Second, the presence of residual confounding in the estimates of effect sizes cannot be definitively ruled out, particularly for those without evidence from intervention studies, either because they have not yet been done or the risk is not amenable to intervention. For example, no large-scale trials have been done of interventions for high body-mass index that measured cause-specific deaths although effects on disease incidence have been investigated in trials.193 Observational studies of the effect sizes for body-mass index have controlled for some potential confounders.75–77 As noted, the pooled effect of risks and interventions trends towards the null result over time;189,190 the implication being that risks for which only a few studies have been done might have their effect overestimated compared with risks for which a large body of evidence exists.
