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BackgroundNurse-led monitoring of patients for signs and symptoms associated with documented 'undesirable effects' of medicines has potential to prevent avoidable harm, and optimise prescribing.InterventionThe Adverse Drug Reaction Profile for polypharmacy (ADRe-p) identifies and documents putative adverse effects of medicines commonly prescribed in primary care. Nurses address some problems, before passing ADRe-p to pharmacists and prescribers for review, in conjunction with prescriptions.ObjectivesWe investigated changes in: the number and nature of residents' problems as recorded on ADRe-p; prescription regimens; medicines optimisation: and healthcare costs. We explored aetiologies of problems identified and stakeholders' perspectives.Setting and participantsIn three UK care homes, 19 residents completed the study, December 2018 to May 2019. Two service users, three pharmacists, six nurses gave interviews.MethodsThis mixed-method process evaluation integrated data from residents' ADRe-ps and medicines charts, at the study's start and 5-10 weeks later.ResultsWe recruited three of 27 homes approached and 26 of 45 eligible residents; 19 completed ADRe-p at least twice. Clinical gains were identified for 17/19 residents (mean number of symptoms 3 SD 1.67, range 0-7). Examples included management of: pain (six residents), seizures (three), dyspnoea (one), diarrhoea (laxatives reduced, two), falls (two of five able to stand). One or more medicine was de-prescribed or dose reduced for 12/19 residents. ADRe administration and review cost ~£30 in staff time. ADRe-p helped carers and nurses bring residents' problems to the attention of prescribers.ImplicationsADRe-p relieved unnecessary suffering. It supported carers and nurses by providing a tool to engage with pharmacists and prescribers, and was the only observable strategy for multidisciplinary team working around medicines optimisation. ADRe-p improved care by: a) regular systematic checks and problem documentation; b) information transfer from care home staff to prescribers and pharmacists; c) recording changes.RegistrationNLM Identifier NCT03955133; ClinicalTrials.gov.