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Abstract
To evaluate meta-analyses with trial sequential analysis (TSA). TSA adjusts for random
error risk and provides the required number of participants (information size) in
a meta-analysis. Meta-analyses not reaching information size are analyzed with trial
sequential monitoring boundaries analogous to interim monitoring boundaries in a single
trial.
We applied TSA on meta-analyses performed in Cochrane Neonatal reviews. We calculated
information sizes and monitoring boundaries with three different anticipated intervention
effects of 30% relative risk reduction (TSA(30%)), 15% (TSA(15%)), or a risk reduction
suggested by low-bias risk trials of the meta-analysis corrected for heterogeneity
(TSA(LBHIS)).
A total of 174 meta-analyses were eligible; 79 out of 174 (45%) meta-analyses were
statistically significant (P<0.05). In the significant meta-analyses, TSA(30%) showed
firm evidence in 61%. TSA(15%) and TSA(LBHIS) found firm evidence in 33% and 73%,
respectively. The remaining significant meta-analyses had potentially spurious evidence
of effect. In the 95 statistically nonsignificant (P>or=0.05) meta-analyses, TSA(30%)
showed absence of evidence in 80% (insufficient information size). TSA(15%) and TSA(LBHIS)
found that 95% and 91% had absence of evidence. The remaining nonsignificant meta-analyses
had evidence of lack of effect.
TSA reveals insufficient information size and potentially false positive results in
many meta-analyses.