How and when the FDA solicits outside advice on drug approval | India News

C Joseph Ross Daval, JD, Amit Sarpatwari, Ph.D., JD, and Aaron S. Kesselheim, MD, JD, MPH (left to right)

The U.S. Food and Drug Administration can increase public confidence in drugs through greater transparency in its decisions about when to seek expert feedback and instructions to its advisory committees, argue members of a group that the agency closely monitors. does. A recent paper from Harvard’s Program on Regulation, Therapeutics and Law (Portal) may help journalists who want to dig more deeply into the question of when and how the FDA seeks advice on drug approval.

In this blog post, we’ll first recap why FDA staff would need to call in outside experts and then look at two recent sports papers and suggest reporting on the topic.

Expert feedback, or why the FDA has advisory committees

FDA staff often have a complex task trying to decide whether drugs for the US market are safe and effective.

The agency expects pharmaceutical companies to make a good case when it comes to data on the effectiveness and safety of their drugs when seeking approval. This usually involves successfully taking the drugs through three phases of testing, Phase 1, Phase 2 and Phase 3, as defined in the graphic below.

An excerpt from the FDA graphic

Sometimes companies present strong bodies of evidence to support applications filed with the FDA.

For example, Bristol Myers Squibb’s application for approval of its Sotyktu (deucravcitinib) drug for psoriatic arthritis, based on data from two successful Phase 3 trials (NCT03624127 And NCT03611751, 9 approval letter for Sotyktu, FDA employees said they had not convened an advisory committee regarding the application because it did not “raise significant safety or efficacy issues that were unexpected for a drug in this class.”

Other times, drug manufacturers seek approval based on small sets of data, or for applications where the results do not make a clear case for approving the drug for sale. In these cases, the FDA will convene a meeting of the relevant advisory committee.

The FDA also schedules advisory committee meetings when a drug uses a new approach to combat the disease. In the early stages of introducing COVID vaccines, the FDA applied for emergency use authorizations for these new products and then expanded their use several times before the Vaccines and Related Biological Products Advisory Committee (VRBPAC).

However, the FDA has drawn criticism for skipping the VRBPAC review on some extension of authorizations for these shots. The agency thus missed opportunities for public debate on emerging science that could help foster trust, C Joseph Ross Daval, JD, Aaron S Kesselheim, MD, JD, MPH, and Amit Sarpatwari, PhD, JD. , has written. One August perspective article in the New England Journal of Medicine. All are affiliated with the portal.

“Under a narrow view, advisory committees exist only to provide additional information to the agency – an independent, multidisciplinary review to help the agency better understand the questions facing it. can also be seen as an essential part of science-led governance,” he wrote. “When an advisory committee provides its recommendations, it gives the FDA an opportunity to legitimize the decision through transparent consultations with experts outside the political umbrella under which it operates.”

Kesselheim is among members of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee, who resigned following the agency’s controversial decision to approve EduHelm for Alzheimer’s disease. This decision went against the recommendations made by the Peripheral and Central Nervous System Drugs Advisory Committee, as Discussed in a New York Times story. (For more background on Aduhelm, see these AHCJ posts: New Alzheimer’s drug grabs the attention of federal, independent groups (7/8/21), Tips for Covering Medicare’s Plan to Limit Coverage of Controversial Alzheimer’s Drug (1/25/22).)

The FDA is not obligated to accept the recommendations of its advisory committees, although it often does.

In cases where it does not, holding an advisory committee meeting should provide the public with more information about the product, as these meetings “force the agency to clarify its reasoning,” Daval, Kesselheim And the gallantry wrote.

More reluctant to seek outside advice?

In a May paper in Health Affairs, titled unwanted advice? Frequency, characteristics and results of negative advisory committee votes for FDA-approved drugsDaval, Sarpatwari and Kesselheim pointed out that the agency’s chances of convening advisory committees for drugs have been diminishing over the years.

The decline was evident even before the pandemic. The authors reported that 59%, or 17 of the 29 new drugs approved, were referred to an advisory committee in 2011. That number dropped from 9%, or 4 out of 46, in 2017.

Leaving aside the potential impacts of the pandemic, there appears to have been a decline in the use of outside advice. Of the 46 new drug applications included in the 2017 Portal study, only four were put before a panel. In 2019, the FDA convened six meetings for 48 relevant applications, meaning 13% of these drugs were put up for public scrutiny through advisory committees prior to approval.

And there is notable inconsistency in how the FDA questions its advisory committees, Daval, Gallopwari and Kesselheim. They urge the FDA to be more transparent about its use of advisory committees, especially in cases where the agency ultimately rejects the committee’s advice.

“Through meaningful reforms, the FDA can better ensure public confidence in its decision to allow the drug to be brought to market, especially when an advisory committee has recommended otherwise,” they wrote.

In the August NEJM paper, titled “Improving the use of FDA advisory committees,” Daval, Kesselheim and Sarpatwari examine the agency’s September 2021 VRBPAC meeting. This was conducted in connection with Pfizer-BioNtech authorizing the third dose of the COVID vaccine.

“At the end of the meeting, experts voted against the proposed authorization — for all individuals 16 or older — by a wide margin (16 to 2). The FDA then sought a vote on a separate question that was on the original agenda. Wasn’t: whether the agency should authorize a third dose for people 65 years of age or older and those at high risk for severe COVID-19. The advisory committee voted unanimously (18 to 0) in favor of this authorization did, and the following week the FDA issued an emergency use authorization for those groups,” wrote Daval, Kesselheim and Sarpatwari.

In his view, the addition of “last-minute questions after negative vote” fostered a belief that the FDA was inclined for a “yes” vote to better align with the Biden administration’s promise of a “booster for all”. . They noted that the FDA later expanded eligibility to all adults in November, then in December to 16- and 17-year-olds, without consulting VRBPAC.

The authors noted that there were “reasonable justifications” for the FDA’s decision to authorize the third dose. The new question was added in response to suggestions from committee members, and the FDA pointed to “rapidly evolving evidence” on the safety and efficacy of the third dose as a justification for authorizations, the authors noted.

“But the maladaptive role of the advisory committees in these decisions contributed to a general lack of clear messaging about the usefulness of vaccines and raised widespread concerns about the original purpose of the FDA advisory committees,” wrote Daval, Kesselheim and Sarpatwari.

In an email to the AHCJ, Sarpatwari offered suggestions for journalists covering the FDA’s decisions on the drugs. He suggested paying attention to how the FDA develops the questions it asks for its advisory committees. Journalists should also report conflicts of interest to advisory committee members over time to monitor voting patterns.

please look AHCJ’s Tip Sheet on Covering FDA Advisory Committee Meetings, Also, if you’re new to the FDA’s cover, consider taking A free online course portal has been developed on this subject.

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