Would you say the industry has used RBM and adaptive trials to their fullest potential?
We are only just at the threshold. The well touted statistic of 01 success per 10 trials is all too familiar and far too many trials continue to fail. A large proportion of these failures can be attributed directly to clinical trial design, amendments to design or clinical trial conduct. There is a long way to go to incorporate these tools into our everyday processes and implement RBM effectively.
Still, things are looking up. The USFDA indicated that 46 drugs were approved in 2016, more than ever before. So we must be getting it right, one step at a time. However, we must take steps as an industry to remove the ambiguity that enshrouds many of the newer concepts and keeps us from adopting them for the betterment of clinical trials.
Take Risk Based Monitoring (RBM) for one. The scope of RBM is often misunderstood by several sponsors and CROs to apply simply to site monitoring, rather than the identification, assessment and monitoring of risks over the entire trial. Let me relate an incident from an actual sponsor’s experience. Their conclusion after attempting adhoc measures to reduce Source Data Verification (SDV) and to introduce remote site monitoring on a vaccine trial, was that Risk Based Monitoring is better in theory than in practice and has no place in the real world. The Risk identification and Assessment exercise, which should always be the starting point, didn’t even come into the picture! So how could this attempt at RBM yield expected results?
Let’s look at Adaptive Trials. We need more expertise and planning to go into the designing of a protocol to allow adaptations within a trial without the need for protocol or operational amendments. Take for example, a sponsor that required a dose change on an oncology trial. Because the study design did not allow for this right at the beginning, a protocol amendment, IRB and other approvals, database design amendments were all required to allow this lowering of dosage for exceptionally weak patients. The dosing for these subjects had to be stopped until the new protocol was in place. This is not desirable considering the stage and condition of these patients. Designing the protocol and the database to allow different doses to be captured would have allowed the trial to continue smoothly without undue delay or threats to patient safety. Designing of adaptive trials takes experience, careful thought and the ability to look ahead.
This is an excerpt from the Executive Director's interview with the organizers of the GCT Meet held in Barcelona in 2018.