title: Accounting for Heterogeneity in Relative Treatment Effects for Use in Cost-Effectiveness Models and Value-of-Information Analyses.
abstract: Cost-effectiveness analysis (CEA) models are routinely used to inform health care policy. Key model inputs include relative effectiveness of competing treatments, typically informed by meta-analysis. Heterogeneity is ubiquitous in meta-analysis, and random effects models are usually used when there is variability in effects across studies. In the absence of observed treatment effect modifiers, various summaries from the random effects distribution (random effects mean, predictive distribution, random effects distribution, or study-specific estimate [shrunken or independent of other studies]) can be used depending on the relationship between the setting for the decision (population characteristics, treatment definitions, and other contextual factors) and the included studies. If covariates have been measured that could potentially explain the heterogeneity, then these can be included in a meta-regression model. We describe how covariates can be included in a network meta-analysis model and how the output from such an analysis can be used in a CEA model. We outline a model selection procedure to help choose between competing models and stress the importance of clinical input. We illustrate the approach with a health technology assessment of intravenous immunoglobulin for the management of adult patients with severe sepsis in an intensive care setting, which exemplifies how risk of bias information can be incorporated into CEA models. We show that the results of the CEA and value-of-information analyses are sensitive to the model and highlight the importance of sensitivity analyses when conducting CEA in the presence of heterogeneity. The methods presented extend naturally to heterogeneity in other model inputs, such as baseline risk.
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK (NJW, AEA)
authors.forename: Nicky J
authors.initials: NJ
authors.lastname: Welton
authors.affiliation: Centre for Health Economics, University of York, York, UK (MOS, SP)
authors.forename: Marta O
authors.initials: MO
authors.lastname: Soares
authors.affiliation: Centre for Health Economics, University of York, York, UK (MOS, SP)
authors.forename: Stephen
authors.initials: S
authors.lastname: Palmer
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK (NJW, AEA)
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Ades
authors.affiliation: Intensive Care National Audit & Research Centre, London, UK (DH, KMR)
authors.forename: David
authors.initials: D
authors.lastname: Harrison
authors.affiliation: Guy's and St Thomas' Hospital NHS Foundation Trust, London, UK (MS-H)
authors.forename: Manu
authors.initials: M
authors.lastname: Shankar-Hari
authors.affiliation: Intensive Care National Audit & Research Centre, London, UK (DH, KMR)
authors.forename: Kathy M
authors.initials: KM
authors.lastname: Rowan
mesh_terms: D001499:Bayes Theorem; D015982:Bias; D003362:Cost-Benefit Analysis / Q000379:methods*; D003661:Decision Support Techniques; D006801:Humans; D015201:Meta-Analysis as Topic; D012044:Regression Analysis; D018805:Sepsis / Q000188:drug therapy
keywords: Bayesian meta-analysis; cost-effectiveness analysis; value of information