Mindfulness-Based Stress Reduction for Adults With Low-Risk Chest Pain Associated With Anxiety: A Pilot Trial
Phase: NA
Conditions: Chest Pain, Anxiety, Mindfulness
Sponsor: Indiana University

Musey, Paul I 
MBSR for LRCP-A, v4.0, 02.27.2019 
1 
 
 
 
 
 
 
 
 
 
Mindfulness-Based Stress Reduction for Adults with Low-Risk 
Chest Pain Associated with Anxiety: A Pilot Trial  
 
 
PI: Paul Musey, Jr., MD 
Assistant Professor of Emergency Medicine 
Indiana University School of Medicine 
Fifth Third Faculty Office Building, Third Floor 
720 Eskenazi Avenue, Indianapolis, IN 46202 
Office (317) 880-3900 
Fax (317) 880-0545 
 
Co-Is: 
1. Shelley A. Johns, PsyD, ABPP. Assistant Clinical Professor of Medicine, Indiana University School of 
Medicine; Research Scientist, Indiana University Center for Health Services and Outcomes Research; 
Research Scientist, William M. Tierney Center for Health Services Research, Regenstrief Institute, Inc. 
 
2. Alexander B. Niculescu, MD, Ph.D. Professor of Psychiatry; Director, Laboratory of Neurophenomics 
 
3. Jeffrey A. Kline, MD. Professor of Emergency Medicine; Vice Chair of Research Department of 
Emergency Medicine.  
 
Biostatistician: 
1. George Eckert. Indiana University School of Medicine, Department of Biostatistics 
 
 
 
 

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Table of Contents: 
 
Study Schema 
1. 
Background 
2. 
Rationale and Specific Aims 
3. 
Inclusion/Exclusion Criteria 
4. 
Enrollment/Group Assignment 
5. 
Study Procedures 
6. 
Reporting of Adverse Events or Unanticipated Problems involving Risk to Participants 
or Others 
7. 
Study Withdrawal/Discontinuation 
8. 
Statistical Considerations 
9. 
Privacy/Confidentiality Issues 
10. 
Follow-up and Record Retention 
11. 
References 
 
 
 

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1. 
Background 
Patients who present with chest pain accounted for approximately 7 million visits to US Emergency 
Departments in 2011 [1]. Most resources, research and clinical efforts focus on detection and treatment of acute 
coronary syndrome (ACS); however, about 80% of all patients presenting to Emergency Departments with 
complaints of chest pain do not have cardiac disease or any other cardiopulmonary emergency by conventional 
testing [2-8]. Thus, these patients display the symptomatic syndrome of non-cardiac chest pain, also referred to 
as low risk chest pain (LRCP), specifically, angina-like pain in the absence of coronary stenosis [2, 8-11]. Studies 
suggest that 50-80% of these patients go on to develop low-risk chronic chest pain and continue to seek medical 
attention despite negative cardiac evaluations and reassurance [4, 12]. Further, previous findings indicate that 
up to 55% of patients diagnosed with LRCP may suffer from anxiety or panic disorders, and these psychiatric 
disorders remain undiagnosed in almost 90% of cases [5-9, 13-21]. Additionally, while epidemiologic data 
estimates the 12 month prevalence of anxiety disorders in the general population to be approximately 18% [22, 
23], these psychiatric disorders are absent from the top 20 discharge diagnoses of patients from US emergency 
departments based on ICD-9 codes [1].Thus, patients with low-risk chest pain associated with anxiety (LRCP-
A) do not get the true care and management they require and continue to access the healthcare system 
inappropriately. The cost for LRCP evaluations is estimated to be approximately $8 billion per year, usually with 
no definitive cause contributing to recurrent ED visits [24, 25]. Conventional emergency care practice ignores 
this opportunity to improve patient health and health service delivery. Usual ED care to exclude ACS and other 
cardiopulmonary emergencies can require 6-48 hours, multiple tests, radiation exposure, and high cost [26]. 
Moreover, emergency clinicians perceive that their primary duty in the ED is to treat life-threatening issues. Our 
exploratory data demonstrate that physicians believe they currently lack the necessary evidence-based 
resources to comfortably detect and initiate treatment for patients with contributing psychological and psychiatric 
factors [27]. This leaves ED clinicians unable or unwilling to explore the psychological causes of LRCP. Our work 
will provide the first step toward introducing evidence-based solutions for the identification and management of 
patients with LRCP-A.  
One of these solutions could involve mindfulness-based stress reduction (MBSR) as a means to help 
patients manage their anxiety. MBSR is a structured meditation training program originally developed by Kabat-
Zinn to assist adults in managing chronic pain [28]. MBSR has also been used widely to manage chronic disease 
processes and their psychological comorbidities [29-35]. MBSR has been shown to have a positive effect on 
individuals with either comorbid anxiety symptoms or anxiety disorders [31, 36-42]. MBSR usually consists of 8-
10 weekly group sessions aimed at developing mindfulness skills which focus on non-judgmental moment to 
moment awareness through meditation, yoga, and psychoeducation [31]. Through guided training in mindfulness 
meditation practices, individuals trained in MBSR learn to focus their attention on present-moment experiences 
with an attitude of open curiosity and acceptance, facilitating adaptive coping with stress and stress-induced 
physical sensation.  
The theoretical basis for the positive effect of mindfulness is that it supports the cultivation of emotional 
regulation skills through decreases in the habitual tendency to react to and ruminate about transitory thoughts 
and physical sensations[36, 43-46]. This emotional regulation has been shown to occur through strengthening 
prefrontal cognitive control mechanisms and downregulation of regions responsible for affective processing, such 
as the amygdala [44, 47]. Panic, anxiety and worry are often underpinned by overwhelming thoughts about what 
will happen in the future along with catastrophic misinterpretations of bodily sensations. Thus, it has been 
theorized that “present-moment mindful awareness may provide a useful alternative way of responding for 
individuals with generalized anxiety disorders” [48]. This intervention may provide patients with LRCP-A with the 
tools necessary to respond adaptively to present moment thoughts, feelings, and bodily sensations that may 
drive their recurrent episodes of anxiety associated chest pain [49].  
 
2. 
Rationale and Specific Aims 
Hypothesis: ED patients with LRCP-A can be accurately identified and successfully referred for MBSR leading 
to improved patient-centered outcomes. These hypotheses will be tested by the following two Specific Aims: 
 
Specific Aim 1: To determine the feasibility of employing rapid cardiac risk stratification and 
psychological screening to identify patients with LRCP-A in the ED for subsequent referral to MBSR. 
Currently there are no tools regularly used in the ED to screen for LRCP-A, however, our working hypothesis is 
that evidence-based tools can be used to identify patients at risk for LRCP-A. To accomplish this, we will execute 

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a two-step prospective screening approach: 1. Determine score on the validated and widely used HEART scale 
[50, 51]. 2. Those with a HEART score <4 will complete the General Anxiety Disorder 7-item (GAD-7) 
questionnaire.  Scores ≥10 are indicative of the criterion standard for moderate to severe symptoms of anxiety 
[52]. In this pilot study, feasibility will be assessed in a number of ways including the determination of the rate of 
eligible subjects per month, proportion of eligible subject who enroll, and proportion who complete the MBSR 
intervention. Expected outcome: This aim is designed to provide data regarding the feasibility of the risk 
stratification, psychological screening, and MBSR referral approach.  
 
Specific Aim 2: To determine the effect of an MBSR training program for patients with LRCP-A on mental 
health (longitudinal GAD-7 scores, quality of life (PROMIS Global Short Form), and ED resource 
utilization (return ED visits). Our working hypothesis is that early referral to MBSR will help patients better 
regulate their thoughts, feelings, and bodily sensations related to their anxiety symptoms and have a significant 
positive effect on patient-centered outcomes such as mental health, quality of life as well as decreased ED 
resource utilization. To this end we will assign LRCP-A patients identified in SA1 to usual care referrals versus 
MBSR. We will then follow these patients for outcomes including change in GAD-7 scores, PROMIS Global Short 
Form, ED utilization among other outcomes at 6 weeks, 3 months, 6 months, and 1 year. Impact: This aim will 
establish a viable and novel treatment pathway for ED patients identified to be at risk for LRCP-A to ensure the 
possibility of early directed intervention.  
 
3. 
Inclusion/Exclusion Criteria 
Inclusion: 
• 
Age: 18 through 70 
• 
Chief complaint of chest pain 
• 
HEART Score of 0-3 indicating Major Adverse Cardiac Events (MACE) risk equivalent to ≤2% 
• 
GAD-7 score ³ 10 
Exclusion: 
• 
Age <18 or ≥ 71 
• 
Chief complaint of anxiety, panic, or similar 
• 
Prior personal ACS history (known at time of provider interview) 
• 
Previous enrollment in the study 
• 
Traumatic injury to the chest 
• 
Suicidal ideation or active psychosis or behavioral issues requiring psychiatric monitoring 
• 
Hemodynamic instability 
• 
Non-English speaking 
• 
Potential issues affecting follow up  
o Prisoners, homeless patients, out-of-town residences 
 
4. 
Enrollment/Group Assignment 
We will screen patients presenting to the Methodist ED with the chief complaint of chest pain. Sources 
for this information include the ED tracking systems and electronic medical records systems. Patients will be 
evaluated with the HEART score by their treating physician to determine if the patient initially qualifies to 
participate in the study. The treating physician will provide the information necessary to calculate the HEART 
score.  Qualifying subjects will then be approached for final eligibility assessment using the GAD-7 and 
consented if interested and eligible.  
Enrolled subjects will be assigned to either arm depending upon enrollment period. In the 8 weeks prior 
to the MBSR course commencement all subjects enrolled will be assigned to Arm 2: MBSR. This period will be 
immediately followed by 8 weeks of enrollment in Arm 1: Standard Referral. To decrease subject bias with regard 
to the interventional arm, potential enrollees will remain blinded to the enrollment period until informed consent 
is complete. This method of assignment has been chosen to help maximize intervention enrollment given the 
limited recruitment period. 
 
 
 

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5. 
Study Procedures (see figure 1 
for an overview of protocol)  
Figure 1 illustrates an overview of 
the flow of screening and enrollment for 
both specific aims. The patients who 
screen eligible in Aim 1 are the population 
of interest for assignment in Aim 2. The 
goal is to assign 40 subjects for the 
intervention arms. Each enrolled subject 
will have follow up evaluations at 45 days, 
3 months, 6 months, and 1 year. Two ED 
physicians 
will 
independently 
review 
medical records of each enrolled patient for 
the described outcome variables and 
adjudicate 
any 
discordances 
by 
consensus. 
 
Specific Aim 1:  To determine the 
feasibility of employing rapid cardiac 
risk stratification and psychological 
screening to identify patients with 
LRCP-A in the ED for subsequent 
referral to MBSR. 
Under a waiver of informed consent 
for recruitment, we will initially screen 
patients between the ages of 18 and 70 
who present to Methodist Emergency 
Department (ED) in Indianapolis, IN. We 
will assess their risk for major adverse 
cardiac events (MACE) using the HEART 
score [50, 51]. This score is a validated 
tool, which is used to risk stratify patients 
who present to the ED with chest pain and 
to predict the 6-week risk of MACE. The 
HEART score defines MACE as all-cause 
mortality, acute myocardial infarction, or 
coronary revascularization [53]. This tool 
assigns a numeric score from 0-9. A score 
of 0-3 corresponds to a low risk, with less 
than 2% risk of MACE. Scores of 4-6 
indicate moderate risk, and scores of 7-9 
are considered high risk. Patients who 
score between 0 and 3 on the HEART 
score, indicating a low risk for MACE, will 
be 
approached 
for 
final 
eligibility 
determination using the self-report GAD-7 
questionnaire.  
The GAD-7 [54] is a rapid screening 
tool for the presence of a clinically 
significant 
anxiety 
disorder 
such 
as 
General Anxiety Disorder (GAD), Panic Disorder (PD), Social Phobia (SP) & Post Traumatic Stress Disorder 
(PTSD) in outpatient settings. It has been prospectively validated and is used to objectively determine symptom 

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severity and monitor symptom changes and effect of treatment over time. It is comprised of 7 items with an 
unscored item which assesses patient-rated global impression their symptom related impairment. The scores 
range from 0-21 with cutpoints at 5, 10, and 15 for mild, moderate, and severe anxiety, respectively. A cutoff of 
10 has a sensitivity for generalized anxiety disorder of 89% and specificity of 82% with test-retest reliability of 
ICC=0.83 [52, 55]. Patients who score >10 on the GAD-7, indicating at least moderate levels of anxiety, will be 
eligible for enrollment if their ED provider agrees with the high likelihood of LRCP-A. We plan to delay informed 
consent until after the GAD-7 determination for practical purposes as having knowledge regarding the study 
objective may affect the patient’s responses the GAD-7. Patients will have opportunity to consent to retain the 
collected information as well as continue on with the study. For ineligible subjects, we will only retain counts and 
total scores for feasibility calculations but no identifiable information will be kept. For eligible patients, trained 
research personnel (investigator, research assistant, or social worker) will discuss the results of the screening 
tests with the patient and introduce the study and a research assistant or coordinator will obtain informed consent 
for assignment from interested subjects.  Those who enroll will answer questionnaires assessing the domains 
presented and described further in table 2 below. 
  
Outcome assessments:  
1. Protocol feasibility will be assessed via patient eligibility, recruitment, and retention. 
a. Rate of eligible patients: # of eligible patients per month based on heart score, and the % of those patients 
who have an eligible GAD-7 score. We believe that 30% of subjects screened will be eligible for 
enrollment based on prior work.  
b. Proportion of eligible patients who enroll. Based on prior work with this population in an observational 
study, our target is 40%.  
c. Proportion of enrolled patients with an intervention session or follow up visit. We aim to have 75% of 
those assigned to MBSR complete at least 1 session.  
d. Proportion of enrolled patients who complete the study and follow up evaluations. We aim to show that 
70% of those assigned to MBSR will complete at least 6/8 intervention sessions. Additionally, assuming 
a 10% loss to follow up at each follow up time point we expect to have 65% who have completed all 
follow up evaluations.  
e. Time to first follow up PCP or mental health professional visit.  
 
2. The presence of MACE at 45 days as defined by the following diagnostic criteria:  
a. Any death of an enrolled patient within 45 days of index ED visit. 
b. Acute myocardial infarction and coronary revascularization as defined in the Third Universal Definition of 
Myocardial Infarction.[56] 
c. Electronic medical record (EMR) review to assess intervening significant cardiopulmonary related 
diagnoses at 45 days.  
 
 
Specific Aim 2: To determine the effect of an MBSR training program for patients with LRCP-A on mental 
health (longitudinal GAD-7 scores, quality of life (PROMIS Global Short Form), and ED resource 
utilization (return ED visits).  
Forty subjects who screen positive for LRCP-A using the process outlined above will be assigned to one of two 
treatment arms. Enrolled subjects will be referred for standard primary care and/or psychiatric referral for therapy 
using IU Health’s existing consult and referral infrastructure (Arm 1) or for therapy sessions using MBSR (Arm 
2) [28, 31]. We plan to recruit eligible subjects for assignment in the 40 days prior to the start of each 8-week 
MBSR class series.  
1. Arm 1: Standard psychiatric referral: Subjects will be referred for primary care provider (PCP) follow 
up and/or to psychiatry for further management and treatment of elevated anxiety levels according to 
standard of care. The treating ED provider will have discretion as to which referral option they believe to 
be more appropriate for each patient. This will occur using the hospital system’s current infrastructure 
and act as a “time from referral to treatment” control. Thus, we will have a baseline for the average time 
it would take for an individual referred for evaluation or treatment to be seen. Subjects will receive a 
standard set of discharge instructions which will discuss anxiety, chest pain, and instructions for follow 
up with their PCP. For those patients without a PCP, we will provide a list of PCPs with whom they could 
establish care. Patients will also be given a resource list of mental health professionals with whom they 

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could also schedule follow up with if directed by the ED provider. This list will be a custom list provided 
by our social work colleagues based upon individual patient factors (proximity to residence, insurance 
status, etc.) which is currently standard practice. We plan to also send a letter or EMR communication to 
the patient’s PCP if they have one alerting them to their participation in the study, their study assignment, 
and encouraging further evaluation and management of their anxiety symptoms. For those without a PCP 
at time of enrollment we will query the patient at each follow up time-point for the establishment of primary 
care and send this letter if they have been able to do so at that time.  
2. Arm 2: MBSR intervention: In addition to the standard referrals and discharge instructions discussed 
above, subjects assigned to MBSR will be offered a referral to a local MBSR course. The standard MBSR 
course meets one day per week for 8 weeks, with sessions being 2.5 hours in duration. A full day retreat 
(7 hours in length) is offered on a Saturday between sessions 6 and 7. The primary techniques are the 
“body scan”, a noncritical assessment of bodily sensations when directing attention in a deliberate 
manner from the feet through the head and focused meditation with a special attention to breathing [57]. 
The full training program is presented in the intervention instruction manual and Table 1 outlines the 
contents of each weekly session. Our study interventionist will provide several options for the MBSR 
course (e.g., different days of the week and times of day) from which to choose to maximize convenience. 
To maximize MBSR availability for this pilot, these blocks will include groups open to non-study 
participants as well as closed dedicated study groups.  
 
Table 1. Description of Mindfulness-Based Stress Reduction Sessions 
Session # 
Session Themes 
Meditation Exercises 
Didactic Teaching 
Home Practice 
Orientation Describe mindfulness in 
words and embodied 
engagement.  
 
Explanation of participant 
commitment to actively 
engage in class 
participation and daily 
mindfulness practice.  
§ 
Provide participants 
with an experience of 
mindfulness in an 
atmosphere of trust 
and non-judgmental 
awareness.  
§ 
Familiarizing potential 
participants with what 
MBSR is and is not. 
§ 
Explain class logistics 
and content. 
§ 
Examples of clinical 
evidence of MBSR 
program. 
§ 
Describe possible 
physical, emotional, 
social, and time risks 
and benefits.  
§ 
Meet with each 
participant individually 
for a brief screening 
interview. 
§ 
Describe formal and 
informal home 
practice. 
§ 
Explain what to wear 
and bring to class. 
1 
Describe and experience 
theoretical underpinnings 
of mindfulness. 
 
Explain development of 
regulatory skills in formal 
practice and meeting 
ourselves where we are 
in honesty and kindness.  
§ 
Raisin exercise 
§ 
Body scan 
§ 
Brief mindful 
movement (MM). 
§ 
Participants introduce 
themselves and begin 
building trust within 
the group as a 
learning community. 
§ 
Establish contract of 
confidentiality.  
§ 
Practice body scan 
daily. 
§ 
Eat one meal 
mindfully (handout 
provided). 
§ 
Mindfulness of one 
daily activity. 
2 
Experiential mindfulness 
skill development. 
 
Wholeness no matter 
what is here. 
§ 
Body scan 
§ 
MM 
§ 
Awareness of breath 
(AOB) sitting 
meditation 
§ 
Perception and 
creative responding: 
how we see things 
determines how we 
respond.  
§ 
Explore universality of 
the wandering mind 
and how to work with 
this and other 
challenges in practice.  
§ 
Continue body scan 
practice. 
§ 
Bring MM into daily 
movement. 
§ 
Sit quietly 10 min 
daily with AOB. 
§ 
Pleasant events 
calendar. 
§ 
Mindfulness of 
another daily activity. 
 
3 
The pleasure and power 
of embodied presence:    
 
Investigating knowing 
how things are in the 
body and mind in the 
present moment through 
Integrating and expanding 
multiple practices: 
§ 
MM 
§ 
Body scan 
§ 
Sitting meditation 
§ 
Possible walking 
meditation 
 
§ 
Reflections and 
challenges of direct 
experience in formal 
and informal 
mindfulness practice. 
§ 
Pleasant events 
reflection: appreciating 
§ 
Alternate body scan 
and MM daily 
§ 
AOB 10-20 minutes 
§ 
Unpleasant events 
calendar 
§ 
Mindfulness of daily 
activity 

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formal and informal 
practice. 
 
 
what we have in the 
present moment. 
 
4 
Exploration of 
mindfulness as a means 
of recognizing and 
reducing negative effects 
of automatic, habitual 
stress reactivity 
 
Supporting healthy 
responsiveness 
 
§ 
MM  
§ 
Body scan 
§ 
Sitting meditation 
All practices with 
emphasis on 
concentration, 
embodiment, and capacity 
to redirect attention. 
§ 
Stress reactivity (fight-
or-flight response) 
§ 
Exploration of 
reactivity in health and 
illness 
§ 
Development of more 
effective ways of 
responding pro-
actively to stressful 
situations and  
       experiences 
§ 
Alternate body scan 
and MM daily  
§ 
Unguided sitting 
meditation 15-20 min 
daily 
§ 
Unpleasant events 
calendar 
§ 
Be aware of 
automatic stress 
reactions during the 
week without trying to 
change them  
5 
Exploring conditioned 
patterns as previously 
adaptive but no longer 
functionally adaptive 
 
Awareness of mind/body 
patterns as a doorway to 
adaptive responses to 
everyday challenges and 
stressors  
§ 
Open awareness 
sitting meditation 
§ 
MM 
§ 
Body scan 
§ 
On-the-spot brief 
practice for use in 
times of stress if not 
previously introduced 
 
§ 
Theories and studies 
of mindfulness 
developing stress 
hardiness and 
resilience. 
§ 
Expanding ways of 
working with 
uncomfortable 
physical sensations 
and emotions  
§ 
Emotion- and 
problem-focused 
coping reflection 
§ 
Alternate new guided 
sitting meditation, 
MM, or body scan 
daily 
§ 
Problem- and 
emotion-focused 
coping handout 
§ 
Reading on mindful 
communication 
§ 
Challenging 
communication 
calendar 
6 
Continuing to enhance 
stress hardiness through 
mindfulness  
 
Identifying and 
expressing emotions 
accurately and mindfully 
 
Exploration of stress in 
the domain of 
communication: 
cultivating mindfulness in 
listening and speaking  
 
§ 
Open awareness 
sitting meditation 
§ 
MM 
§ 
Possible walking 
meditation 
 
§ 
Communication styles 
explored didactically 
and experientially 
§ 
Mindful listening and 
speaking skills  
§ 
Embodiment in 
exploring flexible ways 
of communicating in 
challenging 
interpersonal 
interactions 
 
§ 
Alternate sitting 
meditation, MM, or 
body scan daily 
§ 
Emphasis on 
observation and 
application of 
mindfulness in daily 
activities 
 
Retreat 
Establishing mindfulness 
in multiple situations; 
cultivating mindful 
attention from moment to 
moment and being open 
to any experience, 
whether evaluated as 
pleasant, unpleasant or 
neutral 
 
Seamless awareness 
moment to moment.   
§ 
MM 
§ 
Sitting meditation 
§ 
Body scan 
§ 
Lake meditation 
§ 
Walking meditation 
§ 
Outdoor visual 
meditation 
§ 
Lovingkindness 
mediation 
§ 
Talk drawing on a core 
theme of class that 
gives encouragement 
§ 
Alternate MM, sitting 
meditation, body 
scan, and 
lovingkindness 
mediation; 
participants are also 
encouraged to create 
their own flexible 
blend of practices for 
45 minutes 
§ 
Continue application 
of mindfulness in daily 
activities including 
communication 
 
7 
Taking care of yourself: 
healthy living choices 
arising from practice 
 
Mindfulness as a means 
to explore the familiar and 
the unfamiliar 
§ 
Self-guided MM 
§ 
Sitting meditation  
§ 
Lovingkindness 
practice 
§ 
Mind/body input; 
reflecting on what is 
nurturing/depleting 
§ 
Connect what was 
experienced in the all-
day retreat and 
afterwards to 
automatic habitual 
stress reactions and 
§ 
Daily sitting 
meditation, MM, or 
body scan  
§ 
Practice informally by 
pausing throughout 
the day and resting in 
awareness 
§ 
Develop plan for 
continuing practice 

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Outcome assessments: The schedule of assessments is shown in Table 2. These assessments will take place 
in the method most convenient for the patient (telephone, mail, or online REDCap survey completion). These 
are all methods the PI and his research team are currently using. The primary outcome of interest will be the 
mean longitudinal change in GAD-7 scores between intervention groups at each time point.  
 
 
 
    
Subject Compensation: Subjects who enroll after informed consent will receive compensation for their time 
spent answering validated surveys and follow up evaluations. Enrolled subjects in both arms would be eligible 
for up to $160 in direct which will be structured as follows: $40 for the ED interview and another $30 for 
completing each of the follow-up phone evaluations (45 day, 3 months, 6 months, and 1 year). These payments 
will be in the form of generic gift cards which will be disbursed at the completion of each follow up evaluation. 
Because the MBSR intervention involves travel to a non-hospital site that is not always easily accessible by 
public transport, these subjects will be eligible for additional compensation to defray travel costs ($10/session 
attended) to be paid at end of MBSR course. The study will also provide indirect compensation to those assigned 
mindfulness-mediated 
stress responses in 
meeting whatever was 
encountered  
8 
The rest of your life: 
Making the practice your 
own 
§ 
Body scan 
§ 
MM 
§ 
Sitting meditation 
§ 
Review of the course 
with an emphasis on  
daily strategies for 
maintaining and 
deepening 
mindfulness skills 
§ 
Sharing of participant 
perspectives on the 
program; welcoming 
all comments 
§ 
Mindfulness 
resources handout  
§ 
Continuing the 
practice & making it 
your own 
§ 
Bringing seamless 
attention to life 
 

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to ARM 2 (MBSR) by covering the cost of their therapy sessions ($350), which would be paid to the interventionist 
if the subject attends.  
 
Fidelity Monitoring: We will utilize strategies across four domains to ensure treatment integrity in the MBSR 
arm and minimize protocol deviations.[58] Co-Investigator Dr. Shelley Johns has expertise in MBSR research 
and will oversee this process. Additionally, at each of the 4-specified time-points for follow up, we will assess via 
EMR review if mindfulness interventions have been used in the management of subjects in the psychiatric referral 
arm.  
1. Study design— The MBSR intervention will be delivered consistently with the standardized MBSR 
manual developed at the Center for Mindfulness in Medicine, Health Care, and Society at the 
University of Massachusetts, where MBSR was developed [59].  
2. Treatment delivery— Interventionists will keep field notes to document duration, frequency, and 
uptake of study conditions. EMR review will be performed for those assigned to standard psychiatric 
referral to obtain information regarding treatment.  
3. Treatment receipt—use of engaging therapeutic activities to increase participants’ practice of 
skills; interventionist provision of frequent summaries of session content and query of participants’ 
understanding and active use of session material; collection and review of participant self-
monitoring data.  
4. Treatment enactment—Mechanisms of action specific to mindfulness as assessed with the 
Toronto Mindfulness Scale (TMS)[60] and the Cognitive and Affective Mindfulness Scale (CAMS-
R)[61] will be measured to assess intervention receipt and enactment.  
 
 
6. 
Reporting of Adverse Events or Unanticipated Problems involving Risk to Participants or Others 
All adverse and severe adverse events will be reported in compliance with IU regulations. Some 
anticipated adverse events include discomfort with the subject material and psychological distress when thinking 
about stressful events. Participants will be able to decline to answer any questions or withdraw at their discretion, 
which will help to alleviate this risk. Subjects found to have severe depression at any time point as assessed by 
a PHQ-8 score > 19 will be referred for depression specific treatment. Subjects who disclose suicidal ideation or 
have active psychotic symptoms during the initial ED interview will not be eligible for continued participation and 
will be directed to seek appropriate care in the Emergency Department.  If they disclose suicidal ideation or 
exhibit active psychotic symptoms at follow up the PI will be immediately contacted to evaluate for the need for 
intervention (referral to the ED, notification of the PCP etc.). There is also a risk for loss of confidentiality. 
Participants’ paper and electronic records will be appropriately protected to help minimize this risk.  
 
7. 
Study Withdrawal/Discontinuation 
Participants will be able to withdraw themselves from the study at any point in time without issue.  The 
PI may withdraw the patient from this study if the participant is unresponsive and/or unable to participate in a 
timely manner. 
 
8. 
Statistical Considerations 
The goals are to collect preliminary data regarding the feasibility and effectiveness of the MBSR referral 
and approach compared with standard of care referral. Eligibility, recruitment, and retention information will be 
tabulated. Frequencies and percentages will be summarized by group for categorical variables, and continuous 
and count variables will be summarized by group using the mean, standard deviation, and range. The primary 
outcome of interest will be a comparison of the mean change in GAD-7 scores at 3 months using the t-test. 
Secondary analysis will look at the comparison of mean change in GAD-7 longitudinally using repeated 
measures ANOVA. The repeated measures ANOVA will compare scores between groups and compare scores 
over time within groups. Similar analyses will be used for the other efficacy outcomes. The proportion of subjects 
with a visit, time to first visit, and number of visits will be compared using chi-square, log-rank, and Wilcoxon 
rank sum tests, respectively. A 5% significance level will be used for all tests. 
Because there is minimal published data to guide power calculations in this population for our outcome 
of interest we have chosen a sample size of 12 for each interventional arm in this pilot study on the basis of 
feasibility as described by Julious [62]. This sample size of 12 will be increased to 20 per arm to account for an 

Musey, Paul I 
MBSR for LRCP-A, v4.0, 02.27.2019 
11 
estimated 40% drop out rate prior to completion of the MBSR intervention. Thus, the total number of subjects 
we expect to enroll to the intervention is 40. All subject data will be analyzed on an intention to treat basis.  
 
9. 
Privacy/Confidentiality Issues 
All information will be entered and REDCap Software Version 7.0.10 - © 2017 developed by Vanderbilt 
University (licensed to Indiana University) will be used for all data entry and survey tools. The patient’s health 
information used in these analyses will be protected by a number of mechanisms. Collaborative Institutional 
Training Initiative (CITI) training in the protection of patient confidentiality will be required of all research 
assistants and coordinators involved in the study. All interviews will occur in a patient care area with all efforts to 
provide privacy. Participants' paper records will be stored under double locks. All electronic records will be behind 
password protection and firewalls, including secured department shared drives and/or REDCap. Research 
personnel will be provided with usernames and passwords in order to access electronic subject records or to 
use the EDC system. Data analysis will be performed on de-identified information.  
 
10. 
Follow-up and Record Retention 
Chart review and/or patient follow-up will be performed at the 4-specified time-points: 45 days, 3 months, 
6 months, and 12 months. After the final scheduled follow up, the patient’s record will then be de-identified. Study 
records will be retained according to the longest most applicable timeline according to federal, state and 
institutional regulations from the close of study with the IRB.  After this timeline has been reached, study records 
will be destroyed according to the policies of the archive repository contracted to house these records.   
 
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