Nurse-led Medication Self-management Intervention in the Improvement of Medication Adherence in Adult Patients With Multi-morbidity: A Feasibility Randomized Control Trial
Phase: NA
Conditions: Heart Diseases, CKD, Diabetes, Cancer, Asthma, Thyroid, Hypertension
Sponsor: Hamad Medical Corporation

HMC RESEARCH 
PROTOCOL  
 
 
Page 1 of 22 
 
 
 
 
Nurse-led medication self-management intervention in the improvement of medication adherence in 
adult patients with multi-morbidity: A Feasibility Randomized controlled trial 
 
Dr. Badriya Lenjawi 
Dr. Kalpana Singh 
 
 
 
Date-2 Nov 2022 
NCT- Not available 
 
 

 
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1. Summary 
 
      Back ground & Aims 
Adult patients suffering from multimorbidity are at high risk of medication non-adherence. It has been well established 
that self-management support is an effective strategy to enhance medication adherence for patients with chronic 
conditions. However, little is known about the effect of the medication self-management intervention in Adult patients 
with multimorbidity. The aim of this study to evaluate the effectiveness of a nurse-led medication self-management 
intervention in improving medication adherence and health outcomes in adult patients with multimorbidity. 
Methods 
This study is a single centre, single-blind, two-arm randomised controlled trial. Adult patients with multi-morbidity will 
be recruited from NCCCR Qatar. A total of 100 participants will be randomly allocated to receive standard care or 
standard care plus the medication self-management intervention. The intervention will be delivered by clinical nurse 
specialists. The 6-week intervention includes three face-to-face education sessions (2st week, 4rd week and 6th 
week) and two weekly (8th week and 10 week) follow-up phone calls. Participants in the control group continue to 
receive all respects of standard care offered by healthcare providers, including chronic disease management, drug 
prescription, referral to hospital specialists, health education and consultations regarding patients’ diseases and 
treatments during centre visits.  
Outcome  
The primary outcome is medication adherence as measured by the 5-item Medication Adherence Report Scale. 
Secondary outcomes include medication self-management capacity (medication knowledge, medication beliefs, and 
medication self-efficacy), treatment experiences (medication treatment satisfaction and treatment burden). All 
outcomes will be measured at baseline, immediately post-intervention (7th week), and at 3-month post-intervention. 
 
 
 
 
2. Abbreviations and Acronyms 
NCCCR- National Cancer Care Center and Research 
CNS-  Clinical Nurse Specialist 
IMB- Information-Motivation-Behavioral Skills 
 
 
 
 

 
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3. Introduction / Background 
Adherence is a key factor in the potential effectiveness of the treatment of chronic conditions in patients. According 
to the World Health Organization, however, 50 per cent of these patients do not comply with the drug regime in 
developed countries(1). In developing countries, access to health services is limited and there is a shortage of health 
care providers and financial resources, so it is assumed that this number is higher. Medication non-adherence is often 
linked to adverse clinical results (2) and decreased quality of life (3)and higher use of health resources(4). Drug non-
adherence is widespread among the elderly, and over 55% live with multiple diseases (i.e., multiple chronic diseases) 
together(5). In addition to the high complexity of multi-morbidity, patients are more likely to receive complex 
medications(6) , adverse drug reactions(7), and substantial drug burdens (8). Patients need to spend a lot of energy 
and time taking and administering medicines(9, 10). Multi-morbidity is an obstacle to the self-management of drugs 
that lead to disease, leading to poor compliance and treatment results(11, 12) . Support for the self-management of 
medications is an effective strategy for addressing the challenges of taking medications and giving patients the 
opportunity to take care of themselves. In general, medication self-management programs integrate multiple 
components to help patients take drugs efficiently and safely, such as changes in health behavior change, patient 
education, shared decision making, and goal setting. Drug self-management interventions have been established in 
several conditions(13-15). However, Current clinical trials focus on specific diseases or drugs, limiting their 
generalization to older patients with multiple diseases(16, 17). Some studies have found the effectiveness of self-
management interventions in this complex patient group(18-21) . Unfortunately, most have not significantly improved 
compliance and health outcomes. A six-month self-management support program for the treatment of multiple 
diseases based on cognitive behavioral therapy and motivational interviews did not result in any improvements in the 
outcome of patients, except for self-assessment of health(18). Another personalized self-management intervention 
by nurses in patients with coronary disease and depression also did not show significant differences in compliance 
and health outcomes between the intervention and the control group(19) . One explanation is that most self-care 
programs for elderly patients with multiple diseases are designed to address all aspects of self-care, but not 
specifically to improve medication self-management capacity or focus on patients with adherence problems. A study 
by Cochrane concluded that interventions were more effective in targeting specific problems experienced by multi-
morbidity patients., such as depression, functional limitation, and non-adherence to medication non-adherence(22) . 
Interventions with a broader focus, such as case management and changes in treatment for multi-morbid patients, 
seem to be less effective. Drug management interventions are more effective in addressing specific problems related 
to the use of drugs. Information about the need to move health education intervention way from the tradition 
information based and advice-giving model to health coaching using evoking, focusing, planning and motivational 
interview process. Furthermore, the social behavior model was rarely used to guide study design and explain the 
mechanisms of previous studies underlying important or non-significant intervention effects. Therefore, although 
interest in the study of adult patients with multiple diseases is growing, promoting medication adherence of this group 
of patients is still a challenge for healthcare providers and researchers(23). Information about the need to move health 
education intervention way from the tradition information based and advice-giving model to health coaching using 

 
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evoking, focusing, planning and motivational interview process.  The current study aims to implement evidence-based, 
theoretical and nurse-led drug self-management interventions in adult patients with multi-morbidity. 
 
      
 
 

 
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4. Objectives 
The primary objective 
To evaluate the effectiveness of a six-week intervention led by a nurse in medication self-management to improve 
medication compliance in adult patients with multimorbidity and going to discharge, as compared with standard 
care.  
Secondary objectives 
To evaluate the effectiveness of the intervention on the improvement of patients’ medication self-management 
capacity (medication knowledge, medication beliefs, and medication self-efficacy), treatment experiences 
(medication treatment satisfaction and treatment burden), as compared with standard care. (Retrospective means 
the data is already in existence when the project is submitted to the IRB for initial (if this is a retrospective chart review, 
the end date must come before the submission date):  mm/dd/yyyy to mm/dd/yyyy       

 
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5. Study Methodology  
This is a single Centre open label, two-arm randomized controlled trial with 1:1 randomization at the participant level. 
The patient population will be patients with at least two comorbidities. The patient recruitment will be done in the 
National Centre for Cancer Care and Research (NCCCR) in the outpatient department in the clinical nurse specialist 
counselling room. Participants will randomly be allocated to receive standard care(control) and standard care plus the 
medication self-management intervention (Motivational Interview). Primary and secondary outcomes of study will 
measure better medication adherence, medication self-management capacity and treatment experiences, which will 
be collected from both group including the intervention group and control group (Participants in the control group will 
continue to receive all respects of standard care offered by healthcare providers) at baseline (T0), in the 7th week 
immediately post-intervention (T1), and at 3-month post-intervention (T2). This protocol is presented based on the 
recommendations of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 
statement(24). The results of this trial will be reported as per the Consolidated Standards of Reporting Trials 
(CONSORT) 2010 statement(25). 
An overview of the study design is shown in Fig. 1. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Excluded (n=) 
Not meeting inclusion 
criteria (n=) 
Decline to participate (n=) 
Other reason (n=)
Randomization of patients (n=) 
Allocation to the intervention (n=) 
Received allocation 
intervention(n=) 
Did not received allocated 
intervention (give reasons) (n=) 
Allocation to control (n=) 
Received allocation usual care 
(n=) 
Did not receive usual care (give 
reasons) (n=)
Lost to follow up (give reasons) (n=) 
Discontinued intervention (give reason) 
(n=)
Lost to follow up (give reasons) (n=) 
Discontinued intervention (give 
reason) (n=)
Immediately Post 
intervention
3 months’ Post-intervention 
Allocation
Recruitment of patients meeting inclusion 
criteria (n=) 
Enrolment 

 
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Fig. 1 CONSORT flow diagram of the study protocol 
 
Theoretical framework  
Motivational strategies, to reiterate, are built on sophisticated understandings of human behavior in the social 
environment (HBSE), most of which have been confirmed through real-life experimentation. The theoretical foundation 
of Motivational intervention(MI) is first and foremost the knowledge that people often modify their behavior as a result 
of their interaction with others. A related assumption is that therapists who possess critical counselling skills can help 
facilitate personal change in their clients(26).                                                                                                                     
Development, implementation and evaluation of interventions are guided by a framework adapted from the Information-
Motivation-Behavioral Skills (IMB) model of Fisher and Fisher (27). The IMB model is a well-established social 
behavioral model for understanding and predicting health-related behaviors. In consideration of the complexity of 
patients living with multimorbidity, the IMB model was extended by including four interrelated variables (that is, disease 
burden, treatment burden, depressive symptoms, and medication treatment satisfaction) emerging from 
comprehensive literature reviews. The extended IMB model demonstrated that in addition to adherence information, 
motivation, and behavioral skills, medication treatment satisfaction and treatment burden could also directly or 
indirectly impact medication adherence. Based on the model, it is proposed that individuals who are well informed, 
highly motivated, having skills to perform medication self-management, highly satisfied with medication treatment, and 
experiencing low treatment burden are more likely to enact and maintain adherence behavior. The medication self-
management intervention might be effective if intervention components focus on addressing each of the above 
behavioral determinants that affect medication adherence. 
 
      
 
 
Analyzed (n=) 
Excluded from the analysis (give 
reason) (n=)
Analyzed (n=) 
Excluded from the analysis (give 
reason) (n=) 
Lost to follow up (give reasons) (n=) 
Discontinued intervention (give reason) 
(n=) 
Lost to follow up (give reasons) (n=) 
Discontinued intervention (give reason) 
(n=) 
Analysis 

 
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6. Study Population and Study Setting/ Location 
In this section describe the study population that is to be enrolled in the study, planned recruitment number and 
Inclusion and Exclusion Criteria to be listed here. Also list the Hospitals in which this study will be conducted ( e.g. 
HGH, Rumailah etc) 
The trial will be conducted at NCCCR in QATAR. NCCCR Physician, clinical pharmacist and nurses work 
collaboratively to provide essential health services to discharged multi-morbidity patients including health education, 
medical treatment services, and chronic disease management in NCCCR.  
Participants  
The participants of the trial are discharged adult patients with multi-morbidity. Multi-morbidity is defined using a cut-
off of three or more chronic conditions as patients with at least three conditions are more likely to have complex 
needs and great utilization of healthcare services (28). To avoid the ceiling effect and improve study power to detect 
changes in adherence, only participants with low medication adherence (Morisky scale<2) are considered eligible 
for the trial.  
Participants’ inclusion criteria are  
 
+18 years old or over,  
 
patients with at least two of the identified comorbidities (Hypertension, Chronic painful condition, Cancer, 
Inflammatory connective tissue disorders, Diabetes, Lipid disorder, Dyspepsia and gastroenteritis, Heart disease, 
Chronic obstructive pulmonary disease, Stroke and cerebrovascular disease , chronic kidney disorder , Asthma   Thyroid 
disorders, Anemia,  Chronic liver disease, Depression, Epilepsy, Anxiety & other stress related disorders), (3) having at 
least one medication prescribed for a chronic condition over at least the 3 months prior to inclusion in the study,  
 
non-adherence to medications, as defined by scoring zero on the 8-item Medication Adherence Report Scale (Morisky 
-8)(29),  
 
independently managing their medications (i.e., not rely on a care taker),  
 
able to speak or understand English/Arabic,  
 
able and willing to receive phone calls, and  
 
capable of providing a written informed consent to participate in the study.  
Exclusion criteria are  
 
being institutionalized in a long-term care facility,  
 
planning to move away from the community in the next 6 months,  
 
cognitive impairment (Mini-cog scores < 4), and  
 
currently participating in research involving chronic disease management. Patients with cognitive impairment are 
excluded because they may not be able to provide valid answers to the questionnaires. 
 
 

 
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Fig2. Theoretical framework of the study: the extended information motivation behavioral skills model of medication 
adherence 
 
Recruitment  
Three clinical nurse specialist as a part of research team from NCCCR will deliver the intervention. Nurses’ inclusion 
criteria are (1) Senior clinical nurses with a Master degree or above, (2) having at least 3 years of working experience 
in HMC, (3) taking on chronic disease management in routine work, and (4) not planning to quit the job in the next 6 
months and Nurses who are participating in other research studies on chronic disease management at the time of 
this study will be excluded. Nurses will recruit participants through approaching potentially eligible participants in 
NCCCR. Centre appointments by Clinical nurse specialists will be arranged for interested participants and the 
principal investigator/ co-investigator will determine the eligibility of participants, describe the study to them, obtain 
written consent forms, and collect baseline data. A one-week period will be allowed for participants to decide whether 
or not they wish to participate in the study. Participants’ reasons for nonparticipation will be recorded. 
Sample size; data collection methods 
Sample size  
Depressive 
s mptoms
Medication 
treatment 
Treatment Burden 
Disease Burden 
Adherence 
I f
ti
Adherence Motivation 
(Adherence Social 
M ti
ti
)
Adherence 
Behavioral 
Medication 
Adherence 
Adherence Motivation 
(Adherence Personal 
Motivation) 
Necessity of 
Medication 
Concerns about 
Medication  
Harm of 
medication 
Overuse of 
Medication 

 
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Sample size calculation was performed using G*Power Version 3.1.9.7. Estimation is based upon 
the primary outcome, medication adherence, at 3 months of follow-up between the intervention 
and control group. Medication adherence is calculated as sum of the scores from each item using 
Morisky 8. Based on our recent systematic review and meta-analysis on medication adherence 
interventions among patients with multimorbidity Cohen’s effect size (d) of 0.52 on medication 
adherence is estimated for a medication self-management intervention program. The required 
sample size will be 94 participants (47 in the intervention group and 47 in the control group) to 
attain an 80% power with a two-sided α of 0.05. Therefore, for a 5% attrition rate, the final sample 
size required is 100 participants.  
For Arabic speaking patients, the questions will be translated to Arabic by the Arabic speaking research team member. 
 
 
Randomization & blinding 
Consenting participants will be randomized in outpatient clinic in NCCCR. Randomization will be block randomization, 
and generated by a computer program centrally (Nursing/ Midwifery Research department). 
Following recruitment, patients will be randomized to either the intervention or the control arm in a near 1:1 ratio, 
using a computer-generated randomized permuted block design. The design will use random block lengths of 2, 4 or 
6, and include an initial unbalanced block, with a maximum of one additional patient in either arm, to further hide 
allocation sequences, which means that the ultimate sample size and allocation ratio will vary very slightly from what 
is planned depend on the unbalanced block. 
Each participant will be assigned a special code generated by the computer. The randomization will be kept by the PI 
and CNS. After the eligibility assessment by CNS, data will be obtaining at the baseline (after completion of informed 
consent), 7th week and 12th week. 
Intervention group 
The medication self-management intervention consists of three face-to-face education sessions and two weekly 
telephone follow-up over 6 weeks. Intervention components are derived from an extensive review of the literature, 
including the related theoretical framework and current practice. Based on the extended IMB model of medication 
adherence, this intervention is designed to offer information related to medication treatment, motivate patients to 
adhere, help build medication self-management skills, and develop adherence improvement plans. The face-to-face 
meeting will take place in the clinical nurse specialist counselling room in NCCCR. The face-to-face sessions will 
include all of the following: exploration of medication treatment experience and expectation, medication knowledge 
education, motivation feedback tailored to the individual’s personal and social barriers to adherence, medication self-

 
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management skills building, and goal setting. A patient-centered approach will be adopted considering the complex 
needs of patients with various combinations of chronic conditions.  
A comprehensive assessment of adherence problems will be firstly conducted to identify the factors that affect 
adherence, including how and why these factors contribute to poor adherence. Medication-related knowledge and 
skills will be provided based on individual treatments and barriers to adherence. Motivational interviewing techniques 
will be used for a better understanding of patients’ cognitive factors of adherence behavior. Nurses will discuss with 
patients to explore their preferences and priorities in medication treatments, setting goals that are practical and 
acceptable for addressing their problems in medication use, and develop individualized adherence improvement plan 
to reach these goals. Taking patients’ complexity into account, strategies to reduce treatment burden will also be 
incorporated into intervention sessions, including prioritizing medication and other self-management activities using 
shared decision making, providing communication skills with healthcare providers and encouraging patients to discuss 
with the physicians about burdensome regimens, exploring patients’ family and social network to support their self-
care, and helping them to incorporate self-care activities into daily life. Each face-to-face session will last 
approximately 30– 40 min and will be delivered individually in NCCCR by CNSs. The duration of each session can 
be adjusted by CNSs in accordance with the patients’ barriers and problems to medication adherence. The three 
face-to-face sessions are designed to complete at 7–10-day intervals over 4 weeks. Before the first face-to-face 
session, nurses will review patients’ clinical health records to confirm the screening criteria.  
Patients will be asked to bring all medications to HMC. After the conclusion of the last face-to-face session, education 
materials containing instructions and information on the name, purpose, side effects, and special tips for each usual 
chronic medication and medication skills will be provided to participants. After the face-to-face sessions, patients are 
followed up by two weekly by telephone. Each telephone encounter lasted 10–20 min. The aim, content, and delivery 
strategy of each session are shown in Table 1. 
Control group Participants in the control group will continue to receive standard care from Physicians, nurses, and 
clinical pharmacists in the NCCCR. Physicians are the primary providers and coordinators of care for patients with 
chronic conditions. Physicians provide patients consultations and education regarding their diseases and treatments 
(typically clinician-centred) at each patient visit to the chronic disease clinic. Referral to hospital specialists will be 
made by physicians as needed. For patients diagnosed with hypertension and/or diabetes, Physicians are required 
to provide scheduled follow-up via telephone contact. CNSs assist physicians with chronic disease management. In 
respect of medication management, Physicians will prescribe medication regimens, provide medication consultations 
(including instructions on the medications’ dosage, methods, and frequency), and adjust regimens where appropriate 
through discussion with patients. No structural medication self-management education session will be provided for 
patients in standard care group. 
 
 
Table 1 The Nurse-led Medication Self-Management Intervention Sessions 

 
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Aim 
Content 
Delivery strategy 
1st face-to-face education 
session  
• 
To 
identify 
patients’ 
problems and barriers to 
medication adherence.  
• To educate patients on the 
right 
information 
about 
medication 
taking 
and 
adherence. 
(1) Inform patients about the purpose and procedure of the 
whole intervention.  
(2) A structured patient-centered adherence assessment, 
covering a checklist with all the questions about patients’ 
medication experiences, including effectiveness and side 
effects of the drugs, treatment burden, and barriers to 
adhering to medications.  
(3) Educate patients on disease- and medication-related 
information and correct misinformation, including the name, 
dosage, frequency, timing, purpose of each medication, 
potential 
side 
effects, 
and 
special 
administration 
considerations.  
(4) Encourage patients to ask questions and ensure that they 
understand what is said to them. 
❖ 
Individualization 
❖ 
Teach-back 
technique 
 
 
 
2nd face-to-face education 
session  
• To help patients change 
negative attitudes and beliefs 
about medication treatments 
and become motivated to it. 
 •  
(1) Give patients the opportunity to understand the 
importance of medication adherence and the consequences 
of non-adherence. 
 (2) Encourage patients to express feelings and barriers to 
family members and seek assistance, where appropriate. (3) 
Provide a list of local resource information to patients (e.g., 
medical 
care 
institutions, 
psychological 
support 
organizations, and peer support teams). 
❖ 
Motivational 
interviewing  
❖  
3rd face-to-face education 
session 
• To help patients develop 
skills 
and 
strategies 
to 
overcome practical barriers of 
their medication treatments.  
• To help patients set goals 
and 
develop 
a 
workable 
adherence improvement plan. 
(1) Nurses will educate patients about six skills in medication 
self-management:  
1. Identifying and coping with medication side effects;  
2. Incorporating medication treatments into daily life; 
3. Obtaining and updating medication adherence-related 
information;  
4. Acquiring, self-cueing and self-administering medications;  
5. Effectively communicating with healthcare providers;  
6. Acquiring social and instrumental support for adherence. 
(2) Ask patients to select three skills they most want to learn 
or help most to take their medications; Discuss with patients 
❖ 
Planning 
coping responses  
❖ Goal setting 

 
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about strategies on how to apply the three skills to their self-
management.  
(3) Set goals and help make an individualized adherence 
improvement plan based on patients’ expectations and 
preferences. 
2-week Telephone follow-  
• To further explore the 
challenges and difficulties in 
medication self-management.  
• To provide feedback and 
suggestions 
according 
to 
patients’ performance. 
(1) Ask whether patients can adhere to the medications in 
the last week and if not, the reasons for medication non-
adherence will be asked and discussed with patients.  
(2) Ask whether patients can apply skills in medication self-
management and encounter any challenges and concerns in 
medication-taking.  
(3) Further adherence education where needed.  
(4) Conclude what is discussed and encourage patients to 
contact healthcare providers when they have adherence 
problems 
❖ Active listening  
❖ 
Personalized 
feedback 
 
 
Nurses’ training Intervention  
 The certified clinical nurse specialists will be informed of the study objectives, procedure, detailed intervention 
protocol, and ethical considerations. Training sessions will involve medication self-management support, teach-back 
techniques, shared decision making, and basic motivational interviewing skills, e.g., posing open-ended questions, 
reflective listening, and expressing empathy(32). Nurses will also receive a detailed study protocol and a manual 
containing instructions for delivering the intervention.  
 

 
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7. Study procedures  
Provide an outline and describe in detail the processes and operations of the study, including logistics 
Study Duration and Timelines 
The evaluation of the project process will be against the key milestones as described below. 
 
 
      
Month 
1-3
•Obtain all governance ethical approvals
Moth 4-
6
•Screening the participants
•Recruitment to conduct the trial
•Contacting concern authority to make data collection smooth
•Prepare the data management plan
Month 
7-9
•Start of conduct Trial
•Prepare the do files  in statistical software  and dummy tables according to questionnaire
•Start data management ( checking the fabricated data, outliers  using central  statistical 
monitoring techniques using R software
Month 
9-10
•start Data analysis
Month 
10-12
•Complete the data Analysis 
•Start report writing
•Study dissemination and publications

 
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Informed Consent 
 
a) How people will be NOTIFIED OR APPROACHED to consider being a research subject in this study? 
During the OPD visit of the patient the CNS will approach the patients directly based on the inclusion exclusion criteria. 
All the study details will be explained to the patient in detail at the CNS office. After explaining the study details to the 
patients, a minimum of one-week time will be given to them before they are decided to take part in the study. After 
the written informed consent patient will be enrolled to the study and allocated randomly to control and intervention 
group. For Arabic speaking patients, the informed consent form will be translated in Arabic by the Arabic speaking 
research team member. 
      
b) Describe the CONSENT PROCESS procedures (When, Where, How, by Whom). 
CNS will approach the patients directly based on the inclusion exclusion criteria. All the study details will be 
explained to the patient in detail at the CNS office. After explaining the study details to the patients, a minimum 
of one-week time will be given to them before they are decided to take part in the study. We will contact the 
patient to confirm their participation in the study. If they agreed to participate in the study, will advise to come to 
the outpatient visit for face to face interview. 
 
c) 
 Describe HOW LONG potential participants will have to decide on participation. 
1 week 
d) Describe how subjects will be SCREENED FOR ELIGIBILITY for the study. 
Based on Inclusion and exclusion criteria 
e) Describe how subjects will be ENROLLED into the research study below. 
Based on screening & randomization tool 
 
Risk 
In this section describe the anticipated risks associated with participation in the research (i.e. illness, injury, death) 
No risk is anticipated as part of study 
Bio-Specimens & Sample Collection 
In this section describe what specimens or samples will be collected specifically for research, if specimens will be 
stored long-term and/or destroyed. Consider what happens to data/specimens if subject withdraws consent 
NA 
Outcomes 
In this section provide details on the outcome measures and the anticipated primary & secondary outcomes 
Outcome assessment  
The nurses masked to the participant allocation will collect follow-up data through telephone interview. Participants 
will be assessed at baseline (T0), in the week immediately post-intervention (7th week) (T1), and at 3-month post-
intervention (T2). Table 2 provides an overview of primary and secondary outcomes as well as covariates at each 
time point. Permission will be obtained from the original authors to use the scales for this study. 

 
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Primary outcome 
 Medication Adherence 
 The English version of Morisky-8 will be administered to assess medication adherence of the participants(29). The 
Morisky-8 is a self-reporting measure of unintentional and intentional medication non-adherent behaviors with a yes 
and no response. The total score of the moresky-8 ranges from 0 to 8, with a higher score representing higher 
adherence to medication.  
 
Table 2 Schedule of enrolment, interventions, and assessments 
TIMEPOINT 
STUDY PERIOD 
 
Enrolment 
Baseline 
T0 
Intervention 
Follow-up 
 
 
 
 
T1 
T2 
ENROLMENT 
 
 
 
 
 
Eligibility screen 
X 
 
 
 
 
Informed consent 
X 
 
 
 
 
Allocation  
 
X 
 
 
 
INTERVENTION 
 
 
 
 
 
Intervention group 
 
 
X 
 
 
Control group 
 
 
X 
 
 
ASSESSMENTS 
 
 
 
 
 
Primary outcome 
 
 
 
 
 
Medication adherence (Moresky-8) 
 
X 
 
X 
X 
Secondary outcomes 
 
 
 
 
 
Medication knowledge (PKMUQ) 
 
X 
 
X 
X 
Medication beliefs (BMQ) 
 
X 
 
X 
X 
Medication self-efficacy (SEAMS) 
 
X 
 
X 
X 
Treatment burden (TBQ) 
 
X 
 
X 
X 
Potential covariates 
 
 
 
 
 

 
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Socio-demographics 
(Patients 
questionnaire) 
 
X 
 
 
 
Number of prescribed medications 
(one-item question) 
 
X 
 
 
 
 
 
 
 
 
 
Depressive symptoms (PHQ-9) 
 
X 
 
 
 
 
 
Secondary 
outcomes 
 Medication Knowledge 
 The Patients’ Perceived Knowledge in Medication Use Questionnaire (PKMUQ) is used to determine participants’ 
medication knowledge(33). The PKMUQ comprises five items covering two dimensions: general knowledge in 
medication use and drug interaction knowledge. The response scale ranges from 1 = strongly disagree to 5 = strongly 
agree, and the response scores of all 5 items will be summed. Higher scores indicate a higher level of medication 
knowledge.  
 Medication beliefs  
Medication beliefs will be measured by using the Beliefs about Medication Questionnaire BMQ). The BMQ is an 18-
item self-reported questionnaire consisting of two subscales: the BMQ-Specific which evaluates representations of 
medications prescribed for personal use and the BMQ-General which evaluates beliefs about medications in 
general(34). The BMQ-Specific subscale consists of two subscales: the 5-item Specific-Necessity subscale assesses 
beliefs about the necessity of medications and the 5-item Specific-Concerns measures concerns about the 
medications. The BMQ-General contains 8 items which include two 4-item subscales: The General-Harm subscale 
which evaluates beliefs about the harm of medication and the General-Overuse subscale which evaluates beliefs 
about overuse of medication by doctors. Participants will be asked to rate the degree of agreement with each 
statement. A 5-point Likert scale ranging from 1 = strongly disagree to 5 = strongly agree is used. A higher score 
indicates stronger beliefs about the corresponding concepts in each subscale.  
Medication self-efficacy  
The Self-Efficacy for Appropriate Medication Use Scale (SEAMS) will be used to determine participants’ medication 
self-efficacy(35). The SEAMS consists of 13 items that evaluate participants’ confidence in taking medications under 
various challenging circumstances. Each item has a 3-point scale ranging from 1 = not confident to 3 = very confident. 
The score of scale ranges from 13 to 39, with a higher medication self-efficacy by a higher score.  

 
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Treatment burden  
The treatment burden will be measured by the 10-item Multi-morbidity Treatment Burden Questionnaire (MTBQ)(36) 
. It assesses the wide range of behavioral and emotional burdens involved in treatment implementation and treatments 
associated with taking multiple medicines, self-monitoring their health and making lifestyle changes. Each item is 
scored on 6-point Likert scale, ranging from 0 = does not apply to 5 = most difficult. Scores are summed to derive a 
total score ranging from 0 to 50 with a higher score indicating a higher level of treatment burden.  
 
Potential covariates  
Socio-demographic characteristics and the number of prescribed medications  
Socio-demographic characteristics will be collected at baseline from patients. Patients will be asked about age, 
gender, educational level, marital status, monthly income, and the number of prescribed medications. 
Intervention fidelity and contamination  
The principal investigator will be responsible for monitoring the procedure of the whole study. The intervention logbook 
will be used by participating nurses to record the number, duration, and administration date of face-to-face sessions 
and follow-up phone call sessions. To ensure that the delivery of motivational interviewing is consistent with its 
principals, all motivational interviewing sessions will be audiotaped if permitted by the participant. A random 20% 
sample will be reviewed using Motivational Interviewing Treatment Integrity Coding Manual 4.2.1  (37)  by the local 
motivational interviewing nurse expert throughout the duration of the intervention. The principal investigator will meet 
with intervention nurses to discuss the experiences and difficulties to deliver the intervention sessions and provide 
feedback weekly. Intervention logbooks will also be examined weekly by the principal investigator and further training 
for nurses will be considered if the delivery of the intervention is not per protocol. Contamination may occur whereby 
control group participants also receive usual nursing care or interact with intervention group participants. However, 
the current study is expected to be at a low risk of contamination because (1) patients with chronic diseases 
predominately receive medication management by physicians, the involvement of nurses in medication treatment and 
consultation is rare, (2) the multifaceted interventions with individualized cognitive behavior component cannot easily 
be transferred from one participant to another. Also, the following strategies will be introduced to minimize 
contamination. First, participants and nurses will be provided with clear information on the nature and purpose of the 
study. Second, Nurse/researchers will ask participants keep the education materials to themselves until the end of 
the study. Finally, only intervention nurses will receive training to deliver the intervention and they will be requested 
not to discuss the intervention with their colleagues who might be involved in the control group. At the end of the trial, 
participants in the control arm will be asked whether they have received any information or education on their 
medications, causal average effect analysis will be considered if high degree contamination occurs (38). 
 

 
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Data Collection, Management & Confidentiality  
 
a) Indicate below HOW study data will be collected for the proposed research. 
 
 Study Forms    
 Study Database     
 Study Web-Based/App    
 Other       
 
Please detail how study data will be coded: 
 
The research data including participants’ personal information will be recorded in two different files. All 
research-related data will be linked with a study ID number with no identifying information. Original 
questionnaires and tapes will be locked in a secure cabinet, with limited access by designated research team 
members only. The link between the code and the identifier will be destroyed once the study finishes and the 
de-identified data will be stored for at least five years. 
 
 
b) Describe below WHERE and HOW the study data is physically stored. 
 
Research data will be stored on a password-protected computer and backed up on a password-protected hard 
drive Research Department 322A 3rd floor 302.  
 
c) Describe below WHO controls access to the study data 
 
Only the PI and Statistician 
 
d) Describe below WHO has access to the study data. 
 
PI and statistician will have the access of full data 
 
e) Describe below HOW the study data is accessed. 
 
The collected data from the questionnaire will be transferred to Microsoft excel.  
 
f) Will subject identifiers be shared outside of HMC? If YES describe below WHOM the study data is shared 
 
     No 
 
 
Subject Withdrawal/ Withdrawal of Consent 
In this section describe why a subject may be withdrawn from the study by the PI, what happens to the data or bio-
specimens if a subject withdraws consent 
     If the subject withdrawn from the study before the randomization, then we will report as a screened participant 
if the subjects withdrawn from the study after the randomization we will include him / her in the analysis. 
   
 
 

 
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8. Statistical Consideration and Data Analysis 
Our primary analysis will be the ‘intention-- to-treat’ population, which will include all randomized patients analyzed 
according to their original treatment allocation, irrespective of their subsequent adherence or how they were actually 
treated. All data will be analyzed using STATA 17.0 software. Descriptive statistics will be used to describe and compare 
socio-demographic data on participants between the intervention and control group. Continuous variables that follow a 
normal distribution will be expressed as means and standard deviations, whereas categorical variables will be presented 
as frequency counts and percentages. Median values and interquartile ranges will be calculated for continuous data with 
a skewed distribution. Mann-Whitney U-test or t-test will be performed for continuous data to compare baseline 
characteristics between groups, and Chi-squared test or Fisher’s exact test will be used for categorical variables. The 
distributions of the outcome variables will be evaluated, and normalizing transformation will be applied as needed. 
Primary and secondary outcomes will be analyzed following the intention to treat principle at the individual participant 
level. Changes in repeated outcome measures across different time points between the intervention and control group 
will be analyzed using generalized estimating equation models with adjustment for potential confounders of the baseline 
variables. All statistical tests are two-sided, and p < 0.05 will be statistically significant. 
 
 
      
 
 
9. Adverse Event Reporting 
In this section, provide a definition of anticipated adverse events that are related to the research, including a 
description of how SAEs will be assessed, tracked and reported 
     There will not be any adverse events related to intervention because it is educational intervention. If some 
adverse event related to out outcome reported during the study, we will notify to the IRB.  
 
 
10. Ethical Consideration 
A statement that the study will be conducted in full conformance with principles of the “Declaration of Helsinki”, 
Good Clinical Practice (GCP) and within the laws and regulations of MoPH in Qatar. 
      The study will be conducted in full conformance with principles of the “Declaration of Helsinki”, Good Clinical 
Practice (GCP) and within the laws and regulations of MoPH in Qatar. 
 
 
11. Sponsor, Funding & Collaborator Information  
Provide basic details of the lead sponsor and/or funding bodies, including name, and contact information, allocated 
number for the research, etc. For example QNRF 
 
     From  Medical Research Center’ . 
 
 
12. Dissemination of Results and Publication policy 
List any meetings or conferences where you will be presenting the data and the results of your study.  Please 
provide timeline for finalizing manuscript and when and where you plan to submit for publication. Any presentation, 
abstract, or manuscript must be made available for review by The Medical Research Center prior to submission. 
       
We plan to conduct stakeholder’s workshops, conferences, public forum that will help us to disseminate the study 
results by reporting and presentation the various interdisciplinary health care professional and policy makers.  
 
 

 
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We plan to publish our study results in both internationally known journals and electronic open access journals. Finally, 
our plans for dissemination include assisting other researchers on the phases of the project, trans –disciplinary 
perspective and other related methodological issues.  
 
13. References  
Cite the sources of all reference materials used to support the hypothesis 
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and adverse health outcomes in ageing populations: A systematic review and meta‐analysis. British journal of clinical 
pharmacology. 2019;85(11):2464-78. 
3. Khayyat SM, Mohamed M, Khayyat SMS, Hyat Alhazmi RS, Korani MF, Allugmani EB, et al. Association between medication 
adherence and quality of life of patients with diabetes and hypertension attending primary care clinics: a cross-sectional survey. 
Quality of life research. 2019;28(4):1053-61. 
4. Aznar-Lou I, Fernández A, Gil-Girbau M, Sabés-Figuera R, Fajó-Pascual M, Peñarrubia-María MT, et al. Impact of initial 
medication non-adherence on use of healthcare services and sick leave: a longitudinal study in a large primary care cohort in 
Spain. British Journal of General Practice. 2017;67(662):e614-e22. 
5. Marengoni A, Angleman S, Melis R, Mangialasche F, Karp A, Garmen A, et al. Aging with multimorbidity: a systematic review 
of the literature. Ageing research reviews. 2011;10(4):430-9. 
6. Wimmer BC, Cross AJ, Jokanovic N, Wiese MD, George J, Johnell K, et al. Clinical outcomes associated with medication 
regimen complexity in older people: a systematic review. Journal of the American Geriatrics Society. 2017;65(4):747-53. 
7. Calderón-Larrañaga A, Poblador-Plou B, González-Rubio F, Gimeno-Feliu LA, Abad-Díez JM, Prados-Torres A. Multimorbidity, 
polypharmacy, referrals, and adverse drug events: are we doing things well? British Journal of General Practice. 
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8. Eton DT, de Oliveira DR, Egginton JS, Ridgeway JL, Odell L, May CR, et al. Building a measurement framework of burden of 
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persons living with multimorbidity: protocol of a mixed-methods systematic review. BMJ open. 2021;11(12):e050990. 
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qualitative data. PloS one. 2017;12(6):e0179916. 
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cardiovascular medications. International journal of cardiology. 2014;177(2):477-82. 
12. Smaje A, Weston‐Clark M, Raj R, Orlu M, Davis D, Rawle M. Factors associated with medication adherence in older patients: 
a systematic review. Aging medicine. 2018;1(3):254-66. 
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Preventive medicine. 2017;99:269-76. 
14. Marcum ZA, Hanlon JT, Murray MD. Improving medication adherence and health outcomes in older adults: an evidence-
based review of randomized controlled trials. Drugs & aging. 2017;34(3):191-201. 
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pilot study. PloS one. 2014;9(6):e98704. 
 
 

 
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20. Bogner HR, de Vries HF. Integrating type 2 diabetes mellitus and depression treatment among African Americans. The 
Diabetes Educator. 2010;36(2):284-92. 
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high-risk older patients. J Gen Intern Med. 2013;28(5):612-21. 
22. Smith SM, Wallace E, O'Dowd T, Fortin M. Interventions for improving outcomes in patients with multimorbidity in primary 
care and community settings. Cochrane Database of Systematic Reviews. 2016(3). 
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European Journal of Hospital Pharmacy. 2019;26(4):187-92. 
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elementos estándares del protocolo de un ensayo clínico. Rev Panam Salud Publica. 2015;38(6):507. 
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26. Corbett G, Trainer RMC, Valley PLNM. Motivational interviewing. 2012. 
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toward a more uniform methodology. The Annals of Family Medicine. 2012;10(2):142-51. 
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medication adherence scale (MMAS-8). INNOVATIONS in pharmacy. 2014;5(3):5. 
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and biomedical sciences. Behavior research methods. 2007;39(2):175-91. 
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65: a randomized, controlled trial in primary care. Age and ageing. 2001;30(3):205-11. 
32. Miller WR, Rollnick S. Motivational interviewing: Helping people change: Guilford press; 2012. 
33. Renier CM, Morse J. Development and validation of a survey to assess patient-perceived medication knowledge and 
confidence in medication use. Journal of Nursing Measurement. 2014;22(1):120. 
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method for assessing the cognitive representation of medication. Psychology and health. 1999;14(1):1-24. 
35. Risser J, Jacobson TA, Kripalani S. Development and psychometric evaluation of the Self-efficacy for Appropriate Medication 
Use Scale (SEAMS) in low-literacy patients with chronic disease. Journal of nursing measurement. 2007;15(3):203-19. 
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4.1 (MITI 4.1). Unpublished manual. 2014. 
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interventions. 2007. 
 
 
14. Appendices 
List in this section all intended forms or resources that will be used in the conduct of research to collect data, 
interview people, recruit participants. 
1. Screening & randomization questionnaire 
2. Medication adherence using Morisky scale 
3. BMQ questionnaire 
4. The Self-Efficacy for Appropriate Medication Use Scale (SEAMS)