Collider and reporting biases involved in the analyses of cause of death associations in death certificates: an illustration with cancer and suicide

Mortality data obtained from death certificates have been studied to explore causal associations between diseases. However, these analyses are subject to collider and reporting biases (selection and information biases, respectively). We aimed to assess to what extent associations of causes of death estimated from individual mortality data can be extrapolated as associations of disease states in the general population. We used a multistate model to generate populations of individuals and simulate their health states up to death from national health statistics and artificially replicate collider bias. Associations between health states can then be estimated from such simulated deaths by logistic regression and the magnitude of collider bias assessed. Reporting bias can be approximated by comparing the estimates obtained from the observed death certificates (subject to collider and reporting biases) with those obtained from the simulated deaths (subject to collider bias only). As an illustrative example, we estimated the association between cancer and suicide in French death certificates and found that cancer was negatively associated with suicide. Collider bias, due to conditioning inclusion in the study population on death, increasingly downwarded the associations with cancer site lethality. Reporting bias was much stronger than collider bias and depended on the cancer site, but not prognosis. The magnitude of the biases ranged from 1.7 to 9.3 for collider bias, and from 4.7 to 64 for reporting bias. These results argue for an assessment of the magnitude of both collider and reporting biases before performing analyses of cause of death associations exclusively from mortality data. If these biases cannot be corrected, results from these analyses should not be extrapolated to the general population.