Fig. 1. Forest plots of underlying data for chewing tobacco and two cardiovascular outcomes.

These forest plots depict the estimated mean relative risk (blue vertical line) and its 95% uncertainty interval (blue shaded intervals) for the association between chewing tobacco and stroke (panel a) and for the association between chewing tobacco and ischemic heart disease (panel b) and the underlying data points. The narrower darker blue intervals correspond to the 95% uncertainty interval estimated without accounting for between-study heterogeneity in accordance with traditional meta-analytic approaches. The light blue intervals correspond to the 95% uncertainty interval that incorporates between-study heterogeneity and the uncertainty around it. Similarly, the red vertical lines are the Burden of Proof Risk Function (BPRF), which correspond to the 5^th quantile and is used to derive our risk-outcome score (ROS) for risk-outcome pairs in which the darker blue intervals (the 95% uncertainty interval without between-study heterogeneity) do not include the null value at relative risk = 1. The black dotted vertical lines reflect the null relative risk at 1. The black data points and horizontal lines each correspond to an effect size and 95% uncertainty interval from the study noted in on the y-axes that were included in the models. Neither model qualified for trimming, so no observations are marked with red Xs. Studies noted with an asterisk include effect sizes from overlapping samples whose uncertainty interval was scaled based on the number of overlapping observations to avoid overrepresenting one sample in the models.