Joint synthesis of conditionally related multiple outcomes makes better use of data than separate meta‐analyses

S Anwer, AE Ades, S Dias - Research Synthesis Methods, 2020 - Wiley Online Library
S Anwer, AE Ades, S Dias
Research Synthesis Methods, 2020Wiley Online Library
Background When there are structural relationships between outcomes reported in different
trials, separate analyses of each outcome do not provide a single coherent analysis, which
is required for decision‐making. For example, trials of intrapartum anti‐bacterial prophylaxis
(IAP) to prevent early onset group B streptococcal (EOGBS) disease can report three
treatment effects: the effect on bacterial colonisation of the newborn, the effect on EOGBS,
and the effect on EOGBS conditional on newborn colonisation. These outcomes are …
Background
When there are structural relationships between outcomes reported in different trials, separate analyses of each outcome do not provide a single coherent analysis, which is required for decision‐making. For example, trials of intrapartum anti‐bacterial prophylaxis (IAP) to prevent early onset group B streptococcal (EOGBS) disease can report three treatment effects: the effect on bacterial colonisation of the newborn, the effect on EOGBS, and the effect on EOGBS conditional on newborn colonisation. These outcomes are conditionally related, or nested, in a multi‐state model.
This paper shows how to exploit these structural relationships, providing a single coherent synthesis of all the available data, while checking to ensure that different sources of evidence are consistent.
Results
Overall, the use of IAP reduces the risk of EOGBS (RR: 0.03; 95% Credible Interval (CrI): 0.002–0.13). Most of the treatment effect is due to the prevention of colonisation in newborns of colonised mothers (RR: 0.08, 95% CrI: 0.04–0.14). Node‐splitting demonstrated that the treatment effect calculated using only direct evidence was consistent with that predicted from the remaining evidence (p = 0.15). The findings accorded with previously published separate meta‐analyses of the different outcomes, once these are re‐analysed correctly accounting for zero cells.
Conclusion
Multiple outcomes should be synthesised together where possible, taking account of their structural relationships. This generates an internally coherent analysis, suitable for decision making, in which estimates of each of the treatment effects are based on all available evidence (direct and indirect). Separate meta‐analyses of each outcome have none of these properties.
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