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Review
. 2021 Apr;16(2):138-150.
doi: 10.17085/apm.21038. Epub 2021 Apr 30.

Trial sequential analysis: novel approach for meta-analysis

Hyun Kang  1
Affiliations
Review

Trial sequential analysis: novel approach for meta-analysis

Hyun Kang. Anesth Pain Med (Seoul). 2021 Apr.

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.

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

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Conflict of interest statement

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1.
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.
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.
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.
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.
See this image and copyright information in PMC

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