Overview
Experts discuss platform trials, highlighting their unique features, how clinicians should interpret results, and lessons from their use in the COVID-19 pandemic. Key aspects include trial design, ethical considerations, statistical efficiency, and challenges for future application.
Introduction to Platform Trials
- Platform trials allow multiple interventions to be evaluated simultaneously with flexibility to add new interventions over time.
- Unlike conventional trials, platform trials can be perpetual and adapt to emerging therapies.
- The term "master protocol" refers to the standardized documents guiding trial conduct; the platform trial is the study itself.
Need for Clinician Guidance
- Platform trials became prominent during COVID-19, making interpretation skills essential for clinicians.
- Traditional trial interpretation may not apply directly due to evolving interventions and designs.
Key Features and Advantages
- Enable quick evaluation of multiple therapies, crucial during urgent situations like pandemics.
- Infrastructure built for one condition (e.g., COVID-19) can later be adapted to other diseases.
- Common control groups and adaptive designs create statistical and operational efficiencies.
Ethical and Regulatory Considerations
- New interventions are submitted as amendments to IRBs based on the master protocol, expediting review.
- Adaptive randomization can favor better-performing arms, potentially increasing patient trust.
Statistical and Methodological Aspects
- Response adaptive randomization modifies assignment ratios based on emerging trial data, improving overall probability of detecting effective treatments in multi-arm settings.
- Greater efficiency is achieved in platform trials through common controls and adaptive stopping rules.
Bias and Rigorous Interpretation
- Clinicians should check for pre-specified interim/statistical plans and consistent application across interventions.
- Concurrent control groups minimize temporal bias; non-concurrent controls raise risks of confounding due to changes in patient characteristics or standard care.
- Investigators must guard against bias from information flow within and outside the trial.
- Adherence to existing and updated reporting guidelines improves transparency.
Managing Changing Standards of Care
- Platform trials must adapt control therapies as standards evolve, especially during rapidly changing situations like COVID-19.
- Statistical plans must consider temporal effects to maintain trial validity.
Future Challenges
- Setting up platform trials requires significant resources, expertise in adaptive and Bayesian methods, and sustained funding.
- More suitable for public sector or fields with limited drug development; industry use presents challenges regarding objectivity.
Recommendations / Advice
- Clinicians and researchers need to understand platform trial design, bias risks, and reporting standards.
- Ongoing adaptation and transparency are essential as platform trials expand beyond COVID-19.
Questions / Follow-Ups
- How best to statistically adjust for evolving standards of care in perpetual platform trials remains an open question.