Comparative effects of the restriction method in two large observational studies of body mass index and mortality among adults.

BACKGROUND: A method applied in some large studies of weight and mortality is to begin with a well-defined analytic cohort and use successive restrictions to control for methodologic bias and arrive at final analytic results.

MATERIALS AND METHODS: Two observational studies of body mass index and mortality allow a comparative assessment of these restrictions in very large data sets. One was a meta-analysis of individual participant data with a sample size of 8 million. The second was a study of a South Korean cohort with a sample size of 12 million. Both presented results for participants without pre-existing disease before and after restricting the sample to never-smokers and deleting the first 5 years of follow-up.

RESULTS: Initial results from both studies were generally similar, with hazard ratios (HRs) below 1 for overweight and above 1 for underweight and obesity. The meta-analysis showed higher HRs for overweight and obesity after the restrictions, including a change in the direction of the HR for overweight from 0·99 (95% CI: 0·98-1·01) to 1·11 (95% CI: 1·10, 1·11). The South Korean data showed little effect of the restrictions and the HR for overweight changed from 0·85 (95% CI: 0·84-0·86) to 0·91 (95% CI: 0·90, 0·91). The summary effect size for overweight was 0·90 (95% CI: 0·89-0·91) before restrictions and 1·02 (95% CI: 1·02, 1·03) after restrictions.

CONCLUSIONS: The effect of the restrictions is not consistent across studies, weakening the argument that analyses without such restrictions lack validity.