The USPSTF developed its recommendations for lipid screening on the basis of a specific analytic framework used to narrow the evidence review to the key questions that would have the greatest leverage on a decision to recommend, not recommend, or abstain from recommending lipid screening. Ten possible questions (Figure and Table 2) were derived for the analytic framework, all of which can be reviewed in the USPSTF evidence synthesis.15 The searches for relevant studies were based on these questions. Evidence from key question 1 would provide direct evidence of the effectiveness of lipid screening among children by identifying controlled trials of screening compared with no screening, with information on long-term health outcomes, reaching into adulthood. Because no literature of this type was found in this review, the USPSTF focused on the remaining key questions (2-10) in an effort to assemble a chain of indirect evidence, using the sequential steps of the screening process. An example of an indirect chain of evidence to support screening is one that shows that a screening test accurately identifies persons with or at high risk for the target condition, that effective treatments are available to treat the target condition, and that harm due to screening and treatment is outweighed by the benefits. For adult obesity screening, the USPSTF recommendations were based on indirect evidence of health benefits of screening using body mass index as an outcome associated with important clinical outcomes. To achieve this threshold of benefit, evidence was independently assembled to assess the accuracy and reliability of the screening test, the effectiveness of interventions on weight loss, the effectiveness of weight loss on intermediate outcomes (eg, blood pressure and lipid levels), and the effectiveness of weight loss on clinical outcomes (eg, mortality, daily functioning, prevention of chronic disease).16 Gaps in any sequence of the evidence chain because of insufficient or poor-quality studies affect the level of certainty regarding the balance of benefit and/or harm associated with the screening process.