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Estimands and Complex Innovative Designs.

Olivier Collignon1, Anja Schiel2, Carl-Fredrik Burman3

  • 1GlaxoSmithKline, Hertfordshire, UK.

Clinical Pharmacology and Therapeutics
|March 7, 2022
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Summary
This summary is machine-generated.

The estimand framework, crucial for clinical trials since 2019, needs clear implementation guidelines for complex innovative designs. This work provides practical approaches for applying estimands in advanced trial designs, enhancing protocol clarity.

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Area of Science:

  • Biostatistics
  • Clinical Trial Design
  • Pharmaceutical Development

Background:

  • The International Council for Harmonisation E9(R1) guideline introduced the estimand framework for clinical trials.
  • Complex innovative trial designs are increasingly used, particularly in early drug development.
  • There is limited experience applying the estimand framework to these complex designs.

Purpose of the Study:

  • To discuss and propose methods for implementing the estimand framework in complex innovative clinical trial designs.
  • To address challenges in defining estimands for adaptive, multi-arm, or population-selecting trials.
  • To clarify statistical issues related to estimation versus estimands in these designs.

Main Methods:

  • Review and discussion of the application of the estimand framework to various complex innovative designs.
  • Consideration of trials with dynamic treatment arms, control arms, and population selection/pooling.
  • Analysis of data-driven, adaptive estimand selection and related statistical concepts.

Main Results:

  • The study outlines potential strategies for defining estimands in basket, platform, and adaptive trials.
  • It distinguishes estimand specification from estimation challenges, such as borrowing information.
  • The discussion aims to facilitate consistent application and clear documentation of estimands in complex trial protocols.

Conclusions:

  • Implementing the estimand framework in complex innovative trial designs requires careful consideration and clear strategies.
  • This work offers guidance to improve the definition and documentation of estimands in advanced clinical trial protocols.
  • Facilitating the use of the estimand framework in complex designs will enhance the rigor and interpretability of trial results.