Deborah McCahon

Introduction Medicines are a key healthcare intervention. Medicines optimisation aims to ensure safe and effective use of medicines, with medication reviews a critical component. However, evidence around how reviews should be structured and delivered is limited. The Bristol Medication Review Toolkit comprises a review model and practical supporting materials to facilitate comprehensive, patient-centred, structured medication reviews. The BRISMED trial aims to evaluate the clinical effectiveness and acceptability of the Toolkit compared with standard general practice care. Methods BRISMED is a multicentre, open-label, cluster-randomised controlled trial, with two parallel groups. General practices within the Oxford RCGP Research Surveillance Centre (RSC) network will be selected to participate, representing 500 primary care networks (PCNs) in England. Randomisation will occur at PCN level. The intervention will take place at the practice level, with no patient-level recruitment. Practices will either undertake usual care (control group, 250 PCNs) or receive the BRISMED Toolkit (intervention group, 250 PCNs) over the same 12-month intervention delivery period. The primary outcome will be potentially inappropriate prescribing (PIP), defined as the proportion of patients with ≥1 STOPP/START indicator at 12 months (binary outcome per patient). Secondary outcomes will include additional prescribing metrics and healthcare utilisation. Outcomes will be determined using routinely collected electronic health data. The primary analysis will use mixed-effects logistic regression, on an intention-to-treat basis. A parallel mixed-methods process evaluation in a subset of practices will examine intervention implementation and provide context for interpretation of the trial findings, alongside a cost consequence analysis. Findings will be disseminated through publications, conferences and stakeholder engagement. Patients and the public will contribute throughout the study, supporting research delivery and dissemination. Ethics and registration The study has received approval from the West of Scotland NHS Research Ethics Committee 1 (reference 24/WS/0031). The trial is prospectively registered with ISRCTN (reference 12979016, registration date 3/6/2024).

Polypharmacy is a major challenge for patient safety and effective resource use. High-quality evidence supporting polypharmacy management is lacking. To develop, optimise and evaluate a primary care complex intervention for reducing medically defined potentially inappropriate prescribing among patients experiencing polypharmacy. Phase 1: Qualitative interviews and focus groups with patients and professionals explored views/experiences of existing National Health Service Scotland interventions, informing development of core intervention components. Phase 2: An external pilot-feasibility study was conducted in five general practitioner practices to optimise the Improving Medicines use in People with Polypharmacy in Primary care intervention. A formative mixed-methods process evaluation examined intervention implementation, alongside evaluating trial processes and collecting data to inform phase 3. Phase 3: A pragmatic, open-label two-arm parallel cluster-randomised trial was conducted in English general practice. The intervention (19 practices) comprised a structured, collaborative and patient-centred approach to medication review, supported by informatics, clinician training, performance feedback and financial incentivisation. The comparator was usual care (18 practices). Up to 50 adults receiving ≥ 5 regular medications, with ≥ 1 indicator of potentially inappropriate prescribing, were reviewed per practice over 6 months. Primary outcome was number of potentially inappropriate prescribing indicators at 26-week follow-up. Secondary outcomes included patient-reported measures and service use. Cost-effectiveness and cost-utility analyses were conducted (primary economic outcome quality-adjusted life-years). A mixed-methods process evaluation (patient surveys, patient/clinician interviews, audio-recorded observations) explored implementation. Phase 1: Intervention component design was informed by findings related to elements of the medication review, informatics and clinician training. Phase 2: Core intervention elements were successfully implemented in the pilot, although clinical delivery was hampered by disruptions due to the coronavirus disease pandemic. Phase 3: Participants were recruited between January and June 2022 (intervention N = 891, usual care N = 836), median age 73 years, 49% female, with median four long-term conditions and eight medications. No improvement in the primary outcome was observed (mean difference potentially inappropriate prescribing count - 0.007; 95% confidence interval -0.21 to 0.199). Treatment burden was slightly improved, and subgroup analysis suggested potential improvements in less complex patients. The process evaluation found general practitioners and pharmacists valued and benefitted from the model of interprofessional collaboration, which strengthened working relationships and provided an opportunity for knowledge sharing and joint decision-making that supported management of clinical uncertainty. Most patients (73.2%) reported satisfaction with the review, with satisfaction strongly associated with perceptions of shared decision-making. There was no evidence of cost-effectiveness, although the economic evaluation did not quantify the aforementioned benefits or other broader factors of potential interest to decision-makers. Key limitations include concurrent changes in usual care, potentially insensitive outcome measures and limited study-population generalisability. A complex medication optimisation intervention did not reduce potentially inappropriate prescribing in patients with polypharmacy. Findings strongly support revisiting current medication optimisation policy, with one-off structured reviews, even when enhanced with digital healthcare solutions and clinical pharmacy investment, not guaranteed to improve key clinical outcomes. Nevertheless, the positive patient and clinician findings are important: protected time for interprofessional collaborative working, plus effective integration of shared decision-making within patient-facing reviews, may facilitate improved patient care more broadly. Research should develop new patient-centred outcomes and identify higher-risk patients. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number 16/118/14.

Background: Structured medication reviews (SMRs) were introduced in 2020 to address polypharmacy in patients most at risk of medicines-related harm. Aim: To evaluate the impact of SMRs on prescribing in primary care. Design and setting: Retrospective observational cohort study of electronic health records from patients aged ≥65 years, prescribed ≥1 medications, and fulfilling the specific eligibility criteria for an SMR, registered at practices contributing data to the Oxford Clinical Informatics Digital Hub, between 1 April 2020 and 30 September 2022. Method: The association between SMRs and prescription changes was examined by matching individuals who received an SMR to individuals who did not receive an SMR, according to age, sex, and primary care practice, using cumulative density sampling. Analyses were undertaken using adjusted logistic regression. Results: Of 635 698 eligible patients, 82 285 (12.9%, 95% confidence interval [CI] = 12.9 to 13.0) received ≥1 SMR during the study observation period. In those prescribed potentially inappropriate drug combinations prior to an SMR, between 12.5% and 40.0% were corrected up to 3 months later. In matched analyses, SMRs were most strongly associated with an increase in new prescriptions of angiotensin-converting enzyme inhibitors (adjusted odds ratio [aOR] 1.56, 95% CI = 1.35 to 1.81), statins (aOR 1.78, 95% CI = 1.57 to 2.02), and antidepressants (aOR 1.45, 95% CI = 1.28 to 1.63). SMRs were also most strongly associated with stopping these drug classes in those previously prescribed treatment. Conclusion: SMRs were associated with starting new medications and stopping existing prescriptions compared with usual care. Further work is needed to understand if these changes improved patient outcomes.

Background: Structured Medication Reviews (SMRs) were introduced into primary care in England for patients living with multiple long-term conditions (MLTCs), polypharmacy, increased frailty, in care homes or at risk of medicines-related harm. SMRs aim to optimise the therapeutic potential of medication and reduce medicine-related harms through holistic reviews. Aim: To explore the day-to-day work being undertaken with, and by, clinical pharmacists to implement, embed and integrate SMRs into practice, and consider how to optimise SMRs. Design and setting: Qualitative one-to-one interviews with clinical pharmacists undertaking SMRs and SMR service leaders/managers (SMR leads) in England between February 2023 and November 2024. Method: Participants were recruited as part of a wider evaluation of the roll-out of SMRs in England. Interview topic guides and qualitative data analysis were informed by Normalization Process Theory (NPT). Results: Eighteen clinical pharmacists and five SMR leads participated. Participants reported often having to explain the purpose of SMRs and clinical pharmacists' roles to patients, partly due to patients not being informed about SMRs. Participants valued SMRs and expressed that trust-building and tailored consultations were important for optimising medications. Integration varied due to high workload, inconsistent leadership support, inadequate administrative/pharmacist technician resource and lack of training. However, participants described SMRs as valuable for identifying and addressing unmet needs and supporting holistic, person-centred care across MLTC pathways. Conclusion: The findings demonstrate the need for improved information on SMRs for patients and primary care teams, adequate and appropriate resource allocation, and enhanced support for consultation skills training to optimise medicines use.

Background: Understanding relationships between polypharmacy, treatment burden and other factors (e.g. age, knowledge of medicines), could inform interventions to reduce treatment burden. Aim: To explore sociodemographic, clinical and medication factors associated with high treatment burden. Design and setting: Secondary analysis of multi-centre UK primary care baseline clinical trial data. Methods: Participants were ≥18 years, prescribed ≥5 repeat medicines with ≥1 indicator of potentially inappropriate prescribing (PIP). Survey data captured treatment burden (13-item Multimorbidity Treatment Burden Questionnaire; dichotomised with high burden ≥22), sociodemographic characteristics, quality of life, self-reported knowledge of medicines, and medication adherence. Electronic health records provided data on age, gender, long-term conditions, PIP, medicines use (last 3 months), and consultations (last 12 months). Associations between treatment burden and other factors were modelled using multivariable logistic regression. Results: 1711 adults from 37 general practices were included (mean age 72 years, 51% male). 381 (23%) reported high treatment burden. Multivariable analysis found high treatment burden was associated with younger age, being unemployed or in paid work, university or high education, multimorbidity, anxiety/depression, polypharmacy (≥8 medicines), lower medication adherence, knowledge of medicines, and quality of life. There was strong evidence (p<0.005) that the association between high treatment burden and polypharmacy was greater in people aged <60 years, those with poor knowledge of medicines, more multimorbidity, and those with low/moderate medication adherence. Conclusion: High treatment burden was more common in adults with polypharmacy who were younger, had multimorbidity, poor medication knowledge, or low adherence. This should inform design of interventions addressing treatment burden.

1. The 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.

Background: Structured Medication Reviews (SMRs) were introduced into primary care in England for patients living with multiple long-term conditions (MLTCs), polypharmacy, increased frailty, in care homes or at risk of medicines-related harm. SMRs aim to optimise the therapeutic potential of medication and reduce medicine-related harms through holistic reviews. Aim: To explore the day-to-day work being undertaken with, and by, clinical pharmacists to implement, embed and integrate SMRs into practice, and consider how to optimise SMRs. Design and setting: Qualitative one-to-one interviews with clinical pharmacists undertaking SMRs and SMR service leaders/managers (SMR leads) in England between February 2023 and November 2024. Method: Participants were recruited as part of a wider evaluation of the roll-out of SMRs in England. Interview topic guides and qualitative data analysis were informed by Normalization Process Theory (NPT). Results: Eighteen clinical pharmacists and five SMR leads participated. Participants reported often having to explain the purpose of SMRs and clinical pharmacists’ roles to patients, partly due to patients not being informed about SMRs. Participants valued SMRs and expressed that trust-building and tailored consultations were important for optimising medications. Integration varied due to high workload, inconsistent leadership support, inadequate administrative/pharmacist technician resource and lack of training. However, participants described SMRs as valuable for identifying and addressing unmet needs and supporting holistic, person-centred care across MLTC pathways. Conclusion: The findings demonstrate the need for improved information on SMRs for patients and primary care teams, adequate and appropriate resource allocation, and enhanced support for consultation skills training to optimise medicines use. How this fits in: - SMRs were formally introduced to primary care in 2020 to address the challenges of managing polypharmacy in an ageing population with increasing patient complexity and MLTCs. - SMRs were introduced alongside the expansion of clinical pharmacist roles in General Practice as a comprehensive, person-centred review of all a patient’s medicines. - This qualitative evaluation examines the day-to-day work of implementing and embedding SMRs, highlighting challenges to implementation and integration. - Our findings reveal challenges to the sustainability of SMRs and identify opportunities for optimisation, including addressing pharmacists’ training needs and resource allocation for administrative and pharmacy technician support.

Background: People prescribed multiple medications need regular review to optimise medication and improve health outcomes. Although the most effective method to improve inappropriate polypharmacy remains unclear, medication reviews incorporating patient-centred care and shared decision making are believed to be key to achieving optimal outcomes. Aim: To explore patients’ experiences of an intervention to deliver patient-centred polypharmacy medication review in primary care. Design and setting: A mixed-methods process evaluation was undertaken within the Improving Medicines use in People with Polypharmacy in Primary Care (IMPPP) randomised controlled trial conducted in the Bristol and West Midlands regions of England. Method: Participants receiving the intervention were invited to complete a patient experience survey. Additionally, participants were purposively sampled and invited to participate in an interview and/or audio-recording of their medication review, to explore views and experiences. Results: Survey response rate was 72.5% ( n = 556/767); 28 patients were interviewed, 27 reviews were recorded. Overall, 73.2% ( n = 407) were satisfied with their review, strongly associated with shared decision making, and 79.9% ( n = 444) expressed satisfaction with how the review was delivered (primarily pharmacist-led telephone consultations). Most audio-recordings of reviews demonstrated collaborative decision making. Patients valued reviews when they felt well-informed, prepared, and received clear follow-up. Pharmacist-led delivery was acceptable, although unfamiliarity with the reviewer and concerns about prescribing authority were perceived negatively. Conclusion: Participants were satisfied with their review, although this may be contingent on preparation and support. Findings highlight the importance of communication throughout, and how the clinician role and familiarity shape patient experience. A person-centred review approach has the potential to improve patient experience, satisfaction, and engagement.

Background: There has been significant investment in pharmacists working in UK general practice to improve the effective and safe use of medicines. However, evidence of how to optimise collaboration between GPs and pharmacists in the context of polypharmacy (multiple medication) is lacking. Aim: To explore GP and pharmacist views and experiences of in-person, interprofessional collaborative discussions (IPCDs) as part of a complex intervention to optimise medication use for patients with polypharmacy in general practice. Design and setting: A mixed-method process evaluation embedded within the Improving Medicines use in People with Polypharmacy in Primary Care (IMPPP) trial conducted in Bristol and the West Midlands, between February 2021 and September 2023. Method: Audio-recordings of IPCDs between GPs and pharmacists, along with individual semi-structured interviews to explore their reflections on these discussions, were used. All recordings were transcribed verbatim and analysed thematically. Results: A total of 14 practices took part in the process evaluation from February 2022 to September 2023; 17 IPCD meetings were audio-recorded, discussing 30 patients (range 1–6 patients per meeting). In all, six GPs and 13 pharmacists were interviewed. The IPCD was highly valued by GPs and pharmacists who described benefits, including: strengthening their working relationship; gaining in confidence to manage more complex patients; and learning from each other. It was often challenging, however, to find time for the IPCDs. Conclusion: The model of IPCD used in this study provided protected time for GPs and pharmacists to work together to deliver whole-patient care, with both professions finding this beneficial. Protected time for interprofessional liaison and collaboration, and structured interventions may facilitate improved patient care.