Consequently, the value of PCSK9 inhibitor therapy in FH is uncertain. Table 12. Proposed Integration of Level of Value Into Clinical Guideline Recommendations* Level of Value High value: Better outcomes at lower cost or ICER <$50000 per QALY gained Intermediate value: $50000 to <$150000 per QALY gained Low value: $150000 per QALY gained Uncertain value: Value examined, but data are insufficient to draw a conclusion because of absence of studies, low-quality studies, conflicting studies, or prior studies that are no longer relevant Not assessed: Value not assessed by the writing committee Proposed abbreviations for each value recommendation:Level of value: H to indicate high value; I, intermediate value; L, low value; U, uncertain value; and NA, value not assessed. *Dollar amounts used in this table are based on US GDP data from 2012 and were obtained from WHO-CHOICE Cost-Effectiveness Thresholds.S7.1-9 Reproduced from Anderson et al.S7.1-1 GDP indicates gross domestic product; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life-years; and WHO-CHOICE, World Health Organization Choosing Interventions that are Cost-Effective. CLINICAL STATEMENTS AND GUIDELINES 8. LIMITATIONS AND KNOWLEDGE GAPS 8.1. Randomized Controlled Trials ACC/AHA guidelines are based largely on the outcomes of RCTs. Cholesterol guidelines have fortunately benefited from a large number of RCTs of cholesterol-lowering thera- pies. They have established that greater reductions of LDL- C are accompanied by greater reductions in risk of ASCVD. Robust RCTs exist for both primary and secondary preven- tion. Most of the data from RCTs have been obtained with statin therapy. Important limited data have also been ob- tained with nonstatins as add-on drugs to statin therapy. Nevertheless, more data are needed to determine the full scope of the benefit of nonstatin drugs. Several important questions need to be addressed by additional RCTs. 1. 