Is one type of clinical trial more susceptible to an ominous demise than all the rest?
It’s no secret that conducting successful clinical trials is a difficult undertaking and that event the most talented teams fail. There are many reasons that a trial could be forced to suspend or terminate its operations, and understanding which types of trials are at the highest risk of failure can be an invaluable tool for judging investments and allocating resources. Not all disease areas produce clinical trials of the same difficulty, however.
So far this year, 13 clinical trials in oncology have been suspended, terminated, or withdrawn, dwarfing all other major disease areas. It’s reasonable for this to be the case because oncology trials are currently among the most initiated and underway, but comparing oncology trials to other therapeutic areas visually really drives the point home: oncology trials are experiencing a surge, and they are risky.
But when exactly are these trials being suspended? Phase 1 or first-in-man seem like they’d be the most likely candidates for the stoppage, as bridging the gap between in vivo models and human subjects is unpredictable at best. As it turns out, Phase 1 is a major period of trial suspension and termination, but surprisingly, Phase 2 is the larger culprit for oncology trials this year.
This means that while researchers have grown better at producing therapies that are safer for the first test subjects, creating therapies which are efficacious at the same dosing level as they’re proven safe continues to be extremely difficult.
From this, it’s possible to infer that the differences in sample size between Phase 1 cohorts and Phase 2 cohorts leave room for drugs with more complex efficacy profiles to trigger adverse reactions when exposed to the more diverse Phase 2 cohort. As trial design and the drugs on trial continue to grow more complex, expect larger Phase 1 cohorts to hedge against costlier Phase 2 failures. Somewhat less shockingly, once clinical trials clear Phase 2, they’re practically guaranteed to avoid suspension or termination regardless of their institutional support.
By sponsoring agency, failed oncology trials seem to be the most troublesome for smaller groups like hospitals, represented as “other” in the pie chart above. There are likely systemic factors at play which contribute to this phenomenon—smaller organizations are less likely to have the resources to bring to bear to overcome regulatory objections after adverse events in Phase 1 or 2. Often a single adverse event is enough to cause a trial suspension and subsequent termination.
Unfortunately, these suspensions and terminations often leave a body of research data behind which never reaches the public eye.
Especially for industry-sponsored trials, interventional trials which are suspended or terminated keep the technical details of their failures secret, though this is slowly changing. It goes without saying that full and unimpeded sharing of this data could probably save other trials from subsequent suspensions and terminations as a result of poor study design or adverse events if it were shared.