Simultaneous Multioutcome Synthesis and Mapping of Treatment Effects to a Common Scale

Guobing Lu · Daphne Kounali · Anthony E. Ades

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Meta-analysis and systematic reviews Health Systems, Economic Evaluations, Quality of Life Delphi Technique in Research

Abstract

OBJECTIVES: A new method is presented for both synthesizing treatment effects on multiple outcomes subject to measurement error and estimating coherent mapping coefficients between all outcomes. It can be applied to sets of trials reporting different combinations of patient- or clinician-reported outcomes, including both disease-specific measures and generic health-related quality-of-life measures. It is underpinned by a structural equation model that includes measurement error and latent common treatment effect factor. Treatment effects can be expressed on any of the test instruments that have been used. METHODS: This is illustrated in a synthesis of eight placebo-controlled trials of TNF-α inhibitors in ankylosing spondylitis, each reporting treatment effects on between two and five of a total six test instruments. RESULTS: The method has advantages over other methods for synthesis of multiple outcome data, including standardization and multivariate normal synthesis. Unlike standardization, it allows synthesis of treatment effect information from test instruments sensitive to different underlying constructs. It represents a special case of previously proposed multivariate normal models for evidence synthesis, but unlike the former, it also estimates mappings. Combining synthesis and mapping as a single operation makes more efficient use of available data than do current mapping methods and generates treatment effects that are consistent with the mappings. A limitation, however, is that it can only generate mappings to and from those instruments on which some trial data exist. CONCLUSIONS: The method should be assessed in a wide range of data sets on different clinical conditions, before it can be used routinely in health technology assessment.

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