Combining Broad and Narrow Case Definitions in Matched Case-Control Studies: Firearms in the Home and Suicide Risk

Does having firearms in the home increase suicide risk? To test this hypothesis, a matched case-control study can be performed, in which suicide case subjects are compared to living controls who are similar in observed covariates in terms of their retrospective exposure to firearms at home. In this application, cases can be defined using a broad case definition (suicide) or a narrow case definition (suicide occurred at home). The broad case definition offers a larger number of cases, but the narrow case definition may offer a larger effect size, which can reduce sensitivity to bias from unmeasured confounding. However, when the goal is to test whether there is a treatment effect based on the broad case definition, restricting to the narrow case definition may introduce selection bias (i.e., bias due to selecting samples based on characteristics affected by the treatment) because exposure to firearms in the home may affect the location of suicide and thus the type of a case a subject is. We propose a new sensitivity analysis framework for combining broad and narrow case definitions in matched case-control studies, that considers the unmeasured confounding bias and selection bias simultaneously. We develop a valid randomization-based testing procedure using only the narrow case matched sets when the effect of the unmeasured confounder on receiving treatment and the effect of the treatment on case definition among the always-cases are controlled by sensitivity parameters. We then use the Bonferroni method to combine the testing procedures using the broad and narrow case definitions. With the proposed methods, we find robust evidence that having firearms at home increases suicide risk. Supplementary materials for this article are available online, including a standardized description of the materials available for reproducing the work.