Article Text

Structured medication reviews for adults with multimorbidity and polypharmacy in primary care: a systematic review protocol
  1. Elena Lammila-Escalera1,
  2. Geva Greenfield1,
  3. Reham Aldakhil1,
  4. Hadar Zaman2,
  5. Ana Luisa Neves1,
  6. Azeem Majeed1,
  7. Benedict WJ Hayhoe1
  1. 1 Department of Primary Care and Public Health, Imperial College London, London, UK
  2. 2 School of Pharmacy and Medical Sciences, University of Bradford, Bradford, UK
  1. Correspondence to Elena Lammila-Escalera; elena.lammila-escalera20{at}


Introduction Polypharmacy is common among individuals with multimorbidity, often leading to inappropriate medication use and is associated with an increased risk of frailty, hospitalisation and mortality. Structured medication reviews (SMRs) have emerged as a promising method for optimising medication use. However, research examining their efficacy is limited. This review aims to evaluate the impact of SMRs on improving outcomes for adults with multimorbidity and polypharmacy in primary care settings. Additionally, this review seeks to identify prevailing patterns and trends in the mode of delivery of SMRs.

Methods and analysis A systematic review will be conducted using Ovid MEDLINE, Ovid EMBASE, Web of Science and CINAHL (1997–present). Primary outcomes will include medication-related measures such as dose, frequency and dosage form. Secondary outcomes under investigation will include physical, mental, functional and health service outcomes, as reported. Two independent reviewers will conduct the screening and data extraction, resolving disagreements through discussion. Once eligible studies are identified, the extracted data will be summarised in tabular format. The risk of bias in the articles will be assessed using either the Cochrane Risk of Bias 2 tool or the Newcastle-Ottawa scale, depending on the design of the studies retrieved. Subgroup analysis will be performed using demographic variables and modes of delivery where the data supports. If appropriate, a meta-analysis of the data extracted will be conducted to determine the impact of the SMRs on reported outcomes. If a meta-analysis is not possible due to heterogeneity, a narrative synthesis approach will be adopted.

Ethics and dissemination This proposed review is exempt from ethical approval as it aims to collate and summarise peer-reviewed, published evidence. This protocol and the subsequent review will be disseminated in peer-reviewed journals, conferences and patient-led lay summaries.

PROSPERO registration number CRD42023454965.

  • Patient-Centered Care
  • Systematic Review

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  • This systematic review aims to summarise the evidence on the efficacy of structured medication reviews (SMRs) for enhancing outcomes for adults with multimorbidity and polypharmacy.

  • This systematic review will be the first to assess SMRs for this patient population and aims to offer the highest level of evidence for informed decisions regarding their implementation.

  • The direct enhanced services requirement for primary care networks to conduct SMRs underscores the importance of this review in generating evidence to guide decision-makers within primary care networks in England .

  • Due to the nature of multimorbidity, heterogeneity is expected, which may present challenges during data analysis.


In recent years, the issue of polypharmacy has risen to the forefront of global public health challenges.1 Polypharmacy, the simultaneous use of multiple medications, is very common among older adults, with an estimated average of 32.1% of adults over 65 years of age using five or more medications a day.2 3 This increased prevalence is attributed to growing life expectancies and a higher proportion of the population being diagnosed with multiple chronic conditions (ie, multimorbidity).4 5

Inappropriate polypharmacy, prescribing where the potential harm of the medicines outweighs the benefits, has far-reaching implications for the overall well-being of patients with multimorbidity and creates substantial challenges for both the individual and healthcare systems.6 For example, polypharmacy increases treatment burden, which may contribute to a significant overall burden for affected individuals. Adults with five or more chronic conditions may dedicate 5–8 hours daily to managing their health, contributing to a significant treatment burden.7–10 Health literacy is a barrier to adherence, particularly with complex medication regimes.11 If inappropriately managed, polypharmacy may increase the risk of patient harm.12 Polypharmacy can compromise drug safety, leading to adverse drug reactions and unwarranted medication interactions.13 This, in turn, escalates the risk of frailty, inefficient healthcare utilisation (such as emergency hospital admissions) and death.14–17 Consequently, medicines optimisation plays a pivotal role within contemporary clinical guidelines, particularly when addressing the complex landscape of multimorbidity.18–20

One established intervention to mitigate the adverse implications of inappropriate polypharmacy is medication review (MR).21 MRs involve a thorough assessment of an individual’s medications, considering drug appropriateness, dosage and interactions.22 However, the effectiveness of MR remains unclear, with trials yielding mixed outcomes. A systematic review by Huiskes et al concluded that although MR improved medication-related outcomes, there was a minimal impact on clinical outcomes such as mortality and no effect on the quality of life.23 Duncan et al reported that general physicians and pharmacists regarded remote MR as a ‘tick box’ exercise to be completed as quickly as possible.24 This approach does not align with existing clinical guidelines that advocate for including patients and their families in decisions about their medicines.25 Recognising the need for an enhanced method of medication management, structured medication reviews (SMRs) have emerged as a promising alternative.26–29 An SMR is a comprehensive review of a patient’s medication, focusing on tailoring care to their unique needs, preferences and circumstances. Although clinical pharmacists are expected to lead and conduct SMRs, complex patient cases may necessitate the collaborative expertise of a multidisciplinary team, further ensuring a comprehensive approach.26 30

One of the most significant impacts of the COVID-19 pandemic on healthcare provision has been the rapid integration of technology into routine care, including technology supporting the remote delivery of primary care services. Remote care encompasses all activities in which care is delivered at a distance—through telephone, video or online platforms.31 The need to manage workload, increasing demand for convenient and rapid access to healthcare, and policy drivers on digital healthcare provision may contribute to improving the delivery of medication reviews remotely. However, the extent to which this takes place and the effect, if any, of the mode of delivery on the impact of MR remain unclear.

Despite their promise, urgent clarification is needed on how and to what extent SMRs improve outcomes for this complex patient population. For instance, earlier systematic reviews have explored pharmacist and deprescribing services for individuals with multimorbidity in a broader context, but they lacked a detailed analysis of SMR.32 33 In contrast, prior literature centred on SMR has focused solely on frail, older adult populations with neurodegenerative disease and intellectual disability. Moreover, this literature examines SMR in community, secondary and long-term care.34–38 This confined perspective limits applicability, leaving an evidential gap in understanding the impact of SMR on the broader population attending primary care. In the context of the continuing digitalisation of primary care services, assessing the impact of the remote provision of SMR is also crucial.

Thus, this systematic review aims to bridge this gap by assessing the effectiveness of SMR in improving outcomes for adults with multimorbidity and polypharmacy in primary care. A secondary objective is to examine the mode of delivery of SMRs to identify common themes and trends.

Methods and analysis

A systematic literature review will follow the recommendations of the Cochrane Handbook for Systematic Reviews and use Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.39 40 This systematic review protocol followed PRISMA-prereporting guidelines.41 Eligibility criteria for screening are summarised in table 1. The literature search and data analysis are scheduled to commence in April 2024 and conclude by August 2024.

Table 1

Inclusion criteria categorised by the PICOS framework52

Search strategy

The identification of eligible studies will involve a comprehensive search (1997–present) across multiple electronic databases. These include Ovid MEDLINE, Ovid EMBASE, Web of Science and CINAHL. This time frame was chosen to ensure the search retrieves all relevant evidence, as MRs were first recommended for routine practice in 1997 by the Royal College of Physicians.42 Additionally, no language limitations will be applied. Three automation tools—the ‘Word Frequency Analyser’, the ‘Polyglot Search Translator’ and ‘SearchRefinery’—were employed in the search design.43 44 Moreover, a specialist librarian with experience in evidence synthesis was involved in developing the search strategy (online supplemental materials).

Supplemental material

Eligibility criteria


This systematic review will focus on adults presenting with multimorbidity and polypharmacy to primary care. For this search, this review will adhere to the WHO definition of adults, those aged 19 years or older.45 Multimorbidity will be described as the coexistence of two or more concurrent chronic conditions in an individual without limitation concerning the type of multimorbidity or combination of diseases.46 Polypharmacy will also be identified as the simultaneous prescription of five or more medications.47


The intervention under investigation is the SMR. An SMR will be defined as a ‘comprehensive review of a patient’s medication, considering all aspects of their health’. There are four core components of an SMR: shared decision-making, a personalised approach, effectiveness and safety.26 Consequently, an SMR actively incorporates elements of holistic care, extending beyond a mere MR. Plus, to accommodate variations in terminology and cultural nuances across countries, the search strategy incorporates known synonyms for SMR, such as drug utilisation review.

The SMR should take place in a primary care setting, such as general practice or community pharmacy. An SMR conducted through community care (ie, district or specialist nursing, fall prevention services and community palliative care) will be excluded from this review. There will be no restriction on the type of professional or professionals conducting the review. Eligible trials may also assess SMRs undertaken by multidisciplinary teams or a sole clinician.


The comparator will be either the usual or standard care given to patients who attend primary care and present with multimorbidity and polypharmacy.


The primary outcomes under investigation will be medicine optimisation-related outcomes. This will encompass medication dose, frequency and dosage form changes following the SMR intervention. Additionally, secondary outcomes in the form of changes in physical, mental, functional and health service outcomes will be examined as reported. These include the cost-effectiveness of SMR, changes in health utilisation following an SMR and quantitatively reported patient experience.

Study design

Relevant studies with experimental and observational designs that offer quantitative data will be eligible for inclusion in this review. Specifically, randomised controlled trials, non-randomised controlled trials, cohort, cross-sectional and case-control studies will be considered. Qualitative designs, case reports, systematic reviews, meta-analyses, editorials, commentaries, letters, opinion pieces and unpublished studies will be excluded.

Selection process

A ‘Deduplicator’ automation tool will be employed to ensure the effective deduplication of studies.44 Following this, two reviewers will independently screen the articles’ titles and abstracts for eligibility using the specialist screening platform ‘Covidence’.48 Any reviewer discrepancies will be resolved through discussion, and reviewer agreement during each screening phase will be quantified using Cohen’s kappa. If disagreements persist, a third reviewer will adjudicate to facilitate decision-making. This process will be iterated for full-text screening until all eligible papers have been identified.

Data extraction

The two independent reviewers will extract the following data: publication date, first author, study title, study design, time frame, sample size, participant group characteristics, type of multimorbidity, comparator group characteristics, description of structured medication review, mode of delivery, analysis methods and outcome measures. This data will be organised and summarised in tabular format. Subsequently, the compiled information will undergo a thorough review by the two independent reviewers to ensure consistency and accuracy.

Quality assessment

The risk of bias or quality will be assessed based on the eligible articles’ specific study designs. Randomised controlled trials will undergo evaluation using the Cochrane Risk of Bias 2 tool.49 Observational studies will be assessed using the Newcastle-Ottawa scale.50

Data synthesis

The planned analysis includes subgrouping analysis based on combinations of chronic disease and demographic variables (ie, age, sex, deprivation and ethnicity). Additionally, if sufficient data is available, subgroup analysis by mode of SMR delivery (ie, remote, telephone and online questionnaire) will be considered.

If appropriate, a meta-analysis of the data extracted will be conducted to determine the impact of the SMRs on reported outcomes. A narrative synthesis approach will be adopted if a meta-analysis is impossible due to heterogeneity. This method compiles reported outcomes and their respective effect measures in a tabular format. Furthermore, descriptions of the characteristics of SMRs will be synthesised and presented in tables or figures.

Ethics and dissemination

This systematic review is exempt from ethical approval as it aims to collate and summarise peer-reviewed, published evidence. This review will be disseminated in peer-reviewed journals, conferences and patient-led lay summaries.

Patient and public involvement

Although patients and the public were not directly involved in the design of this systematic review protocol, patient partners will be included to interpret the results, co-develop a dissemination strategy and summarise the review for lay summaries.


Evidence is urgently required to support the current transition of the National Health Service (NHS) in England towards an integrated model of care to improve outcomes and alleviate the burden on adults living with multimorbidity and polypharmacy. While recent evidence hints at the potential of SMRs in enhancing outcomes for this patient population, it is unclear how and to what extent. Additionally, there is a lack of understanding regarding how SMRs are commonly delivered (ie, by face-to-face, telephone, video or online consultation). This systematic review aims to fill this critical knowledge gap by summarising the existing evidence on SMRs.

Strengths and limitations

To our knowledge, this will be the first systematic review of the literature examining the effectiveness of SMR. It aims to expand upon the limited existing research, encompassing a broader primary care population. This is critical to explore, given the potential of SMRs as a significant innovation in enhancing care quality for this complex patient group. Furthermore, this review will use novel automation tools to bolster the efficiency of search string development and screening processes.44 However, some potential limitations are anticipated. Ambiguity might arise during the screening process concerning the intervention under investigation, potentially leading to confusion between SMRs and MRs in eligible studies. To mitigate this risk, a clear definition of SMRs within the ‘PICOS’ framework will guide the screening process. Furthermore, due to the complex nature of multimorbidity, heterogeneity across systematic reviews exploring this patient characteristic is expected. Consequently, a meta-analysis may not be possible, which may later be considered a potential review limitation. However, a narrative synthesis will be planned as a contingency to mitigate this.

Potential implications for research, policy and practice

The management of multimorbidity, as highlighted by current health policy and legislation, faces significant challenges due to the scarcity of evidence supporting effective strategies. Traditional scientific literature has often excluded individuals with multimorbidity, hindering the development of a clear clinical consensusfor practice. This systematic review will address this issue by adopting an inclusive approach to diverse disease combinations. By synthesising existing evidence on SMR effectiveness for individuals with multimorbidity and polypharmacy, this review seeks to identify novel evidence gaps, thereby guiding future research in this critical area.

Furthermore, this review aims to contribute quantifiable evidence supporting the successful implementation of SMRs in primary care. As of October 2020, Primary Care Networks in England must conduct SMRs as part of their direct enhanced services (DES) medicines optimisation contracts.26 28 However, broad guidelines make it unclear which SMR components and what mode of delivery constitute best practice for this intervention. By examining the mode of SMR delivery and synthesising SMR characteristics, this review strives to inform the development of a consistent approach to delivery.

Furthermore, this research aligns with the objectives of the NHS Long-Term Plan, which is to optimise medication provision by targeting inappropriate prescribing.51 The DES requirement to conduct SMRs further underscores the significance of this review in guiding decision-makers within England's primary care system . Providing evidence-based insights is crucial for facilitating informed decision-making and implementing innovative interventions that benefit this complex patient population.

Ethics statements

Patient consent for publication

Ethics approval

Not applicable.


Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.


  • X @@elenaklle, @@RehamDK, @@hadar_zaman1, @@ana_luisa_neves, @Azeem_Majeed, @benedicthayhoe

  • Contributors ELE, GG, ALN, AM, HZ and BWJH contributed to the conception and design of this systematic review protocol. ELE wrote the manuscript with input from all authors. ELE and RA contributed to the development of the search strategy.

  • Funding This work is independent research supported by the National Institute for Health and Care Research (NIHR) Applied Research Collaboration Northwest London (ARC NWL). ALN is also funded by NIHR Patient Safety Research Collaborative, with infrastructure support from Imperial NIHR Biomedical Research Centre.This work is independent research supported by the National Institute for Health and Care Research (NIHR) Applied Research Collaboration Northwest London (ARC NWL). ALN is also funded by NIHR Patient Safety Research Collaborative, with infrastructure support from Imperial NIHR Biomedical Research Centre.

  • Disclaimer The views expressed in this publication are those of the authors and not necessarily those of the NIHR or Department of Health and Social Care.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.