Loss to follow-up in cohort studies: how much is too much?

Loss to follow-up is problematic in most cohort studies and often leads to bias. Although guidelines suggest acceptable follow-up rates, the authors are unaware of studies that test the validity of these recommendations. The objective of this study was to determine whether the recommended follow-up thresholds of 60-80% are associated with biased effects in cohort studies. A simulation study was conducted using 1000 computer replications of a cohort of 500 observations. The logistic regression model included a binary exposure and three confounders. Varied correlation structures of the data represented various levels of confounding. Differing levels of loss to follow-up were generated through three mechanisms: missing completely at random (MCAR), missing at random (MAR) and missing not at random (MNAR). The authors found no important bias with levels of loss that varied from 5 to 60% when loss to follow-up was related to MCAR or MAR mechanisms. However, when observations were lost to follow-up based on a MNAR mechanism, the authors found seriously biased estimates of the odds ratios with low levels of loss to follow-up. Loss to follow-up in cohort studies rarely occurs randomly. Therefore, when planning a cohort study, one should assume that loss to follow-up is MNAR and attempt to achieve the maximum follow-up rate possible.