Uncontrolled confounding in studies of screening effectiveness: an example of colonoscopy

Objective: To estimate the expected magnitude of error produced by uncontrolled confounding from health behaviours in observational medical record-based studies evaluating effectiveness of screening colonoscopy. Methods: We used data from the prospective National Institutes of Health American Association of Retired Persons (NIH-AARP) Diet and Health Study to assess the impact of health behaviour related factors (lifestyle, education, and use of non-steroidal anti-inflammatory drugs [NSAID]) on the association between colonoscopy and colorectal cancer (CRC) mortality. We first examined the difference between adjusted and unadjusted results within the cohort data, and then estimated a broader range of likely confounding errors based on the Breslow-Day approach that uses prevalence of confounders among persons with and without exposure, and the rate ratio reflecting the association between these confounders and the outcome of interest. As dietary factors and habits are often inter-correlated, we combined these variables (physical activity, body mass index, waist-to-hip ratio, alcohol consumption, and intakes of red meat, processed meat, fibre, milk, and calcium) into a "healthy lifestyle score" (HLS). Results: The estimated error (a ratio of biased-to-true result) attributable to confounding by HLS was 0.959-0.997, indicating less than 5% departure from the true effect of colonoscopy on CRC mortality. The corresponding errors ranged from 0.970 to 0.996 for NSAID, and from 0.974 to 1.006 for education (all <= 3% difference). The results for other CRC screening tests were similar. Conclusion: Health behaviour-related confounders, either alone or in combination, seem unlikely to strongly affect the association between colonoscopy and CRC mortality in observational studies of CRC screening.