Dataset Information

Sensitivity of treatment recommendations to bias in network meta-analysis.

ABSTRACT: Network meta-analysis (NMA) pools evidence on multiple treatments to estimate relative treatment effects. Included studies are typically assessed for risk of bias; however, this provides no indication of the impact of potential bias on a decision based on the NMA. We propose methods to derive bias adjustment thresholds which measure the smallest changes to the data that result in a change of treatment decision. The methods use efficient matrix operations and can be applied to explore the consequences of bias in individual studies or aggregate treatment contrasts, in both fixed and random-effects NMA models. Complex models with multiple types of data input are handled by using an approximation to the hypothetical aggregate likelihood. The methods are illustrated with a simple NMA of thrombolytic treatments and a more complex example comparing social anxiety interventions. An accompanying R package is provided.

SUBMITTER: Phillippo DM

PROVIDER: S-EPMC6221150 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Sensitivity of treatment recommendations to bias in network meta-analysis.

Phillippo David M DM Dias Sofia S Ades A E AE Didelez Vanessa V Welton Nicky J NJ

Journal of the Royal Statistical Society. Series A, (Statistics in Society) 20171206 3

Network meta-analysis (NMA) pools evidence on multiple treatments to estimate relative treatment effects. Included studies are typically assessed for risk of bias; however, this provides no indication of the impact of potential bias on a decision based on the NMA. We propose methods to derive bias adjustment thresholds which measure the smallest changes to the data that result in a change of treatment decision. The methods use efficient matrix operations and can be applied to explore the consequ ...[more]

PMID: 30449954

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Project description:BackgroundNetwork meta-analysis (NMA), a generalization of conventional MA, allows for assessing the relative effectiveness of multiple interventions. Reporting bias is a major threat to the validity of MA and NMA. Numerous methods are available to assess the robustness of MA results to reporting bias. We aimed to extend such methods to NMA.MethodsWe introduced 2 adjustment models for Bayesian NMA. First, we extended a meta-regression model that allows the effect size to depend on its standard error. Second, we used a selection model that estimates the propensity of trial results being published and in which trials with lower propensity are weighted up in the NMA model. Both models rely on the assumption that biases are exchangeable across the network. We applied the models to 2 networks of placebo-controlled trials of 12 antidepressants, with 74 trials in the US Food and Drug Administration (FDA) database but only 51 with published results. NMA and adjustment models were used to estimate the effects of the 12 drugs relative to placebo, the 66 effect sizes for all possible pair-wise comparisons between drugs, probabilities of being the best drug and ranking of drugs. We compared the results from the 2 adjustment models applied to published data and NMAs of published data and NMAs of FDA data, considered as representing the totality of the data.ResultsBoth adjustment models showed reduced estimated effects for the 12 drugs relative to the placebo as compared with NMA of published data. Pair-wise effect sizes between drugs, probabilities of being the best drug and ranking of drugs were modified. Estimated drug effects relative to the placebo from both adjustment models were corrected (i.e., similar to those from NMA of FDA data) for some drugs but not others, which resulted in differences in pair-wise effect sizes between drugs and ranking.ConclusionsIn this case study, adjustment models showed that NMA of published data was not robust to reporting bias and provided estimates closer to that of NMA of FDA data, although not optimal. The validity of such methods depends on the number of trials in the network and the assumption that conventional MAs in the network share a common mean bias mechanism.

Dataset Information

Sensitivity of treatment recommendations to bias in network meta-analysis.

Publications

Sensitivity of treatment recommendations to bias in network meta-analysis.

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