Adaptive Design Strategies in Rare Oncology

Traditional trial design use only a priori inputs to obtain final trial results. From first patient in to last patient out, trial execution proceeds without change, following a black box approach. While a standard for clinical research, this strategy doesn’t always suit rare oncology research, which must contend with very small patient populations that are often difficult to treat.

In contrast, adaptive trial design allows for the assessment of accumulating data from the trial during its execution — inside the box. This can lead to a lower trial failure rate and better outcomes for study participants.

What Is Adaptive Design?

The FDA defines adaptive design as “a study that includes a prospectively planned opportunity for modification of one or more specified aspects of the study design and hypotheses based on analysis of data (usually interim data) from subjects in the study.” This includes the potential for trial modification after a study is underway but before unmasking/unblinding. This strategy allows for greater flexibility, letting study designers “hone in” on approaches that may not be working and correct them.

Ideally, interim data comes from an aggregate maintaining blind to treatment group. Adaptive design does not include retrospective, ad hoc changes after outcomes are known or attempts to salvage failed trials. Plans are always outlined in detail prospectively in the protocol or statistical analysis plan and submitted to regulatory agencies for review and approval.

Adaptive design in rare cancer research can be seen as an effort to make each and every participant count, maximizing the amount of useful data that can be collected.

Common Adaptations

Adaptations in rare oncology studies can include:

  • Alterations to eligibility criteria
  • Sample size adjustments
  • Dropping, adding or changing treatment arms for maximum efficiency
  • Changes to statistical analysis plan or hypotheses
  • Endpoint changes
  • Study duration

It’s important to remember that the decision makers (study staff and steering committee) remain blinded to ensure the scientific integrity of these studies. However, protocols may designate an unblinded independent group for interim review.

The Advantages

The specific advantages of adaptive design for rare oncology research include:

  • Improved study power
  • Reduced necessary sample size and overall costs
  • Greater patient protection, with more patients receiving effective treatments
  • The correct identification of efficacious drugs for patient subgroups based on biomarker profiles
  • Shorter time to market for new treatments

The Drawbacks

While a great tool for rare oncology researchers, adaptive design is not without its drawbacks. The greater amount of complexity involved may exacerbate logistical difficulties. These studies also have an unknown duration, with some trials possibly going longer than expected.

Whether or not adaptive design principles are right for a particular study is a complex, multifaceted decision that isn’t easy to make. For a more in-depth look at the process, as well as other strategies for expediting rare cancer research, check out our recent webinar.