In my view, the authors raise a sensitive issue but come to a dangerous conclusion.
AA is granted due to an unmet medical need - for drugs that have the potential to satisfy this unmet need. For proving this, confirmatory trials are imperative.
However, how do you handle the situation, when those trials fail to confirm?
The authors propose to decide in a view of other available therapies, as it may happen that "the available therapies have not changed and an unmet medical need still exists".
This ignores the fact that with the results of the confirmative trial one important factor has changed - trial results now argue against the assumption of benefit.
The authors further argue that the "inability to verify clinical benefit may be due to issues with confirmatory trial methodology, dosage selection, and population". This is true, but also something that needs to be addressed in the planning of the confirmatory trial. As such, I see the need to address this within scientific advice. We must not squander patient and doctors for insufficiently planned clinical trials!
In a way, the authors argue for a repetition and prolongation of AA. I wonder whether this is really feasible. They propose the FDA should "allow the sponsor to pursue alternative confirmatory trials, provided such trials are feasible and can be conducted in a timely manner".
However, there is a reason that FDA "may now require that confirmatory trials be underway before granting AA": We are very aware of the fact that confirmatory trials face severe challanges in patient recruitment and conduct, if the drug is already commercially available.
Thus, the proposal leads in the exact pitfalls that were thought to be avoided with coupling AA to confirmation. In addition, health systems already today struggle with deciding upon the use of drugs with sparse data and ever higher prices - the situation will not become any better by this.
What do you think?:
Harald Enzmann Tom Mayer Anja Schiel Maximilian Blindzellner Anna B. Robert Sauermann Michael Berntgen Marc Van de Casteele
Oncology Accelerated Approval Confirmatory Trials: When a Failed Trial Is Not a Failed Drug - via Journal of Clinical Oncology / American Society of Clinical Oncology (ASCO). FDA authors Gautam Mehta, MD, and Richard Pazdur, MD.
https://lnkd.in/eXak34u9
#OCEPublications #OCEProjectConfirm
Clinical Pharmacy Technician at Prime Therapeutics
1moVery informative