{"paper_id":"4b7c7d3a-b697-4ebb-8e99-556ff604fc55","body_text":"1. Abstract\nThe prescribing of multiple medicines to one individual, or polypharmacy, is increasingly common. While the use of multiple medications by a patient is often appropriate, in some cases prescribed medicines may not have the intended benefit and may even cause harm, and it is important to understand the clinical and economic implications of polypharmacy and interventions to optimise prescribing. In the UK, most ongoing clinical management of polypharmacy takes place in primary care. We estimated the cost-effectiveness of the Improving Medicines use in People with Polypharmacy in Primary Care (IMPPP) trial from a UK NHS perspective. IMPPP was a pragmatic, open-label, two-arm cluster-randomised trial across 37 English general practices, including 1,715 patients. The intervention comprised a structured, enhanced process for delivering patient-centred polypharmacy reviews, and was compared to control arm practices delivering usual care. Costs were derived from routine electronic health records including primary and secondary care service utilisation data whilst QALYs were estimated via SF-12v2. Follow-up was assessed at 6 months compared to pre-randomisation baseline. Cost-effectiveness was assessed using multilevel modelling with bias-corrected and accelerated bootstrapping to calculate 95% confidence intervals. Additional one-way sensitivity analyses were conducted to explore uncertainty. Adjusted mean QALYs were slightly higher in the intervention group (0.629) versus control (0.624), with a non-significant difference of 0.006 (95% CI: -0.002 to 0.014). Mean adjusted costs were also higher in the intervention group (£4166 vs. £3655), with a non-significant cost difference of £511 (95% CI: -£73 to £949). The probability of cost-effectiveness at National Institute for the Health and Care Excellence’s £20,000/QALY and £30,000/QALY thresholds were 6% and 12% respectively. Complete case analysis showed a £138 NHS cost reduction (95% CI: -£652 to £376) and a QALY gain of 0.012 (95% CI: 0.004 to 0.021). Polypharmacy medication review as conducted in the IMPPP trial is not cost-effective. This probably reflects multiple factors, including clinical effectiveness outcomes and key cost outcomes being relatively insensitive to the intervention.\nCompeting Interest Statement\nThe authors have declared no competing interest.\nClinical Trial\nISRCTN90146150\nClinical Protocols\nhttps://openresearch.nihr.ac.uk/articles/2-54/v1\nFunding Statement\nThis study was funded by the NIHR Health and Social Care Delivery Research programme (reference, 16/118/14)\nAuthor Declarations\nI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.\nYes\nThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:\nResearch Ethics Committee (Wales 6, reference 19/WA/0090) of the National Health Service gave ethical approval for this work.\nI confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.\nYes\nI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).\nYes\nI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.\nYes\nData availability\nRequests for data sharing should be submitted to the Chief Investigator (RP) for consideration. Access to anonymised participant-level data might be granted following appropriate institutional review.","source_license":"CC-BY-4.0","license_restricted":false}