Anesth Pain Med.  2021 Apr;16(2):138-150. 10.17085/apm.21038.

Trial sequential analysis: novel approach for meta-analysis

Affiliations
  • 1Department of Anesthesiology and Pain Medicine, Chung-Ang University College of Medicine, Seoul, Korea

Abstract

Systematic reviews and meta-analyses rank the highest in the evidence hierarchy. However, they still have the risk of spurious results because they include too few studies and participants. The use of trial sequential analysis (TSA) has increased recently, providing more information on the precision and uncertainty of meta-analysis results. This makes it a powerful tool for clinicians to assess the conclusiveness of meta-analysis. TSA provides monitoring boundaries or futility boundaries, helping clinicians prevent unnecessary trials. The use and interpretation of TSA should be based on an understanding of the principles and assumptions behind TSA, which may provide more accurate, precise, and unbiased information to clinicians, patients, and policymakers. In this article, the history, background, principles, and assumptions behind TSA are described, which would lead to its better understanding, implementation, and interpretation.

Keyword

Interim analysis; Meta-analysis; Statistics; Trial sequential analysis.

Figure

  • Fig. 1. Trial sequential analysis graph. The graph presents monitoring boundaries, futility boundaries, conventional boundaries and required information size. The graph is divided by monitoring boundary and futility boundary into four zones: area of benefit, area of harm, inner wedge, and not statistically significant zone.

  • Fig. 2. Probabilities according to the number of analyses. Dark line represents probability of overall Type I error and gray line represents probability of accepting null hypothesis.

  • Fig. 3. Trial sequential analysis graph and monitoring boundary. (A) The last point of Z-curve stays within the monitoring boundaries. (B) The last point of Z-curve stays within the monitoring boundaries after new study is added. (C) The last point of Z-curve stays outside of the monitoring boundary.

  • Fig. 4. Trial sequential analysis graph and futility boundary. (A) The last point of Z-curve stays outside futility borders. (B) The last point of Z-curve stays gets within the futility borders after adding the study. (C) The last point of Z-curve stays outside of futility borders.


Cited by  2 articles

Use, application, and interpretation of systematic reviews and meta-analyses
Hyun Kang
Korean J Anesthesiol. 2021;74(5):369-370.    doi: 10.4097/kja.21374.

A message from the Editor-in-Chief and Editorial Board, 2023: journal metrics and statistics, and appreciation to reviewers
Jun Hyun Kim, Hyun Kang
Anesth Pain Med. 2024;19(1):1-4.    doi: 10.17085/apm.24008.


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