FDA criticized and defended over looser data requirements

Accelerated Approval

FDA criticized and defended over looser data requirements

Rigorous and lengthy research of candidate drugs, aimed at being maximally sure of their safety and effectiveness before their being released to the public, was once the norm. The downside was that drugs were kept from patients who would have benefitted from them. In recent years the Food and Drug Administration (FDA) has shifted emphasis in drug approval from prudence to speed, according to some critics.

This has generated controversy in the medical and research communities over the volume and types of clinical trial information now needed for faster approval. Some say the FDA is allowing new drugs to appear based on insufficient data and then not mandating more trials following approval.

Writing in Fierce Biotech, Nick Paul Taylor describes a study in the Journal of the American Medical Association (JAMA) that reviewed 22 drugs in 24 indications that have been approved under the new quick approval system between 2009 and 2013. Two thirds of the clinical trials involved did not use controls, i.e., administration of placebos or inactive substances with which to compare the candidate drug’s performance. Such trials are called “single arm studies.”

Also, while research has continued following approval, half of the cases took three years to conclude, and many used indirect or abstract indicators rather than actual clinical results. Finally, the number of study participants was smaller than in the past with nearly all of the cases reviewed using less than 200 patients.

One JAMA study author, Huseyin Naci, Ph.D., said, “We have found numerous situations in which required confirmatory studies with rigorous designs and outcomes are not pursued or are not completed in a timely fashion, and in these cases, we are concerned that regulators appear to accept data that would not otherwise meet FDA standards.”

On the other hand, the FDA has required more research following approval in 38 studies involving continuing safety and effectiveness of new drugs, and 80 percent of these new studies are in progress.

Robert Califf, M.D., former head of the FDA, responded to the JAMA review, saying it posed “issues that merit deeper study and discussion within the FDA and in the clinical and payer ecosystems affected by the agency’s standards.” Nonetheless, Califf, defending the FDA and the accelerated approval pathway, added, “In general, the current approach is acclaimed by those with the most at stake — patients and their families.”

As Taylor summarizes, “Those patients and their families have helped swing the pendulum away from caution and toward faster approvals based on less conclusive evidence. And, unless a safety scandal drives it back the other way, it is currently hard to see the FDA reversing course and facing down the backlash that would likely follow.”

This is a powerful argument that shows where the balance of opinion is now, in favor of quicker approval and release versus more trial evidence, in order to get drugs to market faster. This view is likely to remain dominant for some time.