Drugs that follow the U.S. Food and Drug Administration’s (FDA’s) accelerated approval pathway can be greenlit based on surrogate or intermediate end points. While this is a valuable option for a medication, it often means there is more uncertainty surrounding its clinical benefit at the time of approval. Confirmatory, follow-up trials are required as a condition of expedited approval, and these are meant as a protective measure, providing a mechanism to flag any alarming safety signals that could emerge as a result of the treatment.
Nearly all of the drugs (19 of 24) that were approved within the accelerated approval pathway between 2009 and 2013 were for cancer indications.1
According to a recent Nature Reviews Clinical Oncology article, this period of postapproval monitoring may be too long.2 The authors cite prior research that found that approximately 1 in 10 anticancer therapies remain on the market for more than 5 years before the required confirmatory trial results are made public.1
The researchers proposed that the FDA take measures to try to shorten the time between when a drug is approved via a fast track and when manufacturers would be required to provide data on the drug’s proof of benefit. They wrote that medications that already had confirmatory trials underway at the time of accelerated approval were able to demonstrate this benefit more quickly; the median time to prove safety and efficacy was reduced by 1.4 years in these cases compared with the fast-tracked medications that had no validation trials in the works at the point of approval.
Postmarketing trials should consistently employ clinically meaningful end points, according to the authors, with a focus on outcomes such as overall survival or improved quality of life in cancer (as opposed to relying on surrogate results for postmarketing trials).
The point of accelerated approval is to get therapies to patients more quickly. But an approval does not, by default, make the drug more accessible to patients — and the high prices that are often assigned drugs that flow through the accelerated regulatory pathway could stunt their accessibility. A solution to this problem could come from the Department of Health and Human Services, proposed the authors; the agency could create a rule mandating each new drug undergo an independent economic analysis 1 to 2 years after hitting the market.
Editor’s note: This article has been corrected to clarify that the paper was published in Nature Reviews Clinical Oncology, not Nature.
- Zettler M, Nabhan C. Fulfillment of postmarketing requirements to the FDA for therapies granted oncology indications between 2011 and 2016[published online May 10, 2018]. JAMA Oncol.doi: 10.1001/jamaoncol.2018.0610
- Gyawali B, Kesselheim AS. Reinforcing the social compromise of accelerated approval[published online July 3, 2018]. Nat Rev Clin Oncol. 2018. doi: 10.1038/s41571-018-0066-3