Confounding by indication refers to a determinant of the outcome parameter that is present in people at perceived high risk or poor prognosis and is an indication for intervention. This means that differences in care, for example, between cases and controls may partly originate from differences in indication for medical intervention such as the presence of risk factors for particular health problems. The latter has frequently been reported in studies evaluating the efficacy of pharmaceutical interventions. A good example can be found in Confounding and indication for treatment in evaluation of drug treatment for hypertension (BMJ 1997;315:1151-4).
The article Confounding by indication: the case of the calcium channel blockers (Pharmacoepidemiol Drug Saf 2000;9:37-41) demonstrates that studies with potential confounding by indication can benefit from appropriate analytic methods, including separating the effects of a drug taken at different times, sensitivity analysis for unmeasured confounders, instrumental variables and G-estimation.
With the more recent application of pharmacoepidemiological methods to assess effectiveness, confounding by indication is a greater challenge and the article Approaches to combat with confounding by indication in observational studies of intended drug effects (Pharmacoepidemiol Drug Saf 2003;12:551-8) focusses on its possible reduction in studies of intended effects. An extensive review of these and other methodological approaches discussing their strengths and limitations is discussed in Methods to assess intended effects of drug treatment in observational studies are reviewed (J Clin Epidemiol 2004;57:1223-31).
|Annex 1.||Guidance on conducting systematic revies and meta-analyses of completed comparative pharmacoepidemiological studies of safety outcomes|