March 28, 2022 – As FDA Commissioner Robert Califf, M.D., determines how to fulfill his promise to re-examine the agency’s accelerated approval pathway and Congress continues to push for action, the FDA’s Office of Prescription Drug Promotion (OPDP) is tackling one piece of the puzzle: How well consumers understand the limitations of accelerated approval drugs and whether disclosures used in direct-to-consumer (DTC) promotion on websites for these products properly convey risks and benefits.

The planned study builds on prior OPDP research which showed in preliminary results that although a consumer-friendly disclosure using simpler language helped, still participants’ overall understanding of accelerated approval drugs was low. The FDA announced in the March 24 Federal Register that it would be conducting two additional studies which would test the same experimental conditions as the previous study but with a different population – cancer survivors and cancer caregivers – as well as testing additional consumer-friendly disclosures. The studies will look specifically at disclosures in DTC promotion on prescription drug websites.

“Replication is an important part of science and, if confirmation of prior results is seen, can increase confidence in the results from our first study,” the agency’s notice states.

OPDP will examine disclosure effects

While the issue percolates in the FDA Commissioner’s office, OPDP plans to conduct two studies in an attempt to learn more about what consumers know about the accelerated approval process and which promotional disclosures are helpful in explaining what a drug approved through this pathway both is and is not. OPDP also will examine how disclosures may affect a patient’s decision to pursue an accelerated approval treatment. Comments on the planned studies may be submitted through April 25.

Study 1 will involve cancer survivors and cancer caregivers and will test the “three-element’ version of the promotional disclosure: (1) approval basis; (2) unknown outcomes; and (3) confirmatory trials. Study 1 will also test the prominence of the disclosure. It is OPDP’s hypothesis that participants will be more likely to notice a disclosure that is more prominent, and to use it to form their perceptions of the drug if it is in more consumer-friendly language.

Study 2 will test four versions of the consumer-friendly disclosure, to include the version in Study 1 and three other versions, in order to evaluate “the impact on participants’ comprehension of the disclosure and perception of the fictitious drug” as well as perceptions of the drug’s risk and risk-benefit trade-offs, the notice states. The prominence of the disclosure will be the same – high prominence – as tested in Study 1. OPDP notes that at least one comment submitted after the prior study questioned whether “over-disclosure could dissuade consumers from considering accelerated approval products.”

This research, OPDP states, “has practical utility to expand our information regarding website disclosures regarding accelerated approval drugs, both by extending to additional versions of the disclosure related to our overall questions, and to determine if results are consistent with those of the earlier study.”

OPDP intends to publish the results of its research when complete.

Califf looking at accelerated approvals

Accelerated approval is limited to certain products intended to treat serious or life-threatening conditions and may be granted based on a determination that a drug has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit or on a clinical endpoint that is reasonably likely to predict an effect on a condition.

The approval of Aduhelm, Biogen’s drug to treat Alzheimer’s disease, through the accelerated approval pathway has been controversial, leading to calls for investigation of this decision and proposed legislation to rein in the pathway. Before the vote on his confirmation, Califf promised Sen. Ron Wyden (D-Ore.), chair of the Senate Finance Committee, that he would prioritize improvements in the accelerated approval pathway, particularly to ensure that companies do, in fact, complete required confirmatory clinical trials after receiving product approvals.