Denial of Access as an Unmeasured Outcome in Nonprescription Statin Self-Selection Studies
Molinari, K. P.
Show abstract
Background: Five nonprescription statin attempts have failed; a sixth attempt, under the FDA's 2025-issued Additional Condition for Nonprescription Use (ACNU) pathway, is under way. Self-selection evidence is evaluated by whether ineligible consumers are excluded; how often eligible consumers are denied has never been reported. Objective: To quantify denial of access to eligible consumers across the published self-selection record. Methods: Secondary analysis of the three published United States self-selection studies (SELECT, CREST, TACTiC), the FDA guidance, and four advisory committees' questions and votes. We recomputed diagnostic accuracy from published cross-tabulations, derived TACTiC's prespecified unmitigated endpoints, and compared access strategies by decision curve analysis. Results: The guidance's endpoints contain no measure of denial, and every committee question addressing a selection error concerns admission of the ineligible. CREST's sensitivity was 59.0% (95% CI 42.1%-74.4%), 29.5 percentage points below its reported positive predictive value; 41% of clinician-eligible participants were not approved. TACTiC's reference standard reached only application-approved consumers; none of the 10,332 rejected was assessed; sensitivity is inestimable and its prespecified unmitigated endpoints, 84.2% and 80.9% against the published mitigated 90.7% and 98.1%, remain unpublished. Decision curve analysis favors the application over both alternatives across reasonable thresholds at the sample prevalence. Conclusions: For nonprescription statin applications, the self-selection evidence framework counts errors of admission and leaves errors of denial unmeasured; its public health objective, fewer eligible adults untreated, cannot be evaluated on evidence counting only admissions. Four design and reporting changes, none requiring new methodology, would let the next application measure it.
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