Blinded-Into-Unblinded Interim Analyses for Clinical Trials With Time-to-Event Endpoints
Stephen Schüürhuis1, Jan Meis2, Björn Bokelmann1
1Institute of Biometry and Clinical Epidemiology, Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Biometrical Journal. Biometrische Zeitschrift
|July 24, 2026
Summary
Clinical trial recruitment challenges are addressed by a new hybrid design. This approach combines blinded and unblinded interim analyses for adaptive sample size adjustments in time-to-event trials.
Area of Science:
- Biostatistics
- Clinical Trial Design
- Pharmaceutical Research
Background:
- Clinical trials frequently fail to meet patient recruitment targets.
- Time-to-event trials face complexities due to random event observation, impacting data availability at fixed times.
- Accurate sample size determination is crucial for clinical trial validity.
Purpose of the Study:
- To propose a flexible, hybrid interim analysis approach for clinical trials.
- To combine the benefits of blinded and unblinded interim analyses.
- To address challenges in adaptive trial design, particularly for time-to-event outcomes.
Main Methods:
- Development of a hybrid group-sequential trial design.
- Conditional on early stopping probabilities, the design utilizes either blinded or unblinded interim analyses.
- Focus on trials with time-to-event as the primary outcome, often characterized by long durations.
Main Results:
- The proposed hybrid approach offers flexibility in adaptive sample size determination.
- It integrates advantages of both blinded and unblinded interim analyses.
- Aims to improve trial efficiency and reliability, especially in long-duration studies.
Conclusions:
- The hybrid design provides a robust strategy for adaptive clinical trials.
- It enhances the ability to adjust sample size based on interim data while managing potential biases.
- This approach is particularly beneficial for time-to-event studies requiring design flexibility.
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