Exploring the Role of Mindfulness Training in the Promotion of Medication Adherence in Heart Failure Outpatients.
Phase: NA
Conditions: Medication Non-adherence
Sponsor: The Miriam Hospital

 
Study Name:   
 
Mind Your Heart Study 
NCT number:  
 
NCT03571581 
Grant Title:   
 
Mindfulness Training to Promote Medication Adherence 
 
 
 
  
in Patients with Chronic Heart Failure 
Grant #: 
 
 
R21HL140492 
Date of document: 
 
4/10/2020 
Principal Investigator:  
Elena Salmoirago-Blotcher, MD, PhD 
 
 
 
 

 
 
 
Exploring the role of mindfulness training in the 
promotion of medication adherence in heart failure 
outpatients. 
 
 
 
 
 
Study Protocol 
 
 
 
 

 
 
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Principal Investigator 
Elena Salmoirago-Blotcher, MD, PhD, FAHA 
Division of Behavioral and Preventive Medicine  
The Miriam Hospital 
Assistant Professor of Medicine & Epidemiology 
Warren Alpert Medical School and School of Public Health  
Brown University 
 
 
 
 
 
Supported by 
  
The National Heart Lung and Blood Institute 
R21HL140492 
 
 

Tool Revision History 
Version Number: 1 
Version Date: 3-21-2018 
Summary of Revisions Made: n/a 
 
Version Number: 2 
Version Date: 7-30-2018 
Summary of Revisions Made:  
• Adherence inclusion criteria modified 
• Pittsburg Sleep Quality Index, Voils adherence assessment, program evaluation survey, Five 
Facets of Mindfulness, phone screening script added to study instruments/measures 
• Morisky scale and SF-8 no longer included in study surveys 
 
 
Version Number: 3 
Version Date: 10-19-18 
Summary of Revisions Made: 
• Minor amendment to protocol to incorporate obtaining physician clearance for participant 
eligibility purposes.  
• Physician Clearance form & fax cover sheet added to study instruments for approval 
• Phone Screen updated with physician clearance criteria for approval (stamped, tracked 
and clean versions attached) 
• Participant home practice log updated to incorporate two recordings instead of three 
(tracked & clean versions attached) 
 
 
Version Number: 4 
Version Date: 10-30-18 
Summary of Revisions Made: 
• Minor amendment to protocol to incorporate obtaining confirmation of a diagnosis of 
heart failure for patients recruited from the community.  
• Minor protocol amendment to add "Statin" as an additional medicine which will qualify 
as a medication to be monitored.  
• Confirmation of heart failure form added to study instruments for approval 
• Phone Screen updated with heart failure confirmation for approval (stamped, tracked and 
clean versions attached) 
• Participant home practice log updated to incorporate two recordings instead of three 
(tracked & clean versions attached) 
• Requesting to add authorization/release form to give to patient in order for their physician 
to confirm a heart failure diagnosis.   
Version Number: 5 
Version Date: 3-5-19 

 
 
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Summary of Revisions Made: 
• Removing staff (Rachel Kelly) from personnel & protocol. They are no longer assisting 
on project   
•  Updating Preparatory to Research & HIPAA Waiver of Authorization to remove staff 
that is no longer with the project 
 
Version Number: 6 
Version Date: 4-9-19 
• Changes to adherence inclusion criteria  
• Administrative modifications to study instruments and consent form where indicated  
 
Version Number: 7 
Version Date: 4-10-20 
• Due to COVID-19 Pandemic, minor amendment to protocol to collect 3M & 6M follow 
up survey data over the phone, online, or by mail.

 
 
RESEARCH TEAM 
 
 
 
 
 
 
 
 
Name 
Role  
 
Elena Salmoirago-Blotcher 
 
Principal Investigator 
Kristen Walaska 
Project Director 
Dyuti Trivedi 
Research Assistant 
 
Christopher Breault 
 
Data manager 
 
Shira Dunsiger 
 
Biostatistician 
 
Beth Bock 
 
Co-Investigator 
 
Ronald Cohen 
 
Co-Investigator 
 
Jia-Rong Wu 
 
Co-Investigator 
Daniel Levine 
Co-Investigator  
 
Priscilla Szneke 
 
Mindfulness Instructor 
 
Erin Sharaf 
 
Mindfulness Instructor 
Carole Legro  
Mindfulness Instructor 
1 

 
 
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AE 
Adverse Event 
AHA 
American Heart Association 
BOMC  
Blessed Orientation Memory Concentration test 
CBPM 
Centers for Behavioral and Preventive Medicine 
Co-I 
Co-Investigator 
FFMQ 
Five Factors of Mindfulness Questionnaire 
IMC 
Independent Monitoring Committee 
MAIA 
Multidimensional Assessment of Interoceptive Awareness 
HADS 
Hospital Anxiety and Depression Scale 
HF 
Heart failure 
HIPAA 
The Health Insurance Portability and Accountability Act 
IRB 
Institutional Review Board 
MBSR 
Mindfulness Based Stress Reduction 
MT 
Mindfulness training 
PCP 
Primary Care Provider 
PHI 
Protected Health Information 
PI 
Principal Investigator 
RCT 
Randomized Clinical Trial 
SAE 
Serious Adverse Event 
RA 
Research Assistant 
TMH 
The Miriam Hospital 
2 
  
LIST OF ABBREVIATIONS 

 
3.1 . Background  
Heart failure (HF) is characterized by the heart’s inability to pump the necessary amount 
of blood to the peripheral tissues.1 The prevalence of HF is increasing worldwide; in the United 
States alone, 5.7 million individuals are currently affected.2  The most common causes of HF are 
atherosclerotic coronary heart disease, hypertension, diabetes, and the metabolic syndrome. 
Symptoms include shortness of breath, fatigue, limited exercise tolerance, and fluid retention.3 
Although clinical outcomes improve with medical therapy,4 HF has an unfavorable prognosis, 
with hospital re-admission rates of 50% within 6 months of discharge5,6 and mortality rates of 
50% within 5 years of the initial diagnosis.1,7,8 Hospitalizations cost an average of $23,000 per 
patient9 and combined costs for HF treatment reached almost $31 billion in 2012. A number of 
medications improve HF symptoms and significantly reduce re-hospitalizations and mortality.4,10 
Pharmacological treatment, however, can ultimately be effective only if patients take their 
prescribed medications regularly. Unfortunately, only 50% of HF patients are adherent to 
prescribed pharmacological treatments11 and adherence tends to decline even among patients 
who are initially adherent.12-14 Poor medication adherence has serious consequences, including 
higher rates of hospital re-admissions,15 emergency room visits,16,17 and mortality.18-20  
3.1.1. Factors associated with poor medication adherence in HF patients. Cognitive 
impairment is a strong predictor of poor adherence and is highly prevalent in this population, 
affecting about 60% of patients.21,22 A recent large prospective cohort study (n=309) conducted 
among community-dwelling patients with HF and no history of dementia found that poorer 
cognitive function predicted poor medication adherence independent of important covariates 
(depressed mood, social support, and disease severity). Memory and attention lapses reduce the 
patients’ ability to develop consistent adherence patterns and have been significantly associated 
with poor medication adherence.11,23-26 In addition to cognitive impairment, depression is also 
highly prevalent among HF patients and contributes to the poor medication adherence observed 
in these patients.11,23,24,27-29 30  
3.1.2. Gaps in current knowledge. A review by the Agency for Health Care Research 
and Quality found that policy-level interventions to reduce out-of-pocket expenses, case 
management, and educational interventions were the most effective approaches to improve 
adherence to medications.31 Such approaches, however, often do not address important patient-
level factors such as cognitive impairment and depression and have not been universally 
effective. A Cochrane review of 182 randomized controlled trials (RCTs) found inconsistent 
effects across studies and small-to-medium effect sizes.32 Of studies conducted among HF 
patients, 7 showed an improvement in medication adherence33-39 but only 4 showed an effect on 
clinical outcomes, and most studies did not include objective assessments of medication 
adherence.33-35,38 Further, studies often employed complex interventions with limited scalability 
and sustainability in “real life” clinical circumstances.32,40 Clearly, more comprehensive, scalable 
approaches addressing patient-level determinants of medication adherence are needed.  
3.1.3. Mindfulness training (MT) and medication adherence. MT involves learning to 
notice to which object the attention is drawn to at any given moment and to re-direct attention to 
the breath (or to any other chosen focus of attention) and is, in essence, a form of intensive 
3 
  
BACKGROUND AND RATIONALE 

 
 
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attention training.41 Although the potential effect of 
MT on medication adherence has been purported as 
a possible mechanism by which MT could improve 
cardiovascular health,42 no studies have yet 
formally investigated the possible effect of MT on 
adherence among patient with cardiovascular 
disease and data are scarce also in other 
populations. Results from a pilot RCT of 
Mindfulness-Based Stress Reduction (MBSR) in 
HIV-infected youth have shown that the 
intervention group was more likely to have a lower viral load at follow-up (p = .04) compared to 
the control group, a finding that was interpreted as due to improved ART adherence.43 
Observational evidence generated from our group (detailed in C.1) and others shows that higher 
mindfulness skills are associated with higher medication adherence and that MT can improve 
self-reported medication adherence in patients with stable cardiovascular disease.44,45 We also 
note that both observational and experimental studies have shown that MT improves attention 
and working memory, which, as explained above, are important predictor of poor adherence in 
HF patients. Specifically, the initial phases of MT, which emphasize concentration practices (i.e., 
focusing the attention on the breath or another chosen object of attention) have been shown to 
improve attention skills.46-48 A RCT of a 2-week MT intervention has shown that MT improved 
working memory capacity and reduced the occurrence of distracting thoughts during completion 
of the graduate record examination in graduate students. 49 Jha et al. observed an increase in 
working memory capacity among military personnel who underwent an 8-week mindfulness 
intervention compared to both military and civilian control groups. 50 A study conducted among 
experienced meditators showed better performances on measures of attention compared to 
controls without meditation experience.51 Finally, a RCT has shown significant improvements in 
mindfulness skills and in measures of executive function among 201 older adults trained in 
MBSR compared to a wait-list control group.52 There is also robust evidence that MT can 
improve depression, another important predictor of poor adherence in HF patients.53-56 
3.1.4. Conceptual model linking MT and medication adherence. The conceptual 
model proposed for this study builds upon the model proposed by Malinowski and others, 57-60 on 
meta-analytical studies of the mechanisms of the efficacy of MT on health outcomes,61 and on 
empirical evidence supporting of the efficacy of MT on attention and working memory.46-51 In 
the proposed model, the refinement of attentional skills is central to the development of the 
cognitive and emotional flexibility needed to bring about changes in health behaviors (in our 
case, adherence to medications) (Figure 1). In this study, we are particularly interested in 
exploring pre/post intervention effects of MT on measures of attention and working memory and 
whether such changes are associated with changes in adherence. A full mediational analysis is 
beyond the scope of this study and thus, these analyses will be only exploratory. If results from 
this exploratory study are promising, this model will be tested in a fully powered randomized 
controlled trial (RCT), which will formally investigate the efficacy of MT on medication 
adherence as well as the mediating role of emotional (i.e., depression) and cognitive (attention, 
working memory) factors in bringing about changes in the tar 

 
  
Aim 1: To determine the feasibility and acceptability of mobile phone-delivered MT in 
HF outpatients. Hypothesis: We will be able to reach our recruitment goal (n=50) within the 
study timeline, with < 20% drop out rates by the end of the study and > 80% of participants 
reporting high (=grade 4) enjoyment ratings on a scale from 0 to 4.  
     
Aim 2: To determine whether mobile-delivered MT can improve self-reported and 
objectively assessed medication adherence as well as functional capacity (a clinical marker of 
medication adherence, per PA requirements). Hypothesis: we will observe significant pre-post 
intervention improvements in medication adherence and functional capacity.  
     
Aim 3: To explore whether memory and attention change over time and whether such 
changes are associated with changes in medication adherence. The goal is to explore potential 
mediating effects that will be formally tested in a future fully powered RCT. We hypothesize for 
example, that MT will improve working memory, and that such changes will in turn be 
associated with improvements in adherence. Although measures of memory and attention are our 
primary posited mediators, we will also explore the role of mindfulness and depressive 
symptoms (additional potential mediators of MT effect). 
  
5.1. Overview.   
Mindfulness training is a behavioral, low-risk intervention. Thus, we anticipate that patients will 
incur minimal risks due to their participation in this study. Potential untoward events that may 
occur include:  
a. Emotional discomfort during mindfulness practice  
b. Transient, mild discomfort during awareness of breath practice  
c. Breach of confidentiality 
The level of risk for each of these events is minimal.  
5.2. Expected Risks and Protection Against Risks  
a) Emotional discomfort during mindfulness practice is a rare occurrence. When occurring, it is 
mild, of short duration, and rarely occurs in absence of ongoing serious psychiatric 
conditions. Measures for protection will include: 
• Participants with severe depression or ongoing psychosis will be excluded from 
participation in the study.  
• In case a patient presents signs of severe psychological discomfort during or between 
sessions, he/she will be excused from participating in the mindfulness intervention. The 
instructor will inform the RA and conduct an assessment of suicidality (see Suicidality 
Assessment Protocol). The mindfulness instructor will actively inquire about 
psychological side effects that might occur during the session or during individual 
5 
  
SAFETY ASSESSMENT 
 
4 
  
STUDY AIMS  

 
 
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practice. Mindfulness instructors are experienced and trained on how to help individuals 
presenting such issues. Participants will also be instructed to contact the RA should any 
discomfort arise during the training.  
b) The likelihood of loss of privacy or confidentiality is rare and its impact on participants is 
likely to be minimal.  Risks to privacy and confidentiality associated with this study will be 
described in the consent form along with our procedures to minimize this risk.   
• Confidentiality of study data will be maintained by numerically coding all data, by 
disguising identifying information, and by keeping all data in locked file drawers.  All 
information obtained from participants will be accessible only to research staff.  In weekly 
staff meetings when study procedures are reviewed and issues of compliance are raised, 
participants will not be identified by name unless necessary, and then, only by first name 
and only to the study personnel who require this information. 
• Audio recordings of mindfulness classes will be reviewed promptly to ensure treatment 
fidelity and then destroyed.  Checklists and paper records of the treatment fidelity review 
will not include identifying information but will be stored and handled using the same 
methods as with other paper data.  
• Study staff will maintain participant privacy by conducting phone interviews in private 
offices, by securing records in locked cabinets and by using password-protected databases. 
Project staff meetings will be held in private conference rooms.  Instructions for 
maintaining privacy and confidentiality will be given to participants at the start of the first 
mindfulness class.  In addition, participants will be reminded of these instructions and to 
respect each other’s privacy and not repeat information shared with the group outside of 
the study setting.   
 
5.3. Expected Benefits 
The proposed research may result in direct benefits to participants and we expect that these 
benefits will outweigh the minimal risk associated with participating in this research study. 
Individuals who complete the mindfulness training may experience reduced levels of distress and 
an improved quality of life. 62 The magnitude of the benefit may be mild to moderate, and such 
benefits may last for the duration of the intervention and for the following months.  
 
Several different entities will safeguard the participants’ safety and the integrity and quality of 
the data. 
• Institutional Review Board (IRB): The study is submitted for approval and will meet all 
IRB requirements and directions.  
6 
  
DATA AND SAFETY MONITORING PLAN  
 

 
• The PI will closely supervise all study activities. Dr. Salmoirago-Blotcher will meet weekly 
with the RA and the data manager to monitor recruitment procedures, accrual and retention, 
side effects, and data integrity in order to take the necessary measures in a timely fashion.  
• Independent Monitoring Committee (IMC): Consistent with NIH guidelines for smaller 
studies (see: http://nccam.nih.gov/grants/policies/data-safety-monitoring) an IMC will be 
responsible for monitoring the safety of participants and the validity and integrity of the data. 
IMC members will include a biostatistician and an expert in mindfulness. The IMC will meet 
once a year, either in person or via conference call. However, the IMC will convene on a 
more frequent basis should urgent study concerns arise. At both scheduled and ad hoc 
meetings, the IMC will review adverse events, re-evaluate measures for the protection of 
human subjects if needed, and re-assess the risk/benefit ratio of the study. A report will be 
compiled after each meeting and will include (a) a list of adverse and serious adverse events 
classified by severity and likelihood of being related to the study intervention; (b) whether 
adverse event rates are consistent with pre-study assumptions; (c) rates and reasons for study 
withdrawal; (d) whether all participants met entry criteria; (e) whether continuation of the 
study is justified. Summary reports of IMC meetings will be sent to the PI and to the IRB and 
included in the annual reports for the project. 
Study safety and progress will be monitored according to the schedule outlined in table1 (more 
frequently if needed).  
6.1. Adverse Events and Serious Adverse Events  
a. Definition. An adverse event (AE) is defined as any untoward medical occurrence in a 
participant temporally associated with participation in the clinical study. An adverse finding 
can include a sign, symptom, abnormal assessment (laboratory test value, vital signs, 
electrocardiogram finding, etc.) or any combination of these. A Serious Adverse Event 
(SAE) is any adverse event that results in one or more of the following outcomes: 
• Death 
• A life-threatening event 
• Inpatient hospitalization or prolongation of existing hospitalization  
• A persistent or significant disability/incapacity 
Table 1. 
 
Frequency of 
data collection 
Frequency of 
data review 
Data type 
RA 
PI 
IMC 
Accrual, retention and attrition  
Weekly 
Every 2 weeks 
Every 12 months 
Adverse events* 
Weekly 
Weekly 
Every 12 months 
Participants’ compliance  
to the intervention protocol 
Weekly 
Every 2 weeks 
Every 12 months 
Providers’ compliance  
to intervention protocol 
Weekly 
Every 2 weeks 
Every 12 months 
Missing data/data integrity 
Weekly 
Every 2 weeks 
Every 12 months 
* Please note: serious adverse events will be reported within 24 hours to the IMC, IRB, 
and to the sponsor in accordance with their requirements. 

 
 
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• Important medical event based upon appropriate medical judgment 
Note: A birth defect is a highly unlikely event considering the age of our population. This 
outcome has been excluded. 
 
b. Classification of AE Severity. AEs will be labeled according to severity, which is based on 
their impact on the patient. An AE will be termed ‘mild’ if it does not have a major impact on 
the patient, ‘moderate’ if it causes the patient some minor inconvenience and ‘severe’ if it 
causes a substantial disruption to the patient’s wellbeing. 
 
c. AE Attribution Scale. AEs will be categorized according to the likelihood that they are 
related to the study intervention. Specifically, they will be labeled either definitely, probably, 
possibly or unrelated to the study intervention. The determination of whether an AE is related 
to the study intervention will be made by the PI. If relatedness is unclear, the PI will seek the 
guidance of the study cardiologist.  
 
Reportable and non-reportable events. The IRB requires reporting of all SAEs as well as of 
those AEs that are unanticipated and related to the study protocol or procedures (that is, they are 
“unlikely”, “possibly”, “probably” or “definitely” related). Unanticipated AEs are events, signs 
and symptoms that are not listed as risks on the consent form. Please note that AEs that are either 
anticipated or are “definitely not” related to the intervention procedures are not reportable to the 
IRB at TMH. 
 
6.2. AE Reporting Procedures and Follow-Up 
All reportable (see 6.1. for definition) adverse events (AEs) will be reported by the PIs to the 
IRB at TMH. Serious adverse events (SAEs) are reported to the IRB within 24 hours as 
described below (“SAE reporting”). All other reportable adverse events will be reported during 
the routine annual continuation reports to the IRB. In addition, all AEs (reportable and non-
reportable) will be provided to the Chair of the IMC prior to each meeting. 
All intervention visits (mindfulness sessions) and follow-up assessments will include proactive 
assessments of potential adverse events. The RA will record all AEs and SAEs in a secure 
database using the format in the example below: 
Subject 
Identifier 
AE Onset 
AE 
End 
AE 
Code 
Severity 
SAE? 
(y/n) 
Relatedness 
Action 
Taken 
Outcome 
Comments 
Subj001 
11/1/15 
 
 
1 
N 
2 
1 
1 
Subject felt anxious 
during MT; 
resolved within 15 
minutes 
 
Subj002 
12/3/2015 
 
 
2 
N 
3 
1 
1 
Dizziness during 
exercise session 
Subj003 
12/18/15 
 
 
3 
N 
0 
4 
4 
Subject fell while 
hiking; broke leg; 
withdrew from 
study 
Severity of AE: 
Relatedness to 
Action Taken: 
Outcome: 

 
1 = Mild 
2 = Moderate 
3 = Severe 
4 = Life threatening or 
disabling 
 
intervention: 
0 = Definitely unrelated 
1 = Unlikely 
2 = Possibly related 
3 = Probably related 
4 = Definitely related 
0 = None 
1 = Intervention modification 
2 = Medical intervention (specify in 
comments) 
3 = Hospitalization 
4 = Intervention discontinued 
5 = Other (specify in comments) 
1 = Resolved 
2 = Recovered with minor 
sequelae 
3 = Recovered with major 
sequelae 
4 = Continuing treatment 
5 = Condition worsening 
6 = Subject death  
 
Participants will be asked about all AEs at each intervention session and at each follow up 
assessment. AEs will be recorded on the AE log and noted on the CO form. The RAs will report 
all AEs to the PIs as soon as possible. All AEs will be assessed to determine their classification 
and whether they meet criteria for an SAE. The study RAs will refer participants to their own 
physician for assistance with adverse symptoms. Each week the PIs will review AE reports from 
the previous week for events that were reported as new or continuing and will follow all AEs to 
the point of a satisfactory resolution. The PIs will be available at all times to discuss other 
adverse symptoms with the RA and the study participants.  
 
SAE Reporting. SAEs that are unanticipated, serious, and/or possibly related to the study 
intervention will be reported to the IMC, the IRB at TMH, and to the sponsor (NHLBI) in 
accordance with their requirements (see 6.1).  
Stopping rules. Considering the low-risk of this study, stopping rules have not been established.  
However, the IMC will closely monitor the risk/benefit ratio and the progress of the study and 
should issues in accrual, retention, data quality or safety arise, will take prompt action including 
considering the interruption of the study. Given the low risk of this study, no interim analyses are 
proposed. 
6.3. Monitoring of Study Progress (Table 1) 
Accrual, retention. Review of the number of screened and eligible participants/month, accrual 
rates, adherence to inclusion/exclusion criteria will occur weekly. This will help evaluate the 
adequacy of the eligibility criteria and of the recruitment procedures and to address concerns in a 
timely fashion. 
Compliance with the intervention protocol. Protocol compliance will be assessed in an ongoing 
fashion. Participants’ compliance will be monitored by the instructors and research assistant and 
will involve tracking of the number of sessions attended and of the total time of individual 
mindfulness practice. Instructors’ compliance will be supervised by Dr. Salmoirago-Blotcher 
according to the Treatment Fidelity Workgroup guidelines. At the end of each MT session the 
instructor will complete a checklist in which duration and delivery of the intervention as 
specified in the intervention script will be evaluated, as well as the patient’s level of engagement 
during the session. In order to monitor the consistency of the delivery of the intervention, each 
session will be digitally recorded. Ten percent of all recorded sessions will be randomly 
reviewed.  
Data accuracy. The RA and data manager will be responsible for tracking participants to ensure 
that all data are collected in a timely and efficient fashion; for developing and generating 
monitoring reports; for providing timely and relevant feedback to the project leadership 
regarding the accuracy and precision of data. The following data verification procedures are 
planned:  

 
 
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Research Electronic Data capture (REDCap) technology will be used to for direct data entry 
during the interviews.  REDCap employs automatic checks for values that are out of range or 
represent errors of logic. Outliers will be corrected with verification from participants.  
Calculations (i.e., from self-report measures, when necessary) will be independently performed 
by two different persons and any invalid score (i.e. scores that differ between the two people) 
will be recalculated. 
 
 
 
 
     
  
7.1. Population  
Participants (n=50) will be recruited from the HF clinic at Rhode Island Hospital (RIH), located in 
Providence, RI as well as among community dwelling adults in the Providence area.  
 
Vulnerable populations. This study will not recruit individuals from vulnerable populations (i.e.: 
adults unable to consent, Infants, children, teenagers or pregnant women). Subjects with severe 
cognitive impairment (and thus, unable to provide informed consent) are excluded from 
participation in the study (see 9.2 for details). 
7.2. Inclusion Criteria 
Participants must meet all of the following inclusion criteria to participate in this study (see 
sections 9.1 and 9.2 for a description of the screening visit and of the screening assessments): 
• Age >18  
• Fluency in English language 
• A diagnosis of HF (based on medical record or confirmation from participant’s physician) 
• Access to a telephone 
• Ability to understand and speak English 
7.3. Exclusion Criteria 
Participants must meet all of the following exclusion criteria to participate in this study: 
• Unwillingness/inability to provide informed consent  
• New York Heart Association63 (NYHA) class IV heart failure or clinically unstable 
• Severe hearing impairment not allowing phone delivery  
• Severe depressive symptoms (defined as Hospital Anxiety and Depression Scale [HADS] 
depression subscale scores >14)  
• Acute psychosis (from medical record) 
• Severe cognitive impairment (BOMC79 scores > 10)  
• Unable to obtain confirmation of HF diagnosis 
• Recent hospitalization (< 6 weeks) 
7 
  
ELIGIBILITY  

 
• Current (at least once a month) mind/body practice (i.e., mindfulness meditation, yoga, or tai 
chi)    
 
 
 
 
8.1. Participants’ Recruitment 
Recruitment approaches will include the following:  
1) The recruitment research assistant will identify patients scheduled for a visit at the Heart 
Failure Clinic at RIH (a HIPAA waiver and HIPAA preparatory to research requests are attached 
to this application). Patients will receive an invitation letter signed by the PI and Dr. Levine and 
a copy of the consent form either in person after their visit or by mail. The invitation letter will 
not contain any PHI nor personal identification. This package will be sent from the CBPM and 
mailed by study staff.  
2) Flyers placed in clinics and in local public venues (e.g., community centers, libraries, 
supermarkets) 
3) Social media (e.g. Facebook and Twitter) and on-line resources (hospital intranet; Craig’s 
List) 
4) Lifespan physician referrals  
5) For items 2 & 3 physician clearance will be needed to confirm a medical diagnosis of Heart 
failure per study inclusion criteria. 
All study recruitment materials will be submitted to IRB for approval. 
We will track returns from the different recruitment venues in order to identify the most efficient 
recruitment strategies for the future RCT. 
8.2. Screening and Consenting Procedures 
Interest assessment phone call: Initial contact will be made via telephone by interested individuals using 
a dedicated phone number that will be included in the invitation letter and all recruitment materials. 
Individuals calling about the study will be screened by the study RA in a phone conversation to 
determine initial eligibility.  The RA will briefly describe the study and its requirements and enquire 
whether the caller is still interested.  The RA will explain the need to collect some information from the 
caller to determine whether they are eligible to participate and request verbal permission to proceed. A 
script and screening instrument will be used to standardize this phase of enrollment.  Upon obtaining 
verbal consent the RA will complete the phone screen. A standardized formula will guide the RA to 
determine whether the caller is (a) eligible, (b) potentially eligible-pending or (c) not eligible.  
If the caller has been recruited via options 2 and 3, the RA will request contact information for the 
participant’s physician and obtain verbal permission to send the participant’s physician a letter to obtain 
a confirmation of heart failure diagnosis. Once the confirmation is received, the RA will contact the 
individual to schedule a screening orientation session.  If the physician does not confirm a diagnosis of 
heart failure, the individual will be called and notified that they are not eligible for the study. Patients 
signaling interest will be invited for a screening visit. 
 
Screening visit: Once the potential participant has confirmed interest in participating, he/she will 
receive a consent form to read discussing the purpose of the study, its risks and benefits and 
clearly stating that he/she can withdraw at any time without any adverse consequences. This 
study will involve only ONE informed consent process. Full informed consent will be obtained in 
 8 
  
ENROLLMENT 

 
 
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person by the RA in a private room at the CBPM after a thorough explanation of the study 
design, of the study intervention, and of the risks and benefits involved. Since the study requires 
access to protected health information (PHI), HIPAA authorization will be required from each 
individual in order to access his or her medical records.  Signed informed consent forms will be 
kept in locked filing cabinets separate from all data. Participants will receive a copy of the 
consent for their records. Once informed consent procedures are completed, participants will 
undergo a battery of screening assessments (described in section 9.2). The RA will complete a 
screening log checking that all eligibility criteria are met at this point. 
 
Screening failures: Microsoft ACCESS© will be used for tracking all participants who expressed 
interest in participating and were screened for eligibility. We will collect data from all 
individuals assessed for eligibility (i.e., individuals who consented but then resulted non-eligible 
at the completion of the screening process) so that we can provide a complete Consort diagram 
and description of the recruitment process both for publication purposes and as an indicator of 
future generalizability of the study. We estimate that our screen failure rates will be ~30%, and 
that 70% of screened participants will be eligible for this study. 
 
Screening window. We anticipate that the time between the completion of all screening 
procedures and the beginning of the intervention will not exceed 4 weeks.  In case > 4 weeks 
have lapsed, patients will be re-contacted and re-assessed for eligibility. 
 
Randomization. n/a. This is a pre-post design study. NO randomization is involved.  
 
8.3. Retention plan 
Patients will be asked to provide two different telephone numbers (home and mobile phone 
number) and an email address. The study tracking system will identify participants due for a 
visit. We will send mail/email reminders or phone messages to remind patients of their follow-up 
appointments or class sessions. We will also maintain contact by sending birthday and holiday 
cards. Participants who wish to drop out of the study will be queried as to their reasons for doing 
so and every attempt will be made to address their concerns. To encourage compliance with 
assessment visits, we will provide a $ 50 incentive at each visit (baseline, end of intervention, 
and 6 months - $150 total). No incentive will be provided for participation in intervention 
sessions, as this might bias attendance and threaten the validity of our findings. 
9.1. Study Outcomes  
Primary outcomes:  
1) Feasibility.  Key feasibility metrics will include the number of screened, eligible, consented 
and randomized participants; retention rates; session attendance; and individual mindfulness 
practice.  
2) Acceptability will be assessed using a satisfaction survey.  
9 
  
STUDY DESIGN AND PROCEDURES 

 
 
Secondary outcomes:  
1) Pre/post intervention change in self-reported and objectively assessed medication adherence 
and functional capacity (a clinical marker of medication adherence). Hypothesis: we will 
observe significant pre-post intervention improvements in medication adherence and 
functional capacity.  
2) Changes in memory and attention change over time and associations between changes in 
memory and attention and changes in medication adherence. The goal is to explore potential 
mediating effects that will be formally tested in a future fully powered RCT. We hypothesize 
that MT will improve working memory, and that such changes will in turn be associated with 
improvements in adherence. Although measures of memory and attention are our primary 
posited mediators, we will also explore the role of mindfulness and depressive symptoms 
(additional potential mediators of MT effect). 
 
9.2. Design Overview 
This is a pilot study use a pre-test/post-test design. The overall duration of this study will be 2 
years; each individual (n=50) will be involved for 6 months. Assessments will be conducted at 
baseline, end of treatment, and 6- months after baseline.  
 
9.3. Study Intervention  
Intervention setting. Intervention sessions will be individually delivered over the phone. Prior to 
the beginning of the intervention instructors will contact participants to set up the best time to 
deliver the intervention.  
Session frequency. Participants will receive a 30-minute phone call session once a week for 8 
weeks.  
Mindfulness training (MT). The intervention protocol is based on the MT protocol pilot-tested in 
our preliminary work (see Appendix 1 for a script of each session). This intervention maintains 
the basic components of Mindfulness Based Stress Reduction (MBSR) but has been streamlined 
to distill the active ingredients for phone delivery. The MT intervention involves training in the 
following practices: (1) Awareness of breath, a technique in which trainees learn to attend to the 
sensations associated with breathing; and (2) Body scan, a technique based on the cultivation of 
attention to bodily sensations that would normally go unnoticed. Later, participants are gradually 
trained to (3) direct their attention to simple activities of daily life and (4) to become aware of 
their own thoughts and emotions. Only at the final session they (5) practice “open awareness” – a 
technique by which the participant is invited to direct his/her attention to any event arising in 
their field of experience at a given moment, whatever it may be, e.g., a physical sensation, sound, 
emotion, or thought.  
 
Table 2. Session by Session Overview of the MT Intervention Components  
 
Session 
1 
Session 
2 
Session 
3 
Session 
4 
Session 
5 
Session 
6 
Session 
7 
Session 
8 
Awareness of 
breath 
X 
X 
X 
X 
X 
X 
X 
X 
Body scan 
 
 
X 
X 
X 
X 
X 
X 

 
 
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Awareness of 
daily experience 
exercise 
 
X 
 
 
 
 
 
 
Informal 
practice exercise 
 
 
 
X 
 
 
 
 
Awareness of 
sounds exercise 
 
 
 
 
X 
 
 
X 
Awareness of 
emotions 
exercise 
 
 
 
 
 
X 
 
X 
Awareness of 
thoughts 
exercise 
 
 
 
 
 
 
X 
X 
Open awareness  
 
 
 
 
 
 
 
X 
 
Individual home practice. In addition to the weekly training session, participants will practice 
mindfulness techniques for 20 minutes daily on their own with the guidance of a digitally 
recorded, standardized guided mindfulness practice containing the techniques learned with the 
instructor. The mindfulness practice digital recording will be provided in different formats (CD 
or MP3 file) depending on the participant’s preference; CD players will be offered to participants 
who do not possess one and MP3 versions will be uploaded onto the patient’s smartphone or 
other device. (Please see Appendix for a script of the CD/MP3 recording).  
MT instructors. The MT instructors (Szneke, Sharaf, Legro) will be graduates of the teachers’ 
training program at the University of Massachussetts Center for Mindfulness with ≥ 5 years 
teaching experience who have already participated in studies involving phone-delivered MT. To 
ensure consistency of delivery, each patient will be trained by the same instructor throughout the 
intervention. Instructor will receive one 2-hour long training session (review of MT protocol. 
Fidelity procedures).   
9.4. Concomitant Interventions  
Allowed Interventions: Participants are allowed to continue ALL the medications and follow all 
behavioral recommendations prescribed by their care providers (i.e. dietary recommendations). 
Prohibited Interventions: Concurrent yoga, tai chi, or other mind-body training.  
  
9.5. Blinding 
The RA will be responsible for the day-to-day management of the study and will not be blinded 
to the exposure status of the participants. We note, however, that study participants will 
independently perform cognitive tests and enter other data via computer interface with no RA 
involvement. All personnel responsible for data management and analysis will be blinded to 
participants’ exposure status.   
 
The mindfulness instructors cannot be blinded to exposure status but will be blinded to study 
hypotheses. 

 
 
 
Screening, baseline and follow-up assessments will be completed in a private room located at the 
CBPM. The CBPM occupy 20,000 square feet of space in the Coro Building, of which 3700 for 
the exclusive purpose of meeting with research subjects. This area consists of conference rooms 
for orientations and group meetings, private assessment rooms for one-on-one appointments, and 
two control rooms from which an operator can monitor private observation rooms. The CORO 
Building has 24-hour security including security officers, a panic system to alert security, and 
any other emergency response system if necessary. We also have several staff certified in CPR 
and Basic Life Saving response. In response to the COVID-19 pandemic, and due to the fact that 
this is a high-risk population, follow-up assessments will now be completed over the telephone, 
via video-conference (using secure, HIPAA compliant videoconferencing software), or by 
mailing study surveys (that will be returned using pre-stamped envelopes) depending on the 
participant preference and internet accessibility. 
The full assessment package will take approximately 45 minutes to complete. Since not all 
participants can be reached for assessments on their due date, windows have been established to 
determine when assessments are counted as missed (table 3).  
 
Table 3.  
Assessment 
Window before 
Window following 
 3 months 
+/-1 week 
 +/- 1 week 
6 months 
+/-1 week 
 +/- 1 week 
 
10.1. Study Assessments Schedule 
This table diagrams the study measures and the schedule of administration. 
 
 
Screening Baseline 
At each 
session  
3 m  
6 m  
Consent form 
X 
 
 
 
 
HIPAA 
X 
 
 
 
 
Contact information 
X 
 
 
 
 
Eligibility check log  
X 
 
 
 
 
Cognitive impairment (BOMC) 
X 
 
 
 
 
Adherence (Voils scale part 1)  
 
X 
 
X 
X 
Depression (HADS) 
X 
 
 
X 
X 
Height, weight, hip, waist measures 
 
X 
 
X 
   X 
Blood pressure 
 
X 
 
X 
X 
Demographics 
 
X 
 
 
 
Medical history  
 
X 
 
 
 
Medications & other therapies 
 
X 
 
X 
X 
N screened  
 
X 
 
 
 
N eligible  
 
X 
 
 
 
10 
  
STUDY ASSESSMENTS  

 
 
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N refusing to participate 
 
X 
 
 
 
Reasons for refusal 
 
X 
 
 
 
Dropouts and lost to follow-up 
 
 
 
X 
X 
Reason(s) for dropping out 
 
  
X 
X 
Sessions attendance 
 
 
X 
 
 
Individual MT practice 
 
 
X 
X 
X 
Program satisfaction scale   
 
 
 
X 
X 
Program evaluation survey  
 
 
 
X 
 
Sleep Quality (PSQI)  
 
X 
 
X 
X 
Cognitive assessment battery 
 
X 
 
X 
X 
Walking test 
 
X 
 
X 
X 
Social Support  
 
X 
 
X 
X 
Depression (HADS) 
 
X 
 
X 
X 
Mindfulness (MAIA) 
 
X 
 
X 
X 
Five Facets of Mindfulness (FFM) 
 
X 
 
X 
X 
Adherence (MEMS caps)  
 
X 
 
X 
X 
Voils Self-Reported Adherence (part  
2) 
 
X 
 
X 
X 
MT = mindfulness training 
Note: screening and baseline assessments occur at same visit 
 
10.2. Screening Assessments  
These evaluations occur to determine if the candidate is eligible for the study (see also 7.2). 
• The Blessed Orientation Memory and Concentration test (BOMC)79 will be used to screen 
for severe cognitive impairment. Patients with BOMC scores ≥10 will be excluded because 
they lack the cognitive skills to learn the intervention.  
• Depression will be assessed using the HADS,64 a self-administered questionnaire with two 
sub-scales (0-21) measuring anxiety and depression, with higher scores indicating greater 
psychological morbidity. A good correlation has been reported between the HADS and other 
commonly used measures of depression.65 Finally, the HADS has been validated in cardiac 
patients;66,67 since the HADS focuses on cognitive symptoms of depression instead of 
physical symptoms, it is particularly useful in these patients, where symptoms of the 
underlying cardiac disease often overlap with the physical symptoms of depression. Scores 
will be calculated immediately after completion. Patients with HADS scores indicating 
severe distress (>14) will be excluded from the study and referred to their primary provider – 
please see Human Subjects section for details.  
• We note that in this version of the protocol we eliminated “suboptimal adherence” as an 
inclusion criterion. The reasons for this modification are as follows: 1) Even if patients report 
to be adherent at baseline, adherence declines over time. By including only participants who 
are non-adherent, we would not be capturing those that later become non-adherent. 2) This 
phenomenon is documented in the HF literature: adherence tends to decline even among HF 
patients who are initially adherent.12-14 
 

 
10.3. Baseline Assessments 
• Medication Event Monitoring Systems (MEMS) will be used as an objective measure of 
medication adherence. MEMS caps (AARDEX USA, Inc., Union City, CA) are medication 
containers and caps equipped with a digital microchip recording date and time of each cap 
opening and are one of the most widely used objective method of adherence assessment in 
research settings.36,68-70 We will monitor ONE medication per patient using the criteria 
adopted by Wu et al.12 Briefly, if the patient takes any HF medication twice a day, this 
medication will be MEMS-monitored. If all HF medications have the same daily prescription 
schedule, the β-blocker will be monitored. If the patient does not receive a β-blocker, the 
ACE inhibitor or the angiotensin receptor blocker will be used instead. If none of these drugs 
is prescribed, the aldosterone antagonist or statin, or digoxin or diuretic will be monitored.12 
Participants will receive a MEMS bottle at the baseline visit and will be instructed to open it 
only when they actually take their medication; they will also be trained to keep track of 
unscheduled lid openings (i.e. refills, accidental openings) in a diary; these events will be 
removed prior to analysis. After the baseline visit, participants will enter a 30-day run-in for 
the assessment of baseline adherence. Participants will start using the cap on the day 
following the baseline visit (=time 0), and the intervention will start 30 days later; this 30-
day period will be considered our baseline.  
• Self-reported medication adherence will be measured using the Voils medication adherence 
measure,71 a validated measure of adherence behaviors (part 1) as well as reasons for non-
adherence (part 2). The item response category consistent with perfect adherence (i.e., “none 
of the time” or “never”) are assigned a value of 1, and the item response category reflecting 
most nonadherence is assigned a value of 5 (i.e., “all of the time” or “always”). Higher scores 
indicate worse adherence behaviors. 
• Cognitive measures (selected from the NIH Toolbox Cognition module, see Appendix) will 
include:  
1) The Flanker Inhibitory Control and Attention Test. This test measures attention and 
inhibitory control. During the test, participants are instructed to focus on a stimulus while 
inhibiting attention to another stimulus (arrows).  Sometimes the middle stimulus points in 
the same direction as the “flankers” (congruent) and sometimes in the opposite direction 
(incongruent) over 20 trials;  
2) The Oral Symbol Digit Test assesses working memory and processing speed. A key with 
nine abstract symbols is presented - each paired with a number between 1 and 9. Participants 
are asked to verbally indicate which numbers go with the symbols that are presented in a long 
string on the computer screen. The participant is given 120 seconds to call out as many 
numbers that go with the corresponding symbols as he/she can – in order, without skipping 
any;  
3) The List Sorting Working Memory Test requires working memory for the sequencing of 
visually and orally presented stimuli. Pictures of foods and animals are displayed with 
accompanying audio recording and written text (e.g., “elephant”), and the participant is asked 
to say the items back in size order from smallest to largest, first within a single dimension 
(either animals or foods) and then on two dimensions (foods, then animals).  
4) The Picture Sequence Memory Test is a measure of episodic memory. Sequences of 
pictured objects and activities are presented in a particular order. The participants are asked 
to reproduce the sequence of pictures that is shown on the screen. Participants respond by 
dragging pictures from the yellow box on the screen into the gray boxes on the screen. 

 
 
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5) The Dimensional Change Card Sort Test is a measure of cognitive flexibility and 
attention. Two target pictures are presented that vary along two dimensions (e.g., shape and 
color). Participants are asked to match a series of bivalent test pictures (e.g., yellow balls and 
blue trucks) to the target pictures, first according to one dimension (e.g., color) and then, 
after a number of trials, according to the other dimension (e.g., shape). The relevant 
dimension for sorting is indicated by a cue word (e.g., “shape” or “color”) that appears on the 
screen for all participants.  
Performance on all these measures correlates significantly with scores on “gold standard” 
neuropsychological tests of each of the cognitive domains of interest and have high test-retest 
reliability, internal consistency, and convergent and divergent validity.72-77 Each test will be 
independently completed by study participants (3-5 minutes each) after a baseline practice 
trial using a study tablet. During phase 1 of this study we will develop a standardized 
protocol for the administration of cognitive tests, which will be included in the study manual 
of operations. The total time needed for the administration of the cognitive battery is 24 
minutes. 
• Social support: The Multidimensional Scale of Perceived Social Support is a 12-item, uni-
dimensional tool to measure how one perceives their social support system, including 
individuals sources of social support (i.e., family, friends, and significant other).  
• Depression will be assessed using the HADS,64 a self-administered questionnaire with two 
sub-scales (0-21) measuring anxiety and depression, with higher scores indicating greater 
psychological morbidity. If at any time during the study a participant scores >14 on the 
depression subscale, the RA will start a suicidality assessment (see suicidality protocol).   
• Mindfulness will be assessed using the Multidimensional Assessment of Interoceptive 
Awareness (MAIA),78 a 32-item, 8-subscale self-report measure (recommended by the NIH 
Science of Behavior Change Research Network), with higher scores indicating higher levels 
of positive awareness as well as the Five Facets of Mindfulness (FFM),79 an instrument 
derived from a factor analysis of questionnaires measuring mindfulness in daily life. 
• Sleep quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI),80,81 a 
measure of sleep quality and quantity, based on recall of sleep behaviors in the past month. 
Scores coded from zero to three; the overall score range is 0-21.  
• Weight, height, waist/hip ratio will be measured using standardized procedures (described in 
the study manual of operations) 
• Blood pressure will be measured using a Dinamap XL automated BP monitor according to 
current recommendations.824 
• Exercise capacity will be assessed via the 6 min walking test, a simple, safe and reliable 
first-line assessment of functional status835 that correlates with peak oxygen uptake846 and 
also predicted survival in HF drug trials.87    
• Socio-demographics (age, sex, race/ethnicity, education, marital status, income, insurance 
status) will be self-reported using standard forms validated in other studies   
• Medical history (coronary risk factors; previous MI or stroke; other co-morbidities): this 
information will be abstracted from medical records using standard abstraction forms that 
have been validated in previous studies 

 
• Medications & other therapies information will be self-reported using a standardized form. 
10.4. Follow-up Assessments 
The following assessments will take place at 3 and 6 months since randomization: 
• Self-reported adherence behaviors (Voils) 
• Objectively assessed adherence  
• Cognitive assessment battery 
• Social support 
• Depression  
• Mindfulness (MAIA and FFM) 
• Sleep Quality (PSQI)  
• Physical capacity (walking test) 
• Weight, height, hip and waist measurements  
• Blood pressure 
• Acceptability. To assess acceptability we will use the intervention enjoyment scale used in a 
previous study.858  We will ask participants to rate the intervention on a scale from 0 to 4.  
• Attendance at classes will be recorded at each session by the instructor using a mindfulness 
attendance log.  
• Individual mindfulness practice at home will be self-reported by means of a diary to be kept 
daily. Logs will be collected in person at follow-up visits.  
• Program evaluation will be determined using a standardized form we used in previous 
studies. 
In response to the COVID-19 pandemic, and due to the fact that this is a high-risk population, 
BP will be self-measured at the planned assessed date and self-reported values will be 
communicated to the RA over the phone. This will be noted in the Access database and in future 
manuscripts and scientific reports.  
 
 
 
 
 
11. 1. Data sources 
Data will be collected and using pre-tested and validated forms, which have been found to be 
acceptable by the type of individuals who will participate in this project. Information about 
medical history, hospital readmissions or unplanned clinic visits will be collected from electronic 
medical records or directly from the patient’s primary care physician or cardiologist using 
previously designed abstraction forms. We will develop electronic versions of each study form 
and data abstraction form for data entry using RedCap technology. 
11.2. Data safety  
Electronic data will be stored in password protected data files accessible only to authorized 
project personnel including the Principal Investigator, Data Systems Analyst, Statisticians and 
SRA.  All data files will be automatically backed up daily. Paper data will be stored in locked 
file cabinets. Data containing identifiers (e.g., name, address, phone number of participants from 
ACCESS files) will be stored on password-protected secure servers separately from de-identified 
study data (e.g., surveys, screeners).  
11 
  
DATA COLLECTION 

 
 
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11.3. Data collection 
The RA will collect data via in-person interviews at each data collection point. In response to the 
COVID-19 pandemic, and due to the fact that this is a high-risk population, follow-up 
assessments will now be completed over the telephone, via video-conference (using secure, 
HIPAA compliant videoconferencing software), or by mailing study surveys (that will be 
returned using pre-stamped envelopes) depending on the participant preference and internet 
accessibility. Research Electronic Data capture (REDCap) technology108 will be used to for 
direct data entry in electronic CRFs during the interviews; clinical data will be entered by the RA 
from the abstraction forms into electronic version of the abstraction forms in REDCap. Any 
ambiguity in the response to a question will be brought to the attention of the Data Systems 
Analysts for clarification.  If the Data Systems Analyst is unsure how to code the response, the 
matter will be brought to the attention of the PI. The Data Systems Analyst will maintain a log so 
that future occurrences of problems will be handled in the same manner. 
 
 
 
 
 
 
12.1. Tracking Systems 
Prior to beginning subject recruitment; the Data Systems Analyst will develop a tracking system 
using Access software.  The tracking system is essentially a reminder and participant tracking 
system to aid the study RA in ensuring that all procedures are followed, treatment are adhered to, 
and assessments administered in a timely fashion. The tracking system will include all steps 
included within the Recruitment, Treatment and Follow up phases of subject participation in the 
trial.  Quantitative data will be entered into an Access database where they will be stored for 
cleaning.    
 
 
12.2. Data entry and storage 
Our major data management and analysis needs for the proposed project can be met by using a 
Pentium-based microcomputer. The data systems analyst will conduct data management under 
the supervision of the study biostatistician and the PI. De-identified data will be exported 
directly through the REDCap interface into study datasets.  STATA©10, Statacorp-LP statistical 
software72 will be used for statistical analyses.  
Electronic data will be stored in password protected data files accessible only to authorized 
project personnel including the Principal Investigator, Data Systems Analyst, Statisticians and 
RA.  All data files will be automatically backed up daily. Paper data will be stored in locked file 
cabinets. Data containing identifiers (e.g., name, address, phone number of participants from 
ACCESS files) will be stored on password-protected secure servers separately from de-identified 
study data (e.g., surveys, screeners).  
The Data Systems Analyst will work with project statistician Dr. Dunsiger and the PI to ensure 
that data are cleaned prior to analysis.  When ready for analysis, he will provide a SAS database 
of collected data to the statistician.   
12 
  
DATA MANAGEMENT 

 
 
 
 
 
 
13.1. Treatment Fidelity  
Assessments of treatment fidelity will be performed following the guidelines developed by the 
Treatment Fidelity Workgroup.86 During the start-up period, auditor checklists will be created 
and used to monitor fidelity to the intervention. Checklists will be reviewed weekly by Dr. 
Salmoirago-Blotcher who will oversee treatment fidelity procedures. Optimal treatment fidelity 
would be evidenced by 100% of objectives met.  If less than 85% of treatment-specific 
objectives are met, the auditor will remediate instructor’s training as needed.  
13.2. Training 
Staff involved in data collection will be trained and certified regarding their competence. The 
RA will receive extensive training in the administration of cognitive tests by Dr. Cohen prior to 
study inception. This includes training on administration and scoring of all questionnaires as well 
as on review assessment instruments immediately for omissions.  When information is missing 
or incomplete, the RA will contact participants to obtain the necessary information.  A manual of 
procedures will be developed during the study start-up period that explicitly describes the 
specific procedures related to data collection and quality assurance.  At study beginning, the first 
10 subjects will have their data audited to make sure there are not any systematic problems with 
regards to entry.  This preliminary audit process will reveal any possible problems at the onset as 
opposed to the end of the study which would result in more work cleaning the data.  
 
13.3. Data monitoring 
Under supervision from the PI and the Biostatistician (Dr. Dunsiger), the Data Systems Analysts 
(Chris Breault) will ensure that entered data accurately represent data collected. She will conduct 
error-checking procedures quarterly on all data to ensure their accuracy. Data entry systems 
developed using Access will include appropriate skip patterns and parameter limits to ensure that 
data are entered accurately (e.g., item response formats from 1-5 will not permit entry of other 
numbers).  Data entry systems will be tested to ensure that these constraints are working 
correctly prior to entering real data. REDCap employs automatic checks for values that are out of 
range or represent errors of logic. Outliers will be corrected if possible with verification from 
participants. 
Quantitative data will be cleaned prior to analysis and then made available to the study 
statisticians for analysis.  Dr. Dunsiger will be primarily responsible for the final outcome 
analyses and will assist in the preparation of manuscripts and reports.  
 
13.4. Metrics 
All data designated as primary outcome data will be subject to a 100% cross-referencing with the 
original paper copy.  This audit must have an error rate less than 1%.  If the verification fails the 
audit, all data will be re-entered, the original computer files discarded, and the newly re-entered 
data audited.  This process will continue until the audit no longer exceeds the maximum 
allowable error rate.  All audits will be supervised and documented by the study's Data Systems 
Analyst.   
 
13 
  
QUALITY CONTROL AND QUALITY ASSURANCE 

 
 
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All other entered information (non-primary outcome data) will be subject to a 20% sample that 
will be cross-referenced with the original paper copy.  This audit must have an error rate less 
than 1%.  If the sample fails the audit, all data will be verified against the paper originals.  If the 
error rate of the complete audit is greater than 1% then all data will be re-entered, the original 
computer files discarded, and the newly re-entered data audited.  This process will continue until 
the audit no longer exceeds the maximum allowable error rate.  At the discretion of the study's 
Principal Investigator, the full audit may be omitted in favor of a complete re-entry of the 
original paper data.  All audits will be supervised and documented by the study's Data Systems 
Analyst.  
 
 
 
 
14.1. Preliminary analyses 
Preliminary analyses will examine comparability of participants at baseline on demographic and 
other characteristics using Fisher or t-tests depending on the specific variable characteristics 
(categorical or continuous).  We will examine the distributional properties of continuous 
variables to determine if normalizing transformations should be applied before conducting 
further analyses. If group differences are found for any variables, we will evaluate them and 
statistically control them in outcome analyses (e.g., employing them as covariates in linear or 
logistic regression analyses to control for their effects on the outcomes).   After all the data have 
been collected, and before conducting the final outcome analyses, we will explore the 
relationship of several key variables that could impact the outcome, such as participant 
attendance and number of study contacts during the study.  If there are group differences on 
these variables and/or there are relationships of these variables to the outcomes, we will include 
them as covariates in our analyses. 
 
14.2. Primary Outcomes: feasibility and acceptability 
We will calculate retention and attendance rates as well as program satisfaction scores at 3 and 6 
months. 
Feasibility. We will consider either dose feasible under the following conditions:  
If we achieve study retention rates of 80% at the last FU visit 
If patients attend at least 70% of the planned classes 
If patients report to have completed 70% of the assigned individual home practice exercises 
Acceptability. A dose will be considered acceptable if at least 80% of participants will indicate 
grade 4 enjoyment ratings on a visual scale from 0 to 4 (4=high enjoyment; 0=no enjoyment).858  
 
14.3. Secondary Outcomes  
To obtain effects of MT on adherence and functional capacity, we will use a series of generalized 
linear models (GLMs), in which secondary outcome measures will be regressed on time, baseline 
value of the outcome and potential confounders (i.e., gender, disease severity, social support). 
Standardized estimates will allow for comparison across different measures of adherence. GLMs 
14 
  
STATISTICAL CONSIDERATIONS 

 
allow for a flexible group of outcome distributions (e.g., binary, continuous); model specification 
includes determining the distribution and appropriate link function. We will use GLMs to 
explore changes over time in potential mediators (cognitive function, mindfulness and depressive 
symptoms) and, in a separate set of models, whether changes in these constructs are associated 
with changes in secondary outcome variables (adherence and functional capacity). Interest is in 
gaining estimates of effect for both of these potential pathways. We will also assess potential 
moderating effects of baseline levels of adherence on our adherence outcomes.  
14.4. Sample Size Considerations 
We aimed to obtain 80% power to detect a significant change over time in secondary outcome 
measures and potential mediators. Consistent with expert opinion,90,91 we integrated several 
sources of evidence to determine an expected effect size for power calculations. We based our 
estimates on (a) correlations between mindfulness and self-reported adherence from our prior 
work (see C.1) (rho=0.68, p<0.01),44 (b) results from an observational study showing association 
between lapses in attention and adherence (OR=2.65, p=0.02)22 and (c) a longitudinal study 
(n=309) among HF outpatients showing associations between memory and medication adherence 
(beta=0.51, p<0.01).26 With n = 50 and two-sided α=0.05 we will have 80% power to detect 
significant effects of MT on adherence, functional capacity, and mediator pathways (changes 
over time in mediators and their association with outcomes). 
 
14.5. Missing data 
Analysis will be performed according to the intention to treat approach. Withdrawals will be 
asked to complete follow-up assessments and home visits or phone interviews will be arranged if 
necessary. If we encounter substantial missing data, possible options will include using accepted 
statistical methods (e.g., use of complete data only, use of multiple imputation, use of modified 
weights and model-based procedures). Sensitivity analyses will be conducted using different 
assumptions regarding the mechanism of missingness. 
 
 
 
 
 
 
 
 
15.1 Institutional Review Board (IRB) Review  
This protocol and any subsequent modifications will be reviewed and approved by the IRB, 
which is responsible for oversight of the study. The consent form and HIPAA forms are attached 
to the IRB submission.   
15.2 Informed Consent and HIPAA 
Consent will be obtained at one time point during this study (at screening visit 1).  
1) Individuals interested the study will be screened by the study RA in a phone conversation to 
determine initial eligibility. The RA will briefly describe the study and its requirements and enquire 
whether the caller is still interested.  If the caller is still interested, the RA will explain the need to 
 
15 
 REGULATORY REQUIREMENTS 
 
14.1 IRB Review 
14.2 Informed Consent, HIPAA Joint Privacy Notice 
14.3 Subject Confidentiality 
14.4 Unanticipated Problems 

 
 
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collect some preliminary information from the caller in order to determine whether they are eligible to 
participate. A script and screening instrument will be used to standardize this phase of enrollment.   
2) Individuals who meet the initial eligibility criteria and who are interested in participating will 
provide written consent using an IRB approved consent form and HIPAA authorization form.  In 
addition to describing the study and the participant’s involvement in detail, the consent form also 
emphasizes that participation is voluntary, that consent may be withdrawn at any time, and that 
participants may withdraw from the study verbally or in writing by contacting the study RA 
and/or the Principal Investigator.  Participants are given ample opportunity to ask questions 
before providing consent.  Contact information for the RA and PI, as well as the IRB (for 
complaints) is provided in the consent form. Signed informed consent forms and HIPAA forms 
will be kept in locked filing cabinets separate from all data. Participants will receive a copy of 
the consent and HIPAA document for their records.  
15.3 Subject Confidentiality  
Protection of Subject Privacy:  All phone contacts with the participants will take place in a 
private, locked office and will be conducted by a trained RA who has been trained and certified 
in the protection of human subjects in research trials and HIPAA requirements according to 
TMH policies. Individuals who are interested in the study will provide Contact Information (e.g., 
name, address, phone, email) and will be scheduled for a screening visit (screening visit 1) n 
orientation visit to learn more about the study requirements and procedures, and to sign written 
informed consent as approved by TMH Institutional Review Board (IRB).   
Data safety  
• Subjects will be identified with a randomly generated identification code unique to the 
subject and all personal identifiers will be removed from the study questionnaires and from 
datasets. Electronic communication with outside collaborators will involve only 
unidentifiable information. AE reports and annual summaries will not include subject-
identifiable material.  
• Data collected for screening (i.e. reasons for ineligibility and refusal) and tracking reasons 
(Access data base) that contain identifiers will be stored into a password-protected server 
separate from other study data and will be destroyed at study completion. This Access 
database is password accessible only to the study SRA, the data systems analyst, and the PI. 
• Signed HIPAA forms and consent forms will be stored in locked filing cabinets separate 
from all other study data. 
• Patients will be informed in the consent form that MT sessions will be digitally recorded for 
assessments of treatment fidelity and digital recordings will be treated as explained above for 
focus groups recordings.  
• All copies of de-identified study questionnaires (paper and/or electronic) will be destroyed at 
the earlier of two dates: 1) seven years after the end of the study; 2) after the manuscript 
based on the work is published. 
15.4. Study Discontinuation  
The study may be discontinued at any time by the IRB as part of their duties to ensure that 
research participants are protected.  

 
15.5. Unanticipated Problems 
The Office for Human Research Protections (OHRP) considers unanticipated problems involving 
risks to subjects or others to include, in general, any incident, experience, or outcome that meets 
all of the following criteria: 
• unexpected (in terms of nature, severity, or frequency) given (a) the research 
procedures that are described in the protocol-related documents, such as the IRB-
approved research protocol and informed consent document; and (b) the characteristics 
of the subject population being studied; 
• related or possibly related to participation in the research (in the guidance document, 
possibly related means there is a reasonable possibility that the incident, experience, or 
outcome may have been caused by the procedures involved in the research); and 
• suggests that the research places subjects or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
 
An incident, experience, or outcome that meets the three criteria above generally will warrant 
consideration of substantive changes in order to protect the safety, welfare, or rights of subjects 
or others.   
 
Unexpected, serious and intervention-related SAEs will be immediately (< 24 hours) reported to 
the chair of the IMC and the IRB in accordance with requirements.    
Participants will be asked about all AEs at each intervention session and at each follow up 
assessment.  AEs will be recorded on the AE log and noted on the CO form.  Procedures for 
handling the reporting of AEs and SAEs to the IRB and the IMC are detailed in the DSM plan 
(section 6).   
 
 
 
 
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