In response to criticisms about drugs staying on the market for years due to delays in obtaining confirmatory results, the FDA has issued guidance favoring randomized controlled trials (RCTs) for the accelerated approval of breakthrough drugs. The FDA believes that prescribing RCTs instead of single-arm studies will reduce uncertainty for patients and ensure the quality and efficiency of initial clinical trials. The FDA's preference for RCTs is presented as the "preferred approach" with single-arm studies only intended for specific situations where RCTs present difficulties. According to the guidelines, sponsors may conduct one RCT to support both accelerated and full approval or opt for two RCTs, one for accelerated approval and another to confirm effects for full approval. Both approaches require sponsors to pick appropriate endpoints for predicting clinical benefit and consult with the FDA on their plans. One significant change in the guidelines is the call for the second trial to commence early to ensure timely verification of clinical benefit. The FDA's draft guidance seeks to address criticisms of the agency's accelerated approval pathway, which has permitted some therapies to remain on the market due to delays in obtaining confirmatory results.