. Maloney.

“Additionally, juggling patient schedules may be required to address the extended manufacturing time for some products. In some cases, clinical trials may be available in a more timely fashion for appropriate patients, and in some cases, switching to an alternative product is possible,” he commented.
 

Complex causes behind bottleneck

The cause of the current bottleneck for myeloma patients is complex. It stems from a shortage of raw materials and supply chain restraints, among other things.

While the biggest impact of shortages has been on patients with multiple myeloma, Dr. Patel pointed out that these constraints are also affecting patients with lymphoma at her institution, but to a lesser degree.

“This is multifactorial as to why, but most of the issues arise from manufacturing,” Dr. Patel said in an interview. “Initially, the FDA limited how many slots each new product could have per month, then there was a viral vector shortage, and then the quality-control process the FDA requires takes longer than the manufacturing of the cells actually do.”

On top of that, “we have about a 5% manufacturing fail rate so far,” she added. Such failures occur when the cells taken from a patient cannot be converted into CAR T cells for therapy.

Matthew J. Frigault, MD, from the Center for Cellular Therapies, Mass General Cancer Center, Boston, explained that the growing excitement about the potential for cellular therapy and recent approvals for these products for use in earlier lines of treatment have increased demand for them.

There are also problems regarding supply. Manufacture and delivery of CAR T is complicated and takes time to scale up, Dr. Frigault pointed out. “Therefore, we are seeing limited access, more so for the BCMA-directed therapies [which are used for myeloma].”

The shortages and delays likely involve two main factors. “For the newer indications, there is a significant backlog of patients who have been waiting for these therapies and have not been able to access them in the clinical trial setting, and manufacturing is extremely complicated and not easily scaled up,” he said.

“That being said, manufacturers are trying to increase the number of available manufacturing slots and decrease the time needed to manufacture cells,” Dr. Frigault commented.

Delays in access to myeloma CAR T-cell therapy are also affecting patient care at Fox Chase Cancer Center in Philadelphia. “We have had about one slot every 2 months for Abecma,” noted Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase. “For Carvykti, there are only 32 certified centers in [the] U.S., and access is very limited.”

Dr. Fung explained that they have had to offer alternative treatments to many of their patients. “There are rumors that there’s shortage in obtaining raw materials, such as the virus used for transduction, although we have not encountered any problems in other CAR T products used for lymphomas.”
 

Pharma companies trying to meet the demand

This news organization reached out to the manufacturers of CAR T products. All have reported that they are doing what they feasibly can to ramp up production.

“The complexity of delivering CAR T-cell therapies is unlike any other traditional biologic or small-molecule medicine, using a patient’s own cells to start a highly sophisticated and personalized manufacturing process,” commented a spokesperson for BMS, which has two CAR T-cell products currently on the market.

“In this nascent field of cell therapy, we continue to evolve every day, addressing supply and manufacturing challenges head on by applying key learnings across our three state-of-the-art cell therapy facilities and two new facilities in progress.

“We have been encouraged by a steady increase in our manufacturing capacity, and we continue efforts to ramp up further to meet the demand for our cell therapies,” the BMS spokesperson commented. “We have already seen improvements in the stabilization of vector supply and expect additional improvements in capacity in the second half of 2022.”

Novartis said much the same thing. They have a “comprehensive, integrated global CAR-T manufacturing footprint that strengthens the flexibility, resilience, and sustainability of the Novartis manufacturing and supply chain. Together with an improved manufacturing process, we are confident in our ability to meet patient demand with timely delivery,” according to a Novartis spokesperson.

The spokesperson also pointed out that the company has continuously incorporated process improvements that have significantly increased manufacturing capacity and success rates for patients in need of CAR T cells.

“Data presented at [the] American Society of Hematology annual meeting in 2021 showed the Novartis Morris Plains facility, our flagship CAR T manufacturing site, had commercial manufacturing and shipping success rates of 96% and 99%, respectively, between January and August 2021,” according to the spokesperson.

Legend and Janssen, the companies behind Carvykti, one of the two approved cell products for myeloma, which launched earlier in 2022, said that they have continued to activate certified treatment centers in a phased approach that will enable them to expand availability throughout 2022 and beyond.

“This phased approach was designed to ensure the highest level of predictability and reliability for the patient and the certified treatment centers,” the spokesperson said. “We understand the urgency for patients in need of Carvyki and are committed to doing everything we can to accelerate our ability to deliver this important cell therapy in a reliable and timely manner.”

With regard to the industry-wide supply shortage of lentivirus, Legend and Janssen say they have put in place multiple processes to address the shortage, “including enhancing our own internal manufacturing capabilities of this essential drug substance, to ensure sufficient and sustained supply.”
 

Incredibly exciting potential

Given the immense potential of CAR T-cell therapy, the supply shortage that myeloma patients are experiencing is all the more poignant and distressing. While not everyone benefits, some patients for whom every other therapy failed and who were facing hospice have had dramatic results.

“Incredibly exciting with unbelievable potential” was how one expert described these new therapies when the first product was about to enter the marketplace. Since then, six CAR T-cell therapies have received regulatory approval for an ever-increasing range of hematologic malignancies.

But these CAR T-cell therapies have their own set of adverse events, which can be serious and even life-threatening. In addition, not all patients become cancer free, although long-term data are impressive.

A study that included one of the longest follow-ups to date was reported at the 2020 annual meeting of the American Society of Clinical Oncology. The researchers reported that remissions lasted over 9 years for patients with relapsed/refractory B-cell lymphoma or chronic lymphocytic leukemia who underwent treatment with Kite’s axicaptagene cilleucel (Yescarta). This review included 43 patients and showed an overall remission rate of 76%. Complete remission was achieved for 54% of patients, and partial remission was achieved for 22%.

The results with CAR T-cell therapy in multiple myeloma are not quite as impressive, but even so, the clinical data that supported the approval of Abecma showed that a third of patients, who had previously received a median of six prior therapies, achieved a complete response.

At the time of the Abecma approval, the lead investigator of the study, Nikhil Munshi, MD, of Dana-Farber Cancer Institute, Boston, commented: “The results of this trial represent a true turning point in the treatment of this disease. In my 30 years of treating myeloma, I have not seen any other therapy as effective in this group of patients.”

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

Some patients with blood cancers for whom all other therapeutic options have been exhausted have one final chance of getting rid of their disease: treatment with chimeric antigen-receptor (CAR) T cells.

Described as a “living drug,” the treatment involves genetically engineering the patient’s own blood cells and reinfusing them back into their system. These CAR T cells then hunt down and destroy cancer cells; in some cases, they manage to eradicate the disease completely.

About half of patients with leukemia or lymphoma and about a third of those with multiple myeloma who receive this treatment have a complete remission and achieve a functional “cure.”

But not all patients who could benefit from this therapy are able to get it. Some are spending months on waiting lists, often deteriorating while they wait. These patients have exhausted all other therapeutic options, and many are facing hospice and death.

The scope of this problem was illustrated by a recent survey of the centers that are certified to deliver this complex therapy.

The survey was led by Yi Lin, MD, PhD, associate professor of medicine at the Mayo Clinic, Rochester, Minn., and medical director for the cellular therapy program. It was published as an abstract at the annual meeting of the American Society of Clinical Oncology recently, although it was not presented there.

“We wanted to find out just how widespread this problem is,” Dr. Lin said, adding: “There had been nothing in the literature thus far about it.”

The team contacted 20 centers across the United States and received responses from 17. Results showed that the median time on the waiting list was 6 months and that only 25% of patients eventually received CAR T-cell therapy. An additional 25% were able to enter a CAR T clinical trial. The remaining 50% of patients either were enrolled in a different type of trial, entered hospice, or died.

For patient selection, all centers reported using a committee of experienced physicians to ensure consistency. They employed different ethical principles for selection. Some centers sought to maximize the total benefit, such as selecting the patients most likely to achieve leukapheresis or a clinical response, while others based their decisions on the time patients spent on waiting list or gave priority to the patients who were the “worst off” with the most limited therapeutic options.
 

Shortage affecting mostly myeloma patients

The shortages in CAR T-cell therapies primarily involve the products used for patients with multiple myeloma.

The problem has not, as yet, noticeably spilled over to lymphoma and leukemia treatments, which use a slightly different type of CAR T-cell therapy (it targets CD19, whereas the cell therapies used for myeloma target BCMA).

“We have backlog of myeloma patients who don’t have access,” said Nina Shah, MD, a hematologist and professor of medicine at the University of California, San Francisco. “We have only four slots for the two myeloma products but about 50-60 eligible patients.”

Long waiting times for CAR T cells for myeloma have been an issue ever since the first of these products appeared on the market: idecabtagene vicleucel (ide-cel; Abecma), developed by Bluebird Bio and Bristol-Myers Squibb. “As soon as it became available in March 2021, we had people waiting and limits on our access to it,” Dr. Shah said.

A second CAR T-cell therapy for myeloma, ciltacabtagene autoleucel (cilta-cel, Carvykti), developed by Janssen and Legend Biotech, received approval in February 2022. While that helped provide centers with a few more slots, it wasn’t sufficient to cut waiting times, and the demand for these myeloma therapies continues to outstrip the capacity to produce CAR-T products in a timely manner.

“For myeloma, the demand is very high, as most patients are not cured from any other existing myeloma therapies, and most patients will make it to fifth-line therapy where the two CAR T-cell products are approved right now,” said Krina K. Patel, MD, medical director of the department of lymphoma/myeloma in the division of cancer medicine at the University of Texas MD Anderson Cancer Center, Houston.

“We likely have 10 eligible CAR-T myeloma patients each month at our center,” she said, “but were getting two slots per month for the past 8 months, and now are getting four slots a month.”

“Our clinic has also experienced the impact of the low number of manufacturing slots offered to each cancer center for some CAR T-cell products,” said David Maloney, MD, PhD, medical director, Cellular Immunotherapy and Bezos Family Immunotherapy Clinic, Seattle Cancer Care Alliance.

He noted that, as with other cancer centers, for multiple myeloma they are provided a specific number of manufacturing slots for each treatment. “Our providers discuss which patients are most appropriate for available slots for that month,” said Dr. Maloney.

“Additionally, juggling patient schedules may be required to address the extended manufacturing time for some products. In some cases, clinical trials may be available in a more timely fashion for appropriate patients, and in some cases, switching to an alternative product is possible,” he commented.
 

Complex causes behind bottleneck

The cause of the current bottleneck for myeloma patients is complex. It stems from a shortage of raw materials and supply chain restraints, among other things.

While the biggest impact of shortages has been on patients with multiple myeloma, Dr. Patel pointed out that these constraints are also affecting patients with lymphoma at her institution, but to a lesser degree.

“This is multifactorial as to why, but most of the issues arise from manufacturing,” Dr. Patel said in an interview. “Initially, the FDA limited how many slots each new product could have per month, then there was a viral vector shortage, and then the quality-control process the FDA requires takes longer than the manufacturing of the cells actually do.”

On top of that, “we have about a 5% manufacturing fail rate so far,” she added. Such failures occur when the cells taken from a patient cannot be converted into CAR T cells for therapy.

Matthew J. Frigault, MD, from the Center for Cellular Therapies, Mass General Cancer Center, Boston, explained that the growing excitement about the potential for cellular therapy and recent approvals for these products for use in earlier lines of treatment have increased demand for them.

There are also problems regarding supply. Manufacture and delivery of CAR T is complicated and takes time to scale up, Dr. Frigault pointed out. “Therefore, we are seeing limited access, more so for the BCMA-directed therapies [which are used for myeloma].”

The shortages and delays likely involve two main factors. “For the newer indications, there is a significant backlog of patients who have been waiting for these therapies and have not been able to access them in the clinical trial setting, and manufacturing is extremely complicated and not easily scaled up,” he said.

“That being said, manufacturers are trying to increase the number of available manufacturing slots and decrease the time needed to manufacture cells,” Dr. Frigault commented.

Delays in access to myeloma CAR T-cell therapy are also affecting patient care at Fox Chase Cancer Center in Philadelphia. “We have had about one slot every 2 months for Abecma,” noted Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase. “For Carvykti, there are only 32 certified centers in [the] U.S., and access is very limited.”

Dr. Fung explained that they have had to offer alternative treatments to many of their patients. “There are rumors that there’s shortage in obtaining raw materials, such as the virus used for transduction, although we have not encountered any problems in other CAR T products used for lymphomas.”
 

Pharma companies trying to meet the demand

This news organization reached out to the manufacturers of CAR T products. All have reported that they are doing what they feasibly can to ramp up production.

“The complexity of delivering CAR T-cell therapies is unlike any other traditional biologic or small-molecule medicine, using a patient’s own cells to start a highly sophisticated and personalized manufacturing process,” commented a spokesperson for BMS, which has two CAR T-cell products currently on the market.

“In this nascent field of cell therapy, we continue to evolve every day, addressing supply and manufacturing challenges head on by applying key learnings across our three state-of-the-art cell therapy facilities and two new facilities in progress.

“We have been encouraged by a steady increase in our manufacturing capacity, and we continue efforts to ramp up further to meet the demand for our cell therapies,” the BMS spokesperson commented. “We have already seen improvements in the stabilization of vector supply and expect additional improvements in capacity in the second half of 2022.”

Novartis said much the same thing. They have a “comprehensive, integrated global CAR-T manufacturing footprint that strengthens the flexibility, resilience, and sustainability of the Novartis manufacturing and supply chain. Together with an improved manufacturing process, we are confident in our ability to meet patient demand with timely delivery,” according to a Novartis spokesperson.

The spokesperson also pointed out that the company has continuously incorporated process improvements that have significantly increased manufacturing capacity and success rates for patients in need of CAR T cells.

“Data presented at [the] American Society of Hematology annual meeting in 2021 showed the Novartis Morris Plains facility, our flagship CAR T manufacturing site, had commercial manufacturing and shipping success rates of 96% and 99%, respectively, between January and August 2021,” according to the spokesperson.

Legend and Janssen, the companies behind Carvykti, one of the two approved cell products for myeloma, which launched earlier in 2022, said that they have continued to activate certified treatment centers in a phased approach that will enable them to expand availability throughout 2022 and beyond.

“This phased approach was designed to ensure the highest level of predictability and reliability for the patient and the certified treatment centers,” the spokesperson said. “We understand the urgency for patients in need of Carvyki and are committed to doing everything we can to accelerate our ability to deliver this important cell therapy in a reliable and timely manner.”

With regard to the industry-wide supply shortage of lentivirus, Legend and Janssen say they have put in place multiple processes to address the shortage, “including enhancing our own internal manufacturing capabilities of this essential drug substance, to ensure sufficient and sustained supply.”
 

Incredibly exciting potential

Given the immense potential of CAR T-cell therapy, the supply shortage that myeloma patients are experiencing is all the more poignant and distressing. While not everyone benefits, some patients for whom every other therapy failed and who were facing hospice have had dramatic results.

“Incredibly exciting with unbelievable potential” was how one expert described these new therapies when the first product was about to enter the marketplace. Since then, six CAR T-cell therapies have received regulatory approval for an ever-increasing range of hematologic malignancies.

But these CAR T-cell therapies have their own set of adverse events, which can be serious and even life-threatening. In addition, not all patients become cancer free, although long-term data are impressive.

A study that included one of the longest follow-ups to date was reported at the 2020 annual meeting of the American Society of Clinical Oncology. The researchers reported that remissions lasted over 9 years for patients with relapsed/refractory B-cell lymphoma or chronic lymphocytic leukemia who underwent treatment with Kite’s axicaptagene cilleucel (Yescarta). This review included 43 patients and showed an overall remission rate of 76%. Complete remission was achieved for 54% of patients, and partial remission was achieved for 22%.

The results with CAR T-cell therapy in multiple myeloma are not quite as impressive, but even so, the clinical data that supported the approval of Abecma showed that a third of patients, who had previously received a median of six prior therapies, achieved a complete response.

At the time of the Abecma approval, the lead investigator of the study, Nikhil Munshi, MD, of Dana-Farber Cancer Institute, Boston, commented: “The results of this trial represent a true turning point in the treatment of this disease. In my 30 years of treating myeloma, I have not seen any other therapy as effective in this group of patients.”

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

There was no significant increase in the post-COVID pandemic monthly rate of incident diabetes in children and youth in Ontario, compared with the pre-pandemic rate, in new research.

This contrasts with findings from a U.S. study and a German study, but this is “not the final word” about this possible association, lead author Rayzel Shulman, MD, admits, since the study may have been underpowered.

The population-based, cross-sectional study was published recently as a research letter in JAMA Open.

The researchers found a nonsignificant increase in the monthly rate of new diabetes during the first 18 months of the COVID-19 pandemic, compared with the 3 prior years (relative risk 1.09, 95% confidence interval).
 

New study contrasts with previous reports

This differs from a Morbidity and Mortality Weekly Report from the U.S. Centers for Disease Control and Prevention, in which COVID-19 infection was associated with a significant increase in new onset of diabetes in children during March 2020 through June 2021, “although some experts have criticized the study methods and conclusion validity,” Dr. Shulman and colleagues write.

Another study, from Germany, reported a significant 1.15-fold increase in type 1 diabetes in children during the pandemic, they note.

The current study may have been underpowered and too small to show a significant association between COVID-19 and new diabetes, the researchers acknowledge. 

And the 1.30 upper limit of the confidence interval shows that it “cannot rule out a possible 1.3-fold increase” in relative risk of a diagnosis of diabetes related to COVID, Dr. Shulman explained to this news organization. 

It will be important to see how the rates have changed since September 2021 (the end of the current study), added Dr. Shulman, an adjunct scientist at the Institute for Clinical Evaluative Sciences (ICES) and a physician and scientist at the Hospital for Sick Children, Toronto.

The current study did find a decreased (delayed) rate of diagnosis of new diabetes during the first months of the pandemic when there were lockdowns, followed by a “catch-up” increase in rates later on, as has been reported earlier.

“Our study is definitely not the final word on this,” Dr. Shulman summarized in a statement from ICES. “However, our findings call into question whether a direct association between COVID-19 and new-onset diabetes in children exists.”
 

COVID-diabetes link?

The researchers analyzed health administrative data from January 2017 to September 2021.

They identified 2,700,178 children and youth in Ontario who were under age 18 in 2021, who had a mean age of 9.2, and about half were girls.

Between November 2020 and April 2021, an estimated 3.3% of children in Ontario had a SARS-COV-2 infection.

New diagnoses of diabetes in this age group are mostly type 1 diabetes, based on previous studies.

The rate of incident diabetes was 15%-32% lower during the first 3 months of the pandemic, March-May 2020 (1.67-2.34 cases per 100,000), compared with the pre-pandemic monthly rate during 2017, 2018, and 2019 (2.54-2.59 cases per 100,000).

The rate of incident diabetes was 33%-50% higher during February to July 2021 (3.48-4.18 cases per 100,000), compared with the pre-pandemic rate.

The pre-pandemic and pandemic monthly rates of incident diabetes were similar during the other months.

The group concludes: “The lack of both an observable increase in overall diabetes incidence among children during the 18-month pandemic restrictions [in this Ontario study] and a plausible biological mechanism call into question an association between COVID-19 and new-onset diabetes.”

More research is needed. “Given the variability in monthly [relative risks], additional population-based, longer-term data are needed to examine the direct and indirect effects of COVID-19 and diabetes risk among children,” the authors write.

This study was supported by ICES (which is funded by the Ontario Ministry of Health) and by a grant from the Canadian Institutes of Health Research. Dr. Shulman reported receiving fees from Dexcom outside the submitted work, and she and three other authors reported receiving grants from the Canadian Institutes of Health Research outside the submitted work.

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

There was no significant increase in the post-COVID pandemic monthly rate of incident diabetes in children and youth in Ontario, compared with the pre-pandemic rate, in new research.

This contrasts with findings from a U.S. study and a German study, but this is “not the final word” about this possible association, lead author Rayzel Shulman, MD, admits, since the study may have been underpowered.

The population-based, cross-sectional study was published recently as a research letter in JAMA Open.

The researchers found a nonsignificant increase in the monthly rate of new diabetes during the first 18 months of the COVID-19 pandemic, compared with the 3 prior years (relative risk 1.09, 95% confidence interval).
 

New study contrasts with previous reports

This differs from a Morbidity and Mortality Weekly Report from the U.S. Centers for Disease Control and Prevention, in which COVID-19 infection was associated with a significant increase in new onset of diabetes in children during March 2020 through June 2021, “although some experts have criticized the study methods and conclusion validity,” Dr. Shulman and colleagues write.

Another study, from Germany, reported a significant 1.15-fold increase in type 1 diabetes in children during the pandemic, they note.

The current study may have been underpowered and too small to show a significant association between COVID-19 and new diabetes, the researchers acknowledge. 

And the 1.30 upper limit of the confidence interval shows that it “cannot rule out a possible 1.3-fold increase” in relative risk of a diagnosis of diabetes related to COVID, Dr. Shulman explained to this news organization. 

It will be important to see how the rates have changed since September 2021 (the end of the current study), added Dr. Shulman, an adjunct scientist at the Institute for Clinical Evaluative Sciences (ICES) and a physician and scientist at the Hospital for Sick Children, Toronto.

The current study did find a decreased (delayed) rate of diagnosis of new diabetes during the first months of the pandemic when there were lockdowns, followed by a “catch-up” increase in rates later on, as has been reported earlier.

“Our study is definitely not the final word on this,” Dr. Shulman summarized in a statement from ICES. “However, our findings call into question whether a direct association between COVID-19 and new-onset diabetes in children exists.”
 

COVID-diabetes link?

The researchers analyzed health administrative data from January 2017 to September 2021.

They identified 2,700,178 children and youth in Ontario who were under age 18 in 2021, who had a mean age of 9.2, and about half were girls.

Between November 2020 and April 2021, an estimated 3.3% of children in Ontario had a SARS-COV-2 infection.

New diagnoses of diabetes in this age group are mostly type 1 diabetes, based on previous studies.

The rate of incident diabetes was 15%-32% lower during the first 3 months of the pandemic, March-May 2020 (1.67-2.34 cases per 100,000), compared with the pre-pandemic monthly rate during 2017, 2018, and 2019 (2.54-2.59 cases per 100,000).

The rate of incident diabetes was 33%-50% higher during February to July 2021 (3.48-4.18 cases per 100,000), compared with the pre-pandemic rate.

The pre-pandemic and pandemic monthly rates of incident diabetes were similar during the other months.

The group concludes: “The lack of both an observable increase in overall diabetes incidence among children during the 18-month pandemic restrictions [in this Ontario study] and a plausible biological mechanism call into question an association between COVID-19 and new-onset diabetes.”

More research is needed. “Given the variability in monthly [relative risks], additional population-based, longer-term data are needed to examine the direct and indirect effects of COVID-19 and diabetes risk among children,” the authors write.

This study was supported by ICES (which is funded by the Ontario Ministry of Health) and by a grant from the Canadian Institutes of Health Research. Dr. Shulman reported receiving fees from Dexcom outside the submitted work, and she and three other authors reported receiving grants from the Canadian Institutes of Health Research outside the submitted work.

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

There was no significant increase in the post-COVID pandemic monthly rate of incident diabetes in children and youth in Ontario, compared with the pre-pandemic rate, in new research.

This contrasts with findings from a U.S. study and a German study, but this is “not the final word” about this possible association, lead author Rayzel Shulman, MD, admits, since the study may have been underpowered.

The population-based, cross-sectional study was published recently as a research letter in JAMA Open.

The researchers found a nonsignificant increase in the monthly rate of new diabetes during the first 18 months of the COVID-19 pandemic, compared with the 3 prior years (relative risk 1.09, 95% confidence interval).
 

New study contrasts with previous reports

This differs from a Morbidity and Mortality Weekly Report from the U.S. Centers for Disease Control and Prevention, in which COVID-19 infection was associated with a significant increase in new onset of diabetes in children during March 2020 through June 2021, “although some experts have criticized the study methods and conclusion validity,” Dr. Shulman and colleagues write.

Another study, from Germany, reported a significant 1.15-fold increase in type 1 diabetes in children during the pandemic, they note.

The current study may have been underpowered and too small to show a significant association between COVID-19 and new diabetes, the researchers acknowledge. 

And the 1.30 upper limit of the confidence interval shows that it “cannot rule out a possible 1.3-fold increase” in relative risk of a diagnosis of diabetes related to COVID, Dr. Shulman explained to this news organization. 

It will be important to see how the rates have changed since September 2021 (the end of the current study), added Dr. Shulman, an adjunct scientist at the Institute for Clinical Evaluative Sciences (ICES) and a physician and scientist at the Hospital for Sick Children, Toronto.

The current study did find a decreased (delayed) rate of diagnosis of new diabetes during the first months of the pandemic when there were lockdowns, followed by a “catch-up” increase in rates later on, as has been reported earlier.

“Our study is definitely not the final word on this,” Dr. Shulman summarized in a statement from ICES. “However, our findings call into question whether a direct association between COVID-19 and new-onset diabetes in children exists.”
 

COVID-diabetes link?

The researchers analyzed health administrative data from January 2017 to September 2021.

They identified 2,700,178 children and youth in Ontario who were under age 18 in 2021, who had a mean age of 9.2, and about half were girls.

Between November 2020 and April 2021, an estimated 3.3% of children in Ontario had a SARS-COV-2 infection.

New diagnoses of diabetes in this age group are mostly type 1 diabetes, based on previous studies.

The rate of incident diabetes was 15%-32% lower during the first 3 months of the pandemic, March-May 2020 (1.67-2.34 cases per 100,000), compared with the pre-pandemic monthly rate during 2017, 2018, and 2019 (2.54-2.59 cases per 100,000).

The rate of incident diabetes was 33%-50% higher during February to July 2021 (3.48-4.18 cases per 100,000), compared with the pre-pandemic rate.

The pre-pandemic and pandemic monthly rates of incident diabetes were similar during the other months.

The group concludes: “The lack of both an observable increase in overall diabetes incidence among children during the 18-month pandemic restrictions [in this Ontario study] and a plausible biological mechanism call into question an association between COVID-19 and new-onset diabetes.”

More research is needed. “Given the variability in monthly [relative risks], additional population-based, longer-term data are needed to examine the direct and indirect effects of COVID-19 and diabetes risk among children,” the authors write.

This study was supported by ICES (which is funded by the Ontario Ministry of Health) and by a grant from the Canadian Institutes of Health Research. Dr. Shulman reported receiving fees from Dexcom outside the submitted work, and she and three other authors reported receiving grants from the Canadian Institutes of Health Research outside the submitted work.

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

A new blood test that analyzes DNA shed by metastatic cancers could reveal characteristics unique to each patient’s tumor and allow physicians to develop more personalized treatment plans, according to a new report.

The blood test focuses on circulating tumor DNA (ctDNA). By sequencing the complete genome of ctDNA, researchers can learn about the different metastases spread throughout the body.

“A key goal in cancer research is to better understand metastatic cancer in each affected person so we can select the best treatments and avoid giving toxic therapies to people who will not derive benefit,” senior author Alexander Wyatt, MD, DPhil, assistant professor of genitourinary cancer genomics at the University of British Columbia, Vancouver, and senior research scientist at the Vancouver Prostate Center, told this news organization.

“However, biopsies of metastatic cancer are rarely performed since they are invasive and have risks of complications,” he said. “In the past, this major barrier has prevented the widespread study of metastatic cancer and progress to better treatment of this lethal disease.”

The study was published in Nature.
 

Test methods

Blood-based biopsy technology, also known as “liquid biopsy,” has emerged as a tool for clinical cancer genotyping and longitudinal disease monitoring. Tests that use ctDNA have begun to influence the clinical management of people with cancer, the study authors wrote, though the full potential for understanding metastatic cancer biology hasn’t yet been unlocked.

Dr. Wyatt and colleagues analyzed serial plasma and synchronous metastases in patients with aggressive, treatment-resistant prostate cancer through deep whole-genome sequencing, which allows for a comprehensive assessment of every part of the genetic code within the cancer cells.

The researchers assessed all classes of genomic alterations and found that ctDNA contains multiple dominant populations, indicating that most people with metastatic cancer have different metastases spread around the body. They found that the whole-genome sequencing process provides a host of information about these different metastases.

The research team used newly developed computer programs to provide information about the genetic makeup of each cancer population, which can tell researchers about a person’s overall disease rather than about one metastatic tumor. In the future, this information could allow clinicians to make better decisions about managing a patient’s cancer.

The researchers studied multiple ctDNA samples collected over time to understand how a patient’s cancer evolved in response to treatment. They focused on inhibitors of the androgen receptor pathway. They found that current therapies for metastatic prostate cancer actively change the composition of cancer populations in the body and that treatment often selects for biologically aggressive cancer populations that underlie clinical resistance. This allowed them to pinpoint new genetic resistance mechanisms to the most common treatments for metastatic prostate cancer. The technique could be applied to other cancers as well.

The research team used nucleosome footprints in ctDNA to infer mRNA expression in metastases upon which biopsies were synchronously performed. They identified treatment-induced changes in androgen receptor transcription factor signaling activity. This means whole-genome sequencing of ctDNA can reveal the active processes occurring within cells, allowing clinicians to predict which treatments will be effective or ineffective in each patient.

“Our research significantly expands the breadth of cancer information that can be obtained from only a few drops of blood,” said Dr. Wyatt. “From a clinical perspective, this extra information can be used in new clinical trials that are testing strategies to direct cancer treatments only to those whose quality or whose length of life will be improved.”
 

Clinical trials

The study authors wrote that whole-genome ctDNA sequencing technology, which is minimally invasive, inexpensive, and scalable, is now being deployed in large clinical trials to help discover new treatment resistance mechanisms. These include precision oncology clinical trials that are being conducted with Canadian cancer patients at the Vancouver Prostate Centre and BC Cancer.

The technology can also be implemented in existing commercial ctDNA testing platforms, which means that patients could soon directly benefit from more comprehensive liquid biopsy testing. The research team has made the methods and computer code publicly and freely available so that the technology can be applied to other cancer types and clinical settings.

“Understanding how clonal evolution occurs and what drives it is one of the key questions that need to be addressed in almost all cancers, and this study provides that level of insight for advanced prostate cancer, as well as a model and tools for how to carry out this work,” Christopher Mueller, MD, PhD, a cancer biologist and geneticist at Queen’s Cancer Research Institute and a professor of biomedical and molecular sciences at Queen’s University, both in Kingston, Ont., said in an interview.

Dr. Mueller, who wasn’t involved with this study, has researched biomarkers and ctDNA as avenues for more precise management of advanced prostate cancer. He and his colleagues have developed blood tests for detecting and monitoring metastatic breast cancer, uveal melanoma, and prostate, pancreatic, and lung cancer.

“The expansion of treatment-resistant clones is how we lose almost all cancer patients, and they clearly demonstrate that in castrate-resistant prostate cancer, changes in the androgen receptor locus almost always drive this process,” Dr. Mueller said. “Understanding clonal evolution will allow us to design treatment strategies that overcome or limit their expansion, hopefully extending the lives of these patients.”

The study was funded by the Canadian Institutes of Health Research, the Canadian Cancer Society Research Institute, the Prostate Cancer Foundation, Prostate Cancer Canada, the Movember Foundation, the Jane and Aatos Erkko Foundation, the Academy of Finland Center of Excellence program, the Terry Fox New Frontiers Program, and the BC Cancer Foundation. Dr. Wyatt has served on advisory boards or has received honoraria from AstraZeneca, Astellas, Janssen, and Merck, and his research lab has a contract research agreement with ESSA Pharma. Dr. Mueller disclosed no relevant financial relationships.

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

A new blood test that analyzes DNA shed by metastatic cancers could reveal characteristics unique to each patient’s tumor and allow physicians to develop more personalized treatment plans, according to a new report.

The blood test focuses on circulating tumor DNA (ctDNA). By sequencing the complete genome of ctDNA, researchers can learn about the different metastases spread throughout the body.

“A key goal in cancer research is to better understand metastatic cancer in each affected person so we can select the best treatments and avoid giving toxic therapies to people who will not derive benefit,” senior author Alexander Wyatt, MD, DPhil, assistant professor of genitourinary cancer genomics at the University of British Columbia, Vancouver, and senior research scientist at the Vancouver Prostate Center, told this news organization.

“However, biopsies of metastatic cancer are rarely performed since they are invasive and have risks of complications,” he said. “In the past, this major barrier has prevented the widespread study of metastatic cancer and progress to better treatment of this lethal disease.”

The study was published in Nature.
 

Test methods

Blood-based biopsy technology, also known as “liquid biopsy,” has emerged as a tool for clinical cancer genotyping and longitudinal disease monitoring. Tests that use ctDNA have begun to influence the clinical management of people with cancer, the study authors wrote, though the full potential for understanding metastatic cancer biology hasn’t yet been unlocked.

Dr. Wyatt and colleagues analyzed serial plasma and synchronous metastases in patients with aggressive, treatment-resistant prostate cancer through deep whole-genome sequencing, which allows for a comprehensive assessment of every part of the genetic code within the cancer cells.

The researchers assessed all classes of genomic alterations and found that ctDNA contains multiple dominant populations, indicating that most people with metastatic cancer have different metastases spread around the body. They found that the whole-genome sequencing process provides a host of information about these different metastases.

The research team used newly developed computer programs to provide information about the genetic makeup of each cancer population, which can tell researchers about a person’s overall disease rather than about one metastatic tumor. In the future, this information could allow clinicians to make better decisions about managing a patient’s cancer.

The researchers studied multiple ctDNA samples collected over time to understand how a patient’s cancer evolved in response to treatment. They focused on inhibitors of the androgen receptor pathway. They found that current therapies for metastatic prostate cancer actively change the composition of cancer populations in the body and that treatment often selects for biologically aggressive cancer populations that underlie clinical resistance. This allowed them to pinpoint new genetic resistance mechanisms to the most common treatments for metastatic prostate cancer. The technique could be applied to other cancers as well.

The research team used nucleosome footprints in ctDNA to infer mRNA expression in metastases upon which biopsies were synchronously performed. They identified treatment-induced changes in androgen receptor transcription factor signaling activity. This means whole-genome sequencing of ctDNA can reveal the active processes occurring within cells, allowing clinicians to predict which treatments will be effective or ineffective in each patient.

“Our research significantly expands the breadth of cancer information that can be obtained from only a few drops of blood,” said Dr. Wyatt. “From a clinical perspective, this extra information can be used in new clinical trials that are testing strategies to direct cancer treatments only to those whose quality or whose length of life will be improved.”
 

Clinical trials

The study authors wrote that whole-genome ctDNA sequencing technology, which is minimally invasive, inexpensive, and scalable, is now being deployed in large clinical trials to help discover new treatment resistance mechanisms. These include precision oncology clinical trials that are being conducted with Canadian cancer patients at the Vancouver Prostate Centre and BC Cancer.

The technology can also be implemented in existing commercial ctDNA testing platforms, which means that patients could soon directly benefit from more comprehensive liquid biopsy testing. The research team has made the methods and computer code publicly and freely available so that the technology can be applied to other cancer types and clinical settings.

“Understanding how clonal evolution occurs and what drives it is one of the key questions that need to be addressed in almost all cancers, and this study provides that level of insight for advanced prostate cancer, as well as a model and tools for how to carry out this work,” Christopher Mueller, MD, PhD, a cancer biologist and geneticist at Queen’s Cancer Research Institute and a professor of biomedical and molecular sciences at Queen’s University, both in Kingston, Ont., said in an interview.

Dr. Mueller, who wasn’t involved with this study, has researched biomarkers and ctDNA as avenues for more precise management of advanced prostate cancer. He and his colleagues have developed blood tests for detecting and monitoring metastatic breast cancer, uveal melanoma, and prostate, pancreatic, and lung cancer.

“The expansion of treatment-resistant clones is how we lose almost all cancer patients, and they clearly demonstrate that in castrate-resistant prostate cancer, changes in the androgen receptor locus almost always drive this process,” Dr. Mueller said. “Understanding clonal evolution will allow us to design treatment strategies that overcome or limit their expansion, hopefully extending the lives of these patients.”

The study was funded by the Canadian Institutes of Health Research, the Canadian Cancer Society Research Institute, the Prostate Cancer Foundation, Prostate Cancer Canada, the Movember Foundation, the Jane and Aatos Erkko Foundation, the Academy of Finland Center of Excellence program, the Terry Fox New Frontiers Program, and the BC Cancer Foundation. Dr. Wyatt has served on advisory boards or has received honoraria from AstraZeneca, Astellas, Janssen, and Merck, and his research lab has a contract research agreement with ESSA Pharma. Dr. Mueller disclosed no relevant financial relationships.

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

A new blood test that analyzes DNA shed by metastatic cancers could reveal characteristics unique to each patient’s tumor and allow physicians to develop more personalized treatment plans, according to a new report.

The blood test focuses on circulating tumor DNA (ctDNA). By sequencing the complete genome of ctDNA, researchers can learn about the different metastases spread throughout the body.

“A key goal in cancer research is to better understand metastatic cancer in each affected person so we can select the best treatments and avoid giving toxic therapies to people who will not derive benefit,” senior author Alexander Wyatt, MD, DPhil, assistant professor of genitourinary cancer genomics at the University of British Columbia, Vancouver, and senior research scientist at the Vancouver Prostate Center, told this news organization.

“However, biopsies of metastatic cancer are rarely performed since they are invasive and have risks of complications,” he said. “In the past, this major barrier has prevented the widespread study of metastatic cancer and progress to better treatment of this lethal disease.”

The study was published in Nature.
 

Test methods

Blood-based biopsy technology, also known as “liquid biopsy,” has emerged as a tool for clinical cancer genotyping and longitudinal disease monitoring. Tests that use ctDNA have begun to influence the clinical management of people with cancer, the study authors wrote, though the full potential for understanding metastatic cancer biology hasn’t yet been unlocked.

Dr. Wyatt and colleagues analyzed serial plasma and synchronous metastases in patients with aggressive, treatment-resistant prostate cancer through deep whole-genome sequencing, which allows for a comprehensive assessment of every part of the genetic code within the cancer cells.

The researchers assessed all classes of genomic alterations and found that ctDNA contains multiple dominant populations, indicating that most people with metastatic cancer have different metastases spread around the body. They found that the whole-genome sequencing process provides a host of information about these different metastases.

The research team used newly developed computer programs to provide information about the genetic makeup of each cancer population, which can tell researchers about a person’s overall disease rather than about one metastatic tumor. In the future, this information could allow clinicians to make better decisions about managing a patient’s cancer.

The researchers studied multiple ctDNA samples collected over time to understand how a patient’s cancer evolved in response to treatment. They focused on inhibitors of the androgen receptor pathway. They found that current therapies for metastatic prostate cancer actively change the composition of cancer populations in the body and that treatment often selects for biologically aggressive cancer populations that underlie clinical resistance. This allowed them to pinpoint new genetic resistance mechanisms to the most common treatments for metastatic prostate cancer. The technique could be applied to other cancers as well.

The research team used nucleosome footprints in ctDNA to infer mRNA expression in metastases upon which biopsies were synchronously performed. They identified treatment-induced changes in androgen receptor transcription factor signaling activity. This means whole-genome sequencing of ctDNA can reveal the active processes occurring within cells, allowing clinicians to predict which treatments will be effective or ineffective in each patient.

“Our research significantly expands the breadth of cancer information that can be obtained from only a few drops of blood,” said Dr. Wyatt. “From a clinical perspective, this extra information can be used in new clinical trials that are testing strategies to direct cancer treatments only to those whose quality or whose length of life will be improved.”
 

Clinical trials

The study authors wrote that whole-genome ctDNA sequencing technology, which is minimally invasive, inexpensive, and scalable, is now being deployed in large clinical trials to help discover new treatment resistance mechanisms. These include precision oncology clinical trials that are being conducted with Canadian cancer patients at the Vancouver Prostate Centre and BC Cancer.

The technology can also be implemented in existing commercial ctDNA testing platforms, which means that patients could soon directly benefit from more comprehensive liquid biopsy testing. The research team has made the methods and computer code publicly and freely available so that the technology can be applied to other cancer types and clinical settings.

“Understanding how clonal evolution occurs and what drives it is one of the key questions that need to be addressed in almost all cancers, and this study provides that level of insight for advanced prostate cancer, as well as a model and tools for how to carry out this work,” Christopher Mueller, MD, PhD, a cancer biologist and geneticist at Queen’s Cancer Research Institute and a professor of biomedical and molecular sciences at Queen’s University, both in Kingston, Ont., said in an interview.

Dr. Mueller, who wasn’t involved with this study, has researched biomarkers and ctDNA as avenues for more precise management of advanced prostate cancer. He and his colleagues have developed blood tests for detecting and monitoring metastatic breast cancer, uveal melanoma, and prostate, pancreatic, and lung cancer.

“The expansion of treatment-resistant clones is how we lose almost all cancer patients, and they clearly demonstrate that in castrate-resistant prostate cancer, changes in the androgen receptor locus almost always drive this process,” Dr. Mueller said. “Understanding clonal evolution will allow us to design treatment strategies that overcome or limit their expansion, hopefully extending the lives of these patients.”

The study was funded by the Canadian Institutes of Health Research, the Canadian Cancer Society Research Institute, the Prostate Cancer Foundation, Prostate Cancer Canada, the Movember Foundation, the Jane and Aatos Erkko Foundation, the Academy of Finland Center of Excellence program, the Terry Fox New Frontiers Program, and the BC Cancer Foundation. Dr. Wyatt has served on advisory boards or has received honoraria from AstraZeneca, Astellas, Janssen, and Merck, and his research lab has a contract research agreement with ESSA Pharma. Dr. Mueller disclosed no relevant financial relationships.

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

After the US Supreme Court overturned Roe v Wade in June, Gilbert R. Cisneros Jr., Under Secretary of Defense for Personnel and Readiness, released a memo on “Ensuring Access to Essential Women’s Health Care Services for Service Members, Dependents, Beneficiaries, and Department of Defense Civilian Employees.” In the memo, Cisneros clarified the US Department of Defense (DoD) policies and emphasized, “There will be no interruption to this care.”

Covered abortions—instances where the life of the mother would be endangered if the fetus were carried to term, or when the pregnancy is the result of rape or incest—are still covered. Health care professionals will continue to follow this policy and military medical facilities leadership will implement measures to ensure continued access to care.

The implications of the Supreme Court decision are complicated, Cisneros said. “It is the Department of Justice’s longstanding position that States generally may not impose criminal or civil liability on federal employees who perform their duties in a manner authorized by federal law,” the memo continues. “We will work with the Department of Justice to ensure access to counsel for such civilian employees and Service members if needed and as appropriate.”

The decision also does not affect the DoD’s existing leave policies, which authorize active-duty service members to travel as necessary to receive abortion care. The travel may be government-funded official travel for a covered abortion, or for all other cases, may be undertaken as regular leave at the service member’s expense. DoD civilian employees may continue to use sick leave or other forms of leave to care for themselves or their family members. Sick leave may be used to cover travel to obtain any type of medical treatment.

The Court’s decision “will have significant implications,” Cisneros wrote, adding, “As Secretary Austin has made clear, nothing is more important than the health and well-being of our Service members, the civilian workforce, and DoD families, and we are committed to taking care of all our people and ensuring that the entire Force remains ready and resilient.”

After the US Supreme Court overturned Roe v Wade in June, Gilbert R. Cisneros Jr., Under Secretary of Defense for Personnel and Readiness, released a memo on “Ensuring Access to Essential Women’s Health Care Services for Service Members, Dependents, Beneficiaries, and Department of Defense Civilian Employees.” In the memo, Cisneros clarified the US Department of Defense (DoD) policies and emphasized, “There will be no interruption to this care.”

Covered abortions—instances where the life of the mother would be endangered if the fetus were carried to term, or when the pregnancy is the result of rape or incest—are still covered. Health care professionals will continue to follow this policy and military medical facilities leadership will implement measures to ensure continued access to care.

The implications of the Supreme Court decision are complicated, Cisneros said. “It is the Department of Justice’s longstanding position that States generally may not impose criminal or civil liability on federal employees who perform their duties in a manner authorized by federal law,” the memo continues. “We will work with the Department of Justice to ensure access to counsel for such civilian employees and Service members if needed and as appropriate.”

The decision also does not affect the DoD’s existing leave policies, which authorize active-duty service members to travel as necessary to receive abortion care. The travel may be government-funded official travel for a covered abortion, or for all other cases, may be undertaken as regular leave at the service member’s expense. DoD civilian employees may continue to use sick leave or other forms of leave to care for themselves or their family members. Sick leave may be used to cover travel to obtain any type of medical treatment.

The Court’s decision “will have significant implications,” Cisneros wrote, adding, “As Secretary Austin has made clear, nothing is more important than the health and well-being of our Service members, the civilian workforce, and DoD families, and we are committed to taking care of all our people and ensuring that the entire Force remains ready and resilient.”

After the US Supreme Court overturned Roe v Wade in June, Gilbert R. Cisneros Jr., Under Secretary of Defense for Personnel and Readiness, released a memo on “Ensuring Access to Essential Women’s Health Care Services for Service Members, Dependents, Beneficiaries, and Department of Defense Civilian Employees.” In the memo, Cisneros clarified the US Department of Defense (DoD) policies and emphasized, “There will be no interruption to this care.”

Covered abortions—instances where the life of the mother would be endangered if the fetus were carried to term, or when the pregnancy is the result of rape or incest—are still covered. Health care professionals will continue to follow this policy and military medical facilities leadership will implement measures to ensure continued access to care.

The implications of the Supreme Court decision are complicated, Cisneros said. “It is the Department of Justice’s longstanding position that States generally may not impose criminal or civil liability on federal employees who perform their duties in a manner authorized by federal law,” the memo continues. “We will work with the Department of Justice to ensure access to counsel for such civilian employees and Service members if needed and as appropriate.”

The decision also does not affect the DoD’s existing leave policies, which authorize active-duty service members to travel as necessary to receive abortion care. The travel may be government-funded official travel for a covered abortion, or for all other cases, may be undertaken as regular leave at the service member’s expense. DoD civilian employees may continue to use sick leave or other forms of leave to care for themselves or their family members. Sick leave may be used to cover travel to obtain any type of medical treatment.

The Court’s decision “will have significant implications,” Cisneros wrote, adding, “As Secretary Austin has made clear, nothing is more important than the health and well-being of our Service members, the civilian workforce, and DoD families, and we are committed to taking care of all our people and ensuring that the entire Force remains ready and resilient.”

INDIANAPOLIS – Despite the common prevalence of skin-picking disorder and trichotillomania (hair pulling), no Food and Drug Administration–approved treatments exist for either condition.

And while both body-focused repetitive behavior disorders affect a greater proportion of females than males, “we have no current information that is useful about what hormonal influences may or may not play in terms of picking and pulling behaviors,” Jon E. Grant, MD, JD, MPH, professor of psychiatry and behavioral neuroscience at the University of Chicago, said at the annual meeting of the Society for Pediatric Dermatology. “On a cognitive level, affected children and adolescents often have impaired inhibitory control but they are often 1-2 standard deviations above average IQ. They have Type A personalities [and are] very driven young kids. They also do not tolerate any down time or boredom. They need to be doing something all the time.”

According to the DSM-5, the diagnostic criteria for skin picking includes recurrent skin picking that results in skin lesions and is not attributable to another medical condition or substance. It also involves repeated attempts to decrease or stop the behavior and causes clinically significant distress or impairment.

“The other medical condition that we are interested in is the misuse of or dependence upon amphetamines or other prescription-based or illicit stimulants,” Dr. Grant said. “I saw a young man who was using about 600 mg of Ritalin a day, and he was picking all over the place. He did not have a primary skin disorder.”

The lifetime prevalence of skin picking disorder ranges between 1.4% and 5.4% of the general population. However, about 63% of people in a community sample endorsed some form of skin picking, and in a study of 105 college students, almost 40% said they picked their skin and had noticeable tissue damage as a result.

“Skin picking is not the same as self-injury,” Dr. Grant said. “It is also not simply an anxiety disorder. Anxiety will make people who pick worse, so people will say that they pick when they’re under stress. I can give them benzodiazepines and they’re still going to pick.”

Animal and human studies demonstrate that skin picking and hair pulling primarily affect females. “You will encounter young boys that pick and pull, but it largely affects females, and it tends to start around puberty,” he said. “Picking can have an onset after the age of 30, which is quite uncommon.”

From a cognitive standpoint, pathological skin pickers demonstrate impaired inhibitory control, impaired stop signal reaction time, increased rates of negative urgency (a tendency to act impulsively in response to negative emotions), and increased rates of positive urgency (a tendency to act impulsively in response to exciting or pleasurable emotions).

Trichotillomania

The lifetime prevalence of trichotillomania ranges between 0.6% and 3.9%. The onset is typically from ages 10-13 years, and the mean duration of illness is 22 years.

The DSM-5 criteria for trichotillomania are similar to that of skin-picking disorder, “although we don’t really worry about the substance use issue with people who pull their hair,” Dr. Grant said. “It doesn’t seem to have a correlation.” In addition, sometimes, children “will worsen pulling or picking when they have co-occurring ADHD and they’ve been started on a stimulant, even at a typical dose. For kids who have those issues, we prefer to try nonstimulant options for their ADHD such as bupropion or atomoxetine.”

Individuals with trichotillomania also tend to have low self-esteem and increased social anxiety, he added, and about one-third report low or very low quality of life. “When you notice alopecia, particularly in young girls who often have longer hair, up to 20% will eat their hair,” Dr. Grant said. “We don’t know why. It’s not related to vitamin deficiencies; it’s not a pica type of iron deficiency. There seems to be a shame piece about eating one’s own hair, but it’s important to assess that. Ask about constipation or overflow incontinence because they can get a bezoar, which can rupture” and can be fatal.

Skin-picking disorder and trichotillomania co-occur in up to 20% of cases. “When they do it tends to be a more difficult problem,” he said. These patients often come for mental health care because of depression, and most, he added, say “I don’t think I would be depressed if I wasn’t covered with excoriations or missing most of my hair.”
 

Treatment for both conditions

According to Dr. Grant, the treatment of choice for skin-picking disorder and trichotillomania is a specific psychotherapy known as “habit reversal therapy,” which involves helping the patient gain better self-control. The drawback is that it’s difficult to find someone trained in habit reversal therapy, “who know anything about skin picking and hair pulling,” he said. “That has been a huge challenge in the field.”

In his experience, the medical treatment of choice for skin-picking disorder and trichotillomania is N-acetylcysteine, an over-the-counter amino acid and antioxidant, which has been shown to be helpful at a dose of 2,400 mg per day. “Patients report to me that some of the excoriations clear up a little quicker as they’re taking it,” Dr. Grant said.

There may also be a role for antipsychotic therapy, he said, “but because of the associated weight gain with most antipsychotics we prefer not to use them.”

The opioid antagonist naltrexone has been shown to be effective in the subset of patients with skin-picking or hair-pulling disorders whose parents have a substance use disorder, Dr. Grant said. “The thought is that there’s something addictive about this behavior in some kids. These kids will look forward to picking and find it rewarding and exciting.”

Dr. Grant reported having no relevant financial disclosures.

INDIANAPOLIS – Despite the common prevalence of skin-picking disorder and trichotillomania (hair pulling), no Food and Drug Administration–approved treatments exist for either condition.

And while both body-focused repetitive behavior disorders affect a greater proportion of females than males, “we have no current information that is useful about what hormonal influences may or may not play in terms of picking and pulling behaviors,” Jon E. Grant, MD, JD, MPH, professor of psychiatry and behavioral neuroscience at the University of Chicago, said at the annual meeting of the Society for Pediatric Dermatology. “On a cognitive level, affected children and adolescents often have impaired inhibitory control but they are often 1-2 standard deviations above average IQ. They have Type A personalities [and are] very driven young kids. They also do not tolerate any down time or boredom. They need to be doing something all the time.”

According to the DSM-5, the diagnostic criteria for skin picking includes recurrent skin picking that results in skin lesions and is not attributable to another medical condition or substance. It also involves repeated attempts to decrease or stop the behavior and causes clinically significant distress or impairment.

“The other medical condition that we are interested in is the misuse of or dependence upon amphetamines or other prescription-based or illicit stimulants,” Dr. Grant said. “I saw a young man who was using about 600 mg of Ritalin a day, and he was picking all over the place. He did not have a primary skin disorder.”

The lifetime prevalence of skin picking disorder ranges between 1.4% and 5.4% of the general population. However, about 63% of people in a community sample endorsed some form of skin picking, and in a study of 105 college students, almost 40% said they picked their skin and had noticeable tissue damage as a result.

“Skin picking is not the same as self-injury,” Dr. Grant said. “It is also not simply an anxiety disorder. Anxiety will make people who pick worse, so people will say that they pick when they’re under stress. I can give them benzodiazepines and they’re still going to pick.”

Animal and human studies demonstrate that skin picking and hair pulling primarily affect females. “You will encounter young boys that pick and pull, but it largely affects females, and it tends to start around puberty,” he said. “Picking can have an onset after the age of 30, which is quite uncommon.”

From a cognitive standpoint, pathological skin pickers demonstrate impaired inhibitory control, impaired stop signal reaction time, increased rates of negative urgency (a tendency to act impulsively in response to negative emotions), and increased rates of positive urgency (a tendency to act impulsively in response to exciting or pleasurable emotions).

Trichotillomania

The lifetime prevalence of trichotillomania ranges between 0.6% and 3.9%. The onset is typically from ages 10-13 years, and the mean duration of illness is 22 years.

The DSM-5 criteria for trichotillomania are similar to that of skin-picking disorder, “although we don’t really worry about the substance use issue with people who pull their hair,” Dr. Grant said. “It doesn’t seem to have a correlation.” In addition, sometimes, children “will worsen pulling or picking when they have co-occurring ADHD and they’ve been started on a stimulant, even at a typical dose. For kids who have those issues, we prefer to try nonstimulant options for their ADHD such as bupropion or atomoxetine.”

Individuals with trichotillomania also tend to have low self-esteem and increased social anxiety, he added, and about one-third report low or very low quality of life. “When you notice alopecia, particularly in young girls who often have longer hair, up to 20% will eat their hair,” Dr. Grant said. “We don’t know why. It’s not related to vitamin deficiencies; it’s not a pica type of iron deficiency. There seems to be a shame piece about eating one’s own hair, but it’s important to assess that. Ask about constipation or overflow incontinence because they can get a bezoar, which can rupture” and can be fatal.

Skin-picking disorder and trichotillomania co-occur in up to 20% of cases. “When they do it tends to be a more difficult problem,” he said. These patients often come for mental health care because of depression, and most, he added, say “I don’t think I would be depressed if I wasn’t covered with excoriations or missing most of my hair.”
 

Treatment for both conditions

According to Dr. Grant, the treatment of choice for skin-picking disorder and trichotillomania is a specific psychotherapy known as “habit reversal therapy,” which involves helping the patient gain better self-control. The drawback is that it’s difficult to find someone trained in habit reversal therapy, “who know anything about skin picking and hair pulling,” he said. “That has been a huge challenge in the field.”

In his experience, the medical treatment of choice for skin-picking disorder and trichotillomania is N-acetylcysteine, an over-the-counter amino acid and antioxidant, which has been shown to be helpful at a dose of 2,400 mg per day. “Patients report to me that some of the excoriations clear up a little quicker as they’re taking it,” Dr. Grant said.

There may also be a role for antipsychotic therapy, he said, “but because of the associated weight gain with most antipsychotics we prefer not to use them.”

The opioid antagonist naltrexone has been shown to be effective in the subset of patients with skin-picking or hair-pulling disorders whose parents have a substance use disorder, Dr. Grant said. “The thought is that there’s something addictive about this behavior in some kids. These kids will look forward to picking and find it rewarding and exciting.”

Dr. Grant reported having no relevant financial disclosures.

INDIANAPOLIS – Despite the common prevalence of skin-picking disorder and trichotillomania (hair pulling), no Food and Drug Administration–approved treatments exist for either condition.

And while both body-focused repetitive behavior disorders affect a greater proportion of females than males, “we have no current information that is useful about what hormonal influences may or may not play in terms of picking and pulling behaviors,” Jon E. Grant, MD, JD, MPH, professor of psychiatry and behavioral neuroscience at the University of Chicago, said at the annual meeting of the Society for Pediatric Dermatology. “On a cognitive level, affected children and adolescents often have impaired inhibitory control but they are often 1-2 standard deviations above average IQ. They have Type A personalities [and are] very driven young kids. They also do not tolerate any down time or boredom. They need to be doing something all the time.”

According to the DSM-5, the diagnostic criteria for skin picking includes recurrent skin picking that results in skin lesions and is not attributable to another medical condition or substance. It also involves repeated attempts to decrease or stop the behavior and causes clinically significant distress or impairment.

“The other medical condition that we are interested in is the misuse of or dependence upon amphetamines or other prescription-based or illicit stimulants,” Dr. Grant said. “I saw a young man who was using about 600 mg of Ritalin a day, and he was picking all over the place. He did not have a primary skin disorder.”

The lifetime prevalence of skin picking disorder ranges between 1.4% and 5.4% of the general population. However, about 63% of people in a community sample endorsed some form of skin picking, and in a study of 105 college students, almost 40% said they picked their skin and had noticeable tissue damage as a result.

“Skin picking is not the same as self-injury,” Dr. Grant said. “It is also not simply an anxiety disorder. Anxiety will make people who pick worse, so people will say that they pick when they’re under stress. I can give them benzodiazepines and they’re still going to pick.”

Animal and human studies demonstrate that skin picking and hair pulling primarily affect females. “You will encounter young boys that pick and pull, but it largely affects females, and it tends to start around puberty,” he said. “Picking can have an onset after the age of 30, which is quite uncommon.”

From a cognitive standpoint, pathological skin pickers demonstrate impaired inhibitory control, impaired stop signal reaction time, increased rates of negative urgency (a tendency to act impulsively in response to negative emotions), and increased rates of positive urgency (a tendency to act impulsively in response to exciting or pleasurable emotions).

Trichotillomania

The lifetime prevalence of trichotillomania ranges between 0.6% and 3.9%. The onset is typically from ages 10-13 years, and the mean duration of illness is 22 years.

The DSM-5 criteria for trichotillomania are similar to that of skin-picking disorder, “although we don’t really worry about the substance use issue with people who pull their hair,” Dr. Grant said. “It doesn’t seem to have a correlation.” In addition, sometimes, children “will worsen pulling or picking when they have co-occurring ADHD and they’ve been started on a stimulant, even at a typical dose. For kids who have those issues, we prefer to try nonstimulant options for their ADHD such as bupropion or atomoxetine.”

Individuals with trichotillomania also tend to have low self-esteem and increased social anxiety, he added, and about one-third report low or very low quality of life. “When you notice alopecia, particularly in young girls who often have longer hair, up to 20% will eat their hair,” Dr. Grant said. “We don’t know why. It’s not related to vitamin deficiencies; it’s not a pica type of iron deficiency. There seems to be a shame piece about eating one’s own hair, but it’s important to assess that. Ask about constipation or overflow incontinence because they can get a bezoar, which can rupture” and can be fatal.

Skin-picking disorder and trichotillomania co-occur in up to 20% of cases. “When they do it tends to be a more difficult problem,” he said. These patients often come for mental health care because of depression, and most, he added, say “I don’t think I would be depressed if I wasn’t covered with excoriations or missing most of my hair.”
 

Treatment for both conditions

According to Dr. Grant, the treatment of choice for skin-picking disorder and trichotillomania is a specific psychotherapy known as “habit reversal therapy,” which involves helping the patient gain better self-control. The drawback is that it’s difficult to find someone trained in habit reversal therapy, “who know anything about skin picking and hair pulling,” he said. “That has been a huge challenge in the field.”

In his experience, the medical treatment of choice for skin-picking disorder and trichotillomania is N-acetylcysteine, an over-the-counter amino acid and antioxidant, which has been shown to be helpful at a dose of 2,400 mg per day. “Patients report to me that some of the excoriations clear up a little quicker as they’re taking it,” Dr. Grant said.

There may also be a role for antipsychotic therapy, he said, “but because of the associated weight gain with most antipsychotics we prefer not to use them.”

The opioid antagonist naltrexone has been shown to be effective in the subset of patients with skin-picking or hair-pulling disorders whose parents have a substance use disorder, Dr. Grant said. “The thought is that there’s something addictive about this behavior in some kids. These kids will look forward to picking and find it rewarding and exciting.”

Dr. Grant reported having no relevant financial disclosures.

After a 5-year search, the US Senate in a 66-23 vote, confirmed a new US Department of Veterans Affairs (VA) Under Secretary for Health, filling a role that has been without permanent leadership since 2017. Shereef Elnahal, MD, takes over from Steve Lieberman, MD, who has been serving the role in an acting capacity since July 2021.

Elnahal’s nomination had been in limbo since May after Sen. Rick Scott (R-FL) blocked an attempt to fast-track his confirmation, which was led by Sen. John Tester (D-MT) who chairs the Senate Committee on Veterans’ Affairs. Scott, who had no specific objection to Elnahal, argued that President Joseph Biden’s nominees haven’t been qualified. The debate turned acrimonious, with Tester accusing Scott of “turning his back on America’s veterans.” He called Scott’s objection as “obstruction at the worst, because this stops our veterans from getting the health care that they need.”

Tester urged his colleagues to support Elnahal’s confirmation, stressing the importance of filling the position. “Dr. Shereef Elnahal has an impressive record of leading health care systems and agencies and has shown a strong commitment to serving millions of veterans and hardworking employees at VA. Now more than ever,” Tester said, “the Department needs permanent, qualified leadership to guide the nation’s largest integrated health care system in the right direction.”

In a statement, Rep. Mike Bost (R-IL), ranking member of the US House of Representatives Committee on Veterans’ Affairs, agreed, saying, “Dr. Elnahal’s position is a vitally important one, particularly as the VA health care system prepares to care for millions more toxic-exposed veterans under the PACT [Promise to Address Comprehensive Toxics] Act and the new electronic health record rollout continues to disappoint. Dr. Elnahal has his work cut out for him, and I look forward to working with him to ensure that veterans get the health care they have earned when they need it and where they want it, without having to wait too long or travel too far.”

Elnahal is in fact considered well qualified for the job. He was New Jersey’s 21st health commissioner, confirmed unanimously by the New Jersey Senate. During his nearly 2 years in that position, he led with what has become a signature move for him—increasing transparent access to information—by expanding the New Jersey Health Information Network, an interoperability platform that allows for electronic exchange of patient health information among health care providers.

Most recently, as president and CEO of University Hospital in Newark, New Jersey, he oversaw improvements in care quality and patient safety. He also established a partnership to provide supportive housing to patients experiencing homelessness, a hospital-based violence intervention program that has served as a national model, and a program that deploys trusted chaplains as community health workers. Notably, he led the hospital through the COVID-19 crisis; the hospital has served as a model for urban hospital and regional response efforts. Elnahal also set up one of the first COVID-19 vaccination sites in New Jersey.

Moreover, he’s not actually a newcomer to the VA. He served as Assistant Deputy Under Secretary for Health for Quality, Safety, and Value from 2016 through 2018, where he oversaw national policies around quality of care for the Veterans Health Administration (VHA).

During that earlier tenure, he was at the forefront of making VA care more transparent and responsive. Among other things, he cofounded the VHA Innovation Ecosystem, a program that fosters the spread of innovation and best practices. On his watch the VA also launched accesstocare.gov, which provides public access to performance, wait time, and other data. The rationale, Elnahal said in a 2018 interview with Federal Practitioner, was simple: “If we provide veterans with an easy-to-use tool that lets them see data on wait times and quality, they’ll be able to make informed decisions about where and when they receive their health care.” The site allows users to compare quality of care provided by VA medical centers with that of local private hospitals. For instance, they can see if a local VA facility’s wait time is better, worse, or the same as the regional average of private sector clinics.

In his drive to harness smart, sustainable ideas for improving veteran care, Elnahal also helmed the VA Diffusion of Excellence (VADOE) program, whose Shark Tank Competition gives a platform to employees “passionate about solving some of the toughest challenges across VHA.” The innovative winners have included VIONE, a medication deprescribing program, and the β-Lactam Allergy Assessment, an initiative to clarify which patients are truly allergic to BL antibiotics, reduce the incidence of multidrug-resistant infections, and reduce hospital length of stay. Both programs are being replicated across multiple facilities.

“We really empower and recognize the frontline employees who not only contribute the best practices but who replicate them,” Elnahal told Federal Practitioner in 2016. “Essentially, we give them a systemwide leadership role… This is part of many different initiatives that are trying to recognize and elevate the great work that physicians do and really improve their morale and reduce burnout.”

As Rep. Bost suggested, Elnahal now has even more work cut out for him. At this new starting gate, Elnahal says a top priority is improving recruiting and retention for clinical care positions. “The sacred healthcare mission of VA simply cannot be fulfilled without having people to do it, talented healthcare professionals who put the mission above all else.”

In a LinkedIn post, Elnahal thanked President Biden and VA Secretary McDonough for their confidence in him, and the US Senate for confirming him in a bipartisan vote. But “[m]ost of all,” he said, “my gratitude goes to Veterans, families, caregivers, and survivors…. Beyond thrilled and eager to get to work for them in a health system with more than 300,000 heroes. Onward to an incredible journey!”

After a 5-year search, the US Senate in a 66-23 vote, confirmed a new US Department of Veterans Affairs (VA) Under Secretary for Health, filling a role that has been without permanent leadership since 2017. Shereef Elnahal, MD, takes over from Steve Lieberman, MD, who has been serving the role in an acting capacity since July 2021.

Elnahal’s nomination had been in limbo since May after Sen. Rick Scott (R-FL) blocked an attempt to fast-track his confirmation, which was led by Sen. John Tester (D-MT) who chairs the Senate Committee on Veterans’ Affairs. Scott, who had no specific objection to Elnahal, argued that President Joseph Biden’s nominees haven’t been qualified. The debate turned acrimonious, with Tester accusing Scott of “turning his back on America’s veterans.” He called Scott’s objection as “obstruction at the worst, because this stops our veterans from getting the health care that they need.”

Tester urged his colleagues to support Elnahal’s confirmation, stressing the importance of filling the position. “Dr. Shereef Elnahal has an impressive record of leading health care systems and agencies and has shown a strong commitment to serving millions of veterans and hardworking employees at VA. Now more than ever,” Tester said, “the Department needs permanent, qualified leadership to guide the nation’s largest integrated health care system in the right direction.”

In a statement, Rep. Mike Bost (R-IL), ranking member of the US House of Representatives Committee on Veterans’ Affairs, agreed, saying, “Dr. Elnahal’s position is a vitally important one, particularly as the VA health care system prepares to care for millions more toxic-exposed veterans under the PACT [Promise to Address Comprehensive Toxics] Act and the new electronic health record rollout continues to disappoint. Dr. Elnahal has his work cut out for him, and I look forward to working with him to ensure that veterans get the health care they have earned when they need it and where they want it, without having to wait too long or travel too far.”

Elnahal is in fact considered well qualified for the job. He was New Jersey’s 21st health commissioner, confirmed unanimously by the New Jersey Senate. During his nearly 2 years in that position, he led with what has become a signature move for him—increasing transparent access to information—by expanding the New Jersey Health Information Network, an interoperability platform that allows for electronic exchange of patient health information among health care providers.

Most recently, as president and CEO of University Hospital in Newark, New Jersey, he oversaw improvements in care quality and patient safety. He also established a partnership to provide supportive housing to patients experiencing homelessness, a hospital-based violence intervention program that has served as a national model, and a program that deploys trusted chaplains as community health workers. Notably, he led the hospital through the COVID-19 crisis; the hospital has served as a model for urban hospital and regional response efforts. Elnahal also set up one of the first COVID-19 vaccination sites in New Jersey.

Moreover, he’s not actually a newcomer to the VA. He served as Assistant Deputy Under Secretary for Health for Quality, Safety, and Value from 2016 through 2018, where he oversaw national policies around quality of care for the Veterans Health Administration (VHA).

During that earlier tenure, he was at the forefront of making VA care more transparent and responsive. Among other things, he cofounded the VHA Innovation Ecosystem, a program that fosters the spread of innovation and best practices. On his watch the VA also launched accesstocare.gov, which provides public access to performance, wait time, and other data. The rationale, Elnahal said in a 2018 interview with Federal Practitioner, was simple: “If we provide veterans with an easy-to-use tool that lets them see data on wait times and quality, they’ll be able to make informed decisions about where and when they receive their health care.” The site allows users to compare quality of care provided by VA medical centers with that of local private hospitals. For instance, they can see if a local VA facility’s wait time is better, worse, or the same as the regional average of private sector clinics.

In his drive to harness smart, sustainable ideas for improving veteran care, Elnahal also helmed the VA Diffusion of Excellence (VADOE) program, whose Shark Tank Competition gives a platform to employees “passionate about solving some of the toughest challenges across VHA.” The innovative winners have included VIONE, a medication deprescribing program, and the β-Lactam Allergy Assessment, an initiative to clarify which patients are truly allergic to BL antibiotics, reduce the incidence of multidrug-resistant infections, and reduce hospital length of stay. Both programs are being replicated across multiple facilities.

“We really empower and recognize the frontline employees who not only contribute the best practices but who replicate them,” Elnahal told Federal Practitioner in 2016. “Essentially, we give them a systemwide leadership role… This is part of many different initiatives that are trying to recognize and elevate the great work that physicians do and really improve their morale and reduce burnout.”

As Rep. Bost suggested, Elnahal now has even more work cut out for him. At this new starting gate, Elnahal says a top priority is improving recruiting and retention for clinical care positions. “The sacred healthcare mission of VA simply cannot be fulfilled without having people to do it, talented healthcare professionals who put the mission above all else.”

In a LinkedIn post, Elnahal thanked President Biden and VA Secretary McDonough for their confidence in him, and the US Senate for confirming him in a bipartisan vote. But “[m]ost of all,” he said, “my gratitude goes to Veterans, families, caregivers, and survivors…. Beyond thrilled and eager to get to work for them in a health system with more than 300,000 heroes. Onward to an incredible journey!”

After a 5-year search, the US Senate in a 66-23 vote, confirmed a new US Department of Veterans Affairs (VA) Under Secretary for Health, filling a role that has been without permanent leadership since 2017. Shereef Elnahal, MD, takes over from Steve Lieberman, MD, who has been serving the role in an acting capacity since July 2021.

Elnahal’s nomination had been in limbo since May after Sen. Rick Scott (R-FL) blocked an attempt to fast-track his confirmation, which was led by Sen. John Tester (D-MT) who chairs the Senate Committee on Veterans’ Affairs. Scott, who had no specific objection to Elnahal, argued that President Joseph Biden’s nominees haven’t been qualified. The debate turned acrimonious, with Tester accusing Scott of “turning his back on America’s veterans.” He called Scott’s objection as “obstruction at the worst, because this stops our veterans from getting the health care that they need.”

Tester urged his colleagues to support Elnahal’s confirmation, stressing the importance of filling the position. “Dr. Shereef Elnahal has an impressive record of leading health care systems and agencies and has shown a strong commitment to serving millions of veterans and hardworking employees at VA. Now more than ever,” Tester said, “the Department needs permanent, qualified leadership to guide the nation’s largest integrated health care system in the right direction.”

In a statement, Rep. Mike Bost (R-IL), ranking member of the US House of Representatives Committee on Veterans’ Affairs, agreed, saying, “Dr. Elnahal’s position is a vitally important one, particularly as the VA health care system prepares to care for millions more toxic-exposed veterans under the PACT [Promise to Address Comprehensive Toxics] Act and the new electronic health record rollout continues to disappoint. Dr. Elnahal has his work cut out for him, and I look forward to working with him to ensure that veterans get the health care they have earned when they need it and where they want it, without having to wait too long or travel too far.”

Elnahal is in fact considered well qualified for the job. He was New Jersey’s 21st health commissioner, confirmed unanimously by the New Jersey Senate. During his nearly 2 years in that position, he led with what has become a signature move for him—increasing transparent access to information—by expanding the New Jersey Health Information Network, an interoperability platform that allows for electronic exchange of patient health information among health care providers.

Most recently, as president and CEO of University Hospital in Newark, New Jersey, he oversaw improvements in care quality and patient safety. He also established a partnership to provide supportive housing to patients experiencing homelessness, a hospital-based violence intervention program that has served as a national model, and a program that deploys trusted chaplains as community health workers. Notably, he led the hospital through the COVID-19 crisis; the hospital has served as a model for urban hospital and regional response efforts. Elnahal also set up one of the first COVID-19 vaccination sites in New Jersey.

Moreover, he’s not actually a newcomer to the VA. He served as Assistant Deputy Under Secretary for Health for Quality, Safety, and Value from 2016 through 2018, where he oversaw national policies around quality of care for the Veterans Health Administration (VHA).

During that earlier tenure, he was at the forefront of making VA care more transparent and responsive. Among other things, he cofounded the VHA Innovation Ecosystem, a program that fosters the spread of innovation and best practices. On his watch the VA also launched accesstocare.gov, which provides public access to performance, wait time, and other data. The rationale, Elnahal said in a 2018 interview with Federal Practitioner, was simple: “If we provide veterans with an easy-to-use tool that lets them see data on wait times and quality, they’ll be able to make informed decisions about where and when they receive their health care.” The site allows users to compare quality of care provided by VA medical centers with that of local private hospitals. For instance, they can see if a local VA facility’s wait time is better, worse, or the same as the regional average of private sector clinics.

In his drive to harness smart, sustainable ideas for improving veteran care, Elnahal also helmed the VA Diffusion of Excellence (VADOE) program, whose Shark Tank Competition gives a platform to employees “passionate about solving some of the toughest challenges across VHA.” The innovative winners have included VIONE, a medication deprescribing program, and the β-Lactam Allergy Assessment, an initiative to clarify which patients are truly allergic to BL antibiotics, reduce the incidence of multidrug-resistant infections, and reduce hospital length of stay. Both programs are being replicated across multiple facilities.

“We really empower and recognize the frontline employees who not only contribute the best practices but who replicate them,” Elnahal told Federal Practitioner in 2016. “Essentially, we give them a systemwide leadership role… This is part of many different initiatives that are trying to recognize and elevate the great work that physicians do and really improve their morale and reduce burnout.”

As Rep. Bost suggested, Elnahal now has even more work cut out for him. At this new starting gate, Elnahal says a top priority is improving recruiting and retention for clinical care positions. “The sacred healthcare mission of VA simply cannot be fulfilled without having people to do it, talented healthcare professionals who put the mission above all else.”

In a LinkedIn post, Elnahal thanked President Biden and VA Secretary McDonough for their confidence in him, and the US Senate for confirming him in a bipartisan vote. But “[m]ost of all,” he said, “my gratitude goes to Veterans, families, caregivers, and survivors…. Beyond thrilled and eager to get to work for them in a health system with more than 300,000 heroes. Onward to an incredible journey!”