Objectives: This study examines the cost-effectiveness of the OPTI-SCRIPT intervention on potentially inappropriate prescribing in primary care. Methods: Economic evaluation, using incremental cost-effectiveness and cost utility analyses, conducted alongside a cluster randomized controlled trial of twenty-one general practices and 196 patients, to compare a multifaceted intervention with usual practice in primary care in Ireland. Potentially inappropriate prescriptions (PIPs) were determined by

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... a pharmacist. Incremental costs, PIPs, and quality-adjusted life-years (QALYs) at 12-month follow-up were estimated using multilevel regression. Uncertainty was explored using cost-effectiveness acceptability curves. Results: The intervention was associated with a nonsignificant mean cost increase of €407 (95 percent CIs, −357–1170), a significant mean reduction in PIPs of 0.379 (95 percent CI, 0.092–0.666), and a nonsignificant mean increase in QALYs of 0.013 (95 percent CIs, −0.016–0.042). The incremental cost per PIP avoided was €1,269 (95 percent CI, −1400–6302) and the incremental cost per QALY gained was €30,535 (95 percent CI, −334,846–289,498). The probability of the intervention being cost-effective was 0.602 at a threshold value of €45,000 per QALY gained and was at least 0.845 at threshold values of €2,500 per PIP avoided and higher. Conclusions: While the OPTI-SCRIPT intervention was effective in reducing potentially inappropriate prescribing in primary care in Ireland, our findings highlight the uncertainty with respect to its cost-effectiveness. Further studies are required to explore the health and economic implications of interventions targeting potentially inappropriate prescribing.