Accrual When Starting a Platform Trial vs. in a Stand-Alone Trial
When evaluating the efficacy of a candidate investigational therapy, a standard clinical trial paradigm is to conduct a two-arm randomized trial, typically evaluating that therapy against a control arm. And if multiple therapies are being evaluated against the same disease, there may be multiple parallel two-arm trials. However, this creates redundancies, wasting time and resources.
Master protocols – that is, clinical trial designs that can evaluate multiple therapies and disease populations within a single overarching protocol – are an efficient and adaptive means of reducing such redundancies. One such design are umbrella trials. This type of clinical trial design collapses the previously mentioned multiple parallel two-arm trials into a single multi-arm trial, which includes a common control arm, thus eliminating the need for multiple controls (as each therapy can all be trialed against the same one), and likewise reduces the total sample size required. A platform trial can be thought of as an extension of an umbrella trial: the multi-arm trial is extended into a continual clinical trial process where new arms can be added over time, and other arms dropped after sufficient data is gathered.
Now, it is well established that these platform trials can more efficiently evaluate a set of candidate therapies when compared to a series of independent two-arm trials. However, sponsors may encounter certain practical barriers to initiating such trials: namely, a seemingly longer accrual duration for the first therapy when initiating a platform trial strategy.
In a recently published article in Contemporary Clinical Trials, Kyle Wathen, VP of Scientific Strategy & Innovation, and his co-authors explain that “The platform approach is more complex and will take longer to design and operationalize than a traditional trial supported by standard procedures. From the perspective of the first therapy that may need to bear this additional planning time, the platform trial approach has the risk of lengthening total development time. Additionally, a common concern is that the platform approach would lengthen enrollment times based on the intuition that a two-arm trial should complete accrual more quickly than any multi-armed trial, particularly because the platform trial must additionally share the available patients across the multiple therapies.”
The authors, however, challenge this assumption, taking a closer look at this obstacle by simulating accrual into both a platform trial and a stand-alone trial within a large clinical trial network, under various scenarios. They find that, while it may seem like a platform strategy would result in slower accrual, this is not necessarily the case.
To learn more about the simulations conducted by Dr. Wathen and colleagues, as well as their conclusions, read the full essay, “Who Wants to Go First? A Simulation Study of Accrual in a Stand-Alone Trial versus Starting a Platform Trial,” here: