Manuela Casula ^1,2 Ilaria Ardoino ³ Laura Pierini ³ Lara Perrella ^4,5 Stefano Scotti ⁶ Sara Mucherino ⁵ Valentina Orlando ⁵ Enrica Menditto ⁵ Carlotta Franchi ^3*

• ¹ Epidemiology and Preventive Pharmacology Service (SEFAP), Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Lombardy, Italy
• ² IRCCS MultiMedica, Sesto San Giovanni (MI), Italy
• ³ Laboratory of Pharmacoepidemiology, Department of Public Health, Mario Negri Pharmacological Research Institute (IRCCS), Milano, Lombardy, Italy
• ⁴ Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Campania, Italy
• ⁵ Center of Pharmacoeconomics and Drug Utilization Research (CIRFF), Department of Pharmacy, University of Naples Federico II, Naples, Italy, Naples, Italy
• ⁶ IRCSS Multimedica, Sesto San Giovanni (MI), Italy

Background: Proton pump inhibitors (PPIs) are among the most commonly and inappropriately prescribed drugs by general practitioners (GPs), resulting in increased risk of adverse outcomes for patients and in avoidable costs for the National Health System (NHS). This study aims to assess the effectiveness of a low-cost and easily implementable informative intervention directed at GPs to enhance the appropriate prescription of PPIs.The LAPTOP-PPI study is a pragmatic, cluster-randomized controlled trial designed to improve the appropriateness of PPI prescriptions among community-dwelling individuals aged ≥65 years. In June 2021, GPs in the Local Health Units (LHUs) of Bergamo (Northern Italy) and Caserta (Southern Italy) were randomly allocated to either intervention group (summary reports on prescribing habits, scientific documents on Italian Medicine Agency's therapeutic indications, strategies for PPIs deprescribing, along with educational materials for patients), and control group (standard practice). PPI appropriateness was assessed through an algorithm specifically designed and based on NHS prescription appropriateness and reimbursement criteria. Intervention efficacy was evaluated comparing data from baseline period (July 1 to December 31, 2019) with those from the follow-up period (July 1 to December 31, 2021), six months after randomization. The analysis was performed on the intention-to-treat principle, and according to GPs level. To estimate the effectiveness of the intervention we used a Difference-In-Differences (DID) approach.Results: Overall, 942 GPs (540 from Bergamo and 402 from Caserta LHUs) were included in the analysis. At baseline, 171,978 patients aged ≥65 received drug prescriptions for acid-related diseases and were assessable for evaluation of appropriateness. At follow-up, this number was 137,699. The overall inappropriateness rate at the baseline among GPs included in the analysis was 57.4% (std.dev. 8.4%) in the intervention arm and 57.6% (std.dev. 8.8%) in the control arm; six months after the intervention delivery, they were 59.2% (std.dev. 8.0%) and 58.5% (std.dev. 7.3%), respectively.Given the widespread use, improving prescription quality of PPIs is a major concern. Educational interventions for GPs and patients are routine strategies to address inappropriateness, but they appear to be insufficient to improve prescribing practice independently, especially in a critical situation such as the post-pandemic period.