In a significant update to its existing policies when it comes to conducting clinical trials so as to support an accelerated approval for oncology as well as other life-saving therapies, the FDA is planning a preference for randomised controlled trials-RCTs as compared to single-arm studies so as to support fast nods of breakthrough medications.
As per the new draft guidance which is called Clinical Trial Considerations to Support Accelerated Approvals of Oncology Therapeutics, the clinical uncertainty among patients needs to be reduced by ways of encouraging sponsors to plan RCTs in order to support RCT approval.
According to Richard Pazdur, Director, Oncology Center of Excellence, building quality as well as efficiency when it comes to designing oncology clinical trials is a critical element when it comes to providing maximum benefit to people living with cancer.
In order to move the online research policy as fast as it can, the FDA aims to address criticisms that are mounting by the day about its accelerated approval pathway, which has, as a matter of fact, permitted some therapies to be on the market for years because of delays in obtaining inferences from the confirmatory studies.
Pazdur as well as his colleagues are of the belief that enhancing the quality as well as efficiency of the initial stage of clinical trial studies by way of a broader usage of RCT will for sure avoid challenges that have elongated the clinical benefit confirmation.
As per the guidance, RCTs are termed the preferred approach to aid accelerated approval and look forward to limiting single-arm studies to certain situations where RCTs give out absolute challenges. Sponsors may go on to conduct a particular RCT to support both accelerated and thereafter overall approval or may as well opt for two RCTs, wherein one will be for accelerated approval and another one will be to confirm the effects for the entire approval. In both scenarios, sponsors have to pick endpoints that are suitable for predicting clinical benefit as well as consult with the FDA on any such plans.
When it comes to the two-RCT approach, the first study will gauge an early response rate, whereas the second trial will keep track of progression-free survival or even total survival so as to verify the clinical benefit. A significant change is that the FDA would ask for a second study to be going on at a time of accelerated approval. As per the recent approval legislation, FDA can require the launch of confirmatory trials to document the clinical benefit at the time of awarding accelerated approvals for novel therapies, and that the agency officials are moving at a brisk pace in order to clarify as to how the new authority shall be implemented.
In a draft guidance, the FDA has advised the sponsors to come up with a second or confirmatory study at the time of the approval so as to verify its clinical benefits in a timelier manner. This approach refers to OCE’s Project Confirm, that was launched by the agency in 2022 so as to promote fairness and transparency in the accelerated approval process for cancer therapies and has been adopted more widely by the Center for Drug Evaluation and Research.
At the same time, the advisory also puts forth how sponsors may still determine the adequacy of the single-term studies so as to support an application. In the event that the single-trial approach is retained, the sponsors should make plans to extend the study so as to confirm a longer clinical endpoint.
All said and done, the trials must be large enough to pinpoint clinically meaningful and statistically important improvements in the endpoints of the study and also to verify the long-term benefits.
It is well to be noted that the FDA seeks early consultation with the agency when it comes to the appropriateness of an endpoint that is planned for a single trial as well as its capacity to forecast benefit in order to support an accelerated approval.