Accelerated Approval Program: For the Benefit of Patients

Get Permission

A DIAGNOSIS of any life-threatening cancer or other serious illness has always been a world-shaking event for those touched by significant disease, and most of us have known—or will know—the frustration, helplessness, and desperate sense of urgency provoked by the words, “The disease is worsening, and there is no known cure.” After decades of patient advocacy, the U.S. Food and Drug Administration (FDA) acknowledged that urgency by establishing its Accelerated Approval Program in 1992. This fast-tracking program has extended or saved countless lives in the past quarter-century, improved the lives of countless more, and contributed significantly to the revolutionary progress now being made in treating cancers and other serious illnesses.

Ellen V. Sigal, PhD

Ellen V. Sigal, PhD

Recently, however, in the May 28 online edition of JAMA Internal Medicine, articles were published by multiple authors questioning the validity of the current Accelerated Approval Program and suggesting it may be a flawed system for reviewing and approving drugs.1,2 It is important to note that the articles and accompanying editorial3 were not only incomplete in their technical details, but more important, they failed completely to take into consideration the needs and wishes of patients and families faced with such urgent threats.

Remembering for Whom the Program Was Created

CERTAINLY, ANY major FDA program should be reviewed on a regular basis for effectiveness and efficiency, and there is room for robust debate based on data, facts, and figures. However, in suggesting that the Accelerated Approval Program may be doing more harm than good, the authors of these articles seem to lose sight of the people for whom the program was created—patients— and of its extraordinary value to them.

For one thing, the articles complain that the surrogate endpoints used are unreliable predictors of longer-term results, without seeming to recognize that the surrogate endpoints truly speed further learning and development of the activity and limits of promising new agents. For example, detecting shrinkage of a tumor can always be done prior to fully knowing whether the patient ultimately lived longer from any treatment being researched.

The time it could take to show the effect on overall survival may be months or years longer—time many patients may simply not have to wait. Patients with no other options may be willing to take a drug that has not yet shown overall survival but has shown benefit in other ways. Further, numerous examples have shown these responses ultimately to be durable and meaningful to patients’ lives.

Measuring True Clinical Benefit

SOME OF THE MOST transformative drugs that have been approved through the Accelerated Approval Program and confirmed based on response or progression-free survival are in the space of chronic myeloid leukemia, multiple myeloma, and targeted therapy for life-threatening lung cancer; they have altered the otherwise dismal natural history of these diseases. Although overall survival is important, for these patient populations, it is not the only truly meaningful metric.

“Even drugs with marginal effects can help bridge the gap while patients wait for the next generation of treatments that may be even more effective.”
— Ellen V. Sigal, PhD

Tweet this quote

It is true that once initial data demonstrate patients are responding positively to a drug targeting a rare or life-threatening condition, it may not be feasible to conduct large, randomized confirmatory trials to measure overall survival. Patients may only agree to an experimental intervention or standard of care if they are able to “cross over” if their disease worsens. This is important because it allows access to potentially beneficial treatments but confounds the ability to conclusively measure endpoints such as overall survival. However, this should not be misinterpreted to mean there is no clinical benefit.

It’s also worth noting that innovation in oncology has been fostered in large part by the wave of new cancer drugs that have been successfully launched through the Accelerated Approval Program. At a time when promising new cancer treatments are rapidly being tested, even drugs with marginal effects can help bridge the gap while patients wait for the next generation of treatments that may be even more effective.

Living With the Urgency of Now

THE AUTHORS of the JAMA articles are right to insist that patients deserve therapies developed with sound science, and the FDA agrees. The agency has done an excellent job of following up on initial accelerated approvals to ensure that patients are protected, and many processes of pharmacovigilance are in place to track the safety of approved therapies. The FDA continually evaluates its programs for their scientific rigor and effectiveness in advancing the safety, efficacy, and well-being of the American people.

Cures are coming. Therapies with transformative potential have been approved for treating cancer, and more are in the pipeline, with a likely expansion into other life-threatening diseases. Accelerated approval is necessary to keep patient access up to speed with these innovations and to be certain that our nation’s investment in research can be translated to safe and effective therapies that help patients. It is imperative that we stay focused on moving forward—carefully, without bias, and with the well-being of patients as our top priority. This means, among other things, speed and sensitivity to the “urgency of now” for patients with advanced cancers and other serious diseases.

DISCLOSURE: Dr. Sigal reported no conflicts of interest.


1. Gyawali B, Hey SP, Kesselheim AS: Assessment of the clinical benefit of cancer drugs receiving accelerated approval. JAMA Intern Med. May 28, 2019 (early release online).

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. JAMA Intern Med. May 28, 2019 (early release online).

3. Lehman R, Gross C: An international perspective on drugs for cancer: The best of times, the worst of times. JAMA Intern Med. May 28, 2019 (early release online).