Missing data in meta-analysis: a practical guide

Article type
Authors
Carpenter J
Abstract
Objectives:

- To introduce participants to the key issues raised by missing data in clinical trials;

- To outline a systematic approach for thinking about these issues;

- To provide guidance on reviewing trial reports where the trial has a non-trivial proportion of missing data;

- To review methods for including studies with missing data in meta-analyses;

- To work through examples illustrating these issues in small groups.

Summary: Missing data are ubiquitous in clinical trials. They introduce a level of ambiguity into the analysis and conclusions beyond conventional sampling imprecision. This is because additional assumptions, for example about the reason for the missing observations, must be made to justify the analysis and hence the conclusions. For a broad introduction, see www.missingdata.org.uk. Building on the approach described by Carpenter et al1, we argue that a principled approach to the analysis of partially observed data sets is preferable to an ad hoc approach, and describe how such an approach might work in practice. We show how this approach can inform meta-analysis when some contributing trials have non-trivial proportions of missing data. When faced with such a trial, we propose the initial focus should be on understanding whether the methods used for the analysis are appropriate for the intention-to-treat hypothesis. If not, we consider the likely effects on the presented results. Then we consider how to include such trials in a meta-analysis. We discuss established and recently proposed methods for doing this2. Small group practical work will be an integral part of the workshop and focus on critically reviewing reports of trials with non-trivial missing data issues, with a view to deciding how to allow for this in a subsequent meta-analysis. The workshop will focus on concepts, keeping technical details in the background.

References
1. Carpenter JR, Kenward MG. Missing data in clinical trials - a practical guide. Birmingham, UK: National Health Service Co-ordinating Centre for Research Methodology (forthcoming).
2. Gamble C, Hollis S. Uncertainty method improved on best-worst case analysis in a binary meta-analysis. Journal of Clinical Epidemiology 2005; 58(6):579-88.

Level of knowledge required to attend: advanced