The U.S. Food and Drug Administration (FDA) established the accelerated approval pathway over 30 years ago with a careful balance in mind: allowing access to promising therapies today, while obtaining confirmatory evidence of direct patient benefits later. Specifically, the pathway allows earlier approval through the use of surrogate endpoints, which substitute for direct clinical outcome measures. Sponsors then need to verify the clinical benefit of the drug through adequate and well-controlled confirmatory trials.
The pathway has shown that it can be highly beneficial to patients with an unmet medical need when well-designed clinical trials produce early, promising evidence of clinical benefit. However, some surrogate endpoints are poor predictors of the effects of drugs on patient health outcomes.
In addition, post-approval confirmatory trials are often delayed. As a result, there have been cases where accelerated approval led to patient harms and unnecessary spending after drug companies failed to confirm the predicted clinical benefit in a timely manner.
Given the careful balance described above, FDA has the authority to withdraw a product from the market if the drug ultimately fails to show direct patient benefits that outweigh its risks; however, the agency rarely does so. In addition to the need for additional FDA resources, there are also inadequate incentives in place to motivate manufacturers to complete confirmatory trials in a timely manner. Products granted accelerated approval can command high prices and generate significant profits before demonstrating clinical benefit. This means that manufacturers are more incentivized to delay actions that may ultimately result in withdrawing their product from the market.
For the public, patients, and the medical community to trust the value of accelerated approval drugs, reforms are needed.
