What if, however, treatment is associated with serious toxicity? Were this true, we may be reluctant to recommend treatment unless the absolute stroke reduction is at least 1% (NNT of 100—left verticle line in Fig. 1). Under these circumstances, the precision is insufficient to support a strong recommendation as the CI encompasses treatment effects smaller than this threshold and therefore does not exclude an absolute benefit appreciably less than 1%. Because the point estimate of 1.3% meets the threshold criterion, a recommendation in favor of treatment would still be appropriate, although the imprecision-generated uncertainty regarding the true effect would mandate a weak recommendation (Box 1).

The impact of undesirable consequences on precision

The hypothetical example presented in Fig. 1 and the accompanying text shows that greater levels of precision are required to support a recommendation in favor of a treatment when a large effect is required to make treatment worth the appreciable undesirable consequences. When appreciable undesirable consequences exist, CIs are more likely to span not only regions of effect that would mandate treating but also regions that would mandate not treating. Thus, the existence of appreciable undesirable consequences makes it more likely that guideline developers will rate down the evidence regarding an apparently beneficial intervention for imprecision.