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Proof of Concept: Drug Selection? Or Dose Selection? Thoughts on Multiplicity Issues
Qian H Li1, Qiqi Deng2, Naitee Ting3
1Global Biometrics and Data Sciences, Bristol Myers Squibb - Global Biopharmaceutical Company, NewYork, USA.
Therapeutic Innovation & Regulatory Science
|May 24, 2021
Summary
Establishing proof of concept (PoC) in early drug development requires careful consideration of multiplicity comparison procedures (MCP). This study clarifies whether to control experiment-wise or compound-wise error rates for robust clinical trial design.
Area of Science:
- Clinical Trials
- Biostatistics
- Drug Development
Background:
- Proof of Concept (PoC) is a critical milestone in early Phase II drug development.
- Clinical trial design for PoC studies involving multiple doses or drugs presents challenges in statistical analysis.
- The application of multiplicity comparison procedures (MCP) is a key consideration.
Purpose of the Study:
- To clarify the fundamental question of which error rate to control (experiment-wise vs. compound-wise) in PoC studies.
- To discuss the concept of different types of error rates and their control levels.
- To reconcile the debate surrounding the application of MCP in PoC studies.
Main Methods:
- Analysis of multiplicity issues in two distinct PoC study cases.
- Discussion of error types and error rate control levels.
- Conceptual examination of multiplicity adjustment procedures.
Main Results:
- Highlights the importance of understanding error types in MCP.
- Provides a framework for choosing appropriate error rate control.
- Offers clarity on applying MCP in PoC trial design.
Conclusions:
- A clear understanding of error types and control levels is essential for MCP application in PoC studies.
- This understanding can resolve debates on statistical procedures in drug development.
- Facilitates more robust and reliable PoC trial designs.
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