Baseline selection on a collider: a ubiquitous mechanism occurring in both representative and selected cohort studies

Abstract

There is debate as to whether cohort studies are valid when they are based on a source population that is non-representative of a given general population. This baseline selection may introduce collider bias if the exposure of interest and some other outcome risk factors affect the probability of being in the source population, thus altering the associations between the exposure and those risk factors. We argue that this mechanism is not specific to ‘selected cohorts’ and also occurs in ‘representative cohorts’ due to the selection processes that occur in any population. These selection processes are for example linked to the life status, immigration and emigration, which, in turn, may be affected by environmental and social determinants, lifestyles and genetics. We provide real-world examples of this phenomenon using data on the population of the Piedmont region, Italy. In addition to well-recognised mechanisms, such as shared common causes, the associations between the exposure of interest and the risk factors for the outcome of interest in any source population are potentially shaped by collider bias due to the underlying selection processes. We conclude that, when conducting a cohort study, different source populations, whether ‘selected’ or ‘representative’, may lead to different exposure–outcome risk factor associations, and thus different degrees of lack of exchangeability, but that one approach is not inherently more or less biased than the other. The key issue is whether the relevant risk factors can be identified and controlled.

A novel framework for classification of selection processes in epidemiological research

“…In order to develop the framework, several highly cited original articles from the epidemiological literature as well as from related areas of observational research (economics, sociology and statistics) were reviewed in search of examples of selection processes, used terminology and description of the underlying mechanisms [2,3,8,9,[14][15][16][17][18][19][20][21][22]. The reference lists of these articles, more recent publications and helpful reviewers led to identification of additional examples [1,6,10,11,[23][24][25].…”

“…However, there are also selection processes that result in non-random groupings or changes in the composition of the underlying populations. These are continuously on-going at the population level irrespectively of whether they are subject to sampling in empirical studies [6].…”

“…It represents phenomena that may lead to confounding, i.e. confusion of effects or lack of exchangeability between exposed and unexposed with respect to background risks for the disease outcome [6,7]. The confounding resulting from population selection processes is sometimes apparent, such as differences in health determinants across groups in age, sex or socioeconomic characteristics, and therefore possible to adjust for in statistical analysis.…”

“…Timing of the selection -at exposure entry, during exposure or post-outcome Figure 2A-D all represent selection mechanisms occurring at exposure entry, prior to any exposure or treatment effect in the downstream population. At the study-level, selection occurring at exposure entry corresponds to non-random sample selection at study entry in surveys and baseline selection before follow up starts in cohort studies [6,29]. Selection may also act during exposure and affect continuation and termination of exposure or follow up ( Figure 3A-D), or act post-outcome [2].…”

“…during design, enrolment, follow up or analysis [3][4][5]. The focus on study-related issues when discussing selection bias implies that selection processes occurring at the population level, for example linked to migration, disease occurrence and mortality [6], are often overlooked among applied researchers. As an example of this narrow focus, it is sometimes claimed that selection bias is not an issue in cohort studies involving complete recruitment and follow-up [7].…”