Accelerated Approval of Cancer Drugs—Righting the Ship of the US Food and Drug Administration

Sarah S. P. DiMagno; Aaron Glickman; Ezekiel J. Emanuel

doi:10.1001/jamainternmed.2019.0584

Invited Commentary

Health Care Policy and Law

May 28, 2019

Accelerated Approval of Cancer Drugs—Righting the Ship of the US Food and Drug Administration

Sarah S. P. DiMagno, BA¹; Aaron Glickman, BA¹; Ezekiel J. Emanuel, MD, PhD^1,2

Author Affiliations Article Information

¹Department of Medical Ethics and Health Policy, Perelman School of Medicine, University of Pennsylvania, Philadelphia
²Department of Health Care Management, The Wharton School, University of Pennsylvania, Philadelphia

JAMA Intern Med. 2019;179(7):922-923. doi:10.1001/jamainternmed.2019.0584

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The US Food and Drug Administration (FDA) is caught between Scylla and Charybdis, with competing pressures to speed drugs to market and to ensure they are safe and effective. On one side, patients, families, and advocates are clamoring for faster approval of new drugs that offer treatments for serious and life-threatening diseases. They believe that delay is potentially deadly. Drug companies concur, eager to push new drugs to market as quickly as possible to start generating revenue. On the other side, recalling experiences with thalidomide, rofecoxib, bevacizumab, and other ineffective or harmful drugs, physicians and watchdog groups worry about the safety, real-world efficacy, and financial waste inherent in the rapid approval of drugs that eventually prove to be unsafe or ineffective.

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1 Comment for this article

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July 6, 2019

Primum Non Nocere, bene facitis: First Do No Harm, do good.

Stephen Strum, MD, FACP | Hematologist-Oncologist Focused on Prostate Cancer

The articles by DiMagno et al., Chen et al., and Gyawali et al., are of paramount importance. We, physicians, are taught, early on in our vocation, to "do no harm." But how much emphasis is placed on doing good? Where was the emphasis on improving the quality of life of the patient, and focusing on what is said to be the Holy Grail of Medicine, the TI (therapeutic index): the ratio of benefits to the patient ÷ adverse effects.

As a healthcare practitioner in the community practice of medicine for almost fifty years, I have focused on clinical research and publications concerning the quality of life. On one occasion, I appeared before the FDA's Oncology Drug Advisory Committee (ODAC). I learned that being a member of the ODAC involved political connections. My colleague Emil Freireich and I have volunteered to be members of ODAC for decades, and yet despite outstanding credentials have never been selected. ODAC is not a full-time job, and it is my understanding that there is no compensation. When I presented before ODAC in the early '80s on the dramatic effects of i.v. metoclopramide in preventing chemotherapy-induced nausea & vomiting (CINV) in patients with lung cancer receiving high-dose cisplatin chemotherapy, I was told by one ODAC member that her institution did not have the excellent results that I had presented. She voted against approval. But where was any publication from her institution? Our data had been published in JAMA (4). How can ODAC function as it should if this is not a full-time job, and/or if ego-related interests trump factual results?

In prostate cancer, my area of focus for 37 years, I see new anti-androgens rapidly approved by the FDA based on trials which compare the study drug plus an LHRH-agonist versus placebo plus an LHRH-agonist (5). Why has there not been a head-to-head comparison of the anti-androgen (under study) plus an LHRH-agonist with a counterpart two-drug combination using an anti-androgen of previously documented efficacy? We should be comparing the most effective regimen we currently have with the new approach seeking approval. The placebo arm represents a wasted opportunity to learn.

References
1. DiMagno SSP, Glickman A, Emanuel EJ: Accelerated Approval of Cancer Drugs-Righting the Ship of the US Food and Drug Administration. JAMA Intern Med, 2019

2. Chen EY, Raghunathan V, Prasad V. An overview of cancer drugs approved by the US Food and Drug Administration based on the surrogate end point of response rate [published online May 28, 2019]. JAMA Intern Med. doi:10.1001/jamainternmed.2019. 0583

3. Gyawali B, Hey SP, Kesselheim AS. Assessment of the clinical benefit of cancer drugs receiving accelerated approval [published online May 28, 2019]. JAMA Intern Med. doi:10.1001/jamainternmed.2019.0462

4. Strum SB, McDermed JE, Opfell RW, et al.,: Intravenous metoclopramide. An effective antiemetic in cancer chemotherapy. JAMA 247:2683-2686, 1982.

5. Chi KN, Agarwal N, Bjartell A, et al.,: Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med 381:13-24, 2019

CONFLICT OF INTEREST: None Reported

Accelerated Approval of Cancer Drugs—Righting the Ship of the US Food and Drug Administration

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