Bishal Gyawali  MD PhD Med Onc. Asst. Professor 

Only 1 in 5 Cancer Drugs Receiving FDA Accelerated Approval Have Proven Benefits in Confirmatory Trials Interview with:

Bishal Gyawali  MD PhD Med Onc. Asst. Professor 

Dr. Gyawali

Bishal Gyawali  MD PhD

  • Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
  • Department of Oncology, Department of Public Health Sciences, and Division of Cancer Care and Epidemiology, Queen’s University, Kingston, Ontario, Canada What is the background for this study? What are the main findings?

Response: Accelerated approval pathway from the FDA allows cancer drugs to come to market sooner by showing improvement in surrogate measures such as change in tumor size. Surrogate measures do not reflect clinical benefit in terms of living longer or feeling better. So, when a drug receives accelerated approval, the drug is required to undergo a confirmatory trial to confirm that true clinical benefit from the drug actually exists.

Last year, a paper from the FDA argued that accelerated approval pathway is working effectively because 55% of such drugs confirmed clinical benefit. However, we saw that most of those drugs were actually improving only a surrogate measure even in confirmatory trials. So the confirmatory trials were not confirming clinical benefit but actually confirming benefit in a surrogate endpoint. We investigate that issue in our study using updated results from the confirmatory trials that were ongoing at the time of FDA review.

Our main finding is that only one-fifth of cancer drugs that received accelerated approval actually improved overall survival later in confirmatory trials. For, 20% of other drugs, the confirmatory trials tested the same surrogate endpoint as did the preapproval trial. For another 21%, the confirmatory trial showed benefit in a surrogate endpoint different from the one used in preapproval trial. Furthermore, when drugs fail to confirm clinical benefits in confirmatory trials, they still continue to remain on market. What should readers take away from your report?

Response: Only 20% of cancer drugs approved using accelerated approval pathway have proven benefits in overall survival in a confirmatory trial. Even when the trials are called confirmatory, usually they just confirm effect on surrogate measures and do not confirm actual clinical benefit. Sometimes, when the drug fails in confirmatory trial, appropriate actions to withdraw the drug from the market are rarely taken. What recommendations do you have for future research as a result of this work?

Response: We have policy recommendations rather than research recommendations from our study. We recommend that the success of accelerated approval pathway lies in the fact that confirmatory studies are duly conducted in time, and use clinical endpoints such as overall survival or quality of life to actually confirm benefit rather than test another surrogate measure. When drugs fail in confirmatory studies, quick and decisive steps must be taken to withdraw the drug from the market to prevent undue harm from unhelpful drugs. That is how accelerated approval pathway is supposed to function keeping patient benefits at the center of the agenda. Is there anything else you would like to add? 

Response: In a different paper from last year, we provide 3 suggestions to reinforce the social compromise of AA:

We have no financial conflicts to disclose. Other disclosures are as mentioned in the paper. 


Gyawali B, Hey SP, Kesselheim AS. Assessment of the Clinical Benefit of Cancer Drugs Receiving Accelerated Approval. JAMA Intern Med. Published online May 28, 2019. doi:10.1001/jamainternmed.2019.0462

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Last Updated on May 29, 2019 by Marie Benz MD FAAD