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J Clin Epidemiol. 2008 Jan;61(1):64-75. Epub 2007 Aug 23.

Trial sequential analysis may establish when firm evidence is reached in cumulative meta-analysis.

Author information

1
Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen, Denmark. wetterslev@ctu.rh.dk

Abstract

BACKGROUND AND OBJECTIVE:

Cumulative meta-analyses are prone to produce spurious P<0.05 because of repeated testing of significance as trial data accumulate. Information size in a meta-analysis should at least equal the sample size of an adequately powered trial. Trial sequential analysis (TSA) corresponds to group sequential analysis of a single trial and may be applied to meta-analysis to evaluate the evidence.

STUDY DESIGN AND SETTING:

Six randomly selected neonatal meta-analyses with at least five trials reporting a binary outcome were examined. Low-bias heterogeneity-adjusted information size and information size determined from an assumed intervention effect of 15% were calculated. These were used for constructing trial sequential monitoring boundaries. We assessed the cumulative z-curves' crossing of P=0.05 and the boundaries.

RESULTS:

Five meta-analyses showed early potentially spurious P<0.05 values. In three significant meta-analyses the cumulative z-curves crossed both boundaries, establishing firm evidence of an intervention effect. In two nonsignificant meta-analyses the cumulative z-curves crossed P=0.05, but never the boundaries, demonstrating early potentially spurious P<0.05 values. In one nonsignificant meta-analysis the cumulative z-curves never crossed P=0.05 or the boundaries.

CONCLUSION:

TSAs may establish when firm evidence is reached in meta-analysis.

PMID:
18083463
DOI:
10.1016/j.jclinepi.2007.03.013
[Indexed for MEDLINE]
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