Incorporating estimands into clinical trial statistical analysis plans

Area of Science:

• Biostatistics
• Clinical Trial Methodology
• Pharmaceutical Research

Background:

• The International Council for Harmonisation (ICH) E9 guideline provides principles for statistical methodology in clinical trials.
• Addendum E9 (R1) enhanced ICH E9 by focusing on estimands and sensitivity analyses.
• Current clinical trial protocols show variability in estimand presentation, despite E9 (R1) guidance.

Purpose of the Study:

• To develop a standardized template for presenting estimands and their associated analyses within statistical analysis plans (SAPs).
• To ensure alignment between clinical trial objectives, design, conduct, and analysis as per ICH E9 (R1) recommendations.
• To provide a consistent structure for estimand presentation applicable to diverse trial designs.

Main Methods:

• A table format was developed to create a template for SAPs, aligning statistical analysis with the estimand.
• The template structures estimand attributes (treatment, population, variable, intercurrent events, summary) and their corresponding analysis handling.
• The template was applied to a hypothetical pediatric HIV-1 trial and a placebo-controlled randomized trial.

Main Results:

• The developed template effectively links estimands to planned statistical analyses.
• Application to hypothetical trials demonstrated the template's utility in outlining objectives, populations, intercurrent events, and analysis plans.
• The template facilitates stakeholder discussions and provides a clear overview of key trial elements.

Conclusions:

• The proposed estimand-to-analysis table template offers a consistent and structured approach for SAPs.
• Standardized presentation enhances clarity, facilitates reviews, and ensures alignment across trial components.
• The template is a valuable tool for study design and improving the quality of clinical trial reporting.