3.8. Adverse effects

Any intervention may be associated with adverse effects that are not initially apparent. Thus, one might consider ‘‘as-yet-undiscovered toxicity’’ as an important adverse consequence of any new drug. Such toxicity becomes critical only when sufficient evidence of its existence emerges.

The tricky part of this judgment is how frequently the adverse event must occur and how plausible the association with the intervention must be before it becomes a critical outcome. For instance, an observational study found a previously unsuspected association between sulfonylurea use and cancer-related mortality. Should cancer deaths now be an important, or even a critical, endpoint when considering sulfonylurea use in patients with type 2 diabetes? As is repeatedly the case, we cannot offer hard and fast rules for these judgments.