Companies seeking accelerated approval for oncology drugs should avoid the temptation of single-arm trials and conduct randomized trials, except for indications with small patient populations or when drug activity is high, a Food and Drug Administration advisory panel concluded Feb. 8.
A single-arm trial, which is easier and faster to conduct, should be reserved for rare circumstances, Dr. Gary Lyman of Duke University, Durham, N.C., noted during an Oncologic Drugs Advisory Committee meeting. For Dr. Silvana Martino of the Angeles Clinic and Research Institute in Santa Monica, Calif., that would be when "patients are few and the activity of the drug is considerable."
Modest effects in a single-arm trial are insufficient to justify approval, agreed Dr. Malcolm Smith of the National Cancer Institute, Rockville, Md.
The committee’s preference for randomized trials confirms the direction in which the FDA is already moving. Dr. Richard Pazdur, director of the FDA’s office of oncology drug products in Silver Spring, Md., noted that the agency is encouraging sponsors to think randomization before conducting a single-arm trial.
Marginal response rates found in single-arm trials in a refractory setting make it difficult to judge whether they are predictive of clinical benefit, he pointed out.
It’s not that a single-arm study will never be acceptable, Dr. Pazdur said, but drugs are often submitted with very small response rates and sometimes the true benefit is not known until a randomized trial assesses survival.
Committee members also supported requiring drug sponsors to conduct two postapproval confirmatory trials instead of one, and they agreed that these trials should be ongoing or at least in the final stages of development at the time of accelerated approval.
The FDA sought support for those requirements to ensure that confirmation of accelerated approval can be provided in a timely fashion. If a single trial fails to show efficacy and then a second trial is conducted, it takes too long to determine whether a drug is, in fact, beneficial, Dr. Pazdur said.
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