Do low control response rates always affect the findings? Assessments of smoking and obesity in two Australian case-control studies of cancer

Objective: Participation rates have been declining in case-control studies, particularly among controls, raising concerns about possible bias. Formal assessments of the effect of low participation on odds ratios (OR) are seldom presented however. We sought to quantify possible bias using multiple imputation techniques. Methods: Using data from two Australian case-control studies, we estimated the relative risks of oesophageal squamous cell carcinoma (OSCC) and adenocarcinoma (OAC), and serous ovarian cancer (SOC) associated with smoking and body mass index (BMI). We compared ORs observed using self-reported data from participating controls with ORs derived using imputed exposures for non-participating controls. Results: Participating controls were less likely than non-participants to smoke currently. Smoking remained significantly associated with oesophageal cancer even under the most extreme assumption of smoking prevalence among non-participants (OSCC: observed OR 6.54, 4.62-9.28, imputed OR 3.94, 2.83-5.49; OAC: observed OR 2.69, 1.87-3.85 imputed OR 1.58, 1.13-2.22). For SOC however, risks associated with smoking were attenuated to null under plausible smoking assumptions among non-participants. BMI distributions were similar among participating and non-participating controls, and risk estimates were essentially unchanged. Conclusion and implications: Bias is not an inevitable consequence of low control participation and depends on the association examined. Sensitivity analyses can assist in interpretation of results.