Adaptive Clinical Trial Design – Part II

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What is Adaptive design clinical trial:

  • An adaptive design is defined as a design that allows modifications to the trial and/or statistical procedures of the trial after its initiation without undermining its validity and integrity.
  • The purpose is to make clinical trials more flexible, efficient and fast. Due to the level of flexibility involved, these trial designs are also termed as “flexible designs.”

Types:

Adaptive Design Options 2

  • Prospective Adaptation
    • Adaptive randomization design
    • Group Sequential Design
    • A sample size re-estimation design
    • A drop-the-loser design
    • An adaptive dose finding design
    • A biomarker-adaptive design
    • An adaptive treatment-switching design
  • Concurrent (ad-hoc) Adaptation
    • Trial procedures
  • Retrospective Adaptations
    • Statistical Analysis procedures..

Implementation of Adaptive Design in Clinical Trials:

An adaptive design method in clinical trials is very attractive due to its flexibility and efficiency for identifying best clinical benefits of the treatment under investigation. The flexibility, however, may introduce possible operational biases and consequently have an impact on the overall type I error rate. Some practical issues that are commonly encountered when implementing adaptive design methods in clinical trials are necessarily considered to ensure the validity and integrity of the clinical trials.

These practical issues are key to the success of the clinical trials utilizing adaptive design methods.

Challenges and Prospectus:

Adaptive Pros and Cons 2

  • Difficult to control the type 1 error in adaptive trials.
  • Ad hoc changes based on unblinded data may jeopardize the credibility of the study.
  • Possibility of damaging the integrity of a trial due to frequent interim analyses.
  • Rewards of adaptive designed clinical trials are many. These not only have a positive-predictive value, in the sense that efficacy of a drug is established earlier by using seamless designs, but also have a negative-predictive value, in the sense that ineffective treatments can be eliminated at an earlier stage. Regulatory agencies have also taken positive positions on adaptive trials. But, at this stage, caution is advised as drastic changes are often considered as lack of planning and can be met with criticism, especially when performed in late Phase II or Phase III trials for efficacy.
  • Although, presently, there might be some problems in the execution of adaptive designs, with the release of draft guidance for industry on adaptive design clinical trials, more and more companies are bound to use adaptive designed clinical trials thus making the drug development process shorter and cheaper.
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