Mobile Mindfulness to Improve Psychological Distress After Critical Illness
Phase: NA
Conditions: Psychological Distress, Depression, Anxiety, Post-traumatic Stress Disorder, Informal Caregivers, Family Members
Sponsor: Duke University

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
1
Effects of mindfulness training programs delivered by a self-directed mobile app and by 
telephone compared to an education program for survivors of critical illness:  a pilot 
randomized clinical trial   
 
1. 
PROTOCOL TITLE  
Mobile Mindfulness to Improve Psychological Distress after Critical Illness (LIFT Study) 
  
2. 
PURPOSE OF THE STUDY  
A majority of the >1 million people who require life support in an intensive care unit (ICU) now survive.  
As survival has improved however, growing numbers suffer not only from subsequent physical 
disability, but also persistent symptoms of depression, anxiety, and post-traumatic stress disorder 
(PTSD).  Few interventions address ICU survivors’ psychological distress.  Fewer still address the 
physical, geographical, and logistical barriers to receiving post-discharge support that medically ill 
populations encounter.  Consequently, this population suffers with an unmet need of great public health 
importance. 
 
Mindfulness is an adaptable self-regulation practice that alleviates psychological distress symptoms 
using a variety of meditative techniques, typically taught face-to face over months.  As an extension of 
standard mindfulness practices, we developed a telephone-/web-delivered mobile mindfulness-based 
training (mMBT) system informed by ICU survivors’ input that could address medically ill patients’ 
delivery barriers.  Our recent pilot study demonstrated early support for mMBT’s feasibility and 
acceptability, now with enhanced content and electronic patient-reported outcomes capability.  
 
Our early work on mMBT, while promising, identified key knowledge gaps in population targeting, 
plausible ranges of psychological distress estimates relevant to study design, and assurance of 
acceptability that must be addressed before a definitive clinical trial is conducted.  Therefore, we 
propose a 2-year pilot study including approximately 25 patients in a usability assessment and 90 in a 
pilot randomized trial.  In the trial, ICU survivors will be randomized to one of three arms: (1) an 
education control, (2) 4 weekly telephone sessions of mMBT, or (3) a 4-week course of self-directed 
mMBT.  Our specific aims will use quantitative and qualitative methods to: (1) evaluate mMBT and self-
directed mMBT feasibility, acceptability, and usability as well as (2) better estimate the effect of both 
mMBT or self-directed mMBT on psychological distress symptoms 
 
Aim 1:  To test the feasibility, acceptability, and usability of a telephone- and web-delivered 
mobile mindfulness-based training (mMBT) interventions for distressed ICU survivors.      
     Understanding participants’ perceptions about mMBT and self-directed mMBT—and making 
responsive refinements—is critical to the success of a future RCT.  We will assess feasibility by 
examining observed vs. benchmark rates of enrollment, session completion, and website use.   We will 
assess acceptability and usability using quantitative and qualitative measures of satisfaction, 
usefulness, and system performance 
 
Aim 2:  To provide a plausible range of psychological distress estimates for each treatment 
group at both post-intervention and long-term follow up. 
     To improve our understanding of how these outcomes are operationalized and reflect change 
relevant to the planning of a larger RCT, we will evaluate to what extent mMBT, self-directed mMBT 
(using electronic patient reported outcomes (ePRO)-based symptom monitoring to efficiently direct 
therapist calls on an as-needed basis), and the education program reduce symptoms of depression, 
anxiety, and post-traumatic stress over 3 months post-intervention.  We will also explore associations 
between changes in symptoms and clinical/demographic characteristics to refine inclusion and 
exclusion criteria for future study. 
 

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
2
We propose an exploratory pilot project that represents an important transition from past description of 
a serious public health issue to an innovative, conceptually strong, patient-centered intervention that 
addresses the problem.  It also represents a paradigm shift from the standard focus on reducing ICU 
death to improving long-term ICU patient survivorship, described as “the defining challenge of critical 
care for the 21st century.”1  This proposal addresses key national research priorities in post-discharge 
critical illness treatment and in the management of persistent psychological distress. 2, 3  Innovative 
qualities include the new direction in critical illness treatment, its low cost, its ability to be personalized, 
its adaptability to new delivery formats as technology advances, and its likely future applicability to 
broader populations.  Importantly, this study is both necessary and sufficient to inform a future definitive 
RCT that could substantially improve and advance our approach to critical care.  Overall, data derived 
from this study will be necessary and sufficient to inform the development of a future definitive RCT that 
could change the current approach to critical care—and improve ICU survivorship. 
 
3. 
BACKGROUND & SIGNIFICANCE 
Psychological distress after critical illness is common, important, and understudied. Acute 
respiratory failure requiring mechanical ventilation life support is the most common admission diagnosis 
for the more than 5 million patients managed annually in intensive care units (ICUs)—a number 
expected to double by 2020 because of our aging population (Figure 
1).4 
Because of technological and process advances, the majority of 
these patients now survive this once fatal condition.5  However, 
nearly all experience important emotional and physical symptoms 
that 
impair their quality of life, act as barriers to workplace reentry, and 
strain family units.6-12  In fact, ICU survivors suffer from psychological 
distress at rates 5- to 10-fold greater than the US population 13-15 
including symptoms of depression (35-62%), anxiety (24-63%), and 
post-traumatic stress disorder (PTSD) (22-63%).16-26  A recent study 
of 
1-year ICU survivors found that a third sought psychiatric care and 
nearly half required psychiatric medications.27  This distress can 
persist for >10 years and diminish quality of life.18, 28-31  However, very few studies have addressed ICU 
survivors’ distress and the numerous physical, financial, and social barriers that limit their access to 
care.32  Therefore, we aim to improve the 
experience of critical care survivorship with a 
novel telephone-based intervention designed to 
reduce post-discharge psychological distress and 
promote quality of life.2, 33 
 
Mindfulness is an innovative, promising 
treatment for ICU survivors’ distress. 
Mindfulness is awareness of one’s experience in 
the present moment.34  Mindfulness can be honed 
through a variety of meditative techniques to help 
patients cope with stress, illness, and pain.  
Mindfulness works to reduce distress in two 
primary ways:  (1) by developing mindful qualities 
that help patients change the way they relate to 
emotional and physical symptoms, and (2) by 
facilitating mindful coping that helps patients 
skillfully regulate difficult emotions, thoughts, and 
memories (Figure 2).35-42  Mindfulness is based in 
centuries of meditative practices, and over the 
past 30 years has been shown to reduce 
depression, anxiety, and stress, as well as 

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
3
improve health-related quality of life for patients with diverse medical and mental disorders. 34, 43-47  We 
have found that although ICU survivors report that coping skills and the ability to manage emotions are 
important to their overall sense of well being, they use these skills infrequently and ineffectively—a 
pattern that maintains psychological distress and poor quality of life. 7, 48  MBT could directly target these 
foundational elements of distress among ICU survivors, including the subjective experience of the ICU 
and its association with post-traumatic stress.7, 26, 49, 50  Therefore, we propose to examine an innovative 
telephone-based MBT intervention designed to reduce psychological distress among ICU survivors.  
 
4. 
DESIGN & PROCEDURES 
Overview of study design.  We propose a 2-year pilot study comparing three arms: (1) a 4-session 
telephone-based, therapist-directed mMBT program, (2) a self-directed mMBT program where both the 
intervention and data collection are digitally automated (features that could enhance future 
dissemination to broader populations), and (3) a similar length critical illness education program control.  
For the therapist-directed mMBT program, ICU survivors will participate in the intervention calls using 
standard conferencing technology.  For all three study arms, we will measure pre- and post-intervention 
outcomes as the primary effect assessment, as well as at 3 months post-intervention (~4 months post-
randomization) to determine the long-term impact.  
 
Settings and participants.  
Settings: The setting will be medical and surgical ICUs at Duke University (medical ICU, 
surgical/trauma ICU, and cardiac ICU) and the University of Washington. These centers have a long 
history of ICU-based research among diverse populations of critically ill persons, and admit 2,500 
patients with acute respiratory failure annually.  Assuming conservative rates of ICU death (25%), 
exclusions (50%), and refusal (25%), over 350 patients would be eligible annually.  We will enroll 
approximately 25 patients during months 1-2 for the purpose of evaluating the usability of our computer 
interface and intervention.  We will enroll 90 patients during months 3-15, aiming for at least 50 to 
complete the entire study protocol (conservative dropout rate ~30%).15,63  At each proposed study site, 
patients will be enrolled into the study.  Baseline interviews will be completed in-hospital at each site 
with subjects.  Follow up interviews will be completed by telephone by study staff or online via a secure 
website.  Drs. Cox and Hough will be responsible for supervising all local aspects of enrollment, data 
collection, and data storage. 
 
Screening, enrollment, study subjects:  Clinical research coordinators (CRCs) will review electronic 
records daily to identify all ICU patients receiving mechanical ventilation using our sites’ well-
established electronic health record-based daily ICU screening protocol.  After identifying a potential 
subject, the CRC will then obtain permission from the primary physician to approach the patient for 
informed consent after transfer from the ICU to the ward, but before hospital discharge—a practice that 
markedly increases the likelihood that patients possess the decisional capacity required for informed 
consent.70 Our inclusion criteria, informed by our recent studies and Davydow et al’s recent work 
defining the strong association between in-hospital distress and subsequent long-term psychological 
disability,15,37,63 target patients at high risk for long-term psychological distress (see below):  
 
5. 
SELECTION OF SUBJECTS  
We will target patients at high risk for psychological distress.   
 
Patient inclusion / eligibility criteria:   
 
age ≥18 years 
 
acute cardiorespiratory failure managed in an intensive care unit ≥24 hrs* 
Acute cardiorespiratory failure defined as: 
    Respiratory failure  
     ≥1 of these: 

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
4
 
* 
o 
reside at home before hospital admission (i.e., not in a facility) 
 
Other issues relevant to the consent process:   
o 
unable to approach patient for logistical reasons (e.g., off ward in test at time of approach, etc) 
o 
patient discharged before consent could be obtained 
o 
patient dies before consent obtained  
 
 
Patient exclusion / ineligibility criteria (present before consent):  Patients will be excluded if they 
have characteristics that would prohibit adequate participation including:   
 
pre-existing significant cognitive impairment (e.g., dementia) 
 
treated for severe or unstable mental illness within 6 months preceding current admission* 
 
hospital inpatient within 3 months before current admission 
 
active substance abuse at the time of admission 
 
lack decisional capacity** 
 
current significant cognitive impairment (≥3 errors on the Callahan cognitive status screen; see 
below)  
 
need for a translator because of poor English fluency [many study instruments are not validated 
in other languages] 
 
expected survival <6 months per attending physician 
 
ICU length of stay >30 days 
 
lack of either:  
 
reliable or sufficient smartphone with cellular data plan or  
 
reliable computer online access plus telephone access 
 
unable to complete study procedures as determined by study staff 
 
discharge to a location other than a home setting  
 
complex medical care expected soon after discharge*** 
 
*e.g., depression with psychosis, suicidality, schizophrenia (as per medical record) 
 
**We define “decisional capacity” as the ability to participate in effective decision making and provide 
informed consent.  That is, in the judgment of the examiner, the patient—after reading the IRB 
approved patient consent document (or having it read to them): 
--Can generally understand the terms of participation in the study 
 
the purpose of the study 
 
what will be required of study participants 
 
the potential risks, benefits and alternatives of study participation 
 
pros & cons of study involvement 
--Can communicate a choice in his/her own words (or write on a communication board) 
 
***e.g., multiple planned surgeries, transplantation evaluation (including outpatient daily 
cardiopulmonary rehabilitation), extensive travel needs for hemodialysis, disruptive chemotherapy/XRT 
regimen, etc. 
 
- mechanical ventilation via endotracheal tube for ≥12 hours 
- non-invasive ventilation (CPAP, BiPAP) for >4 hours in a 24-hour period 
provided for acute respiratory failure in an ICU (not for obstructive sleep 
apnea or other stable use) 
 
- high flow  nasal cannula or optiflow  (≥15L/min) or face mask O2 w ith FiO2 ≥ 
0.5 for ≥4 hours 
    Circulatory failure 
     ≥1 of these: 
- use of vasopressors for shock of any etiology for > 1 hour 
- use of inotropes for shock of any etiology for > 1 hour 
- use of aortic balloon pump for cardiogenic shock 

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
5
 
Patient exclusion criteria present after consent but before randomization:  After providing 
informed consent, patients will become ineligible if any of the following are present: 
 
they become too ill to participate (or die) 
 
they exhibit significant cognitive disability 
 
they exhibit suicidality 
 
patient was unexpectedly discharged to location other than a home setting and then did not 
arrive home within 1 month from hospital discharge 
 
Patient suicidal ideation will be monitored by trained study staff (study coordinators, mindfulness 
instructors) during study interactions (telephone surveys, mindfulness sessions, etc.) and by monitoring 
the response to the suicidality question (Item 9 in the PHQ-9 survey).  Staff suspecting suicidality will 
alert the PIs and utilize site based resources as described in Section 10.   
 
 
6. 
SUBJECT RECRUITMENT AND COMPENSATION  
Clinical research coordinators (CRCs) will review daily electronic records daily to determine which ICU 
patients have acute cardiorespiratory failure.  After identifying a potential subject, the CRC will then 
obtain permission from the primary physician to approach the patient for informed consent after transfer 
from the ICU to the ward, but before hospital discharge.  By delaying consent until transfer, we will 
reduce subject distress and enhance enrollment efficiency.  We aim to enroll 90 patients overall in the 
clinical trial and ~25 in the pre-trial usability evaluation, approximately 60 of whom will be enrolled from 
Duke University Medical Center (the remainder will be from the University of Washington).   
 
We will recruit consecutive patients in the study, and will work to ensure adequate representation of all 
relevant demographic groups.  In our past research, we have enrolled a higher percentage of minority 
subjects than the average population demographics. 
 
Although studies of families of the critically ill are challenging logistically and emotionally, we have 
enjoyed low refusal rates (<20%) in past studies and have also achieved 90% follow up with telephone 
interviews with patients over the course of 6 months.  Retention will be enhanced by the use of 
telephone-based follow up interviews augmented by email, our use of short questionnaires to reduce 
respondent fatigue, and our experience that participants develop a trusting bond with the research team 
over time.  
 
We will compensate participants for time spent performing study activities.  It is expected that the time 
required for participants will differ based on the arm to which they are randomized; differential group-
based payment reflects this reality.  Participants in the education group will receive $25 for each post-
discharge interview they complete plus $25 for completing both calls (for a possible total of $100).  
Participants in the standard mindfulness group can receive up to $150 ($25 for each of the 3 post-
discharge interviews and $75 for completing all intervention calls).  Participants in the self-directed 
mindfulness group can receive up to $150 ($25 for each of the 3 post-discharge interviews, $50 for 
completing the initial intervention call and listening to the weekly audio sessions, and $25 for 
completing weekly online questionnaires).   
 
For the purpose of testing and evaluating the design and usability of the webapp (essentially a web 
page viewable as an app), will conduct a small sub-study among patients or family members of ICU 
patients. We expect that only 20-25 total participants will be needed to identify any errors and concerns 
about problematic usability issues.  We will aim to meet with these participants prior to enrolling in the 
clinical trial.  Participants will be chosen randomly by convenience from ICU waiting rooms or in patient 
rooms after first clarifying with the treating ICU team that it would be appropriate to approach them 
(e.g., ensuring that there were no conflicts, serious decisions at hand, etc).  The purpose of this study 

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
6
will be to test the usability of the technological components of the treatment arms (webapp & website).  
We will ask patients/families/friends to review the webapp and website, and then answer a few brief 
questions about:  what they liked/disliked, recommendations for improvement, how satisfied they were 
with the program, and how easy it was to understand.  We will not record PHI, names, or birthdates.  
While no PHI will be collected, we will record participants’ responses on written questionnaire forms 
which will be stored in a locked cabinet in Dr. Cox’s locked office. We expect this entire process will 
take 15-20 minutes, depending on the amount of feedback the patient/family wishes to provide.  The 
introductory script for this small substudy is provided below under Point 7, “Consent Process.”  User 
testing participants will receive a coffee card with a value of $5 for their time. 
 
7. 
CONSENT PROCESS  
If the ICU physician agrees to allow the team to approach the patient, we will meet them in their private 
ICU room (or ward room) to discuss the study and obtain signed informed consent.  We will do so when 
no other staff or visitors are present and will close the door.  An unlimited time (though this generally 
requires less than 1-2 hours) will be allowed to describe the study and answer all questions.  The full 
informed consent form will be provided and read by the potential subject.  Consent forms will be read to 
those who are blind or unable to read.  Potential subjects will be given 48 hours to decide if they wish to 
be in the study.   
 
Patients will be assessed for decisional capacity by a medically qualified professional who is also a 
member of the study staff or by the patient’s clinical care provider.  In general, this includes assessing 
the ability to communicate a choice, to understand the study information, to understand the pros and 
cons of the choice about study participation.  Operationally, the potential subject should be able to 
repeat in his/her own words (or write on an ICU communication board) the purpose of the study, what 
will be required of study participants, and the potential risks, benefits and alternatives of study 
participation.  The potential subject must also pass the Callahan cognitive screen by responding with no 
more than 2 errors. Further, if the medical team, family, or study staff believe that approaching the 
patient would likely provoke serious anxiety or distress we will not do so.  All reasons for lacking 
capacity will be recorded and part of the quarterly DSMB review process.  If the patient lacks decisional 
capacity, study staff will check back periodically to reassess capacity. 
 
After informed consent has been obtained from patients), staff will perform a baseline hospital interview 
to obtain clinical, socio-demographic, and baseline distress information.  A copy of the patient consent 
form will be placed in the patient’s chart, a copy given to the patient, and the original kept in the site PI’s 
locked cabinet in their locked office 
 
For the small usability sub-study described above in Point 6, we will not obtain written consent, as there 
are no major risks involved and no PHI is collected (see “Waiver of Documentation of Consent” Form 
uploaded to IRB site separately).  The following introductory script however will be used to obtain verbal 
consent: 
 
 
Hello!  I am _________ from Duke University Hospital.  We would like to ask for your help in evaluating 
a web-based application that is designed to give information to patients who have been in the ICU after 
they leave the hospital.  In fact, this is why we are asking you—because you or your loved one has had 
firsthand experience with critical illness.  Before we start using the web-based application in research 
studies, we need feedback from patients and families to make the program as clear as it possibly can 
be.   
 
We would like for you to look at the web application (‘webapp’), imagining that you are a patient who 
will be using it to help you feel better.  When you are done, we’ll ask you just a few questions about 
what you liked or disliked about the webapp.  The entire process should take 15-20 minutes.  After that, 

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
7
we will not need to contact you again unless you’d like to give us more feedback after you’ve thought 
about it some more.  We want to assure you that we will not collect your name, data of birth, or any 
other personal information.  Your answers to questions will not be linked you, and they will be used only 
to improve our program and to show others how to design these computer programs better.  There will 
be no direct benefits to you, although we think your feedback will improve the experience of others who 
participate in research later.  There are no physical risks to you, and your confidentiality will be 
protected since we are not recording any personal information about your health or otherwise, from you 
or any other family member.  Remember, there are no treatments involved with this study and your 
involvement is purely voluntary.  That means that it is OK if you don’t want to answer these questions. If 
you would be willing to answer questions, your consent is implied by your verbal agreement now and 
your willingness to give your feedback.  You will receive a coffee card with a value of $5 for your time 
spent with this study activity. 
 
Dr. Christopher Cox from Duke is the main researcher evaluating this webapp.  He can answer any 
questions at (919) 358-6451. 
 
8. 
SUBJECT’S CAPACITY TO GIVE LEGALLY EFFECTIVE CONSENT  
Only participants with legal capacity will be allowed to participate.  We will use a three-part capacity 
assessment procedure.  Part one:  are they comatose or delirious?  That is, if they are delirious (CAM-
ICU positive), they will be deemed as incapacitated.54  If they are not delirious (CAM-ICU negative), 
study staff will then determine that participants have clinical capacity to provide informed consent.  Part 
two:  if patient is not comatose or delirious, study staff must feel confident that the patient has clinical 
capacity to provide consent.  That is, in the judgment of the RA, the potential subject—after reading the 
IRB approved patient consent document—understands the terms of participation in the study.  The 
potential subject should be able to repeat in his/her own words the purpose of the study (or write on a 
communication board), what will be required of study participants, and the potential risks, benefits and 
alternatives of study participation.  Further, the subject must complete the Callahan cognitive screen 
with no more than 2 incorrect responses in order to be considered eligible.  Part three:  It is possible 
that the medical team or research staff believes that approaching the patient for consent while they are 
recovering from life support has a high likelihood of causing the patient serious anxiety or distress.  If 
this is the case, we will not approach the patient for consent.  For patient with whom we determine to be 
incapacitated or psychologically unprepared, we will attempt to re-consent them during the 
hospitalization as study staff are able.   
 
9. 
STUDY INTERVENTIONS  
Study procedures for usability testing 
We expect approximately 20-25 participants will be needed to perform adequate usability testing of our 
website, app, and the intervention itself.  After obtaining informed consent, CRCs will observe 
interactions with the website and app in ‘think-aloud’ protocols in which users’ comments will be 
recorded in real time.  Semi-structured interviews will follow sessions, with usability comments 
classified as positive, neutral, or negative per Nielsen and Zhang.  ‘Negative’ comments will be 
categorized into domains and targeted for editing in successive testing cycles.  We will use the 
Systems Usability Scale (SUS), a well-validated industry standard measure with scores ranging from 0 
to 100, to measure five critical usability domains: ease of learning, efficiency of use, memorability, error 
frequency and severity, and subjective satisfaction.  We will perform successive testing/revision cycles 
with repeat user sampling until we observe a mean SUS score >85, representing ‘excellent’ usability. 
Based on our past experience, we expect two or three 8-10-user samples to achieve this target—
similar to sample sizes needed to reach thematic saturation in qualitative analysis. 
 
Study Procedures for RCT 
General aspects of treatment procedures:  After obtaining informed consent, the CRC will administer 
baseline in-hospital questionnaires to each patient, entering data via an encrypted tablet computer 

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
8
directly into the web-based study electronic clinical 
research forms that we will manage via RedCap, a 
password protected, HIPAA-compliant, web-based 
database system that is built on the RedCap 
framework, an open-source framework originally 
designed at Vanderbilt University for clinical research 
and institutionally supported at Duke.  CRCs will track 
patients thereafter and then perform post-discharge 
Interview 1 within 2 weeks of arrival to a home setting 
(and no greater than 1 month from the time of hospital 
discharge, as dropout escalates thereafter related to 
persistent medical issues).15  Such timing also provides 
higher efficiency compared to an in-hospital approach 
because of fewer exclusions due to illness acuity and 
delirium.84  Next, the study data system will randomize 
patients into treatment groups in a 1.75:1.75:1 ratio, via 
the method of minimization to balance the three study 
aims by the following important prognostic factors: the severity of current psychological distress 
(Interview 1 PHQ-9 score <15 vs. ≥15; representing a cutoff of ‘moderately severe depression 
symptoms’),85 severity of current physical symptom distress (Interview 1 PHQ-10 score <10 vs. ≥10; 
representing a cutoff of ‘high somatic severity’), Age (<50 vs. ≥50), ICU service most proximate to 
enrollment (medical/cardiology vs. trauma/surgical) and study site (Figure 7).  After randomization and 
disclosure of group by the CRC, we will mail to participants printed copies of all study materials (e.g., 
CDs/DVDs of all online content plus instructions on how to access study materials on the study 
website; each treatment group has a separate password-protected section).  Participants will then 
complete the study interventions, performing makeup sessions as needed.  No sessions will be 
provided during readmissions, though based on our pilot data these are infrequent. 15,63   All sessions 
must be completed within 6 weeks of randomization.  While no specific number of completed sessions 
is required, we will consider completion rates in analyses.  Participants will complete follow up 
questionnaires as preferred by either telephone (~30 min) or ePRO at post-intervention (Interview 2:  4-
6 weeks post-randomization) and long-term follow up (Interview 3: 16-18 weeks post-randomization, or 
~3 months post-intervention completion); a short semi-structured interview will conclude Interview 2.  
As an added feature, after Interview 3 we will allow all participants to access all study features of both 
arms (education and mindfulness).   
 
Intervention:  Mobile Mindfulness-Based Training (mMBT) 
• 
Therapist-directed mMBT: mMBT is initiated at the peak incidence of distress—early post-
discharge—to maximally attenuate the overall trajectory of 
distress.1,20,22,28  mMBT includes 4 weekly telephone 
sessions, a dose that should be adequate based on our 
clinical experience and recent piloting.15  Each ~30-minute 
mMBT session is composed of four parts:  (1) brief 
discussion about participants’ major current stressor(s);  (2) 
rationale and discussion of the didactic focus;  (3) practice 
and review, and  (4) discussion about participant’s use of 
mindfulness skills, challenges in applying the skills, and 
how to maintain progress.  As shown in Figure 4, the 
didactic elements of mMBT include:  In Session 1, subjects 
will be provided with a rationale for mindfulness and learn to 
use awareness of breathing, a core meditation technique that begins to cultivate skills of mindful, non-
reactive observation.  Session 2 will introduce awareness of body systems that are working well or less 
well as a way to continue to cultivate skills of observing, describing, and non-judgmental attention.  
Education 
Control
n = 20
standard
mMBT
n = 35
In-hospital interview
Figure 7:  Overview of study performed 
among ICU survivors
see Figure 2
ePRO or phone Interview 1:  pre-intervention
within 2 weeks after arrival home
self-
directed
mMBT
n = 35
see Figure 9
Home
see Figure 10
ePRO or phone Interview 2:  post-intervention
4-6 weeks post-randomization
ePRO or phone Interview 3:  long-term f/u
16-18 weeks post-randomization
*** randomization ***
Figure 4:  Distress Targets—and mMBT Session 
                 Topics That Could Address These Targets
4.  Awareness of sound 
3.  Awareness of emotion and
     Mindful acceptance
2.  Awareness of body
- Day to day impact of critical illness
- Critical illness deﬁnes sense of self
- Inability to cope
- Relationship strain-related stress
- Pervasive traumatic memories
- Physial and emotional symptoms
1.  Awareness of breathing
         Distress Targets 
        for ICU Survivors
               see “Step 2”
mMBT Session Topics 
for Distress Targets
see “Step 3”

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
9
During Session 3, participants will practice awareness of emotion and mindful acceptance, which is 
designed to acknowledge difficult emotions and cultivate feelings of kindness and compassion towards 
oneself and others. Session 4 introduces awareness of sound, a practice in which patients will learn to 
systematically broaden awareness of senses of sound in the context of improving sleeping problems—
a common occurrence for ICU survivors.  Sensory awareness practice simultaneously builds the skills 
of attention, concentration, observation, non-judgment, and non-reactivity.  Overall, this MBT plan is a 
blueprint for therapy that can be adapted in the moment to address stress or crises experienced by 
participants.  mMBT recipients will not view the education control content during the time between 
consent and Interview 3.  
• 
Self-directed mMBT:  A self-directed mMBT intervention will be the second trial arm.  Self-
directed mMBT has a goal of focusing therapist time on highly symptomatic or poorly responding 
patients.  Self-directed mMBT (delivered via a web or app version as preferred) will contain all the 
features of therapist-directed mMBT, with the added features shown in Figure 9.  There will also be an 
introductory video plus an added audio file that addresses maintaining practice.  There is an added 
inclusion of web access or smartphone availability (our past research indicates that <10% would be 
excluded by this criterion).  Also, participants will view a 
short mMBT video in the hospital that familiarizes them with 
the study procedures (e.g., they will know to expect a 
weekly text or email reminder with a link to the relevant 
web-based information starting within 1 week of arrival 
home) and provides an introduction and rationale.  After 
CRCs verify that the patient has arrived home, the patient 
will begin the mMBT program guided by written handouts, 
the study website, and a brief review by the CRC.  Patients 
will complete the PHQ-9 and GAD-7 weekly survey via a 
secure password-protected ePRO system after text or email 
prompting from Redcap.   
 
After an initial introductory call, study staff will manage 
participant contact using a specific protocol:   
1.  At the conclusion of each weekly survey or at a timed 1-
week interval from randomization, the web app will display a 3-
item display with the following responses (see Figure opposite):  
I have technical questions, I need information about the study, 
and I need help applying the Lift program (mindfulness 
program).  A decision logic interface will then allow the 
participant to further specify the problem and request a contact.  
A popup will arise in response to specific questions directing the 
user to information within the app.  For example, a question 
about ‘physical symptoms’ will display a popup with a link to the 
module on this topic.  The therapist will contact the participant 
only if the participant (a) notes physical or emotional symptoms 
and (b) they request a contact.  The therapist will be able to 
note the weekly PHQ-9 and GAD-7 scores as either ‘elevated’ 
or ‘not elevated’ before they call.  We will define ‘elevated’ 
symptoms as PHQ-9 score ≥15 or GAD-7 score ≥15 (standard 
cutoffs for clinically notable distress).    
2.  If PHQ-9 suicidality item is endorsed on either the weekly survey OR at Interview 1, 2, or 3, the site 
PI or therapist (a PhD-level clinical psychologist) will call participant. 
3.  If participant fails to log into the web app within 2 weeks of randomization and each 1 week period 
thereafter.   
4.  If participant fails to complete weekly survey within a week of its due date. 
ePRO system automates targeted therapy 
based on self-report
patient dashboard for progress tracking
Telephone calls if requested or if suicidal 
ideation noted on ePROs*
Content
also includes app version
Figure 9:  Added features of self-directed mMBT 
compared to therapist-directed mMBT 
Delivery
*ePRO = electronic patient reported outcomes
Features

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
10
We have piloted our ePRO system in an ongoing coping skills RCT as a safety tool (not to direct 
therapy) and found it to be safe, reliable, and consistent with current recommendations.74 However, no 
patient ever needed professional psychiatric support based on questionnaire trigger points (see also 
Human Subjects for more details).  This recent experience suggests that ~15% required calls.  By 
allowing collaboration of CRCs and therapists, as well as the assistance of the app itself, self-directed 
mMBT has potential to greatly enhance the feasibility of large-scale mind-body intervention trials—a 
paradigm shift in therapy delivery. 
5.  We will run a RedCAP-based report weekly that will examine participant use of the web app.  
Participants will be highlighted who are ‘app non-users,’ defined as those who do not access the web 
app’s weekly audio file at all.  We will send an email or text message (with no PHI, name, identifiers) to 
the participant (as per their stated preference at Interview 1) with a link to a static web app page.  
Participants will be expecting such messaging, as the therapist will remind them of this system.  On this 
page, a brief message will be displayed reminding the participant about the study purpose, the timeline, 
and study tasks.  There will be a link for the participant to then securely log in to the app.  The 
information displayed on this ‘message’ web page will be identical to that displayed elsewhere in the 
web app.  No PHI, names, etc will be displayed.   
6.  Before making any scheduled or requested telephone call, the therapist will review the participant’s 
RedCAP dashboard that displays their most recent PHQ-9, GAD-7, and physical symptom scores from 
their weekly survey, as well as their ‘active app user’ vs. ‘app non-user’ status.  This information will be 
used to better personalize the experience.  The other study staff (with the exception of the study 
manager) will not be able to access this function. 
 
Control:  Education Program:  The goal of the control condition, developed and piloted by our group, 
is to provide subjects with educational information about the nature and treatment of critical illness, but 
none of the mindfulness training provided to mMBT recipients (Figure 10).  Control subjects will receive 
2 brief, check-in phone calls along with access to 
educational material.   The calls will be targeted 1 
week and 3 weeks after randomization to allow time 
for subjects to receive and review the materials. This 
scripted conventional educational program has a 
presentation and discussion format similar to our 
group’s past multi-session protocols (e.g., PCORI 
PFA 195).62,86  Participants have rated the credibility 
of this education protocol highly in focus groups.  At 
the time of randomization, we will give education group patients access to an education website we 
developed with identical capabilities as the mMBT website, allowing viewing of education handouts and 
videos we developed. Hard copies of materials will be mailed also.  mMBT recipients will not be able to 
view the education program until after completing Interview 3. 
 
Role and training of the CRCs:  The role of CRCs is to enroll subjects, abstract medical charts, 
participate in randomization, perform in-hospital and telephone interviews for site-enrolled participants.  
Also, CRCs will provide the education control intervention for their own site’s subjects, a design that will 
not bias post-discharge questionnaire responses.  Drs. Cox and Hough will train CRCs in acute 
respiratory failure definitions and outcomes, review the education control treatment manual, explain the 
study web-based data entry and management system (Redcap), and address other topics at an initial 
2-day teleconference.  Training will be reinforced by biweekly investigator-CRC conference calls and 
weekly site PI-CRC meetings. 
 
Role and training of the interventionists:  The mMBT interventionists, Tina Gremore, PhD and Julie 
Kosey PhD (both clinical psychologists), has experience in providing MBT and coping skills training for 
medical populations including ICU survivors.  Drs. Porter and Greeson will supervise their training, 
including review of the treatment manual and roleplay of common scenarios.  The CRCs (Brenda 
Figure 10:  Topics for Education Program Sessions
6.  Nutrition and critical illness
3.  Neuromuscular weakness
2.  Hospital & post-discharge 
     treatments
5.  Internet resources for ICU 
     survivors
1.  Acute respiratory failure: 
     causes and diagnosis
4.  Exercise and critical illness

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
11
Walton and Anna Ungar), who have experience interviewing ICU survivors, will be the education control 
interventionists.  Drs. Cox and Hough will train them in the use of the education materials.  Telephone 
sessions for all groups will be scheduled either directly by interventionists or by patients using a 
password-protected, HIPAA-compliant scheduling system (via the study website) and a randomly 
generated ID code.  Interventionist strain is a potential concern, though our pilot work supports the 
adequacy of the budgeted effort.15   
 
Uniformity of treatment and oversight of study staff:  As in our previous investigations, we will take 
steps to ensure that the treatment protocols are uniform and followed consistently throughout the 
project and across sites: detailed interventionist training, use of treatment manuals, and audio recording 
of sessions for supervision.62,66,87  We will develop protocol adherence criteria for each digitally 
recorded session, with satisfactory adherence defined as 90% or more of the maximum score on the 
adherence rating scale.  Drs. Greeson, Cox, and Porter will rate sessions for adherence prior to the 
weekly interventionist supervision meetings, thus providing immediate, ongoing feedback.  As a safety 
measure, we will train all staff to immediately refer subjects with any concerning level of emotional 
distress to a psychiatric expert (using our tested Distress Management System described in Human 
Subjects) and those with concerning physical symptoms or perceived cognitive decline to their primary 
physicians after consultation with the site PI. 
 
Recruitment and retention:  Although ICU studies are challenging because of patients’ residual 
disability, we have enjoyed low refusal rates (<20%) in our past studies and also achieved 100% follow 
up with telephone interviews performed over the course of 12 months. 12, 51  Our use of short telephone-
based follow up interviews should sustain our success in participant retention and reduce respondent 
fatigue.  In our experience, subjects develop a sense of trust with study staff that enhances retention. 
 
10. 
RISK/BENEFIT ASSESSMENT 
Potential risks:  Participants may experience some degree of stress due to the critical illness itself, 
and it is possible that they could experience anxiety when answering survey questions.  In our previous 
studies using similar self-report batteries (and the mMBT itself), we have encountered little resultant 
distress.  In fact, many participants have reported that they were relieved to be able to discuss such 
issues.  Further, our pilot data demonstrate that mMBT reduces distress.  We will, however, continue to 
utilize interviewers who have been trained to be sensitive to the nature of these issues and who have 
experience interacting with seriously ill patients and their families.  When necessary, subjects who 
experience psychological distress related to filling out self- report questionnaires will be referred for 
appropriate psychiatric or psychological care as described below.  Each site will have a protocol in 
place to refer subjects to counseling services appropriate to each setting if significant emotional 
distress is encountered.  These protocols will serve as safety precautions for study participants, though 
we have not observed significant emotional distress among subjects during our pre-testing of the 
mMBT program or in previous questionnaire-based studies of similar populations.  Finally, there is a 
theoretical risk of loss of confidentiality of data given known limitations of data systems and human 
inputs.  However, our group has never experienced such issues in the past.  Further, we have designed 
electronic data systems to include the highest level of security possible.  Nonetheless, we describe our 
approach to this potential issue below. 
 
Adequacy of protection against risks 
Recruitment and informed consent procedures:  First, each research site’s Institutional Review Board 
will review and approve the study protocol before study initiation (as they did for the recent piloting of 
mMBT).  Written informed consent will be required from patients for this study.  Second, we will use a 
standardized screening and enrollment protocol that respects participant privacy and rights.  CRCs will 
first ask each patient’s primary ICU physician for permission to approach the patient.  If permission is 
granted, research coordinators will ask the patient in person to read and sign the study consent form at 
the time of enrollment (day of transfer from intensive care unit to hospital ward).  Patients will have up 

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
12
to 72 hours to consider enrollment, as per Duke policy.  We will take great care to present the study 
group assignment possibilities (“like drawing a number out of a hat”) tactfully and with equipoise, noting 
that assignment to either group is in itself likely an improvement over usual care.  A copy of the consent 
form will be placed in the patient’s medical record, a copy given to the patient, and the original kept in 
the site PI’s locked cabinet in their locked office (later delivered by courier to Dr. Cox).  A brief 
electronic health record note will be entered as well, noting enrollment in the study and providing a 
contact number for the site PI.  For patients who lack decisional capacity initially, we will return for a 
subsequent attempt at consent approximately every 2 days as we do for other ICU-based studies.  Our 
consent procedure is described in detail in the Research Plan.   
 
Protections against risks:   
General oversight   
There are several ongoing mechanisms for monitoring the occurrence of adverse events.  Each Site PI 
will oversee day-to-day monitoring of the study activities.  The Study PI, Dr. Cox, will oversee all study 
activities at all sites as well.  Dr. Cox has demonstrated in past research that he keeps careful records 
of patients’ whereabouts and health status.  Careful monitoring of all persons entering the study will 
minimize attrition and will ensure the clinical safety of these patients.  This monitoring is facilitated by a 
telephone number provided to participants upon entry into the study to report concerns related to study 
participation, weekly meetings between the CRCs and site investigators to discuss study progress and 
any adverse events, and direct supervision of the study by the PI.   
 
Specific longitudinal participant oversight plans—interventionists, CRCs, and the data system 
Although this study does not meet criteria for a biomedical intervention, we recognize that there is a 
slight risk that some patients may become distressed when discussing issues in the treatment 
sessions, as mentioned above.  We will take the following measures to prevent negative reactions as 
well as deal with any that do occur:  
(1)  All of the intervention sessions will be conducted by highly trained professionals who have 
experience with patients with serious medical illness and are sensitive to the issues that arise during 
mMBT or education sessions (e.g., Dr. Cox’s ongoing studies).   
(2)  The interventionists and CRCs will emphasize to subjects that the sessions are patient-controlled.  
Thus, patients will be instructed that they are in control over what they share and generally how long 
they discuss any topic that is addressed.   
(3)  Patients will be told that they can discontinue the discussion at any time and that they are also free 
to discontinue the session at any time.   
(4)  The study staff, including the trained CRCs providing the education condition telephone sessions, 
will monitor participants closely during interviews and will refer those with any concerning level of 
emotional distress and/or relationship distress to psychiatric evaluation/support at the study site nearest 
the participant based on previous arrangement by each site PI.  This is a successful protocol that is 
currently in place in Dr. Cox’s ongoing studies.   
 
Duke 
Call emergency psychiatry at 681-4410 or 681-1316.  Or call Bunny Lewellyn (919) 684-0105, who 
directs these services and can provide weekend or afterhours support. 
 
University of Washington 
Dmitry Davydow, MD MPH.  (206) 744-4534 or the 24 hour crisis line: 1-866-4-CRISIS, or 1-866-427-
4747. 
 
All sites as a backup 
The National Suicide Prevention Lifeline - 1-800-273-TALK (8255) is a free, 24-hour hotline available to 
anyone in suicidal crisis or emotional distress. 
 

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
13
(5)  As an additional safety measure, we will electronically monitor RedCAP daily for a positive 
response to the PHQ-9’s suicidality assessment item.  CRCs performing interviews will also flag this.  
Any positive response to this item will result in a call, text message, or email from the site PI. In the past 
we have used automated depression, PTSD, and anxiety scale scores to appreciate ‘alert values.’  Of 
the approximately 15% of patients who we called in a similar past psychobehavioral study, none 
required referral to an outside psychiatric professional and none endorsed suicidality.  Additionally, 
there are no validated cutpoints of these questionnaires that reliably can be used to direct care.  We are 
very sensitive to the common and pervasive nature of psychological distress among ICU survivors and 
our study staff are experienced in discussing these issues with patients. 
 
(6)  Finally, interventionists and CRCs will be trained to monitor participants closely and discuss with 
them a possible referral to their primary physician if the staff perceives a significant decline in cognitive 
or physical function.  Generally, these are clinical judgments that the experienced CRCs are well 
prepared to make.  Some may be mentioned by participants themselves and referred to the site PI to 
navigate, as in our other studies.  All such referrals will be discussed with the main PI and a resolution 
(and follow up) documented in the ‘contact log’ section of the study data system.  The PI will review the 
recorded session to better target follow up triage to the appropriate physician.  In our past studies such 
referral needs have been uncommon.  More common has been specific requests for assistance 
requiring timely referral (e.g., a likely infected catheter), which we have worked quickly with participants 
and patients to facilitate without incident. 
 
As mentioned before, we recognize that there is a slight risk that some patients may become distressed 
when completing self-report measures.  In our previous studies using similar self-report batteries, we 
have encountered little resultant distress.  In fact, many participants have reported that they were 
relieved to be able to discuss such issues.  We will, however, continue to utilize interviewers who have 
been trained to be sensitive to the nature of these issues.  When necessary, participants who 
experience psychological distress related to completing questionnaires will be referred for appropriate 
psychiatric or psychological care.  For those completing ePRO questionnaires, contact numbers for our 
staff are provided on each page—including the PI’s mobile phone number available 24 hours a day. 
 
We will closely safeguard participant privacy regarding protected health and personal information. 
Study ID numbers, generated randomly at the time of enrollment, are linked in a separate database 
subsystem patient names and medical record numbers.  Further, names, birthdates, telephone 
numbers, addresses, and medical record numbers are only viewable by the head Duke CRC after entry 
of multiple passwords.  The master list of study ID linkage to this personal data will be deleted after 
study completion.  Screening logs will be kept in a password protected folder on a secure Duke server.  
Similarly, electronic audio-recordings will be labeled with a study ID number linked to a master list of 
names kept in a secure, password protected file on a secure Duke server.  All personal identifiers will 
be removed from the audio-recordings at the time of transcription.  All audio-recordings will be stored 
securely on a password protected computer file on a secure Duke server.  The audio-recordings will be 
destroyed at the completion of the study.  All printed data (interviews completed by paper and consent 
forms) will be kept in locked, private storage cabinets in the site PI’s office. 
 
Potential benefits of the proposed research to human subjects and others  
Although the proposed project is an exploratory pilot study, it involves a randomized design with a 
control condition.  The mMBT intervention may reduce psychological distress.  This could in fact hold 
great promise for helping many others in similar situations in the future.  However, this is not certain.  
Additionally, subjects in the education control condition may experience similar or even greater benefits 
to those described for mMBT.  Then again, they may receive no particular benefit.  These facts will be 
stated clearly in informed consent documents.  Nonetheless, study involvement puts subjects at low 

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
14
risk for any adverse physical or psychological risk.  Therefore, the potential benefits justify the minimal 
risk to those enrolled in the proposed study. 
 
Importance of knowledge to be gained 
To our knowledge, this is the first study proposed to address the psychological distress of both ICU 
survivors using a telephone-based or mobile platform-based behavioral intervention.  These persons 
face enormous but common disability as a result of critical illness and its sequelae.  Therefore, the 
implications of this research, designed to mitigate this stress and suffering, are significant for the 
approximately one million such patients and their families treated each year in the US.  We hypothesize 
that our intervention could greatly improve participants’ well being in the future, and we therefore 
believe that important knowledge could come of this proposed study.  Overall, we believe that the 
potential risks are reasonable in comparison to the potential important knowledge to be gained. 
 
11. 
COSTS TO THE SUBJECT  
None.   
 
12. 
DATA ANALYSIS & STATISTICAL CONSIDERATIONS 
Measures and Data Collection.  We will gather data from charts and interviews with patients identical 
in content for both treatment groups with the timing shown in Figure 7.  All patients will complete the 
measures shown in Table 1 (see also Appendix Figure 1).  We chose measures based on 
psychometric properties (validity, responsiveness, reliability), population relevance, performance in pilot 
studies, and brevity.  We have used all measures in past and pilot research.  We expect the total 
questionnaire burden to be approximately 30 minutes per interview. 
 
Primary outcomes:  feasibility, acceptability, usability  
Feasibility will be measured as by comparison of observed frequencies to pragmatic benchmarks of 
enrollment (percent of patients who provide consent among all who either consent or refuse; target 
70%) and randomization success (60% of those who provide informed consent), post-randomization  
dropout at the time of Interview 2 (20% target among those who are alive and did not drop out), 
completeness of responses to telephone interviews (75% target among those neither dropped out nor 
died), completeness of weekly surveys among self-directed MBT participants (60% target among those 
who did not die), and participant session attendance (75% target among those who neither dropped out 
nor died).  We will record the rate of post-enrollment exclusions, noting dropout due to cognitive 
disability—a factor we expect to be uncommon given our pilot-driven protocol changes.15  We will note 
our success in retaining patients who were discharged to a post-acute care facility before arrival home, 
as we have done previously.20 
 
Acceptability will be measured with the Client Satisfaction Questionnaire (CSQ), which assesses 
credibility as well as perceived effectiveness of/satisfaction with services (target mean >15), 88 and with 
a 100-point visual analog satisfaction scale (target rating 80%).  Open-ended feedback will also be 
incorporated in our assessments. 

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
15
 
Usability testing of the web interface and 
intervention components will be guided by 
Usability.gov recommendations, comparing to 
benchmarks (>90%) such as speed (<2 minutes 
to find session), search accuracy (<2 false 
clicks), success in accessing the relevant 
information (yes/no), and with the well-validated 
10-item System Usability Scale (SUS).72  Website 
use and video/audio views will be quantified with 
URL and video/audio “hit numbers.”  We will also 
conduct a semi-structured interview at the end of 
Interview 2, using open-ended probe questions to 
assess feelings about acceptability, usefulness, 
and application of both programs.  Responses 
will be digitally recorded, transcribed, and 
analyzed. 
 
Secondary outcomes 
Psychological distress symptoms will be 
measured using the PHQ-9 depression scale, the 
GAD-7 anxiety scale, and the PTSS PTSD scale.  
The PHQ-9 is a 9-item scale with scores ranging 
from 0 to 27.  Symptom interpretations are as 
follows: 5 or less ‘normal,’ 6-10 ‘mild,’ 11-15 
‘moderate,’ 16-20 ‘moderately severe,’ and >20 
‘severe.’  The GAD-7 is a 7-item scale with 
scores ranging from 0 to 21.  Symptom 
interpretations are as follows: 5 or less ‘normal,’ 
6-10 ‘mild,’ 11-15 ‘moderate,’ 16-21 ‘severe.’  
The PTSS is a 10-item PTSD scale (score range 10-70; >35 likely PTSD) used frequently among ICU 
survivors that assesses ICU-related traumas by anchoring memory recall to hospitalization.101  The 
PTSS has excellent internal consistency and reliability, evidence of concurrent validity, good 
responsiveness in RCTs, is highly specific and sensitive compared to DSM-IV PTSD criteria among 
ICU survivors.102-104  We successfully tested both scales in our IRB-approved, web-based ePRO 
system. 
 
Physical symptoms will be assessed using an adapted version of the PHQ-15 symptom scale that has 
10 items (and is thus termed the PHQ-10 for clarity).  We will measure generalized stress with the 4-
item Perceived Stress Scale (PSS-4). 
 
Mindfulness and mindful coping measures 
We will measure mindfulness qualities using two primary questionnaires.  First, the  
Cognitive and Affective Mindfulness Scale-Revised (CAMS-R) is a 12-item scale that assesses 
awareness, attention, and reactions.  We will measure mindful coping using the avoidance domain of 
the Brief COPE,109 a scale that has excellent psychometric properties 108 and high correlations with 
distress in ICU populations.15,63 
 
 
Statistical analysis & power considerations 
We will use a mixed methods approach to address key knowledge gaps and subsequently use the 
results to refine the mMBT program in an iterative, consensus-driven revision process as done 
Table 1:  Study outcomes measures and timing 
Outcomes for all study aims 
Timing 
Feasibility: Enrollment, randomization, retention, 
adherence to telephone sessions 
Interv iew 
1, 2, 3 
Acceptability and usability:  Client Satisfaction 
Questionnaire,
88 Systems Usability Scale,
72 semi-
structured open-ended exit interview 
Interv iew 
2 
Depression and anxiety symptoms:  PHQ-9 and 
GAD-7 a 
Interv iew 
1, 2, 3 
Post-traumatic stress disorder symptoms:  The 
Post-Traumatic Stress Scale (PTSS) 
Interv iew 
1, 2, 3 
Physical symptoms:  The PHQ-10 
Interv iew 
1, 2, 3 
Mindfulness Measures (Mechanistic Factors) 
 
Mindfulness:  Cognitive and Affective Mindfulness 
Scale- Revised 
Interv iew 
1, 2, 3 
Mindful coping:  Brief COPE avoidance domain 
Sociodemographic and Clinical Variables 
 
Sociodemographics: Age, gender, race/ethnicity, 
employment, insurance, education level, marital status  
Hospital 
Clinical characteristics at enrollment:  prior 
functional status,
89, 90 comorbidities,
91 psychiatric 
medication use, illness severity,
92 ICU delirium (CAM-
ICU),
93 Callahan cognitive screen,
82 diagnosis, duration 
of ventilation, ICU & hospital LOS, disposition. 
Hospital 
Post-discharge factors:  quality of life (Global health 
scale),
94 functional status, use of psychiatric 
medications,  cognitive function (TICSm),
95 frequency of 
mindfulness skills use,
 social support,
35 
hospitalizations/clinic visits/days at home, daily 
caregiving requirement 
Interv iew 
1, 2, 3 
Electronic patient-reported outcomes:
  PHQ-9, GAD-
7, PTSS, numerical quality of life visual scale
96 
Interv iew 
1, 2, 3 
Objective physical measures:  functional status,
89, 90 
key physical symptoms
97  
Interv iew 
1, 2, 3 
a also in hospital 

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
16
previously.15,63,73  Descriptive statistics, including graphical displays, will be used to summarize all study 
variables.  We will examine both the distributional properties (e.g., ceiling and floor effects) of the 
continuous outcome variables and the stratification variables to determine the appropriateness of our a 
priori cutoffs.  We will construct individual and mean trajectory plots of the outcome variables to 
understand their general longitudinal trends as well as their variability and correlation structure.  In 
these analyses, we will focus on 95% confidence intervals (CIs) to contextualize point estimates of 
treatment groups given the potential imprecision of these pilot data. 
 
Aim 1:  To test the feasibility, acceptability, and usability of both a telephone-delivered, mobile 
mindfulness-based training (mMBT) intervention for distressed ICU survivors as well as a self-directed 
mMBT intervention.   
 
Feasibility will be examined by calculating overall rates of eligibility and enrollment.  Rates of attrition, 
adherence to telephone sessions, and interview completion will be compared by treatment group using 
tests for differences in proportions, means, or medians as appropriate.  Clinical and personal 
characteristics associated with feasibility will be explored as well via contingency tables and regression 
analyses.  Acceptability and usability will be evaluated similarly, using between-treatment group 
differences in quantitative measures of perceived satisfaction (CSQ) and usability (SUS). Feasibility 
and acceptability will be the key outcomes of focus in comparing mMBT and self-directed mMBT. Also, 
we will use qualitative analysis to understand participants’ attitudes about the intervention, perceived 
effectiveness (or lack of it), and application to their daily lives in their own words.  We will use a 
grounded theory approach to develop a systematic open coding scheme. 110  Starting with the first five 
participants, the investigators will independently identify major emerging themes related to intervention 
attitudes from de-identified transcriptions.  Axial coding, the process of relating codes to themes using 
both inductive and deductive thinking, will be used to achieve a more robust coding table.111  Codes 
may evolve based on further experience with these data and will be finalized only after reaching 
investigator consensus.  We will use MAXQDA in coding and data management.  Dr. Cox has 
experience in qualitative analysis.1 
 
Aim 2:  To provide a plausible range of psychological distress estimates for each treatment group 
(mMBT, self-directed mMBT, and control) at both post-intervention and long-term follow up.   
 
Psychological distress (PHQ-9, GAD-7, and PTSS scores) will be measured at times 1, 2, and 3.  A 
general linear model will be used to estimate mean changes and corresponding 95% CIs in 
psychological distress between mMBT and control as well as for self-directed mMBT and control over 
the 3 months of post-intervention follow up using SAS PROC MIXED (SAS Institute, Cary NC).  We will 
fit the models with an unstructured covariance matrix to better understand and represent the correlation 
between patients’ repeated measures.  We will also use similar modeling strategies to explore how the 
key clinical (e.g., history of ICU delirium, illness severity, diagnosis grouping), objective physical (e.g. 
functional status), sociodemographic, and mechanistic (e.g. mindfulness qualities) factors are 
associated with changes in psychological distress, both within and between treatment 
groups.5,26,28,68,101,112,113  This part of the analysis aims to refine inclusion/exclusion criteria for a future 
study. 
 
Sample size considerations.  This exploratory pilot study is not intended to test mMBT’s efficacy.  
While the sample size chosen must reflect the pragmatics of recruitment during a short enrollment 
period, we will have adequate sample size to provide meaningful CIs for our estimates.54,114-116  
Additionally, because our primary aim focuses on feasibility and acceptability comparisons between 
mMBT and self-directed mMBT, we plan to enroll more patients in these two groups (1.75:1.75:1 
allocation ratio). Previous work has consistently shown that the standard deviation of PHQ-9 scores in 
this population is ~9.0 and the minimal clinically important difference is 5 units.6,63,85  With 20-35 
patients per treatment group, we will be able to estimate CIs for the PHQ-9 with 6.0-7.6 points of 

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
17
prevision (the total width of the CI); note that a minimal clinically important difference is generally 
considered to be ~3 points.117,118  For the PTSS, a common standard deviation is 14.0.15,63  We will be 
able to estimate 95% CIs with a precision of 4.8-6.0—a width smaller than standard change scores 
seen among ICU survivors.15,63  PASS software was used for precision estimates (NCSS, Kaysville 
UT). 
 
DATA & SAFETY MONITORING 
Plans for assurance of compliance regarding adverse event reporting.  All study sites require 
investigators to report adverse events to the Institutional Review Board (IRB) on both a per case and an 
annual basis.   Additionally, every research project conducted at each study site is required to have a 
yearly Departmental and IRB review.  Also, all adverse events are reported as part of the progress 
reports in the non-competitive and competitive renewals.  Dr. Cox will be responsible for contacting the 
NIH grant program officer in the event that any action resulting in temporary or permanent suspension 
of the study occurs.  The proposed research will adhere to all monitoring requirements imposed by 45 
CFR Part 46. 
 
Plans for assuring data accuracy and protocol compliance.  Dr. Cox will supervise this study at all times 
but will be in close and frequent contact with other investigators, including the University of Washington 
site PI (Dr. Hough).  Dr. Cox and Dr. Olsen, the study biostatistician and Dr. Cox’s current collaborator, 
will be the chief data managers and will adhere to established federal and institutional patient safety 
and protection guidelines.  To assure data accuracy, Drs. Cox and Olsen will review the computer data 
files on a monthly basis.  Additionally, CRC staff will process the RedCap database biweekly to search 
for errors and generate basic reports for dissemination at regular meetings.  Protocol compliance will be 
reviewed during weekly meetings between site clinical research coordinators and Dr. Cox as well as bi-
weekly meetings (more frequent if required) between Drs. Cox, Hough, Porter, and Greeson.  Also, Drs. 
Porter and Greeson will closely review protocol adherence with the psychologist interventionists 
regularly as described in the Research Strategy above. 
 
Data safety monitoring board (DSMB).  Although this is an exploratory pilot study, it will be supervised 
by a single independent central DSMB due to its interventional nature.  Dr. Cox has successfully 
developed 2 independent DSMBs for his recent multicenter RCTs (NIH and PCORI). The DSMB will 
include professionals with significant experience in clinical trials, mind-body interventions, and 
biostatistics who are not directly involved in the study, its interpretation, or any study institution.  
Shannon Carson, MD (University of North Carolina) will serve as the DSMB chair, with other members 
including Samuel Brown, MD (Intermountain Health Care), Judd Brewer (University of Massachusets), 
and Ofer Harel, PhD (University of Connecticut).  Dr. Carson has served on other DSMBs and has 
experience in conducting clinical trials among the critically ill and their families. The main 
responsibilities of the DSMB will be to (a) assess for the presence of potential harms and unintended 
consequences of the intervention, (b) ensure the validity and integrity of the data, and (c) make 
recommendations to the NIH about whether the study should be continued without modification, 
continued with modification, or terminated.  The initial DSMB meeting will occur before the initiation of 
subject enrollment for the purpose of updating members on the study, ensuring agreement on the 
review process, and establishing the review methodology and procedures.  The first DSMB data review 
will then occur either after the first 10 patients (5 per treatment group) have been enrolled or enrollment 
has occurred for 3 months, whichever is observed first.  Thereafter, the DSMB will review cleaned data 
pulled from the RedCap database system every six months during enrollment and will prepare a report 
with any recommendations within the following month.  While this is an intensive DSMB engagement 
schedule, the short enrollment period will demand greater oversight.   
 
The specific study functions and outcomes that the DSMB will review at each meeting include:  dropout 
rate, randomization rate, PHQ-9, GAD-7, and Post-Traumatic Stress Scale (PTSS) scores.  The 
primary safety measures will be Adverse Events reports and post-intervention PHQ-9 scores.  Other 

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
18
items reviewed by the DSMB at each meeting will include: (a) data quality, completeness, and 
timeliness; (b) performance of the Duke and University of Washington centers; (c) adequacy of 
compliance with goals for recruitment and retention, including women and minorities; (d) protocol 
adherence; and (e) presence of factors that could adversely affect study outcome or compromise data 
confidentiality. 
 
During the review process, formal statistical tests for examining the differences in Adverse Event or 
outcome rates between study groups may be performed under DSMB supervision if requested.  
However, this is unlikely given the exploratory pilot study design.  For differences in study dropout 
rates, appropriate changes to the protocol will be made by investigator consensus after DSMB member 
input.  Additionally, the DSMB may request a formal statistical assessment if a suspicious increase in 
PHQ-9 score is observed in either group.  If the intervention group is found to have either a statistically 
significant increase in PHQ-9 score, the DSMB scope of action will include recommendation for 
cessation of the trial.  Dr. Olsen, the biostatistician, will oversee any DSMB statistical requests and 
interpretations.  Any protocol changes, as well as any adverse events, will also be reported to the 
Institutional Review Boards of all study sites, as well as to the NIH. 
 
13. 
PRIVACY, DATA STORAGE & CONFIDENTIALITY  
We have a number of strategies to ensure the quality of the data.  RedCap will be the unique web-
based data collection and recording system that will be used for the proposed study.  RedCap is a web-
based application built to support clinical research studies at universities across the United States.  
RedCap gives us the capability to set up a shared workspace for the study to collect data, as well as 
managing its participants and study activities.  RedCap has been implemented successfully in multi-site 
studies across the United States and is institutionally supported by Duke.  RedCap can “force” 
responses to most questionnaire items before allowing progression through the particular interview’s 
template, thereby avoiding problems with missing data.  After enrollment of the first 10 participants at 
each site, the study investigators will examine electronic summary CRFs to ensure adequacy and 
accuracy of data collection.  Agreement between centers will be reviewed and discrepancies will be 
discussed.   
 
During the analysis phase, experienced RedCap support staff at Duke work with the project staff to 
shape the application design.  For example, during this phase, the typical study participant's timeline is 
worked out.  After frequent incremental meetings to review system design, the system is customized to 
the study needs and design.  A benefit to the current proposed study is that RedCap staff can easily 
revise platforms built for previous studies with similar database and data collection needs.  This 
reduces overall programming costs significantly. 
 
Tablet computers (iPads) will be used by study staff to input and manage data in the RedCap system.  
All tablet computers used are password protected and encrypted.  
 
Reports that are needed on a day to day study management basis are built into the system as real-time 
tables, graphs, or data downloads.  The study staff can log in to the study website at any time and 
download current study data for analysis.  RedCap will also allow timely data preparation for DSMB 
review, as well. 
 
Confidentiality will be safeguarded by a number of strategies. Subjects will not be identified on any 
study reports. We will keep all paper study materials (i.e. consents, paper interviews, etc.) including 
participant names, contact information, and personal identifiers linked to study IDs in a locked filing 
cabinet in the site PI’s office.  Screening logs will be kept in a password protected folder on a secure 
Duke server.  Duke firewalls, multiple passwords, and encryption programs protect the security of the 
electronic data entry system. 
 

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
19
15.   
BIBLIOGRAPHY AND REFERENCES CITED  
 
1. 
Iwashyna TJ. Survivorship will be the defining challenge of critical care in the 21st century. Ann 
Intern Med. 2010;153:204-205. 
2. 
Spragg RG, Bernard GR, Checkley W, Curtis JR, Gajic O, Guyatt G, Hall J, Israel E, Jain M, 
Needham DM, Randolph AG, Rubenfeld GD, Schoenfeld D, Thompson BT, Ware LB, Young D, 
Harabin AL. Beyond mortality: future clinical research in acute lung injury. Am J Respir Crit Care Med. 
2010;181:1121-1127. 
3. 
AHRQ. Institute of Medicine Priority Areas for National Action. 2003. 
http://www.ahrq.gov/qual/iompriorities.htm. Accessed August 30, 2010. 
4. 
Medicine SoCC. Critical care statistics in the United States. 2012. 
http://www.sccm.org/SiteCollectionDocuments/StatisticsBroch_d4.pdf. Accessed July 1, 2012. 
5. 
Phua J, Badia JR, Adhikari NK, Friedrich JO, Fowler RA, Singh JM, Scales DC, Stather DR, Li 
A, Jones A, Gattas DJ, Hallett D, Tomlinson G, Stewart TE, Ferguson ND. Has mortality from acute 
respiratory distress syndrome decreased over time?: A systematic review. Am J Respir Crit Care Med. 
2009;179:220-227. 
6. 
Angus DC, Musthafa AA, Clermont G, Griffin MF, Linde-Zwirble WT, Dremsizov TT, Pinsky MR. 
Quality-adjusted survival in the first year after the acute respiratory distress syndrome. Am J Respir Crit 
Care Med. 2001;163:1389-1394. 
7. 
Cox CE, Docherty S, Brandon D, Whaley C, Attix D, Dore DV, Clay AS, Govert JA, Hough CL, 
White DB, Tulsky JA. Surviving critical illness:  the experience of acute respiratory distress syndrome 
patients and their caregivers. Crit Care Med. 2009;37:2702-2708. 
8. 
Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F, Cooper 
AB, Guest CB, Mazer CD, Mehta S, Stewart TE, Barr A, Cook D, Slutsky AS. One-year outcomes in 
survivors of the acute respiratory distress syndrome. N Engl J Med. 2003;348:683-693. 
9. 
Herridge MS, Tansey CM, Matte A, Tomlinson G, Diaz-Granados N, Cooper A, Guest CB, 
Mazer CD, Mehta S, Stewart TE, Kudlow P, Cook D, Slutsky AS, Cheung AM, Canadian Critical Care 
Trials G. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med. 
2011;364:1293-1304. 
10. 
Hopkins RO, Weaver LK, Collingridge D, Parkinson RB, Chan KJ, Orme JF, Jr. Two-year 
cognitive, emotional, and quality-of-life outcomes in acute respiratory distress syndrome. Am J Respir 
Crit Care Med. 2005;171:340-347. 
11. 
Myhren H, Ekeberg O, Stokland O. Health-related quality of life and return to work after critical 
illness in general intensive care unit patients: a 1-year follow-up study. Crit Care Med. 2010;38:1554-
1561. 
12. 
Unroe M, Kahn JM, Carson SS, Govert JA, Martinu T, Sathy SJ, Clay AS, Chia J, Gray A, 
Tulsky JA, Cox CE. One-year trajectories of care and resource utilization for recipients of prolonged 
mechanical ventilation: a cohort study. Ann Intern Med. 2010;153:167-175. 
13. 
Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, 
Wang PS. The epidemiology of major depressive disorder: results from the National Comorbidity 
Survey Replication (NCS-R). JAMA. 2003;289:3095-3105. 
14. 
Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. Prevalence, severity, and 
comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen 
Psychiatry. 2005;62:617-627. 
15. 
Stein MB, Walker JR, Hazen AL, Forde DR. Full and partial posttraumatic stress disorder: 
findings from a community survey. Am J Psychiatry. 1997;154:1114-1119. 
16. 
Adhikari NK, McAndrews MP, Tansey CM, Matte A, Pinto R, Cheung AM, Diaz-Granados N, 
Barr A, Herridge MS. Self-reported symptoms of depression and memory dysfunction in survivors of 
ARDS. Chest. 2009;135:678-687. 
17. 
Cuthbertson BH, Hull A, Strachan M, Scott J. Post-traumatic stress disorder after critical illness 
requiring general intensive care. Intensive Care Med. 2004;30:450-455. 

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
20
18. 
Davydow DS, Desai SV, Needham DM, Bienvenu OJ. Psychiatric morbidity in survivors of the 
acute respiratory distress syndrome: a systematic review. Psychosom Med. 2008;70:512-519. 
19. 
Davydow DS, Gifford JM, Desai SV, Bienvenu OJ, Needham DM. Depression in general 
intensive care unit survivors: a systematic review. Intensive Care Med. 2009;35:796-809. 
20. 
Davydow DS, Gifford JM, Desai SV, Needham DM, Bienvenu OJ. Posttraumatic stress disorder 
in general intensive care unit survivors: a systematic review. Gen Hosp Psychiatry. 2008;30:421-434. 
21. 
Griffiths J, Fortune G, Barber V, Young JD. The prevalence of post traumatic stress disorder in 
survivors of ICU treatment: a systematic review. Intensive Care Med. 2007;33:1506-1518. 
22. 
Jackson JC, Girard TD, Gordon SM, Thompson JL, Shintani AK, Thomason JW, Pun BT, 
Canonico AE, Dunn JG, Bernard GR, Dittus RS, Ely EW. Long-term cognitive and psychological 
outcomes in the awakening and breathing controlled trial. Am J Respir Crit Care Med. 2010;182:183-
191. 
23. 
Jones C, Griffiths RD, Humphris G, Skirrow PM. Memory, delusions, and the development of 
acute posttraumatic stress disorder-related symptoms after intensive care. Crit Care Med. 2001;29:573-
580. 
24. 
Myhren H, Ekeberg O, Toien K, Karlsson S, Stokland O. Posttraumatic stress, anxiety and 
depression symptoms in patients during the first year post intensive care unit discharge. Crit Care. 
2010;14:R14. 
25. 
Weinert CR, Gross CR, Kangas JR, Bury CL, Marinelli WA. Health-related quality of life after 
acute lung injury. Am J Respir Crit Care Med. 1997;156:1120-1128. 
26. 
Hough CL, Curtis JR. Long-term sequelae of critical illness: memories and health-related quality 
of life. Crit Care. 2005;9:145-146. 
27. 
Needham D. Personal communication.2011. 
28. 
Schelling G, Stoll C, Haller M, Briegel J, Manert W, Hummel T, Lenhart A, Heyduck M, Polasek 
J, Meier M, Preuss U, Bullinger M, Schuffel W, Peter K. Health-related quality of life and posttraumatic 
stress disorder in survivors of the acute respiratory distress syndrome. Crit Care Med. 1998;26:651-
659. 
29. 
Cheung AM, Tansey CM, Tomlinson G, Diaz-Granados N, Matte A, Barr A, Mehta S, Mazer CD, 
Guest CB, Stewart TE, Al-Saidi F, Cooper AB, Cook D, Slutsky AS, Herridge MS. Two-year outcomes, 
health care use, and costs of survivors of acute respiratory distress syndrome. Am J Respir Crit Care 
Med. 2006;174:538-544. 
30. 
Kapfhammer HP, Rothenhausler HB, Krauseneck T, Stoll C, Schelling G. Posttraumatic stress 
disorder and health-related quality of life in long-term survivors of acute respiratory distress syndrome. 
Am J Psychiatry. 2004;161:45-52. 
31. 
Ringdal M, Plos K, Ortenwall P, Bergbom I. Memories and health-related quality of life after 
intensive care: a follow-up study. Crit Care Med. 2010;38:38-44. 
32. 
Pechlaner C, Megarbane B, Fleischhacker WW. Psychiatric disorders and the ICU: gaps and 
opportunities. Intensive Care Med. 2008;34:2136-2138. 
33. 
Needham DM, Feldman DR, Kho ME. The functional costs of ICU survivorship. Collaborating to 
improve post-ICU disability. Am J Respir Crit Care Med. 2011;183:962-964. 
34. 
Ludwig DS, Kabat-Zinn J. Mindfulness in medicine. JAMA. 2008;300:1350-1352. 
35. 
Parrott WG. Beyond hedonism: motives for inhibiting good moods and for maintaing bad moods. 
In: Wegner DM, Pennebaker JM, eds. Handbook of Mental Control. Eaglewood Cliffs, NJ: Prentice-Hall; 
1993:279-305. 
36. 
Chambers RH, Lo BCY, Allen NA. The impact of intensive mindfulness training on attentional 
control, cognitive style, and affect. Cognitve Therapy and Research. 2008;32:303-322. 
37. 
Garland E, Gaylord S, Park J. The role of mindfulness in positive reappraisal. Explore. 
2009;5:37-44. 
38. 
Coan JA, Allen JJ. Frontal EEG asymmetry as a moderator and mediator of emotion. Biol 
Psychol. 2004;67:7-49. 
39. 
Ochsner KN, Gross JJ. The neural architecture of emotion regulation. In: Gross JJ, ed. 
Handbook of emotion regulation. New York, NY: The Guilford Press; 2007. 

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
21
40. 
Carver CS, Pozo C, Harris SD, Noriega V, Scheier MF, Robinson DS, Ketcham AS, Moffat FL, 
Jr., Clark KC. How coping mediates the effect of optimism on distress: a study of women with early 
stage breast cancer. J Pers Soc Psychol. 1993;65:375-390. 
41. 
Folkman S, Moskowitz JT. Positive affect and the other side of coping. Am Psychol. 
2000;55:647-654. 
42. 
Snyder CR. Coping : the psychology of what works. New York: Oxford University Press; 1999. 
43. 
Kabat-Zinn J. An outpatient program in behavioral medicine for chronic pain patients based on 
the practice of mindfulness meditation: theoretical considerations and preliminary results. Gen Hosp 
Psychiatry. 1982;4:33-47. 
44. 
Vollestad J, Nielsen MB, Nielson GH. Mindfulness- and acceptance-based interventions for 
anxiety disorders: a systematic review and meta-analysis. Br J Clin Psych. 2011;doi: 10.1111/j.2044-
8260.2011.02024.x:1-22. 
45. 
Vollestad J, Sivertsen B, Nielsen GH. Mindfulness-based stress reduction for patients with 
anxiety disorders: evaluation in a randomized controlled trial. Behav Res Ther. 2011;49:281-288. 
46. 
Fjorback LO, Arendt M, Ornbol E, Fink P, Walach H. Mindfulness-based stress reduction and 
mindfulness-based cognitive therapy: a systematic review of randomized controlled trials. Acta 
Psychiatr Scand. 2011;124:102-119. 
47. 
Hofmann SG, Sawyer AT, Witt AA, Oh D. The effect of mindfulness-based therapy on anxiety 
and depression: A meta-analytic review. J Consult Clin Psychol. 2010;78:169-183. 
48. 
Cox CE, Porter LS, Hough CL, Kahn JM, Carson SS, Curtis JR, White DB, Keefe FJ. 
Telephone-based coping skills training for acute lung injury survivors & their informal caregivers. 
Intensive Care Med. 2011;37, Supplement 1:S135. 
49. 
Greeson JM. Mindfulness Research Update: 2008. Complement Health Pract Rev. 2009;14:10-
18. 
50. 
Jones C, Backman C, Capuzzo M, Flaatten H, Rylander C, Griffiths RD. Precipitants of post-
traumatic stress disorder following intensive care: a hypothesis generating study of diversity in care. 
Intensive Care Med. 2007;33:978-985. 
51. 
Cox CE, Martinu T, Sathy SJ, Clay AS, Chia J, Gray AL, Olsen MK, Govert JA, Carson SS, 
Tulsky JA. Expectations and outcomes of prolonged mechanical ventilation. Crit Care Med. 
2009;37:2888-2894. 
52. 
Blessed G, Tomlinson BE, Roth M. The association between quantitative measures of dementia 
and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry. 1968;114:797-811. 
53. 
Pfeiffer E. A short portable mental status questionnaire for the assessment of organic brain 
deficit in elderly patients. J Am Geriatr Soc. 1975;23:433-441. 
54. 
Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, Truman B, Speroff T, Gautam S, 
Margolin R, Hart RP, Dittus R. Delirium in mechanically ventilated patients: validity and reliability of the 
confusion assessment method for the intensive care unit (CAM-ICU). JAMA. 2001;286:2703-2710. 
55. 
Porter LS, Keefe FJ, Garst J, Baucom DH, McBride CM, McKee DC, Sutton L, Carson K, 
Knowles V, Rumble M, Scipio C. Caregiver-assisted coping skills training for lung cancer: results of a 
randomized clinical trial. J Pain Symptom Manage. 2010. 
56. 
Porter LS, Keefe FJ, Garst J, Baucom DH, McBride CM, McKee DC, Sutton L, Carson K, 
Knowles V, Rumble M, Scipio C. Caregiver-assisted coping skills training for early stage lung cancer: 
results of a randomized clinical trial. J Pain and Symptom Manage. 2011:1-13. 
57. 
Waltz J, Addis ME, Koerner K, Jacobson NS. Testing the integrity of a psychotherapy protocol: 
assessment of adherence and competence. J Consult Clin Psychol. 1993;61:620-630. 
58. 
Borkovec TD, Nau CD. Credibility of analogue therapy rationales. J Behav Exp Psych. 
1972:257-260. 
59. 
Greeson J, Brantley J. Mindfulness and anxiety disorders: developing a wise relationship with 
the inner experience of fear. In: Didonna F, ed. Clinical Handbook of Mindfulness. New York, NY: 
Springer; 2009:171-188. 

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
22
60. 
Blumenthal JA, Babyak MA, Keefe FJ, Davis RD, Lacaille RA, Carney RM, Freedland KE, 
Trulock E, Palmer SM. Telephone-based coping skills training for patients awaiting lung transplantation. 
J Consult Clin Psychol. 2006;74:535-544. 
61. 
Porter LS, Keefe FJ, Garst J, McBride CM, Baucom D. Self-efficacy for managing pain, 
symptoms, and function in patients with lung cancer and their informal caregivers: associations with 
symptoms and distress. Pain. 2008;137:306-315. 
62. 
Keefe FJ, Caldwell DS, Baucom D, Salley A, Robinson E, Timmons K, Beaupre P, Weisberg J, 
Helms M. Spouse-assisted coping skills training in the management of knee pain in osteoarthritis: long-
term followup results. Arthritis Care Res. 1999;12:101-111. 
63. 
Keefe FJ, Caldwell DS, Baucom D, Salley A, Robinson E, Timmons K, Beaupre P, Weisberg J, 
Helms M. Spouse-assisted coping skills training in the management of osteoarthritic knee pain. Arthritis 
Care Res. 1996;9:279-291. 
64. 
Greeson JM, Webber DM, Smoski MJ, Brantley JG, Ekblad AG, Suarez EC, Wolever RQ. 
Changes in spirituality partly explain health-related quality of life outcomes after Mindfulness-Based 
Stress Reduction. J Behav Med. 2011;34:508-518. 
65. 
Katz S, Ford AB, Moskowitz RW, Jackson BA, Jaffe MW. Studies of illness in the aged. The 
index of ADL: a standardized measure of biological and physiological function. JAMA. 1963;185:914-
919. 
66. 
Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities 
of daily living. Gerontologist. 1969;9:179-186. 
67. 
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic 
comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373-383. 
68. 
Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease 
classification system. Crit Care Med. 1985;13:818-829. 
69. 
Dowdy DW, Eid MP, Sedrakyan A, Mendez-Tellez PA, Pronovost PJ, Herridge MS, Needham 
DM. Quality of life in adult survivors of critical illness: A systematic review of the literature. Intensive 
Care Med. 2005;31:611-620. 
70. 
Porter LS, Keefe FJ, Baucom DH, Hurwitz H, Moser B, Patterson E, Kim HJ. Partner-assisted 
emotional disclosure for patients with gastrointestinal cancer: results from a randomized controlled trial. 
Cancer. 2009;115:4326-4338. 
71. 
Nguyen TD, Attkisson CC, Stegner BL. Assessment of patient satisfaction: development and 
refinement of a service evaluation questionnaire. Eval Program Plann. 1983;6:299-313. 
72. 
Pochard F, Azoulay E, Chevret S, Lemaire F, Hubert P, Canoui P, Grassin M, Zittoun R, le Gall 
JR, Dhainaut JF, Schlemmer B. Symptoms of anxiety and depression in family members of intensive 
care unit patients: ethical hypothesis regarding decision making capacity. Crit Care Med. 2001;29:1893-
1897. 
73. 
Herrmann C. International experiences with the Hospital Anxiety and Depression Scale--a 
review of validation data and clinical results. J Psychosom Res. 1997;42:17-41. 
74. 
Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 
1983;67:361-370. 
75. 
Lautrette A, Darmon M, Megarbane B, Joly LM, Chevret S, Adrie C, Barnoud D, Bleichner G, 
Bruel C, Choukroun G, Curtis JR, Fieux F, Galliot R, Garrouste-Orgeas M, Georges H, Goldgran-
Toledano D, Jourdain M, Loubert G, Reignier J, Saidi F, Souweine B, Vincent F, Barnes NK, Pochard 
F, Schlemmer B, Azoulay E. A communication strategy and brochure for relatives of patients dying in 
the ICU. N Engl J Med. 2007;356:469-478. 
76. 
Nickel M, Leiberich P, Nickel C, Tritt K, Mitterlehner F, Rother W, Loew T. The occurrence of 
posttraumatic stress disorder in patients following intensive care treatment: a cross-sectional study in a 
random sample. J Intensive Care Med. 2004;19:285-290. 
77. 
Schelling G, Briegel J, Roozendaal B, Stoll C, Rothenhausler HB, Kapfhammer HP. The effect 
of stress doses of hydrocortisone during septic shock on posttraumatic stress disorder in survivors. Biol 
Psychiatry. 2001;50:978-985. 

 
Duke IRB Version 10.14.16 / Protocol 00064250 
 
23
78. 
Stoll C, Kapfhammer HP, Rothenhausler HB, Haller M, Briegel J, Schmidt M, Krauseneck T, 
Durst K, Schelling G. Sensitivity and specificity of a screening test to document traumatic experiences 
and to diagnose post-traumatic stress disorder in ARDS patients after intensive care treatment. 
Intensive Care Med. 1999;25:697-704. 
79. 
Twigg E, Humphris G, Jones C, Bramwell R, Griffiths RD. Use of a screening questionnaire for 
post-traumatic stress disorder (PTSD) on a sample of UK ICU patients. Acta Anaesthesiol Scand. 
2008;52:202-208. 
80. 
Baer RA, Smith GT, Hopkins J, Krietemeyer J, Toney L. Using self-report assessment methods 
to explore facets of mindfulness. Assessment. 2006;13:27-45. 
81. 
Gratz KL, Roemer L. Multidimensional assessment of emotion refulation and dysregulation: 
development, factor structure, and initial validation of the difficulties in emotion regulation scale. J 
Psychopathology Behav Assess. 2004;26:41-54. 
82. 
Gross JJ, John OP. Individual differences in two emotion regulation processes: implications for 
affect, relationships, and well-being. J Pers Soc Psychol. 2003;85:348-362. 
83. 
Kraemer HC, Wilson GT, Fairburn CG, Agras WS. Mediators and moderators of treatment 
effects in randomized clinical trials. Arch Gen Psychiatry. 2002;59:877-883. 
84. 
Glaser BG, Strauss AL. The discovery of grounded theory : strategies for qualitative research. 
New York, N.Y.: Aldine de Gruyter; 1967. 
85. 
Corbin JM, Strauss AL, Strauss AL. Basics of qualitative research : techniques and procedures 
for developing grounded theory. 3rd ed. Los Angeles: SAGE Publications; 2008. 
86. 
Cox CE, Carson SS, Hanson LC, Hough CL, Kahn JM, Lewis CL, White DB. Improving 
decision-making for surrogates of prolonged mechanical ventilation patients: a pilot study. American 
Thoracic Society International Conference. Vol Denver2011. 
87. 
Cox CE, Lewis CL, Hanson LC, Hough CL, Kahn JM, White DB, Song MK, Tulsky JA, Carson 
SS. Development and pilot testing of a decision aid for surrogates of patients with prolonged 
mechanical ventilation. Crit Care Med. 2012. 
88. 
Cox CE, Porter LS, Hough CL, White DB, Kahn JM, Carson SS, Tulsky JA, Keefe FJ. 
Development and preliminary evaluation of a telephone-based coping skills training intervention for 
survivors of acute lung injury and their informal caregivers. Intensive Care Med. 2012;38:1289-1297.