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Nurse-led medicines’ monitoring in care homes study protocol: a process evaluation of the impact and sustainability of the Adverse Drug Reaction (ADRe) Profile for Mental Health Medicines

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Journal:

Manuscript ID

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Article Type:

bmjopen-2018-023377

Date Submitted by the Author:

Jordan, Susan; Swansea University, College of Human and Health Sciences Bannner, Timothy; Cardiff University, Welsh School of Pharmacy Gabe-Walters, Marie; Swansea University, College of Human and Health Sciences Mikhail, Jane; Swansea University College of Human and Health Sciences, Round, Jeff; University of Bristol School of Social and Community Medicine Snelgrove, Sherrill; Swansea University, College of Human and Health Sciences Storey, Mel; Swansea University College of Human and Health Sciences Wilson, Douglas; Swansea University Hughes, David; University Wales Swansea, School of Health Science

Keywords:

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Complete List of Authors:

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Adverse events < THERAPEUTICS, Protocols & guidelines < HEALTH SERVICES ADMINISTRATION & MANAGEMENT, Organisation of health services < HEALTH SERVICES ADMINISTRATION & MANAGEMENT, Quality in health care < HEALTH SERVICES ADMINISTRATION & MANAGEMENT, Adult psychiatry < PSYCHIATRY

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Fo Figure 1. The Medication Chain (Mono) 67x53mm (300 x 300 DPI)

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BMJ Open

Figure 2. Study Flow Diagram (Colour) 75x106mm (300 x 300 DPI)

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

BMJ Open

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Page 44 of 53

Figure 2. Study Flow Diagram (Mono) 75x106mm (300 x 300 DPI)

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

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Figure 3. Logic model for ADRe (Colour) 84x114mm (300 x 300 DPI)

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Figure 3. Logic model for ADRe (Mono) 84x114mm (300 x 300 DPI)

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Page 47 of 53

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For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

1

BMJ Open

SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents* Section/item

ItemNo Description

Page No

Administrative information Title

1

Descriptive title identifying the study design, 1 population, interventions, and, if applicable, trial acronym

Fo

Trial identifier and registry name. If not yet registered, name of intended registry

2

2b

All items from the World Health Organization Trial Registration Data Set

Trial registration

2a

2

3

Date and version identifier

As registered

Sources and types of financial, material, and other support

39-40

5a

Names, affiliations, and roles of protocol contributors

39

5b

Name and contact information for the trial sponsor

13

5c

Role of study sponsor and funders, if any, in 13; 39 study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication, including whether they will have ultimate authority over any of these activities

5d

Composition, roles, and responsibilities of the coordinating centre, steering committee, endpoint adjudication committee, data management team, and other individuals or groups overseeing the trial, if applicable (see Item 21a for data monitoring committee)

4

Roles and responsibilities

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Page 48 of 53

39-40

Introduction

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1

Page 49 of 53

6a

Description of research question and justification for undertaking the trial, including summary of relevant studies (published and unpublished) examining benefits and harms for each intervention

4-5

6b

Explanation for choice of comparators

N/A

Objectives

7

Specific objectives or hypotheses

5

Trial design

8

Description of trial design including type of trial (eg, parallel group, crossover, factorial, single group), allocation ratio, and framework (eg, superiority, equivalence, noninferiority, exploratory)

7-11

Background and rationale

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Methods: Participants, interventions, and outcomes

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Study setting

9

Description of study settings (eg, community clinic, academic hospital) and list of countries where data will be collected. Reference to where list of study sites can be obtained

6

Eligibility criteria

10

Inclusion and exclusion criteria for participants. If applicable, eligibility criteria for study centres and individuals who will perform the interventions (eg, surgeons, psychotherapists)

6-7

Interventions

11a

Interventions for each group with sufficient detail 8-9 to allow replication, including how and when they will be administered

11b

Criteria for discontinuing or modifying allocated interventions for a given trial participant (eg, drug dose change in response to harms, participant request, or improving/worsening disease)

11c

Strategies to improve adherence to intervention 10 protocols, and any procedures for monitoring adherence (eg, drug tablet return, laboratory tests)

11d

Relevant concomitant care and interventions that are permitted or prohibited during the trial

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10-11

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

2

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Outcomes

12

Primary, secondary, and other outcomes, 12 including the specific measurement variable (eg, systolic blood pressure), analysis metric (eg, change from baseline, final value, time to event), method of aggregation (eg, median, proportion), and time point for each outcome. Explanation of the clinical relevance of chosen efficacy and harm outcomes is strongly recommended

Participant timeline

13

Time schedule of enrolment, interventions 8-11 (including any run-ins and washouts), assessments, and visits for participants. A schematic diagram is highly recommended (see Figure)

Sample size

Fo

Recruitment

15

14

Estimated number of participants needed to achieve study objectives and how it was determined, including clinical and statistical assumptions supporting any sample size calculations

7

Strategies for achieving adequate participant enrolment to reach target sample size

7

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Methods: Assignment of interventions (for controlled trials) Allocation:

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Sequence generation

16a

Method of generating the allocation sequence N/A (eg, computer-generated random numbers), and list of any factors for stratification. To reduce predictability of a random sequence, details of any planned restriction (eg, blocking) should be provided in a separate document that is unavailable to those who enrol participants or assign interventions

Allocation concealment mechanism

16b

Mechanism of implementing the allocation sequence (eg, central telephone; sequentially numbered, opaque, sealed envelopes), describing any steps to conceal the sequence until interventions are assigned

Implementation 16c

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Page 50 of 53

N/A

Who will generate the allocation sequence, who N/A will enrol participants, and who will assign participants to interventions

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

3

Page 51 of 53

Blinding (masking)

17a

Who will be blinded after assignment to interventions (eg, trial participants, care providers, outcome assessors, data analysts), and how

N/A

17b

If blinded, circumstances under which unblinding is permissible, and procedure for revealing a participant’s allocated intervention during the trial

N/A

Methods: Data collection, management, and analysis Data collection methods

18a

Plans for assessment and collection of 10-11 outcome, baseline, and other trial data, including any related processes to promote data quality (eg, duplicate measurements, training of assessors) and a description of study instruments (eg, questionnaires, laboratory tests) along with their reliability and validity, if known. Reference to where data collection forms can be found, if not in the protocol

18b

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Plans to promote participant retention and complete follow-up, including list of any outcome data to be collected for participants who discontinue or deviate from intervention protocols

N/A

12-14

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Data management

19

Plans for data entry, coding, security, and storage, including any related processes to promote data quality (eg, double data entry; range checks for data values). Reference to where details of data management procedures can be found, if not in the protocol

Statistical methods

20a

Statistical methods for analysing primary and 12 secondary outcomes. Reference to where other details of the statistical analysis plan can be found, if not in the protocol

20b

Methods for any additional analyses (eg, subgroup and adjusted analyses)

20c

Definition of analysis population relating to N/A protocol non-adherence (eg, as randomised analysis), and any statistical methods to handle missing data (eg, multiple imputation)

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N/A

Methods: Monitoring

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

4

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Data monitoring

21a

Composition of data monitoring committee 39-40 (DMC); summary of its role and reporting structure; statement of whether it is independent from the sponsor and competing interests; and reference to where further details about its charter can be found, if not in the protocol. Alternatively, an explanation of why a DMC is not needed

21b

Description of any interim analyses and stopping guidelines, including who will have access to these interim results and make the final decision to terminate the trial

N/A

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Harms

22

Plans for collecting, assessing, reporting, and 11 managing solicited and spontaneously reported adverse events and other unintended effects of trial interventions or trial conduct

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Auditing

23

Frequency and procedures for auditing trial N/A conduct, if any, and whether the process will be independent from investigators and the sponsor

Ethics and dissemination

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24

Plans for seeking research ethics committee/institutional review board (REC/IRB) approval

Protocol amendments

25

Plans for communicating important protocol modifications (eg, changes to eligibility criteria, outcomes, analyses) to relevant parties (eg, investigators, REC/IRBs, trial participants, trial registries, journals, regulators)

Consent or assent

26a

Who will obtain informed consent or assent from 13 potential trial participants or authorised surrogates, and how (see Item 32)

11-12

26b

Additional consent provisions for collection and N/A use of participant data and biological specimens in ancillary studies, if applicable

Confidentiality

27

How personal information about potential and 13-14 enrolled participants will be collected, shared, and maintained in order to protect confidentiality before, during, and after the trial

Declaration of interests

28

Financial and other competing interests for principal investigators for the overall trial and each study site

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Page 52 of 53

39-40

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

5

Page 53 of 53

Access to data

29

Statement of who will have access to the final trial dataset, and disclosure of contractual agreements that limit such access for investigators

N/A

Ancillary and post-trial care

30

Provisions, if any, for ancillary and post-trial care, and for compensation to those who suffer harm from trial participation

N/A

Dissemination policy

31a

Plans for investigators and sponsor to N/A communicate trial results to participants, healthcare professionals, the public, and other relevant groups (eg, via publication, reporting in results databases, or other data sharing arrangements), including any publication restrictions

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Fo 31b

Authorship eligibility guidelines and any intended use of professional writers

39

31c

Plans, if any, for granting public access to the full protocol, participant-level dataset, and statistical code

N/A

Appendices

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Model consent form and other related documentation given to participants and authorised surrogates

6, 13

Biological specimens

Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular analysis in the current trial and for future use in ancillary studies, if applicable

N/A

33

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*It is strongly recommended that this checklist be read in conjunction with the SPIRIT 2013 Explanation & Elaboration for important clarification on the items. Amendments to the protocol should be tracked and dated. The SPIRIT checklist is copyrighted by the SPIRIT Group under the Creative Commons “Attribution-NonCommercial-NoDerivs 3.0 Unported” license.

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6

BMJ Open

Nurse-led medicines’ monitoring in care homes study protocol: a process evaluation of the impact and sustainability of the Adverse Drug Reaction (ADRe) Profile for Mental Health Medicines

BMJ Open

Fo

Journal:

Manuscript ID

Protocol

rp

Article Type:

bmjopen-2018-023377.R1

Date Submitted by the Author:

Jordan, Susan; Swansea University, College of Human and Health Sciences Bannner, Timothy; Cardiff University, Welsh School of Pharmacy Gabe-Walters, Marie; Swansea University, College of Human and Health Sciences Mikhail, Jane; Swansea University College of Human and Health Sciences, Round, Jeff; University of Bristol School of Social and Community Medicine Snelgrove, Sherrill; Swansea University, College of Human and Health Sciences Storey, Mel; Swansea University College of Human and Health Sciences Wilson, Douglas; Swansea University Hughes, David; University Wales Swansea, School of Health Science

Primary Subject Heading: Secondary Subject Heading:

Pharmacology and therapeutics

Mental health, Nursing, Geriatric medicine, Qualitative research Adverse events < THERAPEUTICS, Protocols & guidelines < HEALTH SERVICES ADMINISTRATION & MANAGEMENT, Organisation of health services < HEALTH SERVICES ADMINISTRATION & MANAGEMENT, Quality in health care < HEALTH SERVICES ADMINISTRATION & MANAGEMENT, Adult psychiatry < PSYCHIATRY

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Keywords:

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Complete List of Authors:

02-Jul-2018

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

Page 1 of 50

1 2 3 4

Nurse-led medicines’ monitoring in care homes study protocol: a process evaluation of the impact and sustainability of the Adverse Drug Reaction (ADRe) Profile for Mental Health Medicines Short title: Nurse-led medicines’ monitoring using the Adverse Drug Reaction (ADRe) Profile

5 6

Corresponding author: Professor Sue Jordan, College of Human and Health Sciences,

7

Swansea University, Swansea SA2 8PP. [email protected] 01792518541

Fo

8 9

Authors: Jordan S. College of Human and Health Sciences, Swansea University. Swansea.

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10

Wales; Banner T. Welsh School of Pharmacy, Cardiff University, Cardiff. Wales; Gabe-

11

Walters M. College of Human and Health Sciences, Swansea University, Swansea. Wales;

12

Mikhail JM. College of Human and Health Sciences, Swansea University, Swansea. Wales;

13

Round J. School of Social and Community Medicine, University of Bristol, Bristol. England;

14

Snelgrove S. College of Human and Health Sciences, Swansea University. Swansea. Wales;

15

Storey M. College of Human and Health Sciences, Swansea University, Swansea. Wales;

16

Wilson DW. College of Human and Health Sciences, Swansea University, Swansea. Wales;

17

Hughes D. College of Human and Health Sciences, Swansea University, Swansea. Wales; for

18

the Medicines’ Management Group

19

Word Count: 5019

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BMJ Open

1 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

BMJ Open

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Abstract

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Introduction

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Improved medicines’ management could lead to real and sustainable improvements to the

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care of older adults. The over-use of mental health medicines has featured in many reports,

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and insufficient patient monitoring has been identified as an important cause of medicines-

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related harms. Nurse-led monitoring using the structured Adverse Drug Reaction (ADRe)

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Profile identifies and addresses the adverse effects of mental health medicines. Our study

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investigates clinical impact and what is needed to sustain utilisation in routine practice in

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care homes.

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Methods and Analysis

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This process evaluation will use interviews and observations with the participants of all five

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homes involved in earlier research, and five newly recruited homes caring for people

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prescribed mental health medicines. The ADRe Profile is implemented by nurses, within

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existing resources, to check for signs and symptoms of adverse drug reactions, initiate

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amelioration, and share findings with pharmacists and prescribers for medication review.

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Outcome measures are the numbers and nature of problems addressed, and understanding

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of changes needed to optimise clinical gain and sustain implementation.

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Data will be collected by 30 observations and 30 semi-structured interviews. Clinical gains

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will be described and narrated. Interview analysis will be based on the constant comparative

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method.

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Ethics and Dissemination

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Ethical approval was conferred by the NHS Wales Research Ethics Committee (REC). If the

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ADRe Profile can be sustained in routine practice, it has potential to a) improve the lives of

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patients e.g. by reducing pain and sedation, and b) assist in early identification of problems

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caused by ADRs. Therefore, in addition to peer-reviewed publications and conferences, we

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shall communicate our findings to healthcare professionals, policy makers and sector

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regulators.

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Registration: ClinicalTrials.gov NLM Identifier NCT03110471

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2 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

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Key words

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Adverse drug reactions, patient safety, nursing, long-term care (MeSH checked 14.8.17)

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Strengths and Limitations of this Study

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This intervention is the first simple, low-risk, low-cost, multidisciplinary strategy to check

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patients comprehensively for potential adverse effects of their medicines and

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ameliorate any harms identified.

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For the last decade some 5-8% of UK unplanned hospital admissions have been caused by adverse drug reactions (ADRs), most of which were preventable. Our intervention has

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potential to address this situation, but sustainability needs to be tested.

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The intervention was effective in a pragmatic randomised controlled trial (RCT), but a

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qualitative exploration of how it embeds into routine care is needed to highlight a) how

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clinical gains are achieved and b) the barriers to and facilitators of sustained

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implementation. •

We are working with volunteer care homes in South West Wales and the transferability

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of findings will depend on readers’ interpretations of their practical adequacy, and

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professionals’ assessment of the importance of using ADRe.

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BMJ Open

3 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

BMJ Open

1 2 3

Nurse-led medicines’ monitoring in care homes study protocol: a process evaluation of the impact and sustainability of the Adverse Drug Reaction (ADRe) Profile for Mental Health Medicines

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Background

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The success of the WHO 3rd Global Patient Safety Challenge on Medication Safety will

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depend on effective strategies to address concerns that “medicines sometimes cause

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serious harm if taken incorrectly, monitored insufficiently or as the result of errors,

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accidents or communication problems”.[1] Meeting the challenge of insufficient monitoring

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will demand innovation and change to current practice. Most adverse drug reactions (ADRs)

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or side-effects [glossary, supplementary file 1] are due to poor monitoring, not poor

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prescribing.[2-6]

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Preventable adverse drug reactions (ADRs) have proved an intractable problem over the last

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decade, causing 5-8% of unplanned UK hospital admissions,[7-8] costing the NHS £1bn-

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2.5bn each year.[9] The problem is at least as extensive in developing countries, at ~10% of

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admissions.[10] Most adverse drug events (ADEs) [glossary, supplementary file 1], adverse

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drug reactions (ADRs) [glossary, supplementary file 1], and medicines’ mismanagement

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(including errors by patients and professionals) are preventable,[8, 11] but there are no

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comprehensive systematic approaches to the problem.

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Some 50% of residents in UK care homes [glossary, supplementary file 1] are prescribed

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mental-health medicines,[12] doses in care homes[13], and primary care[14] are often

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excessive,4.8-37% of older people with cognitive impairment have ADRs[15], and the

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proportion of care home residents exposed to inappropriate medications (any) ranges from

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34% (definition from the Swedish National Board of Health and Welfare) [16] to >50%

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(definitions based on instruments selected by each study author) [17]. ADRs to mental-

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health medicines can be life-threatening (e.g. cardiac arrhythmias, cardiac hypo-function),

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or debilitating (e.g. drug-induced Parkinsonism, ataxia, postural hypotension) or subtle, and

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mistaken for signs of ageing or underlying pathology. They can be overlooked, leading to

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behaviour problems, xerostomia, constipation, poor food and/ or fluid intake, tremor,

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restlessness, sedation, pain, double incontinence or other problems, all causing potential

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4 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

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loss of comfort and dignity.[18-19] Eighteen percent of 13,699 UK primary care incident

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reports and 24% of 996 deaths or serious harms recorded 2005-13 were attributed to

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prescription medicines (any), mainly avoidable ADRs, largely due to inadequate monitoring,

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communication or decision-making.[20] We suggest this care gap can be closed by

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formalised structured medicines monitoring.[19, 21-24]

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A consensus is emerging around over-prescribing in care homes,[13-14,16,25-26] and this

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work is now a priority for Welsh Government. However, there is less agreement regarding

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the changes needed in routine care[1, 27-29] and reviewers indicate that evidence

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supporting single-profession interventions is equivocal.[11, 29-34] The UK Department of

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Health’s National Dementia Strategy, launched 2009[13], and Medicines and Healthcare

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products Regulatory Agency (MHRA) recommendations[35] have not reduced antipsychotic

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prescribing[36], whilst the Adverse Drug Reaction (ADRe) Profile succeeded in a randomised

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controlled trial.[19] ADRe, formerly WWADR, is available, with further information, on our

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website: http://www.swansea.ac.uk/adre/ . It has potential to reduce costs,[19] whilst

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addressing concerns over care quality,[25, 27-28, 37] medicines’ over-use,[14] and the

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responsibility of those administering medicines to report patients’ changes to prescribers,

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despite time constraints limiting face-to-face multidisciplinary team meetings.[38]

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The FDA warning on antipsychotic prescribing was followed by a shift towards increased use

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of benzodiazepines,[39] and there is no evidence of benefit from long-term antidepressants

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in older adults,[40] therefore, to ensure a comprehensive approach, ADRe includes all

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current mental health medicines. When used by nurses, both registered nurses and nursing

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assistants, ADRe has improved quality of care by addressing physical health issues for all

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patients monitored and identifying and addressing serious adverse events in ~10% of

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patients. Examples of previously unsuspected problems that we identified and addressed

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include: cardiac arrhythmias and severe hypertension,[21] drug-induced Parkinsonism,[23]

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respiratory tract infections,[41] pain and nausea,[19] chest pain and valproate-induced

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pancreatitis.[24] No harms have been reported from use of ADRe. We now aim to explore

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what is needed to optimise clinical gains and sustain implementation of ADRe in routine

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practice. (Figure 1).

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BMJ Open

5 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

BMJ Open

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Study design and Methods This evaluation will integrate data from observations and interviews to explore clinical gains

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and any challenges in delivering the intervention, differences between intentions and

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delivery, the best way to embed medicines’ monitoring into practice, and relationships

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between ADRe, clinical contexts and processes and outcomes of care.[42-43]

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Setting We are working with 10 care homes in Abertawe Bro Morgannwg University Health Board

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(ABMUHB) whose management teams have volunteered to participate. This includes all 5

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care homes involved in a previous study, who are best placed to report on sustainability [19]

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and 5 new care homes. ABMUHB is in a region of South West Wales that receives EU

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convergence funding because GDP is below 75% of the community mean.[44] It serves a

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population of 525,000 (33,000 aged 75-84, and 13,000 over 85).[45] Care homes are

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governed by legislation[46] and regularly inspected to ensure they meet pre-specified

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standards.[47] Regularity of contact between care homes and pharmacists, consultants and

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GPs varies across South West Wales.

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Participants Inclusion criteria for care homes are: providing residential or nursing care or both to >4

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service users meeting inclusion criteria (vi) and willing to use ADRe in routine practice. We

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excluded three homes participating in a previous feasibility study, as they are affiliated to a

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home is already participating, which would have introduced ties into the data,[23] and

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homes with