Although systematic and explicit, existing evidentiary criteria for clinical guidelines tend to use study design as a surrogate for evidence quality. Moreover, they do not independently characterize evidence quality and net benefits and do not systematically evaluate research needs. Decision analysis, which quantifies the range of potential net benefits based on whatever evidence is available, can augment traditional frameworks. It is particularly useful for pediatric research, where randomized controlled trials are often unavailable and infeasible. Policymakers should incorporate decision analysis into comparative effectiveness research and clinical guidelines.