Comparisons between ITT and treatment emergent adverse event analyses

Area of Science:

• Pharmacovigilance and Clinical Trial Analysis
• Biostatistics in Pharmaceutical Research

Background:

• Pharmaceutical companies frequently employ treatment emergent (TE) analysis for adverse event (AE) safety assessments.
• TE analysis excludes data from post-treatment periods, potentially limiting safety signal detection.
• This contrasts with the intention-to-treat (ITT) analysis typically used for efficacy.

Purpose of the Study:

• To quantitatively compare the unbiasedness and statistical power of ITT versus TE AE analyses.
• To evaluate how different settings and metrics (e.g., difference in rates, relative risk) affect AE analysis outcomes.
• To provide guidance on selecting the appropriate AE analysis method based on trial objectives.

Main Methods:

• Performed quantitative analyses comparing ITT and TE AE analysis approaches.
• Evaluated unbiasedness and power under various simulated clinical trial settings.
• Utilized metrics such as difference in rates and relative risk for comparison.
• Illustrated findings with a practical data example.

Main Results:

• Unbiasedness and statistical power do not consistently align between ITT and TE AE analyses.
• The effectiveness of each method varies depending on the specific analysis parameters and clinical context.
• Dilution of safety signals can occur in TE analysis if residual treatment effects diminish rapidly post-discontinuation.

Conclusions:

• The selection between ITT and TE AE analysis should be tailored to the primary focus of the clinical trial.
• Neither ITT nor TE analysis is universally superior; the choice impacts both unbiasedness and power.
• Careful consideration of the analysis objective is crucial for robust AE safety evaluation.