Optimizing a Self-directed Mobile Mindfulness Intervention for Improving Cardiorespiratory Failure Survivors' Psychological Distress
Phase: NA
Conditions: Cardiorespiratory Failure
Sponsor: Duke University

 
 
Protocol version: 7.0  
Dated: 22DEC2020 
Page 1 of 32 
 
Protocol 
Optimizing a Mobile Mindfulness Intervention for ICU Survivors (LIFT2)  
NCT04038567  
Version: December 22, 2020 
 

 
 
Protocol version: 7.0  
Dated: 22DEC2020 
Page 2 of 32 
 
 
Study Title: Optimizing a self-directed mobile mindfulness 
intervention for improving cardiorespiratory failure survivors' 
psychological distress 
 
Short Title: LIFT2 
 
Study Design: A multi-phase optimization strategy (MOST) 
Framework 
 
Study Site(s): 
Duke University Hospital 
2301 Erwin Road 
Durham, NC 27710 
 
Duke Regional Hospital 
3643 N Roxboro St 
Durham, NC 27704 
Oregon Health Science University 
840 S Gaines St 
Portland, OR 97239 
 
University of Colorado-Denver 
1201 Larimer St 
Denver, CO 80204 
University of Washington-
Seattle/Harborview Medical 
Center 
25 9th Ave 
Seattle, WA 98104 
 
Principal Investigator 
Christopher E. Cox, MD, MPH 
Duke University 
Division of Pulmonary Allergy & Critical Care 
Box 102043 
Durham, NC 27710 
Phone: 919-681-7232 
Email: christopher.cox@duke.edu 
 
Co-Investigator(s) 
Catherine (Terri) Hough, MD 
Oregon Health Science University 
 
Marc Moss, MD 
University of Colorado-Denver 
 
Ruth Engelberg, MD 
University of Washington-Seattle/Harborview Medical 
Center
 
 
Collaborator(s) 
Tina Gremore, PhD 
Duke University 
 
Laura Porter, PhD 
Duke University 
Jeffrey Greeson, PhD 
Rowan University 
 
 
 
Maren Olsen, Ph.D. 
Duke University 
 
John Gallis 
Duke University
 
IRB #: Pro00100252 
 
Clinicaltrials.gov identifier: NCT04038567 

  
 
 
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Table of Contents 
 
Table of Contents 
2 
Abbreviations and Definitions 
5 
Clinical Protocol Synopsis 
7 
1. 
Title 
7 
2. 
Background 
7 
3. 
Study Design 
8 
4. 
Study Objectives, Hypotheses, and Outcomes 
9 
5. 
Study Population 
10 
Eligibility Criteria: 
10 
Inclusion Criteria (at the time of hospital admission) 
10 
Exclusion Criteria (at the time of hospital admission) 
11 
Inclusion Criteria (at the time of hospital discharge; at home) 
10 
Exclusion Criteria (at the time of hospital discharge; at home) 
11 
6. 
Study Procedures 
12 
Screening, Recruitment and Consent 
12 
Study Visits 
14 
Compensation 
15 
7. 
Enrollment sites 
15 
8. 
Statistical Design, Analyses Plan, and Sample Size and Power 
16 
Statistical Design and Analyses Plan 
16 
Sample Size and Power 
16 
9. 
Subject Participation Duration 
18 
10. 
Study Duration 
18 
11. 
Risk-Benefit Assessment 
18 
Potential risks 
18 
Adequacy of protection against risks: 
18 
Protections against risk 
18 
Suicidality Response Plan 
19 
Patient Death While in Study 
21 
Patient Withdraw While in Study 
21 
Vulnerable Populations 
21 
Adverse events (AEs), serious adverse events, (SAEs) and unanticipated problems (UPs). 
21 
Period and Frequency for Event Assessment and Follow-Up 
21 

  
 
 
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Characteristics of an Adverse or Serious Adverse Event 
22 
Relationship to Study Intervention 
22 
Expectedness 
22 
Severity 
22 
Reporting Procedures 
22 
Protocol Deviations and Other Unanticipated Problem Reporting 
23 
Privacy 
23 
12. 
Data management 
24 
13. 
Data & Safety Monitoring Plan 
25 
Plans for Assurance of Compliance regarding Adverse Event Reporting. 
25 
Plans for Assuring Data Accuracy and Protocol Compliance. 
25 
Data Safety Monitoring Board (DSMB). 
25 
Quality Assurance and Confidentiality 
26 
Confidentiality 
26 
14. 
Privacy, Data Storage & Confidentiality – see Research Data Security Plan. 
26 
15. 
IRB of Record 
26 
Appendix 1: Schedule of Events 
30 
Appendix 2: Study Workflow 
310 
Appendix 3: Randomization Arms 
31 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

  
 
 
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Abbreviations and Definitions 
• 
Activities of Daily Living (ADLs) 
o An assessment designed to assess one’s ability to complete basic self-care skills.  
• 
Adverse Event (AE) 
o Any untoward medical occurrence associated with or observed in the context of a study 
procedure. For this study and patient population, an AE will be considered any suicidal 
ideation. No other events will be considered AEs as this patient population is ill and it is 
expected that other untoward medical occurrences will occur.  
• 
Clinical Trial Management System (CTMS) 
o For this study, a CTMS known as OnCore will be utilized to manage the study’s 
administrative responsibilities and subject level documentation.  
• 
Duke Regional Hospital (DRH) 
o Study site in which eligible patients will be enrolled.  
• 
Duke University Hospital (DUH) 
o Study site in which eligible patients will be enrolled. 
• 
Oregon Health & Science University (OHSU) 
o Study site in which eligible patients will be enrolled.  
• 
University of Colorado-Denver (COL) 
o Study site in which eligible patients will be enrolled.  
• 
University of Washington-Seattle (UW) 
o Study site in which eligible patients will be enrolled.  
• 
Electronic Data Capture (EDC) 
o For this study, the EDC will be supported and secured by Duke University via REDCap 
in which relevant study data, such as screening, enrollment, and clinical variables both 
from research participants’ medical records and app will be documented.  
• 
Electronic Health Record (EHR) 
o Used interchangeably with EMR; the EHR is the patient-specific medical record located 
in the secure MaestroCare (aka: EPIC) or other electronic medical record platform.  
• 
Electronic Medical Record (EMR) 
o Used interchangeably with EHR; the EMR is the patient-specific medical record located 
in the secure MaestroCare (aka: EPIC) or other electronic medical record platform. 
• 
Electronic Patient Reported Outcomes (ePRO) 
o ePRO can be used to describe study source, such as the patient-completed 
questionnaires (e.g.,PHQ-9, GAD-7, PTSS, PHQ-10), or can refer to the system that 
houses patient-derived data. For this study, ePRO may refer to the patient-
questionnaires for psychological distress OR it may refer to the system, which houses 
the patient-derived data, which is the mMT app known as “LIFT.”  
• 
General Anxiety Disorder (GAD-7) 
o An assessment designed to assess anxiety and depression symptoms 
• 
Institutional Review Board (IRB) 
o Ethical and regulatory committee who provides approval and oversight of clinical trial at 
study site.  
• 
Instrumental Activities of Daily Living (IADL) 
o An assessment designed to assess one’s ability to complete complex self-care skills.  
• 
Intensive Care Unit (ICU) 
o Defined as any medical, surgical, trauma, neurological, cardiac, or cardio-thoracic unit in 
which a patient is receiving cardiac or respiratory support for survival means.  
• 
Mindful Attention Awareness Scale (MAAS) 

  
 
 
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o 15-item scale designed to assess a core characteristic of mindfulness. 
• 
Mobile Mindfulness Training app (mMT, also known as ‘LIFT’) 
o A native mobile app that uses a self-contained program and is subject to the device 
operating system. The mMT created for this study known as “LIFT”, was developed, and 
is maintained by Pattern Health (212 W Main St Suite 213, Durham, NC 27701). 
• 
Patient Health Questionnaire-9 and Patient Health Questionnaire-10 (PHQ-9 and PHQ-10) 
o Physical and emotional symptoms assessment, including suicidal ideations with intent to 
act.  
• 
Post-Traumatic Stress Scale survey (PTSS) 
o Scale designed to assess Post Traumatic Stress Disorder (PTSD) symptoms 
• 
Protocol Deviation (PD) 
o An inadvertent event or event this is out of the control of the study team and/or the 
subject that occurs outside of the study protocol design and/or procedures.  
• 
Protocol Violation 
o An act of intentionality that is committed by the study team and/or the subject that occurs 
outside of the study protocol design and/or procedures.  
• 
Serious Adverse Event (SAE) 
o Defined as an adverse event that is both serious and expected in nature; the event may 
have a reasonable possibility that it is related to a study. SAEs for this study are defined 
as a suicide attempt, a hospitalization, or death. 
• 
Suicide Ideation (SI) 
o The idea of committing self-harm and/or the intent to act on the idea of committing self-
harm.  
• 
Unanticipated Problem (UP) 
o Any other event, not meeting the definition of PD, UP, AE or SAE that, in the opinion of 
the principal investigator, merits documentation as it occurred outside the expected 
design of the study and/or study procedures. These events, like PDs, UPs, AEs, or 
SAEs, may be reported to the IRB and/or the study sponsor, as applicable.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

  
 
 
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Clinical Protocol Synopsis 
 
 
1. Title  
Optimizing a self-directed mobile mindfulness intervention for improving cardiorespiratory failure survivors' 
psychological distress (a.k.a., ‘LIFT2’) 
 
2. Background & Rationale 
As survival has improved for the 2 million people with cardiorespiratory failure managed annually in the US 
intensive care units (ICUs), it has become apparent that these patients suffer from severe and persistent 
post-discharge symptoms of psychological distress including depression, anxiety, and post-traumatic stress 
disorder (PTSD).  However, few targeted interventions exist that are relevant to patients' experiences and 
that accommodate their many physical, and social barriers to personalized care. To fill this gap, we 
developed an innovative app-based mobile mindfulness training program that promotes automated care 
delivery and self-management of symptom-related distress.  
 
Previously, a pilot randomized clinical trial (RCT) called LIFT (R34 AT00819) in which this project is built 
on, compared mobile mindfulness to both a standard telephone mindfulness program and an ICU 
education control among survivors of cardiorespiratory failure. LIFT demonstrated that mobile mindfulness 
was feasibly delivered, acceptable, usable, and had a greater clinical impact on psychological distress than 
either comparator. This trial also highlighted opportunities to improve the intervention's impact related to its 
targeted population, content delivery, and system technology. 
 
Therefore, we propose a 5-year, multi-site project titled “LIFT2” that is conceptualized as the Optimization 
Phase of a multiphase optimization strategy (MOST) framework. The project will be conducted at Duke 
University, Oregon Health & Sciences University (OHSU), and University of Colorado (COL). Mobile 
mindfulness will be optimized via four specific aims (Figure 1): 
 
• 
Aim 1:  Optimize the usability of the mMT intervention's key technological features.  
• 
Aim 2:  Using a factorial experimental trial, identify mMT intervention components that contribute 
most meaningfully to feasibility, usability, and impact on psychological distress. 
• 
Aim 3:  Explore barriers and facilitators to mMT implementation and dissemination.  
• 
Aim 4:  Using lessons learned from Aims 2 & 3, operationalize the final optimized mMT system. 
 
 
 
 
 
 
 
 
 
 
 
 

  
 
 
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3. Study Design 
This is a 5-year, multi-site project that is conceptualized as the Optimization Phase of a multiphase 
optimization strategy (MOST) framework. As mentioned in section 2, this project consists of four distinct 
aims:  
 
Aim 1:  Optimize the usability of the mMT intervention's key technological features 
Informed by lessons learned from the R34, we will add and refine the mMT app user interface features to 
improve interaction and engagement of participants, and thus dose, adherence, and retention. Participants 
eligible for Aim 1 will be an uncontrolled sample of 10-15 individuals which may consist of patients, 
caregivers of patients, and other volunteers. Each participant will be asked to sign and date informed 
consent and then complete one 30-60 minute visit in which they will complete usability testing. Usability 
testing involves the following: 1) registration of user in app, 2) completion of baseline survey, and 3) 
randomization via completion of T1 survey. Additionally, participants will be asked to test certain scenarios, 
such as chat room functionality, suicide ideation, and moving from task to task on a given study day. Tasks 
completed by the participants during this study visit are intended to achieve the following goals: 1) enable a 
"recommender system" which will permit sophisticated logic-driven personalized app-user interaction, 
which includes guidance to specific app content based on response to the weekly ePRO survey; 2) update 
the mMT user interface to ensure that the app is in compliance with the Americans with Disability Act 
(ADA) standards; and 3) automate post-discharge distress screening. During the study visit, participants 
and delegated study team members will be asked to provide their feedback, input and note any errors (e.g., 
typographical or technical) that occur during the usability visit. At the completion of the study visit, 
participants will be asked to complete a standardized usability survey to assess their overall opinion and 
feedback related to the app and its accessibility and usability. All feedback, input, and errors, as well as 
survey results, will be provided to the study PI, study manager, and Pattern Health for review. The study PI, 
study manager and Pattern Health will implement necessary changes and updates to ensure excellent 
usability (mean Systems Usability Scale > 85) and ensure 100% success rate of post-randomization 
distress and randomization. The completion of Aim 1 will ready the mMT for Aim 2.  
 
Aim 2:  Using a factorial experimental trial, identify mMT intervention components that contribute 
most meaningfully to feasibility, usability, and impact on psychological distress. 
Aim 2, which is the focal point of this project is to determine which mMT factors optimize MOST constraints 
(i.e., outcomes). The primary objective of Aim 2's is to determine which mMT factors optimize MOST 
constraints (i.e., outcomes).  The main effects of each factor will be tested as well as the conditional effects 
of factor combinations on a priori-defined operational targets (feasibility, acceptability, usability) as well as 
improvements in psychological distress symptoms (depression, anxiety, PTSD) at 3 months.   
 
To do so, we will conduct a 3-factorial experimental trial with a 3 month follow-up in which 240 patients, 
meeting eligibility criteria as outlined in section 5, will be consented, enrolled and randomized to 1 of 8 
combination of mMT factors:  
• 
Group 1: Team Introduction, High Dose and Team Help 
• 
Group 2: App Introduction, High Dose and Team Help 
• 
Group 3: Team Introduction, High Dose and App Help 
• 
Group 4: App Introduction, High Dose and App Help 
• 
Group 5: Team Introduction, Regular Dose and Team Help 
• 
Group 6: App Introduction, Regular Dose and Team Help 
• 
Group 7: Team Introduction, Regular Dose and App Help 
• 
Group 8: App Introduction, Regular Dose and App Help 
 
Each randomized group will allocate a combination of 3 factors to each participant:  

  
 
 
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1. Dose (standard [4 weeks] versus high [the standard 4-week program with the addition of extra 
audio meditation sessions and the use of a voluntary, anonymous, study interventionist-proctored 
in-app support function]), 
2. Stepped approach to intervening for worsening or persistent symptoms (therapist vs. app), and 
3. Method of initiating mMT (therapist call versus app).  
 
Prior to randomization, each patient will be asked to review, sign, and date the informed consent; register 
the Pattern Health LIFT app using their own personal device (i.e., cell phone, laptop), and complete a 
baseline survey. The participant will then be asked to complete a randomization survey (T1) that will 
ultimately assess psychological distress for enrollment into the trial. If the patient is eligible for 
randomization, he/she will be assigned to 1 of 8 intervention combinations and asked to complete the 
following over a period of 3 months:  
• 
4 weeks of daily mMT 
• 
Four (4) weekly check-ins to assess distress and anxiety 
• 
1 month (T2) survey 
• 
3 month (T3) follow-up survey 
 
The weekly check-ins and surveys completed at baseline, hospital discharge (T1), 1 (T2) and 3 (T3) 
months will be used to assess changes in distress and anxiety levels. Each survey includes a combination 
of the following assessments: PHQ-9, PHQ-10, GAD-7, PTSS, MAAS, as well as medical services, 
sociodemographic, financial and social support, quality of life questions, and ADL/IADL assessments.  
 
Adherence to the mMT plan will be assessed throughout the patient’s participant. Depending on 
randomization group, patients may receive therapist intervention introducing them to the concept of 
mindfulness and then receive frequent follow-ups from the study therapist to provide training, education 
and support. The mMT app provides a built-in safety mechanism that detects increased levels of distress 
and may alert the study team (i.e., site PI, study manager, and study therapist) of the increased distress 
levels. In doing so, a delegated member of the study team will follow-up with the patient and assess their 
safety and overall well-being, as outlined in section 12.  
 
Aim 3:  Explore barriers and facilitators to mMT implementation and dissemination.  
Using qualitative analysis of semi-structured interviews in up to 40 participants enrolled from Aim 2's trial, 
we will explore perceived barriers to accessing, using, and applying mMT effectively. Purposive sampling 
informed by symptom trajectories and mMT app use pattern analytics will allow inclusion of responders and 
non-responders, as well as infrequent and frequent app users. Patients who participate in this Aim will be 
asked a series of questions to determine app access, use and content during a single study visit lasting 30-
60 minutes.  
 
Aim 4:  Using lessons learned from Aims 2 & 3, operationalize the final optimized mMT system. 
Consistent with NIH guidelines on mixed methods research1 we will integrate quantitative (Aim 2) and 
qualitative (Aim 3) data from Years 2-4 to finalize the mMT app build that optimizes MOST outcomes of 
feasibility, usability, and clinical impact.  After updating app software to current standards, we will ensure 
mMT reaches 'excellent' usability (mean SUS score ≥85) among a diverse purposive sample of up to 25 
individuals—and is ready for off-the-shelf use in a next-step RCT. 
 
4. Study Objectives, Hypotheses, and Outcomes 
The overall objective is to optimize the mobile mindfulness training intervention (i.e., mMT) by identifying 
which components contribute most meaningfully to feasibility, usability, and clinical impact on symptoms of 
psychological distress assessed over a 3-month follow up period.  

  
 
 
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We hypothesize that the optimal mMT use case will include the following factor components: high dose, 
app-based approach to responders, and app-initiated study introduction. 
 
Feasibility will be evaluated by comparing observed to targeted benchmark rates of consent (70%), 
completion of weekly surveys (75%), and 3-month retention (75%).  We will use server analytics to quantify 
participants’ app adherence (e.g., frequency of daily use, average session duration).  More specifically, 
adherence will be monitored closely using the app-integrated data system and automated web analytics.  
In particular, mobile web app analytics will allow real-time monitoring of each participant's frequency of app 
use, average duration of app use per session, completion of weekly components, and other behaviors.  
Weekly reports generated by the study data system will allow the study team to make proactive 
interventions (e.g., reminder emails and calls) if needed to either get the participant back on schedule or to 
address a logistical need.  Acceptability will be measured with the Client Satisfaction Questionnaire (CSQ; 
target mean ≥10) and by analysis of Aim 3’s semi-structured interviews.  Usability will be assessed with the 
Systems Usability Scale (SUS; target mean ≥85). 
 
Secondary outcomes will be assessed to ascertain information on the multidimensional effects of the 
intervention.   
• 
Anxiety symptoms: Generalized Anxiety Disorder 7-item scale (GAD-7). 
• 
Post-traumatic distress disorder (PTSD) symptoms: Post-Traumatic Stress Syndrome Inventory 
(PTSS). 
• 
Quality of life: The EuroQOL-5D (EQ-5D) and its 100-unit visual analog scale (VAS).  
• 
Physical symptoms: Patient Health Questionnaire 10-item symptoms scale (PHQ-10). 
 
5. Study Population 
LIFT2 is centered around Aim 2 of the project. As such, the primary characteristics of the targeted study 
population will be those individuals who have experienced an ICU admission and meet eligibility criteria as 
outlined below. For Aim 1, we intend to enroll 2-5 patients who meet eligibility criteria for the clinical trial, 2-
5 caregivers of patients admitted at the enrolling ICU, and up to 5-10 other individuals, if necessary, to 
ensure an adequate sampling of usability. These “other individuals” could include members of our patient 
and caregiver stakeholder cohort whom we have called on in past projects to give feedback on apps and 
websites. For Aim 3, patients previously enrolled in Aim 2 will be purposively sampled and will include both 
responders and non-responders, as well as frequent versus non-frequent app users. For Aim 4, the 
targeted population will be new patients, not previously enrolled in Aim 2 or 3, that meet the criteria outlined 
below or healthy volunteers.   
 
Eligibility Criteria: Patients who are deemed eligible for study  participation will ultimately be those 
individuals who experience high levels of psychological distress (i.e., PHQ-9 > 5).  
 
Specifically, patients enrolled into this pilot, RCT will meet the following criteria:  
 
Inclusion Criteria (at the time of hospital admission) 
1. Adult patient >18 years of age.  
2. Acute cardiorespiratory failure, defined as > 1 of the following *: 
a. Mechanical ventilation via endotracheal tube for > 12 hours 
b. 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) 
c. High flow nasal cannula or face mask for > 4 hours in a 24-hour period 
And/or 

  
 
 
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Acute cardiac/circulatory failure, defined as > 1 of the following: 
d. Use of vasopressors for shock of any etiology for > 1 hour 
e. Use of inotropes for shock of any etiology for > 1 hour 
f. Use of aortic balloon pump for cardiogenic shock for > 1 hour 
 
*In an ICU setting, NOT including the operating room or emergency department 
 
3. Managed in an adult medical, cardiac, trauma, surgical, or neurological ICU for ≥24 hours during 
the time inclusion criterion #2 is met. 
4. Cognitive status intact, defined as: 
a. No history of significant cognitive impairment (e.g., dementia) per electronic medical records 
b. Absence of current, significant cognitive impairment (> 3 errors on the Callahan cognitive 
status screen) 
c. Decisional capacity present 
5. Absence of severe and/or persistent serious mental illness that could disrupt study participation, as 
noted in the electronic medical record (EMR) or affirmed by clinical staff at the time of screening 
and approach for consent.  
Defined as any of the following: 
a. Treatment for severe or unstable mental illness (e.g., psychosis, bipolar affective disorder, 
schizoaffective disorder, schizoid personality disorder, schizophrenia [as per medical 
record], hospitalization for any psychiatric disorder) within the 6 months preceding the 
current hospital admission 
b. No endorsement of active suicidality at time of admission or informed consent 
c. No active substance abuse at a severity that impairs ability to participate 
6.  English fluency 
 
Exclusion Criteria (at the time of hospital admission) 
1. Hospitalized within the preceding 3 months with life-threatening illness or injury.  
a. Patients may be enrolled into the study if they had a hospitalization within the preceding 3 
months that is determined to be non-serious. Non-serious admissions are defined as those 
admissions that are non-life threatening and/or potentially impacting patient’s well-being 
long-term or likely to precipitate additional future admission. Examples of non-serious, non-
life threatening hospitalizations could be, but may not be limited to, admission for a 
bronchoscopy, admission for deep vein thrombosis, or admission to ED resulting in 
overnight stay for cardiac work-up.  
2. Admitted from a location other than home (e.g., nursing home, long-term acute care facility, 
inpatient rehabilitation facility).  
3. Anticipated or actual discharge to a location other than an independent in home setting (e.g., 
nursing home, long-term acute care facility, inpatient rehabilitation facility, home hospice). 
4. Complex medical care expected soon after discharge (e.g., planned surgeries, transplantation 
evaluation, extensive travel needs for hemodialysis, disruptive chemotherapy/radiation regimen) 
5. Unable to complete study procedures as determined by staff. 
6. Lack of reliable smartphone with cellular data plan or Wi-Fi. 
 
Exclusion Criteria (at the time of arrival home) 
1. Low baseline psychological distress symptoms, defined as the absence of the following at T1: 
a. PHQ-9 score < 5 
2. Failure to randomize within 2 months (60 days) post-discharge.   
  

  
 
 
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7. Study Procedures   
Screening, Recruitment and Consent 
For aim 1, eligible patients will be recruited from a pool of diverse individuals willing to participate in the 
study. Prior to approaching individuals for aim 1 consent, the study team will obtain the applicable 
research introduction from the clinical team and ensure approach is acceptable by the eligible 
individual. If the individual is willing to speak with the study team, the study team will approach the 
individual, provide an overview of the study and review the informed consent with the individual. Should 
the individual opt to participate in Aim 1, they will sign and date the informed consent, and then 
complete a singular 30-60 minute study visit in which they will complete usability testing. Usability 
testing involves the following: 1) registration of user in app, 2) completion of baseline survey, and 3) 
randomization via completion of T1 survey. Additionally, participants will be asked to test certain 
scenarios, such as chat room functionality, suicide ideation, and moving from task to task on a given 
study day. Tasks completed by the participants during this study visit are intended to achieve the 
following goals: 1) enable a "recommender system" which will permit sophisticated logic-driven 
personalized app-user interaction, which includes guidance to specific app content based on response 
to the weekly ePRO survey; 2) update the mMT user interface to ensure that the app is in compliance 
with the Americans with Disability Act (ADA) standards; and 3) automate post-discharge distress 
screening. During the study visit, participants and delegated study team members will be asked to 
provide their feedback, input and note any errors (e.g., typographical or technical) that occur during the 
usability visit. At the completion of the study visit, participants will be asked to complete a standardized 
usability survey to assess their overall opinion and feedback related to the app and its accessibility and 
usability. All feedback, input, and errors, as well as survey results, will be provided to the study PI, 
study manager, and Pattern Health for review. The study PI, study manager and Pattern Health will 
implement necessary changes and updates to ensure excellent usability (mean Systems Usability 
Scale > 85). 
 
For aim 2, screening for eligible patients will occur daily via MaestroCare by delegated study team 
members. The study team will maintain a robust screening log of all individuals reviewed and will 
document whether or not each individual was eligible for the study. Additionally, they will document if 
each individual was approached for consent and the outcome of consent. It will be essential, for the 
future projects that it is understood why individuals are or are not eligible for approach and/or 
subsequent consent, therefore the screening log will track reason for ineligibility and reason for non-
consent.  
 
For those individuals who are eligible to consent, the study team will recruit the individual in-person or 
remotely. Patients for aim 2 will be approached, ideally at the time of their hospital admission, just prior 
to their discharge to an in home setting, if possible. Should the study team be unable to successfully 
present the study to the patient during the hospitalization, the study team will contact them once they 
have been discharged home. Patients can be approached earlier in their admission, if well enough, or 
within a week of returning to their home for participation in the study. All patients will be informed at the 
time of recruitment that research is voluntary and they do not have to participate if they do not want to. 
Furthermore, they will be informed that participation will not affect their care in any way. If a patient 
chooses to not participate, he/she will be documented as a ‘declined’ patient and the date of decline, as 
well as reason for decline (if available) will be documented. Should a patient be approached while in the 
hospital and opt to consent, they will be asked to complete the app registration and baseline survey, 
and then a study team member will contact them, once home, to remind them to login to the app to 
complete T1 for randomization. Should a patient be approached post-hospital discharge, he/she will be 
asked to complete app registration, baseline survey and T1 on the same day for study enrollment and 
randomization purposes. As with screening, the study team will be required to maintain a robust 

  
 
 
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enrollment log that documents the patient’s consent status, version of informed consent with reference 
date of IRB approval, and then ultimate study status with associated visit milestones.  
 
It is important to note that for this study, there are several statuses an individual can have. They are 
listed below:  
• 
Screened (in screening or screened): defined as any individual who’s EMR or other general 
data that has been reviewed against protocol for eligibility purposes. Individuals who are 
assigned this status must be noted on the screening log.  
• 
Consented: defined as any individual who is approached for consent and voluntarily chooses to 
consent to the study, the procedures, risks and benefits with the understanding that they may 
withdraw at any time. A signed/dated informed consent must be on record to account for this 
individual. Patients, enrolled in the aim 2, who reach this status will be required to complete T1 
at the time of hospital discharge within 1 week but no more than 1 month from returning to 
home. Individuals who are assigned this status must be noted on the enrollment log. 
• 
Declined: defined as any individual who was approached for consent, but opted to NOT 
consent and therefore to NOT participate in the study. Individuals who are assigned this status 
must be noted on the screening log. 
• 
Randomized: defined as any patient who was consented to the study, is discharged from 
hospital to home, completes T1 survey, and continues to meet all eligibility criteria (see Eligibility 
Criteria, section 5). Patients who reach this status will be required to interact with the app on a 
daily basis for 1 month and then complete T2 and T3. Patients who are assigned this status 
must be maintained on the enrollment log.  
• 
Screen Failed: defined as any patient who 
o consents to the study and completes the initial study visit, but prior to discharge is 
determined by the clinical care team to require support and services of a long-term acute 
care facility (LTAC), skilled nursing facility (SNF), acute rehab facility (ARF), or other in-
patient rehabilitation center, the patient’s study participation will be terminated and the 
study team will replace the patient.  
OR 
o consents to the study, completes the initial study visit, is discharged to an independent 
home setting, but is subsequently re-admitted to the hospital prior to randomization (i.e., 
completion of survey T1), the patient’s study participation will be terminated.  
 
Note: the study team may re-approach the individual in this scenario, re-consent, 
and repeat all study visit procedures.  
• 
Post Randomization Failure: defined as any patient who consents to the study, completes the 
initial study visit, is discharged to an independent home setting, completes survey T1 and is 
randomized to the study, and anytime during the first month study participation is re-admitted to 
the hospital. Should this occur, the patient may be terminated if the hospitalization lasts > 7 
days and/or the patient is unwilling or unable to continue study procedures.  
o Note: If the participant is terminated, he/she will be included in the analyses up to the 
point that they were excluded.  
• 
Withdraw by PI or Self: defined as any individual who voluntarily consents to participate in the 
study, but is then withdrawn from the study.  
o The PI may withdraw a participate at any time without their consent if the PI deems it is 
in their best interest to no longer participate OR the patient demonstrates continuous 
lack of compliance with study protocol and study procedures.  
o The patient may withdraw themselves at any time; the study team will be asked to 
document the reason for withdraw for study records.  

  
 
 
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Patients who reach this status will have no additional follow-ups or study requirements. Patients 
who are assigned this status must be maintained on the enrollment log. A reason for withdraw 
should be recorded in the study records.  
• 
Lost to Follow-Up (LTF): defined as any individual who voluntarily consents to participate in 
the study but after non-compliance and at least 3 documented, attempted contacts appropriately 
spaced 1-5 days apart, the individual will be considered LTF.  
o For aim 2 only:  
 
Patients who reach this status will have no additional follow-ups or study 
requirements. Patients who are assigned this status must be maintained on the 
enrollment log. 
 
A patient who returns the study team’s contacts within 1 week of last attempted 
contact may resume study participation.  
• 
Completed: defined as any individual who both consented and randomized to the study and 
completed T1-T3 (aim 2 only) or any individual who completed assigned study visit (aims 1, 3 
and 4). Individuals who reach this status have no additional follow-up or study requirements. 
Individuals who are assigned this status must be maintained on the enrollment log. 
 
Study Visits 
 
For aims 1, 3 and 4 each participant will be asked to complete a singular study visit that will last 
approximately 30-60 minutes. During this study visit, post consent, the individual may be asked to do 
the following: 
• 
Find and install the Pattern Health app (aim 1 and aim 4) 
• 
Register to the LIFT2 study (aim 1 and aim 4) 
• 
Complete baseline survey (aim 1 and aim 4) 
• 
Randomize to 1 of 3 groups or screen fail purposely (aim 1 and aim 4) 
• 
Audio-recording for interview using qualitative analyses (aim 3) 
• 
Provide feedback on app content and usability (aim 1, 3, and 4) 
 
For aim 2, each consented patient will be asked to complete up to four individual study visits. 
• 
Baseline: this visit is to occur post-consent (same day, ideally) at the time of hospital admission 
just prior to discharge. However, this visit may occur at the time of hospital discharge within 7 
days of returning to home. At this visit, the following will occur: 
o App Registration 
o Baseline Survey Completion 
• 
T1 (Day 0) (+30 days): this visit is to occur at the time of hospital discharge to home, ideally 
within the first week (7 days) of returning to home; however, it can occur up to 1 month (30 
days) from the time of hospital discharge to home. At this visit, the patient will complete the T1 
survey via the app, which includes the PHQ-9, PTSS, PHQ-10, and MAAS surveys. Score 
dependent, the patient will be randomized to 1 of 8 intervention combinations. If the patient’s 
psychological distress score is too low; he/she will receive an automated alert via the app 
describing they are not eligible and their study participation is complete.  
• 
T2 (Day 30) (+60 days): this visit is to occur post 1 month randomization for those patients who 
remain eligible to participate in the study. PHQ-9, PTSS, PHQ-10, and MAAS surveys will be 
administered again. If the patient’s survey scores indicate high levels of distress, as defined by 
a triggered SI alert or increased distress score from T1, a delegated study team member will 
contact the patient for safety precautions. 
• 
T3 (Day 90) (+30 days): this visit is to occur post 3 months randomization for those patients 
who remain eligible to participate in the study. PHQ-9, PTSS, PHQ-10, and MAAS surveys will 

  
 
 
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be administered again. If the patient’s survey scores indicate high levels of distress, as defined 
by a triggered SI alert or increased distress score from T1, a delegated study team member will 
contact the patient for safety precautions. At the completion of this survey and assuming no 
additional follow-up is required due to high levels of distress, the patient’s participation in the 
study is complete.  
 
Additionally, each patient who is randomized will be asked to complete: 
• 
Weekly Check-In: for those patients who are eligible for randomization, a weekly check-in will 
be completed via the app. This weekly check in will be available beginning day 4 of the week 
until day 7 of the week.  
 
Compensation 
Compensation for study participation will be provided. Participates in aim 1 will receive $20 for study 
participation and completion of the singular study visit. Participants in aim 2 may receive up to a total of 
$60 for study completion, $20 for each survey (T1, T2 and T3) to be paid after the participant has 
completed the trial. Participants in aims 3 and 4 will receive $20 for each completed study visit.  
 
8. Enrollment Sites 
This study will be conducted at 3 health systems: Duke University in Durham, NC (includes Duke Medical 
Center [Clinical Coordinating Center] and Duke Regional Community Hospital); Oregon Health & Sciences 
University (OHSU) in Portland, Oregon; and the University of Colorado-Denver in Denver, Colorado.  
 
Each of the 3 sites is expected to randomize approximately 80 patients over 36 months for Aim 2’s factorial 
trial for a total of 240 patients across the network, with the aim of 192 patients completing assessments 
and mindfulness through T2 (1 month study participation post-randomization).  
 
Sites, PIs, Targets, and Available Patients* 
Site 
PI 
Available  
Randomization Target 
Duke University & 
Duke Regional Hospital 
Christopher Cox 
826 (23/mo)  
80 
Univ. of Washington† 
Catherine Hough 
590 (16/mo) 
10 
OHSU† 
Catherine Hough 
630 (18/mo) 
70 
University of Colorado 
Marc Moss 
630 (18/mo) 
80 
*Total for 36 months of screening 
†  University of Washington was an enrolling site from the inception of the study project to 07/31/2020, when Dr. 
Hough moved to Oregon Health & Sciences University (OHSU).  OHSU is anticipated to begin screening and 
enrollment in October, 2020. 
 

  
 
 
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9. Statistical Design, Analyses Plan, and Sample Size and Power 
Statistical Design and Analyses Plan 
Analyses for Aim 1:  After inclusion of Table 7's features in the mMT system, we will employ a user 
testing analytic approach guided by 
Usability.gov guidelines and our past 
studies. ,3,4,26 We will conduct in-
person interviews among enrolled 
individuals identified by stratified 
purposive sampling with characteristics 
that could impact usability (~25% ≥age 
65, ~25% <high school education, 
~25% with low technology confidence). 
27,29 Participants will complete: (1) a 
‘think aloud’ protocol in which 
coordinators record patient comments 
as they use mMT; 30 (2) Systems 
Usability Scale (SUS); 28 (3) all system 
tasks, and (4) a semi-structured interview.  In a parallel approach, staff will test the screening and 
randomization system using a series of 100 simulations, aiming for 100% success in correct and equal 
randomization to Aim 2's factor conditions.  We will organize any identified problems with Nielsen 
usability heuristics to guide subsequent revisions.31  Based on our past work, 3-5,14,15 we anticipate 2-5 
cycles of 2-5 participants each will be sufficient to reach a target of 'excellent' usability (i.e., mean SUS 
score ≥85) 26,32 as well as to ensure confidence in the screening system's feasibility.  
 
Analyses for the trial (Aim 2): The main goal of our intention-to-treat analyses is to estimate main 
effects and interactions of combined experimental conditions to be able to determine which LIFT use 
case is best.  That is, would LIFT impact be greater by accepting the “high” level of a factor instead of 
the simpler default “low” level of the factor.  Our overall analytic approach will be guided by frameworks 
presented by Collins and Collins & Kugler. 33,34 To understand general patterns in the data, we will first 
calculate raw means, medians, and measures of variability at each time point for the primary and 
secondary outcomes.  These will be grouped by the main effect of each factor (e.g. standard versus 
high-dose), collapsed over the other factors.  We will also examine these descriptive statistics by 
groups as defined by the two-way and three-way interactions of the factors. 
 
A constrained longitudinal general linear model with unstructured covariance to take into account 
repeated measures on individuals over time will be used to estimate changes in the primary and 
secondary outcomes from T1 to T2 and from T1 to T3. 35  Often for trial analyses, intervention group 
and time are dummy coded indicator variables (i.e., levels 0 and 1) in model specification.  Instead, 
given our factorial design, the main effects and interactions will be represented with effect coding (i.e., 
levels -1 and 1).  In the scenario of balanced sample sizes across the factors, effect coding results in a 
model with independent coefficients.  
 

  
 
 
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Using the estimated model coefficients, we will first determine if any of the main effects indicate 
improvement of at least 2 points on the PHQ-9 at T2.  Candidate components not reaching these 
benchmarks will be set to the “low” level of the component.  We will then carefully examine the 
interactions, starting with those that include the largest main effect factor.  Estimated means and plots 
will be used to explore the impact of the interactions and whether they are “synergistic” or 
“antagonistic.”  The final “screened in” set of combinations (i.e., main effects and synergistic 
interactions indicating improvement of at least 2 points on the PHQ-9) will provide evidence of possible 
optimized intervention components.   
 
As a next step in the decision-making process, we will examine the secondary outcomes and the 
sustained intervention effects at T3, potentially reconsidering decisions made in the previous step.  As 
an additional part of this step of the decision-making process, we will examine feasibility and adherence 
metrics for all components, as well as open-ended study participant study staff feedback.   
 
Analyses for Aim 3:  We will use modified grounded theory methods 24,26 to inductively and iteratively 
develop frameworks to describe patients’ experiences with the mMT app. 37-39 This approach will avoid 
making incorrect assumptions and also maximize the chance of effectively refining the intervention. To 
develop the preliminary coding frameworks, we will independently perform line by line open coding of 
the first 5 interviews (1) to identify themes and concepts relating to perceived barriers and facilitators to 
mMT use and application of content, (2) to assign codes to each, and (3) to group similar concepts into 
categories.  Categories will be developed further by comparison between transcripts (axial coding).  In 
a series of meetings, all investigators will review these preliminary coding frameworks and arrive at 
consensus on the coding framework. 24,25 Thereafter, coordinators will code each new interview using 
ATLAS.ti, an approach that provides the opportunity to modify the interview guide iteratively and, 
through constant comparison, to collect data that will further enhance an understanding of barriers and 
facilitators.  We will ensure validity by (1) maintaining an audit trial that captures the research design, 
decisions made about data collection, and analyses;40 (2) minimizing bias by using a multidisciplinary 
team to develop the coding framework; and (b) using member checking to present results to 15 study 
patients for confirmation or modification. 22,41 
 
Analyses for Aim 4:  After reviewing transcribed interviews, investigators will organize any usability 
concerns with Nielsen heuristics and then perform revisions. 31  We anticipate 1-2 cycles of iterative 
revisions involving 5-10 participants per cycle to reach a target of 'excellent' usability (defined by a 
Systems Usability Scale [SUS] mean score ≥85). 26,32  Aim 4 will conclude with a full updating of all 
mMT software and hardware components. 
 
Sample Size and Power 
As the project centers around Aim 2 (RCT), we calculated power for the test of a main effect or factor 
interaction in a constrained longitudinal general linear model with unstructured covariance matrix via 
simulation.  Based on LIFT pilot data, the baseline standard deviation of PHQ-9 was assumed to be 5.3 
and the covariance between time points ranged from 3.9 to 11.5. We examined a range of sample sizes 
at T2, from 120 to 200 participants.  500 simulated datasets were simulated under the alternative 
model, with power calculated as the proportion of times the estimated coefficient was found to be 
statistically significant at p<0.05.  Results indicated that with 192 total patients at T2 (24 per 
experimental condition; 240 total at T1 [randomization] assuming 20% dropout by T2), we will have 
>90% power to detect a factor main effect or factor interaction effect of 2 units on the PHQ-9 scale.   

  
 
 
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By targeting 240 randomized participants, we will have ample power to detect factor main and 
interaction effects even with deviations from our assumptions (e.g., higher dropout rate, misspecified 
covariance matrix, etc.). For Aims 3 and 4, these samples should be adequate for theme saturation.  
 
10. 
Subject Participation Duration 
Participating subjects in aims 1, 3 and 4 will be asked to participate in a singular study visit lasting 30-60 
minutes. Participating subjects in aim 2 will be asked to participate for up to a total of 3 months. 
Participating in the factorial trial (aim 2) will require 1 month of daily, active participation in which the patient 
is practicing mMT daily and completing weekly check-ins. At the end of the 1 month (post T1 completion), 
the patient will be asked to complete T2 survey. Once the patient has completed the T2 survey, he/she is 
finished with active study participation for an additional 2 months at which time they will be asked to 
complete T3 survey.  
 
11. 
Study Duration 
We estimate that from the time the factorial experiment trial opens to enrollment during Month 9 of Year 1, 
it will require approximately 41 months to complete data collection (approximately 36 months for cumulative 
enrollment with 4-5 months to complete all long-term follow up; this time does not include start up and 
analyses) and 4-6 months to perform all final data analyses for all Aims. 
 
12. 
Risk-Benefit Assessment 
Potential risks 
It is possible that participating patients could experience a breach of confidentiality should their records be 
accessed unlawfully by an outside party or general, inadvertent error.  Also, it is possible that participants 
may experience mild anxiety when answering survey questions, though we have not observed this in 
similar interventions such as LIFT or CSTEP.  However, we believe that involvement in this study will 
present no significant physical, psychological, financial, legal, or other risks.  Additionally, there is always 
the potential of a breach of data security, as is noted in any IRB-approved consent form.  
 
Adequacy of protection against risks:  
Recruitment and informed consent procedures.   
First, the Duke Institutional Review Board (IRB) will review and approve the study protocol before study 
initiation. Informed consent (e-consent or written) will be required from all participants, including content 
experts.  Second, we will use a standardized screening and enrollment protocol that respects participant 
privacy and rights.  The study team will only approach those patients that are deemed appropriate for the 
study, which will be determined by EMR review, other data, and/or conversations with the clinical team and/or 
PI. The approach of patients may be aided by a short IRB-approved recruitment video. The study team will 
then ask the patient to read and sign the study consent form at the time of enrollment.  Potential subjects will 
be given as much time as they need to consider study participation.  For Aim 2, we will take great care to 
present the treatment group assignment possibilities (“like drawing a number out of a hat”) tactfully and with 
clearly stated equipoise, as we have done successfully in past clinical trials.  A copy of the consent form will be 
given to participant and the original maintained in a secure location at.   
the study site 
 
Protections against risk   
General oversight   
There are several ongoing mechanisms for monitoring the occurrence of adverse events.  The PI or delegated 
study team member will perform day-to-day monitoring of the study activities. Careful monitoring of all persons 
entering the study will minimize attrition and will ensure the clinical safety of these patients.  A telephone 

  
 
 
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number for the study team facilitates this monitoring and an email address (liftstudy@duke.edu) provided to 
participants upon entry into the study to report concerns related to study participation.  
 
Plans to prevent coercion of patients and to ensure voluntary participation 
We will strive to create an environment free of any coercive practices for patients. We will stress that study 
involvement is voluntary and that choosing to participate or not participate will not affect their care in anyway. 
In addition, we will utilize the standardized 2-minute informational video, which has been used successfully in 
past trials describe treatment groups and ensure a similar approach across sites.   
 
Specific longitudinal participant oversight plans for severe psychological distress (including suicidal ideation) 
Given the difficult situations faced by patients, we recognize that there is a slight risk that some participants 
may become distressed completing questionnaires or viewing study materials, as mentioned above.   
 
We will take the following measures to prevent any negative reactions as well as effectively manage any 
serious distress that occurs:  
 
(1)  All of the in-person and telephone-based data collection sessions will be conducted by study team 
members who are sensitive to the issues that arise.  
 
(2) Study team members will emphasize to participants that any interviews or other study interactions are 
participant-controlled.  Thus, participants will be instructed that they are in control over what they share and 
generally how long they discuss any topic that is addressed.   
 
(3)  Participants will be told that they can discontinue an interview or telephone session at any time and that 
they are free to reschedule an interview or treatment session at any time within the week.   
 
(4)  Overall, we are very sensitive to the common and pervasive nature of psychological distress among ICU 
survivors and are experienced in discussing these issues with them.  There is also a potential risk for 
identifying underlying mental health issues through the mMT sessions, telephone calls, and survey responses.  
For issues such as passive suicidal ideation or symptoms of depression, anxiety, or PTSD, an informational 
sheet will be provided with contact numbers for additional mental health services.  Additionally, at the 
beginning of the program, all subjects will be informed that the training program may uncover unresolved and 
distressing thoughts or feelings; and a list of resources will be provided at that time. 
 
Suicidality Response Plan  
 
First, delegated study team members may have in-person or telephone interactions that concern them. 
Second, the study app system will automatically detect any endorsement of active suicidal intent in a 2-step 
process that is contingent on the PHQ-9’s item # 9 which evaluates suicidal thoughts and the C-SSRS item #4 
which evaluates intent by asking “have you had these thoughts and had some intention of acting on them? (as 
shown below:  
 
PHQ-9 item 9 
response 
Suicidal intent 
item response 
Action by app system 
Action by team 
0 
n/a 
n/a 
n/a 
1, 2, or 3 (i.e., ≠ 0)   
NO 
n/a 
n/a 
1, 2, or 3 (i.e., ≠ 0)   
YES 
Alert to study manager, 
therapist, and PIs 
Immediately contact participant 
 
Should a patient indicate to a study team member or via the app, thoughts of suicidality or ideation of 
suicidality, the Suicidality Response Plan could be activated. 

  
 
 
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If the participant is deemed to be at high risk based on direct interaction plus the C-SSRS item response, the 
delegated study team member will administer the C-SSRS to assess the participant to determine if they 
endorse active suicidal ideation.  The trained staff will also determine if the participant is currently being treated 
by a mental health professional.  
 
If the patient is deemed not to be actively suicidal, they will be given a list of local mental health resources as 
follows: 
 
• 
Duke University:  Call Emergency Psychiatry at (919) 681-4410 or (919) 681-1316, available 24 hours a 
day, 7 days a week. 
• 
Oregon Health & Sciences University:  National Suicide Prevention Lifeline - 1-800-273-TALK (8255) 
• 
University of Colorado:  Call Psychiatric Emergency services at (303)-602-7221, a 24-hour resource 
line  
All sites, may use, 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. 
 
If the participant is considered actively suicidal then at least one of the following plans will be followed 
depending on the location of the participant for each of the following situations: 
 
• 
Situation 1 
o If the participant is with one of the study personnel, the study personnel will notify the site PI one 
of the other PIs immediately. 
o The study personnel will either physically walk the subject to the emergency department, or call 
a Psychiatric Emergency services number relevant to the site as described above.  
 
• 
Situation 2 
o If the participant is on the telephone: 
 
The study personnel will notify the site PI one of the other PIs immediately 
 
The study personnel will stay on the telephone with the subject participant. 
 
The study personnel will immediately contact 911 to initiate an on-site rescue if such 
action is clinically indicated. 
o The study personnel will stay on the telephone with the subject until EMS services have 
contacted the participant. 
 
If the participant is determined to be actively suicidal and require immediate medical therapy, they will be 
withdrawn from the study. 
 
As described above, all concerns about participant safety will be discussed immediately with the PI - including 
concerning severe distress that does not involve suicidality.   
 
For these situations, once an “alert situation” is known, the PI will refer the participant if needed (based on a 
PI-led phone call) to local psychological resources. The study team will also make urgent and emergency 
referrals as needed based on information learned.  
 
To date based on some studies that have included over 400 participants, we have found that <5% of 
participants will require a call from the PI during some point in the study period.  Of those, none has required 
referral to acute psychiatric care after a detailed interview from the PI.  After a disposition / solution has been 
made, both the resolution (and follow up) will be documented in the ‘contact log’ section of the data system for 
reporting to the DSMB.   

  
 
 
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Patient Death While in Study 
Finally, we recognize that we are working with a critically ill population that is at risk for death during follow up 
due to their underlying illness.  Before T2 and T3 data collection, the study team will review the EMR to look for 
records of death, halting all study procedures if death has occurred and noting the date. On phoning any 
participant, the study team will initiate a conversation to tactfully ascertain the patient’s vital status should a 
family member answer first.  If the patient has died, the study team will provide brief support and their 
condolences.   
 
Withdraw While in Study 
If an individual states that they wish to drop out, the study team will respect that as well. A follow-up question 
may be asked to ascertain the reason for withdraw; however, this is for documentation purposes only. 
Additionally, the study and/or site PI retain the right with withdraw the participant from the study if they feel that 
participation is no longer in the participant’s best interest and/or the participant is non-compliant despite 
numerous attempts to contact by the study team.  
 
Vulnerable Populations 
This project will not enroll individuals from vulnerable populations (e.g., imprisoned persons, minors). 
 
Adverse events (AEs), serious adverse events, (SAEs) and unanticipated problems (UPs).   
It is recognized that there is a slight risk that some participants may become distressed when completing self-
report measures or participating in interviews.  When necessary, participants who experience psychological 
distress related to completing questionnaires will be referred for appropriate psychiatric or psychological care.  
All participants will have access to the PI’s contact information 24 hours a day (shown in the consent form).  If 
a telephone interview is required, a trained study team member who has been trained to be sensitive to the 
nature of these issues will conduct it.   
 
It is anticipated, in this study, for AEs to be extremely rare as it is a behavioral study. However, it is possible 
that participants could become distressed in a hospital setting or post-discharge due to increased illness and/or 
limitations. As such, participants could exhibit signs of and/or experience suicidal ideations or be admitted for 
mental health symptoms. Therefore, for this study, only increased levels of distress related to completing the 
questionnaires or completing the coping skills practice and/or suicidal ideations will be considered AEs.  
 
Like, AEs, it is not anticipated that SAEs will occur. However, for this study, an SAE would be defined as a 
suicide attempt, a hospitalization (post hospitalization that initiated the patient’s eligibility for study 
participation), or death. All serious adverse events will be reported within the standard timelines required to the 
IRB, study sponsor, and/or DSMB, as appropriate and when applicable.  
 
Given the nature of this study, it is anticipated that most enrolled patients will not complete their study 
visits within the assigned protocol window. Additionally, it is expected that visits and/or mMTpractices 
will be missed. As such, these will not be considered protocol deviations. Should other protocol 
deviations or unanticipated problems occur, they will be discussed with the PI, documented, and 
reported to the IRB, study sponsor, and/or DSMB, as appropriate and when applicable.  
 
Period and Frequency for Event Assessment and Follow-Up 
Protocol deviations and other unanticipated problems, as well as AEs and SAEs, will be recorded in the 
data collection system throughout the study and reported, as appropriate, to the IRB, study sponsor, 
and/or DSMB, when applicable.  
 

  
 
 
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The study team will record all reportable events with start dates occurring any time after informed 
consent is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study 
participation.  At each study visit, the study team will inquire by way of verbal or written request and/or 
EMR review, of the occurrence of AE/SAEs since the last visit.  Events will be followed for outcome 
information until resolution or stabilization. 
 
Characteristics of an Adverse or Serious Adverse Event 
 
Relationship to Study Intervention 
To assess relationship of an event to study intervention, the following guidelines are used: 
1. Related (Possible, Probable, Definite) 
a. The event is known to occur with the study intervention. 
b. There is a temporal relationship between the intervention and event onset. 
c. The event abates when the intervention is discontinued. 
d. The event reappears upon a re-challenge with the intervention. 
2. Not Related (Unlikely, Not Related) 
a. There is no temporal relationship between the intervention and event onset. 
b. An alternate etiology has been established. 
 
Expectedness  
The Study PI will be responsible for determining whether an event is expected or unexpected.  An 
event will be considered unexpected if the nature, severity, or frequency of the event is not consistent 
with the risk information previously described for the intervention.   
 
Severity 
The following scale will be used to grade adverse events: 
1. Mild: no intervention required; no impact on activities of daily living (ADL) 
2. Moderate: minimal, local, or non-invasive intervention indicated; moderate impact on ADL 
3. Severe: significant symptoms requiring invasive intervention; subject seeks medical attention, 
needs major assistance with ADL 
 
Reporting Procedures 
 
Adverse and Serious Adverse Events 
For symptoms that are either great in total burden (i.e., total score is high), a delegated study team 
member (e.g., therapist) will call the participant to check in.  For specific symptoms such as the suicidal 
ideation, a delegated study team member will also call the participant and assess the severity of the 
situation, triaging them as appropriate to psychiatric support.   
 
For other matters, the study team will maintain frequent telephone contact with most participants, and 
can refer those with concerning symptoms.   
 
All deaths will be reported to NIH Program Officer and to the DSMB Chair within 72 hours of study’s 
knowledge of death. For each patient who dies, a brief report containing the following variables will be 
provided: 
• 
Age 
• 
Principal diagnosis 
• 
Number of comorbidities 
• 
Admission APACHE II score 

  
 
 
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• 
Days since enrollment 
• 
Brief description of circumstances surrounding death including expected or unexpected. 
 
Serious (fatal or life-threatening) SAEs that are unanticipated and that are related to the intervention will 
be reported to the NHLBI Program Officer and to the DSMB Chair within 7 days of study staff’s 
knowledge of the SAE.   
 
The summary of all other SAEs will be reported to NIH Program Officer and to the DSMB quarterly, 
unless otherwise requested by the DSMB.   
 
Protocol Deviations and Other Unanticipated Problem Reporting  
Incidents or events that meet the reporting criteria, as outlined by the Duke IRB, will be reported to the 
Duke IRB as needed.  
 
The following will be included, at a minimum:  
• 
A detailed description of the event, incident, experience, or outcome;  
• 
A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the unanticipated problem. 
 
Reporting for Multi-Center Trials 
The study site must immediately report to the coordinating center and study manager any serious 
adverse event, whether or not considered study related, including those listed in the protocol and must 
include an assessment of whether there is a reasonable possibility that the study caused the event 
within 48 hours of PI awareness of the event.  
 
They must also report any unanticipated problems within the same timeframe.  The study site must also 
report any protocol deviations or violations to the coordinating center and study manager within 7 days 
of study team awareness. 
 
Privacy 
The study team will closely safeguard participant privacy regarding protected health and personal information.  
A study ID number will be generated at the time of consent and will be maintained in a secure file (e.g., linker 
file) which will contain the patient name and medical record number.  Further, names, birthdates, telephone 
numbers, addresses, and medical record numbers will be stored securely as described in the RDSP and only 
accessible by delegated study team members. The RedCAP system will store all data on a secure Duke 
University server with a sophisticated dual backup system.  Study participants cannot view data via the ePRO 
system, supported by Pattern Health or the electronic data capture (EDC) system, supported by Duke 
University RedCap. Patients will only have access to the ePRO system and will access the one-way view 
ePRO system via secure, PHI-free email or text links sent from the app.  
 
Digital security 
The study digital infrastructure consists of a mobile (i.e., native) app with a built-in electronic patient reported 
outcomes (ePRO) function and an electronic data capture (EDC) system, RedCAP digital study database. 
• 
mMT app:  The mMT app will be a native app. The programming service providers, Pattern Health, 
endeavor to build technological solutions that preserve the privacy, confidentiality, and security of 
protected health information that may be part of health records or research datasets. Protected Health 
Information (PHI) is handled according to appropriate Health Insurance Portability and Accountability 
Act of 1996 (HIPAA) Privacy and Security Regulations.  All staff who work with sensitive data are 
required to complete appropriate HIPAA training with periodic updates, complete human subjects and 

  
 
 
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data privacy training, comply with site IT Security Policies, and agree to the provisions of the University 
Rules of Behavior and Sanction Policy.  All sites strive to implement reasonable security controls in its 
product builds guided by FISMA, HIPAA, and OMB Circular A-130, Appendix III. Pattern Health has 
implemented and maintains several security protocols and controls for apps as well.  Pattern Health 
has developed a formal information security program, with a named individual responsible for its overall 
execution.  Pattern Health also periodically conducts an information technology (IT) security risk 
assessment on its projects, maintains formal documented protocols for reporting security breaches, 
assesses and manages security risks associated with vendors and subcontractors, maintains employee 
on-boarding and off-boarding policies that protect study data and integrity, and ensures continuing 
employee awareness of and education on security policies, standards, and procedures.  In terms of 
development approaches to security, Pattern Health evaluates and installs security patches in a timely 
fashion, protects systems against self-propagating malware, maintains secure coding policies and 
practices, and utilizes standardized secure build processes to protect Pattern Health hardware that 
accesses customer networks, protecting confidential data against attack.  All storage of confidential 
participant data on Pattern Health hardware is strictly prohibited, and the use of off-shore service 
providers and/or data center facilities is prohibited unless approved by client.  For our study, the native 
app application and supporting backend system that Pattern Health develops will be hosted securely 
per DHTS regulations. 
• 
ePRO: This password protected, HIPAA-compliant, IRB-approved ePRO system is similar to those we 
have successfully used among hundreds of ICU survivors and family members.  Strong passwords 
randomly generated by our study group will be provided for patient participant access of the ePRO 
system.   
• 
REDCap:  The project will utilize a REDCap database system customized for our data needs and EDC.  
For data validation, a series of project-defined data checks and conditional constraints can be required 
to ensure the highest quality data collection.  All system login procedures and data submissions will be 
transported and encrypted via the Transport Layer Security (TLS) protocol to the secure central 
database at Duke University.  The study team will use login/password (reset every 6 months) 
credentialing for authentication of all study staff.  User-level permissions will be based on user roles 
and defined within the project system to limit a user’s access to only those records an individual is 
authorized to see. Duke Health Technology Solutions staff to verify that security measures are 
operational will review audit logs routinely.  The servers are scanned twice weekly for vulnerabilities 
and are currently maintained at the highest level of vendor and CERT security recommendations.  Data 
will never be shared outside the project unless authorized by the project leader and the Duke IRB.  
User authentication is based on user passwords as described earlier.  Password creation requirements 
are in place to guarantee “strong passwords” as defined by the CERT security recommendations.  The 
lead systems administrator is GIAC Security Essentials certified through May 2018. 
 
13. 
Data management 
Most data entry will be self-completed by participants using the validated ePRO system accessed via the 
mMT app. The study team will complete electronic case report forms (eCRFs) securely integrated within 
the EDC by abstracting relevant clinical data from each patient’s EMR.  RedCap will be utilized to maintain 
study screening and enrollment logs and house the eCRFs. The mMT app dashboard, developed by 
Pattern Health for administrative use only, will be accessed and used by delegated study team members to 
create scheduled reports on the trials’ conduct (e.g., study milestones) to enhance the study's quality.  
Through this dashboard, quality and consistency of data, will be monitored. The Project Manager will do 
routine data cleaning and statistical team using customized group-blinded reports that will identify missing, 
outlier, or nonsensical data at time points when remedying them is feasible. 
 

  
 
 
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14. 
Data & Safety Monitoring Plan 
Plans for Assurance of Compliance regarding Adverse Event Reporting.   
The study team will be required to document and report adverse events (including serious adverse events) to 
the Institutional Review Board (IRB), as appropriate and in line with institutional reporting criteria. In addition, 
all adverse events are reported as part of NIH Progress Reports in the non-competitive and competitive 
renewals.   
 
Plans for Assuring Data Accuracy and Protocol Compliance. 
The PI will supervise the study, including data management, data accuracy, and protocol compliance.  The 
study biostatistician and Project Manager will be the chief data managers and will adhere to established federal 
and institutional patient safety and protection guidelines.  To assure data accuracy, the Project Manager will 
review data system reports on a routine basis.  These reports will show enrollment, missing data, and other 
values that are neither study ID- nor outcome-based.  The Project Manager will process detailed reports to 
search for errors and generate basic reports for dissemination for regular staff meetings.   
 
Data Safety Monitoring Board (DSMB).  
Aim 2's factorial trial will be supervised by a single independent DSMB composed of professionals with 
significant experience in clinical trials, mind and body interventions, epidemiology, and biostatistics who are not 
directly involved in the study, its interpretation, or any study institution and have no active research relationship 
with a study team member.   
 
The main responsibilities of the DSMB will be to (a) assess for the presence of potential harms and unintended 
consequences of the mMT intervention, (b) ensure the validity and integrity of the data, and (c) make 
recommendations to the investigators and 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, establishing the review methodology and 
procedures, ensuring all conflicts of interest are disclosed (to be reviewed by NHLBI staff), reviewing the 
protocol, and codifying a written charter.  The NHLBI's Data Safety Monitoring Plan (DSMP) Template will be 
used to guide the drafting of the charter.  This document will specify procedures for protocol amendments, 
ensuring participant confidentiality and privacy, ensuring database protection, coordinating center 
responsibilities, creating adverse outcome definitions (adverse events, unanticipated problems, and serious 
adverse events), protocol for reporting and responding to adverse events while also maintaining subject 
confidentiality, justifying sample size, assessing accrual and compliance, halting and stopping rules (drafted 
with the assistance of the DSMB chair and the DSMB lead statistician), approving informed consent 
documents, and guidelines for quality control and quality assurance.  Before enrollment begins, the DSMB 
charter will be approved by both the DSMB and the NHLBI; additionally, ClinicalTrials.gov registration will be 
finalized as per the Milestone Plan shown in the Research Strategy document. 
 
The first DSMB data review will occur either after the first 60 participants have been enrolled or enrollment has 
occurred for 6 months, whichever is observed first.  Thereafter, the DSMB will review cleaned data reports 
(provided by the Project Manager 2 weeks before the DSMB meeting) every 3 months during enrollment and 
follow up, and will prepare a report with any recommendations within 2 weeks following their review.  The 
specific study metrics that the DSMB will review at each meeting include enrollment rate, dropout rate, HADS 
scores, PTSS scores, and Adverse Events.  The primary safety measures will be Adverse Events reports and 
HADS scores.   
 
Other items reviewed by the DSMB at each meeting will include: (a) data quality, completeness, and 
timeliness; (b) performance of the individual sites; (c) adequacy of compliance with goals for recruitment and 

  
 
 
Protocol version: 7.0 
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retention, including women and minorities; (d) protocol adherence; and (e) presence of factors that could 
adversely affect study outcome or compromise data confidentiality.  Study participants will be recovering from 
life-threatening illnesses managed in intensive care units, which increase the likelihood of death overtime in 
comparison to healthy individuals.  As such, any patient deaths and their cause during the follow up period will 
be recorded, discussed, and highly scrutinized.   
 
The study biostatistician will oversee any DSMB statistical requests and interpretations.  During the review 
process, formal statistical tests may be performed under DSMB supervision if requested (e.g., examining the 
differences in Adverse Event or outcome rates between factor-based groups).  Additionally, the DSMB may 
request a formal statistical assessment if a suspicious increase in HADS score is observed in any factor-based 
group.  If a specific factor group is found to have a statistically significant increase in HADS score, the DSMB 
scope of action may include recommendation for stopping the trial.  For differences in study dropout rates, 
appropriate changes to the protocol will be made by PI consensus after DSMB member input.  Any protocol 
changes, as well as any adverse events, will also be immediately reported to the relevant site IRB, the Central 
Institutional Review Board (located at Duke University), as well as to the NHLBI Program Officer. 
 
Quality Assurance and Confidentiality 
First, the electronic data entry system “forces” responses to key questionnaire items (e.g., primary outcomes 
surveys) before allowing progression through the particular interview’s template, thereby minimizing missing 
data.  For less critical items, delayed data entry is possible (though these data elements are non-essential to 
primary aims analyses). However, each time the study team logs into the secure data entry system, prompts 
appear on the welcome screen that show what data elements remain incomplete (as well as the time frame 
within which they must be entered) for all site participants.   
 
The study PI will ensure the validity of the data system by examining electronic summary case report forms 
within the EDC system to ensure adequacy and accuracy of data collection as well as transcription to the 
database itself after enrollment of the first 5 participants.  Agreement will be reviewed and discrepancies will be 
discussed.   
 
Confidentiality  
Subjects will not be identified on any study reports.  University firewalls, multiple passwords, and encryption 
programs protect the security of the electronic data entry system, which will be housed on a highly secure 
university server.  All personal computers are located in lockable offices and are accessible only by frequently 
changed passwords.  The server room is accessible only to designated University Systems Administrators.   
 
15. Privacy, Data Storage & Confidentiality – see Research Data Security Plan.  
 
16. 
IRB of Record  
Duke University Health System (DUHS) IRB will be utilized as the central IRB of record.  
 
A copy of the most recent DUHS IRB Federal Wide Assurance (FWA) statement may be found at: 
https://irb.duhs.duke.edu/about-us/federal-wide-assurance 
 
DUHS IRB current and historical rosters may be found at: https://irb.duhs.duke.edu/irb-review-
process/rosters 
 
DUHS IRB meeting dates may be found at: https://irb.duhs.duke.edu/irb-review-process/irb-meetings 
 
 

  
 
 
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17. References 
 
1. 
Creswell JW, Klassen AC, Plano Clark VL, Smith KC. Best practices for mixed methods 
research in the health sciences. 2013. https://obssr.od.nih.gov/training/mixed-methods-
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Psychological Distress After Critical Illness. NCT02701361. 2016. 
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Cox CE, Wysham NG, Kamal AH, et al. Usability Testing of an Electronic Patient-Reported 
Outcome System for Survivors of Critical Illness. Am J Crit Care. 2016;25(4):340-349. 
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Cox CE, Wysham NG, Walton B, et al. Development and usability testing of a Web-based 
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Cox CE, Jones DM, Reagan W, et al. Palliative care planner (PCplanner):  a pilot study to 
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sequential multiple assignment randomized trial (SMART): new methods for more potent 
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Collins LM, Kugler KC, Gwadz MV. Optimization of Multicomponent Behavioral and 
Biobehavioral Interventions for the Prevention and Treatment of HIV/AIDS. AIDS Behav. 
2016;20 Suppl 1:S197-214. 
10. 
Cook JW, Collins LM, Fiore MC, et al. Comparative effectiveness of motivation phase 
intervention components for use with smokers unwilling to quit: a factorial screening experiment. 
Addiction. 2016;111(1):117-128. 
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Piper ME, Fiore MC, Smith SS, et al. Identifying effective intervention components for smoking 
cessation: a factorial screening experiment. Addiction. 2016;111(1):129-141. 
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Collins LM, Dziak JJ, Kugler KC, Trail JB. Factorial experiments: efficient tools for evaluation of 
intervention components. Am J Prev Med. 2014;47(4):498-504. 
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Collins LM, Dziak JJ, Li R. Design of experiments with multiple independent variables: a 
resource management perspective on complete and reduced factorial designs. Psychol 
Methods. 2009;14(3):202-224. 
14. 
Cox CE, Hough CL, Jones DM, et al. 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. under review. 2017. 
15. 
Cox CE, Jones D, Reagan W, et al. Lift: a novel, scalable digital mindfulness app intervention 
for ICU survivors. American Thoracic Society International Conference; 2016; San Francisco, 
CA. 
16. 
Sandelowski M. Unmixing mixed-methods research. Res Nurs Health. 2014;37(1):3-8. 
17. 
Bazeley P. Integrative analysis strategies for mixed data sources. Am Behav Scientist. 
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18. 
Guetterman TC, Fetters MD, Creswell JW. Integrating Quantitative and Qualitative Results in 
Health Science Mixed Methods Research Through Joint Displays. Annals of family medicine. 
2015;13(6):554-561. 
19. 
Corbin JM, Strauss AL. Basics of qualitative research : techniques and procedures for 
developing grounded theory. Fourth edition. ed. Los Angeles: SAGE; 2015. 
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Patton MQ. Qualitative research and evaluation methods. 3rd ed. Thousand Oaks, CA: Sage 
Publications; 2002. 
21. 
Sandelowski M. Combining qualitative and quantitative sampling, data collection, and analysis 
techniques in mixed-method studies. Res Nurs Health. 2000;23(3):246-255. 
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Giacomini MK, Cook DJ. Users' guides to the medical literature: XXIII. Qualitative research in 
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Giacomini MK, Cook DJ. Users' guides to the medical literature: XXIII. Qualitative research in 
health care B. What are the results and how do they help me care for my patients? Evidence-
Based Medicine Working Group. JAMA. 2000;284(4):478-482. 
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Strauss AL, Corbin JM. Basics of qualitative research : techniques and procedures for 
developing grounded theory. 2nd ed. Thousand Oaks: Sage Publications; 1998. 
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Charmaz K. Constructing grounded theory: a practical guide through qualitative analysis. 
Thousand Oaks, CA: Sage Publications; 2006. 
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Usability.gov. Research-Based Web Design & Usability Guidelines. In:2013. 
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Greysen SR, Chin Garcia C, Sudore RL, Cenzer IS, Covinsky KE. Functional impairment and 
Internet use among older adults: implications for meaningful use of patient portals. JAMA Intern 
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McClelland AL, eds. Usability evaluation in industry. London: Taylor and Francis; 1986. 
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Andersson G. Age may moderate response to different unguided Internet-delivered 
interventions for depression. Evid Based Ment Health. 2014;17(1):29. 
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Virzi RA, Sorce JF, Herbert LB. A comparison of three usability evaluation methods: heuristic, 
think-aloud, and performance testing. Proc Hum Fact Ergon Soc. 1993;37:309-313. 
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Nielsen J. Heuristic evaluation. In: Nielsen J, Mack RL, eds. Usability Inspection Methods. New 
York: John Wiley & Sons; 1994. 
32. 
Bangor A, Kotum P, Miller J. Determing what individual SUS scores mean: adding an adjective 
rating scale. Journal of usability studies. 2009;4:114-123. 
33. 
Collins LM. Optimization of Behavioral, Biobehavioral, and Biomedical Interventions: The 
Multiphase Optimization Strategy (MOST). Stat Soc Behav Sc. 2018:1-+. 
34. 
Collins LM, Kugler KC. Optimization of Behavioral, Biobehavioral, and Biomedical Interventions: 
The Multiphase Optimization Strategy (MOST). Optimization of Behavioral, Biobehavioral, and 
Biomedical Interventions: Advanced Topics. 2018:1-+. 
35. 
Fitzmaurice GM, Laird NM, Ware JH. Applied longitudinal analysis. Hoboken, N.J.: John Wiley & 
Sons; 2012. 
36. 
Glaser BG, Strauss AL. The discovery of grounded theory : strategies for qualitative research. 
New York, N.Y.: Aldine de Gruyter; 1967. 
37. 
O'Cathain A, Thomas KJ, Drabble SJ, Rudolph A, Hewison J. What can qualitative research do 
for randomised controlled trials? A systematic mapping review. BMJ open. 2013;3(6). 
38. 
Hesse-Biber S. Weaving a multimethodology and mixed methods praxis into randomized control 
trials to enhance credibility. Qual Inq. 2012;18:876-889. 
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Bonell C, Fletcher A, Morton M, Lorenc T, Moore L. Realist randomised controlled trials: a new 
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40. 
Malterud K. Qualitative research: standards, challenges, and guidelines. Lancet. 
2001;358(9280):483-488. 
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Patton MQ. Enhancing the quality and credibility of qualitative analysis. Health Serv Res. 
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42. 
Cox CE. Improving psychological distress among critical illness survivors and their caregivers 
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Appendix 1: Schedule of Events  
 
 
Day 0 (In-Hospital, 
Baseline) 
Day 1 , T1 
(Discharge) (+30 
days) 
Week 1 
Week 2 
Week 3 
Week 4 
Day 30, T2 (+60 
days) 
 
Day 90 (+30 days), 
T3 
Screening* 
X 
 
 
 
 
 
 
Consent (a)* 
X 
 
 
 
 
 
 
App Registration* 
X 
 
 
 
 
 
 
Baseline Survey (b)* 
X 
 
 
 
 
 
 
Usability Survey* 
 
 
 
 
 
 
 
T1 Survey (c) 
 
X 
 
 
 
 
 
T2 Survey (c) 
 
 
 
 
 
X 
 
T3 Survey (c) 
 
 
 
 
 
 
X 
Weekly Check-In (d) 
 
 
X 
X 
X 
 
 
Data Entry (e) 
X 
X 
 
 
 
X 
X 
AE/SAE assessment (f) 
X 
X 
 
 
 
X 
X 
Survival Status (f) 
 
X 
 
 
 
X 
X 
End of Study (g) 
 
 
 
 
 
 
X 
 
a) 
Patients may be approached and consented during their admission, if well enough; their hospitalization (e.g., while in step-down), or within 7 days of returning to their home for 
participation in the study. 
b) 
Completion of the baseline survey includes the patient providing self-reported information such as social and demographic information and general health status.  
c) 
Surveys 1, 2 and 3 will be completed via the app by all study participants, regardless of intervention combination assignments.  
d) 
For those participants randomized to 1 of the 8 intervention combinations, they will complete a weekly check-in to ascertain overall safety of the patient and usefulness of coping 
skills practice.  
e) 
AE/SAE assessment and survival status will be completed via EMR review and/or telephone interview.  
f) 
Study completion for patients enrolled in the study is considered to occur at the completion of T3. However, participants may undergo EOS if they are withdrawn from the study by 
the PI or opt to withdraw from the study voluntarily at any time. Should withdraw of a patient occur, the reason for withdraw and date of withdraw will be documented. AE/SAEs 
and survival status will be noted, as applicable.   
*For aim 1 only.  
 
 

  
 
 
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Appendix 2: Study Workflow 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Daily Screening of EMR for 
Eligible Patients 
Ineligible 
(document 
on screening 
log) 
Note: approach may occur 
while patient is still hospitalized 
or within 1-3 days of discharge.  
Eligible  
(document on 
screening log and 
approach for 
consent) 
Consent  
(document on 
enrollment log) 
Declined 
(document 
on screening 
log) 
App Registration & 
Baseline Survey 
Completion 
Note: Complete data entry in 
RedCap and EDC, as well as 
CTMS (OnCore) 
T1 Survey Completion 
(+30 days from discharge) 
Note: T1 is completed once the 
patient is discharged from the 
hospital. Patients will be 
randomized to 1 of 8 arms or 
screen failed.  
Screen Failed 
(PHQ-9 < 5), EOS 
Randomized (1 of 8 
arms) 
4 weeks of mMT w/ 
weekly check-ins 
T2 Completion (Day 
30, + 60 days) 
T3 Completion (Day 
90, + 30 days) 
Note: 
Complete 
data entry in 
RedCap 
and EDC, 
as well as 
CTMS 
(OnCore) 

  
 
 
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Appendix 3: Randomization Arms