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Trial registered on ANZCTR


Registration number
ACTRN12618000410257
Ethics application status
Approved
Date submitted
17/11/2017
Date registered
21/03/2018
Date last updated
21/03/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Medication adherence management in a community pharmacy setting (AdherenciaMED): a cluster randomized controlled trial
Scientific title
The effect of a medication adherence management service in a community pharmacy setting on patient's adherence to medications: a cluster randomized controlled trial
Secondary ID [1] 293337 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypertension 305431 0
Chronic Obstructive Pulmonary Disease 305432 0
Asthma 305433 0
Condition category
Condition code
Cardiovascular 304708 304708 0 0
Hypertension
Respiratory 304709 304709 0 0
Asthma
Respiratory 304710 304710 0 0
Chronic obstructive pulmonary disease
Public Health 305772 305772 0 0
Health promotion/education

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patient tailored brief complex interventions to improve, reinforce and maintain adherence behaviour and their impact in clinical, economical and humanistic outcomes.

The intervention will be delivered by pharmacists, in community pharmacies distributed in 6 provinces in Spain to patients with medications for treating asthma, COPD and hypertension. A total of six monthly face to face interviews will be agreed between the pharmacist and the patient in a consultation hold on a counselling area. All the data will be recorded in an electronic data collection form specifically developed for the study.

Before patient recruitment, pharmacists allocated to the Intervention group will be trained on the study protocol and service delivery, The training will be provided by the members of the research team, and will involve theoretical and practical (role play) approaches. It will be focused on clinical aspects of the conditions, adherence management, including the application of several frameworks for changing patient behaviour (motivational interviewing, health belief model, necessity and concerns model, information-motivation-strategy model and transtheoretical model).

During each interview a review of the patient's current medications will be undertaken. The dispensing dates of each medication will also be recorded, based on the pharmacy refill data. These variables will be used for the further calculation proportion of days covered.
All the new medications and clinical conditions will be recorded.

The pharmacist then will assess (1) medication adherence (through the Morisky-4 self report questionnaire) and (2) inhaler technique (through a specific inhaler device checklist). This step will only be undertaken in patients with COPD or asthma.
Based on these responses the patient will be identified in one of the four categories of non-adherence (intentional, non-intentional, combined, erratic). The concepts of Motivational Interviewing will be applied throughout the whole pharmacist-patient interaction and specific models will be used based on the patient's classification of non-adherence. For all the non-adherent patients, the health belief model, Necessity and Concerns, Information-Motivation-Strategy and Transtheoretical model will be applied.

A list of barriers and strategies has been defined based on defined determinants of non-adherence according to the World Health Organization; and also strategies to maintain and reinforce adherence in adherent patients. Strategies will cover educational (e.g. written or oral information), social (e.g. family support), healthcare communication (e.g. regimen simplification or change) or medication aids (e.g. dose taking aids, phone messages, alarms) amongst others.

The project will be monitored by Practice Change Facilitators (PCF), who will ensure the quality of the service delivery and will support the participant pharmacists through monthly visits.
Intervention code [1] 299603 0
Behaviour
Intervention code [2] 300371 0
Treatment: Other
Comparator / control treatment
Control group – Usual care

Patients in the control group will follow the same 6 monthly interviews with the pharmacist but only sociodemographic and clinical and medication adherence data will be collected and usual care will be provided. By usual care it means the safe supply of medicines and medication-taking advice to the patient.
Control group
Active

Outcomes
Primary outcome [1] 303933 0
Adherence to medications: Self-Report and Proportion of Days Covered
Timepoint [1] 303933 0
At baseline, month 1, month 2, month 3, month 4, month 5
Secondary outcome [1] 340494 0
Clinical Outcome: Asthma control assessed using the Asthma Control Questionnaire (ACQ)
Timepoint [1] 340494 0
At baseline, month 1, month 2, month 3, month 4, month 5,
Secondary outcome [2] 340495 0
Clinical Outcome: COPD control assessed using the COPD Questionnaire (CCQ)
Timepoint [2] 340495 0
At baseline, month 1, month 2, month 3, month 4, month 5,
Secondary outcome [3] 340496 0
Clinical Outcome: Blood Pressure Levels assessed measuring blood pressure levels with OMROM or similar
Timepoint [3] 340496 0
At baseline, month 1, month 2, month 3, month 4, month 5
Secondary outcome [4] 340497 0
Humanistic Outcome: Health-related quality of life assessed using EuroQol-SD-5L
Timepoint [4] 340497 0
At baseline, month 2 and month 5.
Secondary outcome [5] 340498 0
Economic outcome: Patient use of health resources (number of emergency department visits, hospital admissions, visits to general practitioner) assessed by patient self report during the interviews and cost calculated using prices from the public system.
Timepoint [5] 340498 0
At baseline and month 5
Secondary outcome [6] 343346 0
Economic outcome: Patient use of health resources pharmacist's time) assessed measuring the pharmacist time, in minutes, during the interview with the patient.
Timepoint [6] 343346 0
At baseline, month 1, month 2, month 3, month 4, month 5
Secondary outcome [7] 343348 0
Economic outcome: Patient use of health resources (number of medications used) assessed by patient report during the interviews. Cost calculated from the official list of drug prices.
Timepoint [7] 343348 0
At baseline, month 1, month 2, month 3, month 4, month 5
Secondary outcome [8] 343350 0
Economic outcome: Patient use of health resources (hospital admissions) assessed by patient self report during the interviews and calculated using costs from the public system for diagnosis-related groups.
Timepoint [8] 343350 0
At baseline and month 5

Eligibility
Key inclusion criteria
1) Age>18 years,
2) Having signed informed consent;
3) Able to complete questionnairesEuroQol-5D, Morisky 4 items, ACQ (Asthma Control Questionnaire), COPD assessment test;
4) Being prescribed either a blood pressure medication (medicines included in groups CO2, CO3, C07, C08, C09, according to Anatomical Therapeutical Chemical ATC classification system), an asthma medication (medicines included in group R03), or an COPD medication (medicines included in group R03).
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) People who are collecting someone else’s medication,
2) Patients who are pregnant or lactating,
3) Patients who cannot be at the pharmacy on a regular basis,
4) Patients who have previously participated in any education program or study related to the improvement of adherence to medications,
5) Patients who have communication limitations or any other impairment the recruiting pharmacist considers could preclude them from participating on the study.

Study design
Purpose of the study
Educational / counselling / training
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
An independent researcher will assign the pharmacies (units of randomisation) after they agree to participate in the study, to either intervention group or control group
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated list of random numbers.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The sample size has been calculated based on the difference of proportions expected from number of adherent patients in both study groups by the end of the study. It has been considered of clinical significance, a difference of 15% between both groups. A two-tailed comparison test has been applied considering an 80% power, and alpha=0.05 and a prevalence of non-adherent patients of 50%. An increase in the sample size has been considered due to the characteristics of the trial (cRCT); taking into account the design effect (DEFF), with DEEF= 1 + (n c- 1) * ICC, where nc represents the average size of the cluster and ICC is intraclass correlation for the statistic. Finally, because of the possibility of losing patients, a 20% more has been added to the final sample size, resulting on a total of 1230 estimated patients.

In terms of pharmacies, the selected pharmacies have been distributed in control or intervention group with a ratio of 1:1 by using a list of random numbers. Each pharmacy will include a minimum of 12 patients, with at least 4 on hypertension medication, 4 on asthma medication and 4 on COPD medication, to cover the total number of patients estimated for this phase. The inclusion of more patients will be possible by pharmacist judgment.

Statistical Analysis

Quantitative and qualitative data will be analyzed through SPSS statistics, version 24.0 (SPSS Inc. Chicago. Illinois, USA). Frequency tables will be used for describing qualitative variables whereas arithmetic media and standard deviation will be used for quantitative variables.
Comparison of categorical variables between study groups at baseline will be assessed using the t-test for independent samples. Chi-squared test will be used for quantitative variables.
Intragroup comparisons of quantitative variables between study visits will be performed using t-test for paired samples whereas categorical variables will be analised using McNemar.
Subsequently, a time series analysis will be used. This design includes multiple observations through time that can be normally interrupted as consequence of an intervention. This type of series includes a pre and post intervention phase. Phases can be modelling by utilizing multiple t tests, variance analysis and repetitive measures analysis.

Cost-utility analysis

A cost-utility analysis will be undertaken; adopting the perspective of the National Health-Care System will be adopted. The effectiveness of intervention will be estimated according to the Quality-Adjusted Life-Years (QALY). Associated costs will be calculated by adding all the study variables listed in the Step 4 of this document (Outcomes).
Results of the cost-utility analysis will be expressed as incremental cost-effectiveness ratio (ICER). A non-parametric bootstrapping with 5000 simulations will be performed to analyse uncertainty. This result will be represented in a cost-effectiveness plan and will be used to deploy the cost-effectiveness acceptability curve.

Recruitment
Recruitment status
Active, not recruiting
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 outside Australia
Country [1] 9353 0
Spain
State/province [1] 9353 0
A Coruna, Albacete, Ciudad Real, Guadalajara, Soria y Tenerife

Funding & Sponsors
Funding source category [1] 297961 0
Commercial sector/Industry
Name [1] 297961 0
CINFA, Laboratory
Address [1] 297961 0
Olaz - Chipi, 10 -Poligono de Areta
31620 Huarte (Navarra)-España
Country [1] 297961 0
Spain
Primary sponsor type
Government body
Name
Consejo General de Colegios Oficiales de Farmaceuticos
Address
C/Villanueva 11, 7ª planta, 28001, Madrid
Country
Spain
Secondary sponsor category [1] 297024 0
Individual
Name [1] 297024 0
Prof. Fernando Martinez-Martinez
Address [1] 297024 0
Campus Universitario de Cartuja s/n, 18071, Granada
Country [1] 297024 0
Spain
Other collaborator category [1] 279801 0
Individual
Name [1] 279801 0
Prof. Shalom (Charlie) Benrimoj
Address [1] 279801 0
University of Technology Sydney,
School of Pharmacy,
PO Box 123, Broadway NSW 2007
Country [1] 279801 0
Australia
Other collaborator category [2] 279802 0
Individual
Name [2] 279802 0
Dr. Victoria Garcia Cardenas
Address [2] 279802 0
University of Technology Sydney,
School of Pharmacy,
PO Box 123, Broadway NSW 2007
Country [2] 279802 0
Australia
Other collaborator category [3] 279803 0
Individual
Name [3] 279803 0
Andrea Torres Robles
Address [3] 279803 0
University of Technology Sydney,
School of Pharmacy,
PO Box 123, Broadway NSW 2007
Country [3] 279803 0
Australia
Other collaborator category [4] 279804 0
Individual
Name [4] 279804 0
Dr. Miguel Angel Gastelurrutia
Address [4] 279804 0
Facultad de Farmacia,
Universidad de Granada.
Campus Universitario de Cartuja s/n, 18071, Granada
Country [4] 279804 0
Spain
Other collaborator category [5] 279805 0
Individual
Name [5] 279805 0
Beatriz Perez Escamilla
Address [5] 279805 0
Facultad de Farmacia,
Universidad de Granada.
Campus Universitario de Cartuja s/n, 18071, Granada
Country [5] 279805 0
Spain
Other collaborator category [6] 279806 0
Individual
Name [6] 279806 0
Maria Isabel Valverde Merino
Address [6] 279806 0
Facultad de Farmacia,
Universidad de Granada.
Campus Universitario de Cartuja s/n, 18071, Granada
Country [6] 279806 0
Spain
Other collaborator category [7] 279807 0
Individual
Name [7] 279807 0
Loreto Saez-Benito
Address [7] 279807 0
Facultad de Farmacia,
Universidad de Granada.
Campus Universitario de Cartuja s/n, 18071, Granada
Country [7] 279807 0
Spain
Other collaborator category [8] 279808 0
Individual
Name [8] 279808 0
Amaia Malet Larrea
Address [8] 279808 0
Departamento de Tecnología Farmacéutica,
Facultad de Farmacia,
Universidad del País Vasco.
Paseo de la Universidad 7, 01006 Vitoria-Gasteiz
Country [8] 279808 0
Spain
Other collaborator category [9] 279809 0
Individual
Name [9] 279809 0
Raquel Varas Doval
Address [9] 279809 0
Consejo General de Colegios Oficiales de Farmaceuticos
C/ Villanueva 11, 28001, Madrid
Country [9] 279809 0
Spain
Other collaborator category [10] 279810 0
Individual
Name [10] 279810 0
Laura Martin Gutierrez
Address [10] 279810 0
Consejo General de Colegios Oficiales de Farmaceuticos
C/ Villanueva 11, 28001, Madrid
Country [10] 279810 0
Spain
Other collaborator category [11] 279811 0
Individual
Name [11] 279811 0
Tamara Peiro Zorrilla
Address [11] 279811 0
Consejo General de Colegios Oficiales de Farmaceuticos
C/ Villanueva 11, 28001, Madrid
Country [11] 279811 0
Spain

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299002 0
Comite de Etica de la Investigacion de Centro de Granada (CEI-Granada)
Ethics committee address [1] 299002 0
Edificio Licinio de la Fuente, C/ Dr. Azpitarte nº4, 4ª planta 18012 Granada
Ethics committee country [1] 299002 0
Spain
Date submitted for ethics approval [1] 299002 0
Approval date [1] 299002 0
09/01/2017
Ethics approval number [1] 299002 0

Summary
Brief summary
Non-adherence to medications has a significant impact on health outcomes, affecting patients, health care professionals and health care system, especially in patients suffering from Asthma, COPD and Hypertension. Brief complex interventions based on change behaviour theories have demonstrated to be effective on improving and maintaining adherence; with the ones involving pharmacist having the most positive impact.
This study is a cluster randomized controlled trial targeted at patients using hypertension, COPD and asthma medications.
The study will be undertaken in community pharmacies across 6 Spanish provinces. It is estimated that approximately 120 pharmacies and 1230 patients will participate during this 6-months trial. Pharmacies will be randomised to either intervention or control group. Patients in the intervention group will receive a medication adherence management, based on different evidence-based theoretical frameworks for changing patient behaviour. Clinical, humanistic and economic outcomes will be measured to evaluate the impact of the service.

This study will provide a model of Professional Pharmacy Service focused on improvement and maintenance of adherence on patients being treated with hypertension, asthma or chronic obstructive pulmonary disease (COPD) medicines compared to usual care, and its effectiveness in enhancing health outcomes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78962 0
Prof Fernando Martinez-Martinez
Address 78962 0
Facultad de Farmacia.
Unidad de posgrado planta -2.
Campus de Cartuja s/n. 18071 Granada.
Country 78962 0
Spain
Phone 78962 0
+34 958 24 19 31
Fax 78962 0
Email 78962 0
femartin@ugr.es
Contact person for public queries
Name 78963 0
Dr Victoria Garcia Cardenas
Address 78963 0
University of Technology Sydney,
School of Pharmacy,
PO Box 123, Broadway NSW 2007
Country 78963 0
Australia
Phone 78963 0
+61 (02) 9514 9297
Fax 78963 0
Email 78963 0
Victoria.GarciaCardenas@uts.edu.au
Contact person for scientific queries
Name 78964 0
Miss Andrea Torres Robles
Address 78964 0
University of Technology Sydney,
School of Pharmacy,
PO Box 123, Broadway NSW 2007
Country 78964 0
Australia
Phone 78964 0
+61 (02) 9514 7248
Fax 78964 0
Email 78964 0
andrea.j.torresrobles@student.uts.edu.au

No data has been provided for results reporting
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary