Subgroup analyses involve splitting all the participant data into subgroups, often so as to make comparisons between them. Subgroup analyses may be done for subsets of participants (such as males and females), or for subsets of studies (such as different geographical locations). Subgroup analyses may be done as a means of investigating heterogeneous results, or to answer specific questions about particular patient groups, types of intervention or types of study.
Subgroup analyses of subsets of participants within studies are uncommon in systematic reviews of the literature because sufficient details to extract data about separate participant types are seldom published in reports. By contrast, such subsets of participants are easily analysed when individual patient data have been collected (see Chapter 18). The methods we describe in Section 9.6.3 are for subgroups of trials.
Findings from multiple subgroup analyses may be misleading. Subgroup analyses are observational by nature and are not based on randomized comparisons. False negative and false positive significance tests increase in likelihood rapidly as more subgroup analyses are performed. If their findings are presented as definitive conclusions there is clearly a risk of patients being denied an effective intervention or treated with an ineffective (or even harmful) intervention. Subgroup analyses can also generate misleading recommendations about directions for future research that, if followed, would waste scarce resources.
It is useful to distinguish between the notions of ‘qualitative interaction’ and ‘quantitative interaction’ (Yusuf 1991). Qualitative interaction exists if the direction of effect is reversed, that is if an intervention is beneficial in one subgroup but is harmful in another. Qualitative interaction is rare. This may be used as an argument that the most appropriate result of a meta-analysis is the overall effect across all subgroups. Quantitative interaction exists when the size of the effect varies but not the direction, that is if an intervention is beneficial to different degrees in different subgroups.
Authors will find useful advice concerning subgroup analyses in Oxman and Guyatt (Oxman 1992) and Yusuf et al. (Yusuf 1991). See also Section 9.6.6.