A Model-Based Analysis on Direct Costs of Adverse Drug Events and Related Cost-Savings Achievable by their Prevention in Tuscany, Italy

Background/Introduction: Adverse drug events (ADEs) may represent an important cost item for healthcare systems, since the recall, repair or rework of faults from ADEs and their management are costly and time consuming [1–3]. Their prevention could result in a relevant cost-saving. Objective/Aim: To simulate the annual economic burden for ADEs in Tuscany (Italy) and the potential cost-savings related to avoidable ADEs. Methods: A systematic review was performed, according to PRISMA [4] and MOOSE [5] statements, on observational studies published from 2006 to 2016 in Medline and EMBASE, focusing on direct costs of ADEs in the inpatient setting from high-income Countries. All the included studies were assessed for their methodological quality through the Newcastle– Ottawa Scale. The mean probability of preventable ADEs was estimated over the included studies. The mean ADE cost was calculated by means of Monte Carlo simulation. Then, we extrapolated the Tuscan spontaneous reports of inpatient ADEs in 2016 from the Italian Pharmacovigilance database, and we assumed for Tuscan ADEs the same costs and preventability probability obtained in the systematic review. Finally, we simulated the possible costs of ADEs and the potential cost-savings by using the estimated preventable ADEs in Tuscany. Three sensitivity analyses were performed also to test the robustness of the results [6]. Results: Out of 11,936 articles initially selected, 12 observational studies were included. Four studies were performed in North America and eight in Europe. The mean cost reported for a single ADE ranged from $2620 to $5373 in the American studies, and from €970 to €5461 in the European ones. All the included studies were classified at low risk of bias. The estimated mean ADE cost was €2471.46 (standard deviation (SD): ± €1214.13). The mean probability of preventable ADEs was 45% (SD: ± 21). The simulated Tuscan expenditure for ADEs was €3406,280.63 per million inhabitants [95% confidence interval (CI): €1,732,910.44– €5,079,664.61] and the potential cost-saving was €1,532,760.25 per million inhabitants (95% CI: €779,776.1–€2,285,750.60). The sensitivity analyses confirmed the robustness of our results. Conclusion: The present simulation showed that the management of inpatient ADEs could have a relevant economic impact on the Tuscan healthcare system and the prevention would result in important cost-savings. These findings could be likely extended to other healthcare systems.