Trial Sequential Analysis for dichotomous outcomes - a practical guide for systematic review protocols.

Area of Science:

• Statistical methodology
• Evidence-based medicine
• Clinical trial analysis

Background:

• Trial Sequential Analysis (TSA) is crucial for controlling random errors in meta-analyses of randomized clinical trials.
• The Major Mistakes and Errors in Trial Sequential Analysis (METSA) project identified significant preplanning and reporting flaws in most TSAs.
• This article offers a practical guide for systematic review protocols on planning TSA for dichotomous outcomes.

Purpose of the Study:

• To provide a practical guide for authors of systematic review protocols on planning Trial Sequential Analysis (TSA).
• To address common mistakes and errors identified in the preplanning and reporting of TSAs.
• To improve the interpretation, reproducibility, and validity of TSA results in systematic reviews.

Main Methods:

• The guide is based on the TSA manual and previous recommendations.
• It incorporates findings from the METSA project, which assessed TSA use across medical fields.
• Focuses on practical considerations for planning TSA for dichotomous outcomes.

Main Results:

• Five essential parameters must be defined in protocols before undertaking TSA.
• These parameters include control group event proportion, relative risk change, type I error (alpha), type II error (beta), and meta-analysis diversity.
• Clear definition of these parameters enhances TSA interpretation, reproducibility, and validity.

Conclusions:

• This guide aims to improve the pre-registration and reporting of TSAs for dichotomous outcomes.
• It will aid authors in creating more robust systematic review protocols.
• Ultimately, it seeks to enhance the quality of meta-analyses in randomized clinical trials.