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Trial registered on ANZCTR


Registration number
ACTRN12619000727145
Ethics application status
Approved
Date submitted
1/05/2019
Date registered
14/05/2019
Date last updated
14/05/2019
Date data sharing statement initially provided
14/05/2019
Date results information initially provided
14/05/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
GP-led deprescribing in community living older Australians: A pragmatic, mixed methods, exploratory controlled trial
Scientific title
GP-led deprescribing in community living older Australians: A pragmatic, mixed methods, exploratory controlled trial
Secondary ID [1] 298115 0
None.
Universal Trial Number (UTN)
U1111-1231-3273
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Potentially inappropriate polypharmacy 312645 0
Condition category
Condition code
Public Health 311139 311139 0 0
Health service research

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention consisted of:
1) one five-hour face-to-face interactive deprescribing training workshop for GPs and accredited pharmacists (i.e. pharmacists accredited to undertake Home Medicines Reviews [HMRs]);
2) a 30-minute face-to-face deprescribing consultation between GPs and their usual patients to undertake a comprehensive review of their medicines (CMR) using a standardised software template co-designed by GPs; (1)
3) Option for GPs to refer patients for an HMR by one of the participating pharmacists with full access to the patient’s medical record.

The interactive training workshop was facilitated by a consultant general physician with expertise in deprescribing and an accredited pharmacist experienced in CMR. The workshop involved:
1) one-hour didactic presentation of the evidence around potentially inappropriate polypharmacy (PIP) and deprescribing;
2) three-hour interactive session applying principles of the CEASE deprescribing framework (see below) to two case studies, during which evidence summaries and support resources were presented and barriers and enablers to deprescribing in practice were discussed; and
3) one-hour session to co-design a software template for use in deprescribing appointments which reminded GPs when to consider deprescribing a medicine and served as a tool for collecting data on changes to medicines, including their rationales (as per reference 1).

CEASE PRINCIPLES(2)
• Obtain a best possible medication history
• Reconcile medication and diagnosis list & verify indications
• Estimate patient risk of adverse drug events
• Review utility of each medication
• Prioritise targets for deprescribing & formulate agreed plan
• Implement and monitor the deprescribing plan

The intervention was targeted at the clinician level, with quantitative and qualitative measures gathered at the clinician and patient level. The aspects of the intervention were informed by principles of behaviour change and an awareness of barriers and enablers to deprescribing in primary care which the investigators had identified in previous studies. (3, 4) At all times the patients remained under the care of their usual GP.

1. Anderson K, Foster MM, Freeman CR, Scott IA. A multifaceted intervention to reduce inappropriate polypharmacy in primary care: research co-creation opportunities in a pilot study. Med J Aust. 2016;204(7 Suppl):S41-4.
2. Scott IA, Hilmer SN, Reeve E, et al. Reducing inappropriate polypharmacy: The process of deprescribing. JAMA Intern Med. 2015;175(5):827-34.
3. Anderson K, Stowasser D, Freeman C, Scott I. Prescriber barriers and enablers to minimising potentially inappropriate medications in adults: a systematic review and thematic synthesis. BMJ open. 2014;4(12):e006544.
4. Anderson K, Foster M, Freeman C, Luetsch K, Scott I. Negotiating “Unmeasurable Harm and Benefit”. Qual Health Res. 2017:1049732316687732.
Intervention code [1] 314339 0
Treatment: Other
Comparator / control treatment
Care normally provided by GPs to patients with polypharmacy continued, including referral to specialists, allied health professionals and pharmacists for HMR. The study was described as a quality use of medicines activity for community living older patients with polypharmacy to avoid using the term deprescribing which, while used in the intervention sites, did not apply to the usual care sites.
Control group
Active

Outcomes
Primary outcome [1] 319917 0
Change in the number of ‘agreed’ regular medicines deprescribed (ceased or dose reduced) per patient.

Regular medicines comprised both prescribed medicines and supplements or over the counter medicines not necessarily requiring a prescription. Short course therapies (e.g. antibiotics, high-dose steroids, pain relievers for self-limiting acute complaints) were excluded. ‘Agreed’ medicines were those where the GP record and patient self-report were in total agreement.
Timepoint [1] 319917 0
Baseline and 4 months post intervention (defined as four months after the deprescribing appointment for intervention patients or the time of baseline data extraction from the practice for usual care patients).
Secondary outcome [1] 370190 0
Medication-specific outcome: Change in the number of agreed regular medicines ceased per patient from data collected from GP records and patient self-report.
Timepoint [1] 370190 0
Baseline and 4 months post intervention (defined as four months after the deprescribing appointment for intervention patients or the time of baseline data extraction from the practice for usual care patients).
Secondary outcome [2] 370191 0
Medication-specific outcome: Change in the number of agreed regular medicines dose-reduced per patient from data collected from GP records and patient self-report.
Timepoint [2] 370191 0
Baseline and 4 months post intervention (defined as four months after the deprescribing appointment for intervention patients or the time of baseline data extraction from the practice for usual care patients).
Secondary outcome [3] 370192 0
Medication-specific outcome: Change in the number of agreed regular medicines commenced per patient from data collected from GP records and patient self-report.
Timepoint [3] 370192 0
Baseline and 4 months post intervention (defined as four months after the deprescribing appointment for intervention patients or the time of baseline data extraction from the practice for usual care patients).
Secondary outcome [4] 370193 0
Medication-specific outcome: Change in the number of agreed regular medicines dose-increased per patient from data collected from GP records and patient self-report.
Timepoint [4] 370193 0
Baseline and 4 months post intervention (defined as four months after the deprescribing appointment for intervention patients or the time of baseline data extraction from the practice for usual care patients).
Secondary outcome [5] 370194 0
Medication-specific outcome: Change in the number of agreed as-required (prn) medicines commenced per patient from data collected from GP records and patient self-report.
Timepoint [5] 370194 0
Baseline and 4 months post intervention (defined as four months after the deprescribing appointment for intervention patients or the time of baseline data extraction from the practice for usual care patients).
Secondary outcome [6] 370195 0
Medication-specific outcome: The proportion of regular medicines deprescribed as a proportion of all regular medicines based on data collected from GP records and patient self-report.
Timepoint [6] 370195 0
Baseline and 4 months post intervention (defined as four months after the deprescribing appointment for intervention patients or the time of baseline data extraction from the practice for usual care patients).
Secondary outcome [7] 370196 0
Medication-specific outcome: Classes of medicines deprescribed (using the Australian Medicines Handbook as a guide for therapeutic classification) based on data collected from GP records and patient self-report.
Timepoint [7] 370196 0
4 months post intervention (defined as four months after the deprescribing appointment for intervention patients or the time of baseline data extraction from the practice for usual care patients).
Secondary outcome [8] 370197 0
Patient-reported outcome: Change in health-related quality of life (HRQoL) as measured by the EQ-5D-5L between the intervention and usual care group.
Timepoint [8] 370197 0
Baseline and 4 months post intervention (defined as four months after the deprescribing appointment for intervention patients or the time of baseline data extraction from the practice for usual care patients).
Secondary outcome [9] 370198 0
Patient-reported outcome: Changes in intervention Patients’ Attitudes Towards Deprescribing (PATD) as measured by the PATD questionnaire.
Timepoint [9] 370198 0
Baseline and 4 months post intervention (i.e. after the deprescribing appointment).
Secondary outcome [10] 370199 0
Patient-reported outcome: Difference in the mean number of self-reported unplanned hospital presentations/admissions between the intervention and usual care group during the study period.
Timepoint [10] 370199 0
4 months post intervention (defined as four months after the deprescribing appointment for intervention patients or the time of baseline data extraction from the practice for usual care patients).
Secondary outcome [11] 370200 0
Process-measures: Proportion of patients in the intervention arm who had a deprescribing appointment based on data collected from GP records and patient self-report.
Timepoint [11] 370200 0
Approximately two months from the date of GP attendance at the deprescribing training workshop and at study completion.
Secondary outcome [12] 370201 0
Process-measures: Difference between the proportion of patients who had a Home Medicines Review (HMR) by a pharmacist since recruitment to the study based on data collected from GP records and patient self-report.
Timepoint [12] 370201 0
Baseline and 4 months post intervention (defined as four months after the deprescribing appointment for intervention patients or the time of baseline data extraction from the practice for usual care patients).
Secondary outcome [13] 370202 0
Process-measures: Difference between the mean number GP visits per patient during the study period between the intervention and usual care group based on data collected from GP records.
Timepoint [13] 370202 0
4 months post intervention (defined as four months after the deprescribing appointment for intervention patients or the time of baseline data extraction from the practice for usual care patients).
Secondary outcome [14] 370203 0
Safety-protocol: The completion and submission of reports of suspected/actual adverse outcome (e.g. unplanned hospitalisation, deterioration in clinical status) or experience (e.g. dissatisfaction with deprescribing process/outcome) as reported by study participants. A standardised form (attached) was provided to participating GPs (who remained responsible for patient care at all times) for their completion and submission to the research team.
Timepoint [14] 370203 0
Any time throughout the study period.
Secondary outcome [15] 370204 0
Qualitative measures (intervention group only): GPs’ and patients’ experiences of implementing the deprescribing intervention, specifically an exploration of views regarding adoption of the interventions’ elements (GPs), acceptability (GPs and patients) and sustainability (GPs).
Timepoint [15] 370204 0
4-month follow-up phone interview for intervention patients and face-to-face in-depth interviews at study conclusion for each intervention GP.

Eligibility
Key inclusion criteria
There were three participant groups.

1. General practitioners: Working in primary health care and caring for community living older people with polypharmacy; available to attend a deprescribing training workshop in August or September 2015 (intervention arm only); and working the equivalent of four or more, three-hour sessions per week (to ensure adequate access for patients to their usual GP).
While it was intended to recruit a diverse sample of GPs based on age, years of experience and gender balance, it was anticipated that GPs who had been in practice for a longer period may see a higher proportion of older patients compared to more recently qualified GPs. It was therefore accepted that the eligibility criteria may naturally lead to the recruitment of more experienced GPs and this was accepted as a limitation of the study.

2. Pharmacists: Experienced in and/or actively conducting Home Medicines Reviews (HMRs) (5 or more years since attaining accreditation preferred); available to attend a deprescribing training workshop in August or September 2015; willing to travel to provide HMR services to patients of recruited intervention practices.

3. Patients: Active patient of the practice as defined by the Royal Australian College of General Practitioner (RACGP) standards (i.e. had attended the practice three or more times in the past two years) and a regular patient of one of the GPs recruited to the study; aged 65 years or older and living in the community (and not in a Residential Aged Care Facility); taking eight or more regular medicines as listed in the GPs' electronic medical records; capacity to give consent; proficient in speaking and reading English; and contactable by telephone.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. General practitioners: Primarily caring for people aged 65 years or older with polypharmacy residing in aged care facilities (as this was not the care setting of interest).

2. Pharmacists: Conducting medicine reviews primarily for residents in aged care facilities (as this was not the population of interest).

3. Patients: Confusion, cognitive impairment, mental health disorders with psychosis and/or communication difficulties (as documented or confirmed by the patient’s GP) that would preclude informed consent; terminal illness (life expectancy less than six months); a Home Medicines Review (HMR) in the 12 months prior to recruitment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation was not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Non-randomised trial
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
A non-randomised, controlled pre-post mixed methods design was used for this pragmatic, exploratory study. Both quantitative and qualitative data were collected and analysed to assess the feasibility and impact of the intervention in primary care. The study involved a convenience sample of five general practices and 20 GPs in south east Queensland across two study arms: an intervention arm comprising 10 GPs working at three sites who were exposed to the intervention, and a control (herein referred to as ‘usual care’) arm of 10 GPs at two sites who delivered usual care. Two pharmacists were recruited to ensure timely provision of HMR if intervention GPs chose to refer patients for this service.

Allocation to intervention or usual care was made at a general practice level according to the willingness of the GPs in those practices to participate in either the intervention or usual care arm. The small numbers of practices involved precluded conducting a cluster randomised controlled trial (RCT). It was inappropriate for the unit of allocation to be the GP or patient given the potential for contamination effects within practices. That is, patients could not be the unit of randomisation, as the premise of the study was to have the deprescribing appointment with the patient’s usual GP and intervention GPs could not ‘unknow’ what had been learned at the deprescribing workshop. Furthermore, randomisation of GPs within a practice was equally deemed inappropriate, acknowledging that learnings may be shared between colleagues throughout a practice. A consecutive sample of patients for each GP was generated using a written procedure.
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Sample size –

Arbitrary minimum recruitment targets were set to test the feasibility of the intervention including: Three GPs per site (so the number of practices with whom to liaise was manageable); ten GPs each in the intervention and usual care arms; and five patients per GP.

In total, a provisional sample size of 150 patients (approximately 75 each in the intervention and usual care arms of the study) was determined for this exploratory study. There was limited data available on which to base the sample size. A feasibility study in which the CEASE deprescribing guide was applied to acute hospitalised older patients with polypharmacy (defined as eight or more regular medications in this study) in the inpatient setting demonstrated a statistically and clinically significant effect in a sample of 50 patients. (1) The primary care cohort in this study, however, would be potentially healthier and more robust, and deprescribing would be more likely to be anticipatory, rather than reactive (i.e. in response to a hospital admission), making the process of deprescribing, and its benefits, potentially more difficult to achieve. For this reason, it was speculated a larger sample would be required. It was also reasoned that the larger sample size would deliver a suitably diverse patient group with respect to age, gender, comorbidity burden, chronic prescription medication load and usual GP, whilst also allowing for patient drop-outs.

Statistical methods–

Quantitative data were analysed and reported in accordance with usual statistical convention.

Analyses were conducted on the intent-to-treat (ITT) basis. Post-hoc sensitivity analyses were also conducted to account for patients of two GPs who breached the documented patient screening protocol and those of a single GP who left the practice mid-study.

In assessing relative likelihood of medicine changes per patient according to group assignment, negative binomial or Poisson regression models were used, adjusting for age, gender and number of baseline medicines.

Health-related quality of life was measured using EQ-5D-5L domain data converted to dichotomous ‘worse or not worse’ outcomes and analysed using paired Chi-squared tests.

A qualitative descriptive approach was used with thematic analysis conducted in accordance with the Framework method.

(1) McKean M, Pillans P, Scott IA. A medication review and deprescribing method for hospitalised older patients receiving multiple medications. Internal medicine journal. 2016;46(1):35-42.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 302646 0
Government body
Name [1] 302646 0
National Health and Medical Research Council (Grant ID GNT1001157.)
Address [1] 302646 0
16 Marcus Clarke St
Canberra
ACT 2601, Australia
Country [1] 302646 0
Australia
Funding source category [2] 302647 0
Other Collaborative groups
Name [2] 302647 0
Brisbane South Health Primary Health Network
Address [2] 302647 0
Level 1
Building 20/2404 Logan Rd
Eight Mile Plains
QLD 4113, Australia
Country [2] 302647 0
Australia
Primary sponsor type
University
Name
University of Queensland
Address
Faculty of Medicine
The University of Queensland,
Level 8, Health Sciences Building
Building 16/901, Royal Brisbane & Women's Hospital
Herston Qld 4029, Australia
Country
Australia
Secondary sponsor category [1] 302564 0
None
Name [1] 302564 0
None
Address [1] 302564 0
Country [1] 302564 0
Other collaborator category [1] 280660 0
Individual
Name [1] 280660 0
Dr Kristen Anderson
Address [1] 280660 0
Faculty of Medicine
The University of Queensland
Level 8, Health Sciences Building
Building 16/901, Royal Brisbane & Women's Hospital
Herston
QLD 4029, Australia
Country [1] 280660 0
Australia
Other collaborator category [2] 280661 0
Individual
Name [2] 280661 0
A/Prof Ian Scott
Address [2] 280661 0
Department of Internal Medicine and Clinical Epidemiology
Princess Alexandra Hospital
199 Ipswich Rd
Woolloongabba
QLD 4102, Australia
Country [2] 280661 0
Australia
Other collaborator category [3] 280662 0
Individual
Name [3] 280662 0
Dr Christopher Freeman
Address [3] 280662 0
School of Pharmacy
The University of Queensland
20 Cornwall St,
Woolloongabba
QLD 4102, Australia
Country [3] 280662 0
Australia
Other collaborator category [4] 280663 0
Individual
Name [4] 280663 0
Prof Michele Foster
Address [4] 280663 0
The Hopkins Centre, Menzies Health Institute Queensland, Griffith University
Division of Rehabilitation
Princess Alexandra Hospital
199 Ipswich Road
Woolloongabba
QLD 4102, Australia
Country [4] 280663 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303272 0
University of Queensland’s Human Research Ethics Committee,
Ethics committee address [1] 303272 0
The University of Queensland
Cumbrae-Stewart Building
Research Road
Brisbane
QLD 4072
Australia
Ethics committee country [1] 303272 0
Australia
Date submitted for ethics approval [1] 303272 0
09/01/2015
Approval date [1] 303272 0
04/05/2015
Ethics approval number [1] 303272 0
2015000044.

Summary
Brief summary
There is an urgent and growing need to minimise iatrogenic harm from potentially inappropriate polypharmacy (PIP) in ageing populations with multimorbidity. ‘Deprescribing’ aims to minimise PIP. It is the process of clinician-supervised identification and withdrawal (or dose reduction) of medicines where the harms exceed the benefits in the context of an individual patient’s care goals, current function, life expectancy, values and preferences.

General practitioners (GPs), with tacit knowledge of, and an ongoing relationship with, their patients, play a central role in coordinating and delivering healthcare to older patients who are prescribed medicines for multiple health conditions. Research suggests that patients are receptive to discontinuing medicines if their general practitioner feels it is appropriate and worthwhile.

This study aimed to assess the feasibility, effectiveness and safety of a multi-faceted GP-led intervention to minimise PIP in community-living older Australians. Unlike most other deprescribing studies, this intervention leveraged the existing therapeutic relationship between GPs and their usual patients and used an individually-tailored versus a drug class-specific approach to deprescribing. Recognising the time constraints for GPs in routine care and the potential facilitative role of pharmacists in deprescribing, GPs had the option of referring patients to one of the participating pharmacists for a Home Medicines Review to augment the deprescribing process in this study.
Trial website
Trial related presentations / publications
Public notes
Please note that publication of this study is forthcoming, after which more detailed results will be provided.

Contacts
Principal investigator
Name 93086 0
Dr Kristen Anderson
Address 93086 0
School of Pharmacy
University of Queensland
20 Cornwall St
Woolloongabba
QLD 4102 Australia
Country 93086 0
Australia
Phone 93086 0
+61 07 3346 1900
Fax 93086 0
Email 93086 0
k.anderson8@uq.edu.au
Contact person for public queries
Name 93087 0
Dr Kristen Anderson
Address 93087 0
School of Pharmacy
University of Queensland
20 Cornwall St
Woolloongabba
QLD 4102 Australia
Country 93087 0
Australia
Phone 93087 0
+61 07 3346 1900
Fax 93087 0
Email 93087 0
k.anderson8@uq.edu.au
Contact person for scientific queries
Name 93088 0
Dr Kristen Anderson
Address 93088 0
School of Pharmacy
University of Queensland
20 Cornwall St
Woolloongabba
QLD 4102 Australia
Country 93088 0
Australia
Phone 93088 0
+61 07 3346 1900
Fax 93088 0
Email 93088 0
k.anderson8@uq.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The ethics application for this study was silent on the issue of sharing individual patient data (IPD) for other research projects. Data may be able to be provided, pending submission and approval of an amendment to the existing ethics application, but IPD is not available to be shared presently.
What supporting documents are/will be available?
Other
'Other' documents specified
Workshop and other study resources are available by reasonable request to the Chief Investigator.
How or where can supporting documents be obtained?
Type [1] 2033 0
Other
Citation [1] 2033 0
Link [1] 2033 0
Email [1] 2033 0
Other [1] 2033 0
Form for reporting actual/suspected adverse event or experience from deprescribing
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Yes
Other publication details
Citation type [1] 1973 0
Thesis/dissertation
Citation/DOI/link/details [1] 1973 0
Anderson, Kristen (2018). Minimising potentially inappropriate polypharmacy in community living older people: a multi-phase, mixed methods study to develop and pilot a general practitioner-led deprescribing intervention in primary care. PhD Thesis, Faculty of Medicine, The University of Queensland. https://doi.org/10.14264/uql.2018.441
Attachments [1] 1973 0
Results – basic reporting
Results – plain English summary
After 18 weeks, the difference between intervention and usual care groups in the number of regular medicines deprescribed (ceased or dose reduced) per patient was approximately half a medicine. Adjusting for age, gender and number of regular medicines taken at the start of the study, intervention patients were more than twice as likely to have at least one regular medicine deprescribed than usual care patients. The intervention was not associated with any reported harm or deterioration in health-related quality of life which may have resulted from injudicious deprescribing attempts. A subset of intervention patients reported greater certainty in the necessity and appropriateness of their medicines at study end. The majority of GPs and patients derived satisfaction from the process of medicines review and consultation during deprescribing appointments, irrespective of whether the outcome of successful medicine withdrawal was achieved. Whilst seen as feasible in the short-term, GPs gave mixed responses regarding the sustainability of the intervention in routine care. Study limitations include: short-follow-up, the potential for bias in identifying patients eligible for deprescribing and the use of a convenience sample of interested practices and clinicians. The intervention was shown to be feasible and safe in the short-term, conferring clinically modest effect. This feasibility study holds important lessons for others undertaking research in this field.