To the Editor
We congratulate the members of the International Liaison Committee on Resuscitation (ILCOR) Advanced Life Support (ALS) Task Force on their timely synthesis of the effectiveness of induced hypothermia (IH) or targeted temperature management (TTM) in patients resuscitated from cardiac arrest (CA).
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The authors report clinical heterogeneity among patient populations enrolled and interventions applied. But they also report significant or near significant statistical heterogeneity among the study results (Figure 2). The authors refer further to clinical but not statistical heterogeneity in their discussion, and so we respectfully take this opportunity to highlight this concept and its implications for the study.Statistical heterogeneity in a systematic review can be a consequence of clinical or methodological diversity, or both, among the included studies. It implies that the observed intervention effects are more different from each other than one would expect due to random error (i.e., chance) alone. Importantly, tests for statistical heterogeneity have low power if the number of included trials is small. Thus, a P value of 0.10, rather than the usual level of 0.05, is sometimes used to determine statistical significance. Moreover, the quantitative estimate of inconsistency (I2) reported in this systematic review of the effect of TTM is large enough to represent an important degree of heterogeneity.
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, 3.
The Cochrane Collaboration Handbook on Systematic Reviews states
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:Deeks JJ, Higgins JPT, Altman DG, on behalf of the Cochrane Statistical Methods Group. Analysing data and undertaking meta-analyses. 2021 [cited Oct 23, 2021]. In: Cochrane Handbook for Systematic Reviews of Interventions [Internet]. https://training.cochrane.org/handbook/current: Cochrane Collaboration. 6.2. [cited Oct 23, 2021].
“Meta-analysis should only be considered when a group of studies is sufficiently homogeneous in terms of participants, interventions and outcomes to provide a meaningful summary.”
Following from this, and observing the signatures of significant or near-significant heterogeneity that were reported, one cannot help but wonder whether a reliable pooled estimate of effect is available from this meta-analysis of TTM. In the absence of a convincingly robust pooled estimate of the effect of TTM on patients with cardiac arrest, we would encourage clinicians to be cautious about concluding whether TTM does or does not improve outcomes in patients resuscitated from cardiac arrest.
Conflict of interest
Salcido has received funding from the ZOLL Foundation for unrelated work. Fujise has no conflicts to disclose. Nichol is a consultant to ZOLL Circulation for unrelated work, and is senior mentor for funding from the ZOLL Foundation for unrelated work.
References
- International Liaison Committee on Resuscitation Advanced Life Support Task F. Targeted temperature management in adult cardiac arrest: Systematic review and meta-analysis.Resuscitation. 2021; 167: 160-172
- Statistical heterogeneity in systematic reviews of clinical trials: a critical appraisal of guidelines and practice.J Health Serv Res Policy. 2002; 7: 51-61
- Measuring inconsistency in meta-analyses.BMJ. 2003; 327: 557-560
Deeks JJ, Higgins JPT, Altman DG, on behalf of the Cochrane Statistical Methods Group. Analysing data and undertaking meta-analyses. 2021 [cited Oct 23, 2021]. In: Cochrane Handbook for Systematic Reviews of Interventions [Internet]. https://training.cochrane.org/handbook/current: Cochrane Collaboration. 6.2. [cited Oct 23, 2021].
Article info
Publication history
Published online: November 22, 2021
Accepted:
November 16,
2021
Received:
November 12,
2021
Identification
Copyright
© 2021 Elsevier B.V. All rights reserved.
