Heterogeneity: Subgroups, Meta-Regression, Bias And Bias-Adjustment

The NICE Guide to the Methods of Technology Appraisal i is a regularly updated document that provides an overview of the key principles and methods of health technology assessment and appraisal for use in NICE appraisals. The Methods Guide does not provide detailed advice on how to implement and apply the methods it describes. This DSU series of Technical Support Documents (TSDs) is intended to complement the Methods Guide by providing detailed information on how to implement specific methods. The TSDs provide a review of the current state of the art in each topic area, and make clear recommendations on the implementation of methods and reporting standards where it is appropriate to do so. They aim to provide assistance to all those involved in submitting or critiquing evidence as part of NICE Technology Appraisals, whether manufacturers, assessment groups or any other stakeholder type. We recognise that there are areas of uncertainty, controversy and rapid development. It is our intention that such areas are indicated in the TSDs. All TSDs are extensively peer reviewed prior to publication (the names of peer reviewers appear in the acknowledgements for each document). Nevertheless, the responsibility for each TSD lies with the authors and we welcome any constructive feedback on the content or suggestions for further guides. Please be aware that whilst the DSU is funded by NICE, these documents do not constitute formal NICE guidance or policy. Excellence (NICE) through its Decision Support Unit. The views, and any errors or omissions, expressed in this document are of the authors only. NICE may take account of part or all of this document if it considers it appropriate, but it is not bound to do so. This Technical Support Document focuses on heterogeneity in relative treatment effects. Heterogeneity indicates the presence of effect-modifiers. A distinction is usually made between true variability in treatment effects due to variation between patient populations or settings, and biases related to the way in which trials were conducted. Variability in relative treatment effects threatens the external validity of trial evidence, and limits the ability to generalise from the results, imperfections in trial conduct represent threats to internal validity. In either case it is emphasised that, although we continue to focus attention on evidence from trials, the study of effect-modifying covariates is in every way a form of observational study, because patients cannot be randomised to covariate values. This document provides guidance …