Operationalizing PCplanner, a Needs-focused Palliative Care for Older Adults in Intensive Care Units: a Randomized Clinical Trial
Phase: NA
Conditions: Palliative Care, Critical Illness, Aging, Care Delivery Model, Informal Caregivers, Psychological Distress
Sponsor: Duke University

 
 
Official Title:  Operationalizing PCplanner, a Needs-focused Palliative Care for 
Older Adults in Intensive Care Units: a Randomized Clinical Trial   
 
NCT:  NCT04414787 
 
IRB Document Date:  13 June 2022 
 

 
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Study Title: Operationalizing Needs-Focused Palliative Care for 
Older Adults in Intensive Care Units (ICU) 
 
Short Title: PCplanner  
 
Study Design: Randomized Controlled Trial (RCT) 
 
Version 5.1 dated 13 June 2022 
 
 
 
 
Study Site(s): 
Duke University Hospital 
2301 Erwin Road 
Durham, NC 27710 
Duke Regional Hospital 
3643 N Roxboro St 
Durham, NC 27704 
Duke Raleigh Hospital 
3400 Wake Forest Rd. 
Raleigh, NC 27609 
 
 
Principal Investigators 
Christopher E. Cox, MD, MPH 
Division of Pulmonary Allergy & Critical Care 
Box 102043 
Durham, NC 27710 
Phone: 919-681-7232 
Email: christopher.cox@duke.edu 
 
Sharron Docherty, Ph.D. 
School of Nursing 
BOX 3322 
Durham, NC 27710 
Phone: 919-668-3836 
Email: sharron.docherty@duke.edu 
 
 
Study Sponsor: National Institute of Aging (R01) 
 
IRB Number: Pro00101745 
 
 
 
 
 
 
 
 
 
 

 
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Table of Contents 
Abbreviations and Definitions ................................................................................................................. 4 
Clinical Protocol Synopsis ...................................................................................................................... 6 
1. Title .................................................................................................................................................................. 6 
2. Background .................................................................................................................................................... 6 
3. Study Design ................................................................................................................................................. 6 
a. Study Aims ....................................................................................................................................... 6 
i. Aim 1 .................................................................................................................................... 6 
ii. Aim 2 .................................................................................................................................... 6 
iii. Aim 3 .................................................................................................................................... 7 
b. Primary and Secondary Outcomes ............................................................................................... 7 
i. Primary Outcomes ............................................................................................................. 7 
ii. Secondary Outcomes ........................................................................................................ 7 
c. Study Overview ................................................................................................................................ 7 
i. Aim 1 .................................................................................................................................... 7 
ii. Aim 2 .................................................................................................................................... 8 
iii. Aim 3 ..................................................................................................................... 9 
4. Study Population ........................................................................................................................... 9 
a. Patients - Inclusion Criteria ............................................................................................... 9 
b. Patients - Exclusion Criteria  ........................................................................................... 10 
c. Family Members – Inclusion Criteria ............................................................................... 10 
d. Family Members – Exclusion Criteria .............................................................................. 10 
e. Clinician- Inclusion Criteria .............................................................................................. 11 
f. Clinician- Exclusion Criteria............................................................................................. 11 
5. Study Procedures  ....................................................................................................................... 11 
a. Screening, Recruitment and Informed Consent ............................................................... 11 
b. Study Data Collection...................................................................................................... 13 
c. Compensation  ................................................................................................................ 14 
6. Subject Participation Duration ..................................................................................................... 14 
7. Enrollment Sites .......................................................................................................................... 14 
8. Statistical Design, Analyses, Sample Size and Power ................................................................. 14 
a. Statistical Design and Analyses Plan .............................................................................. 14 
i. Aim 1 ................................................................................................................... 14 
ii. Aim 2 ................................................................................................................... 14 
iii. Aim 3 ................................................................................................................... 15 
b. Sample Size and Power .................................................................................................. 15 
9. Study Duration ............................................................................................................................ 16 
10. Risk-Benefit Assessment ............................................................................................................ 16 
a. Potential Risks ................................................................................................................ 16 
b. Adequacy of Protection Against Risks ............................................................................. 16 
c. Protections Against Risk ................................................................................................. 16 
d. Patient Death While in Study ........................................................................................... 18 
e. Vulnerable Populations ................................................................................................... 19 
f. Potential Benefits ............................................................................................................ 19 

 
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11. Adverse Events (AEs), Serious Adverse Events (SAEs), Protocol Deviations (PDs), and 
Unanticipated Problems (UPs)  ................................................................................................... 19 
a. Adverse Events (AEs) and Serious Adverse Events (SAEs)  .......................................... 19 
b. Protocol Deviations (PDs) and Unanticipated Problems (UPs)  ....................................... 20 
c. Period and Frequency for Event Assessment and Follow-up .......................................... 20 
d. Characteristics of an Adverse or Serious Adverse Event ................................................ 20 
i. Relationship to Study Intervention ....................................................................... 20 
ii. Expectedness ...................................................................................................... 20 
iii. Severity ............................................................................................................... 21 
e. Reporting Procedures ..................................................................................................... 21 
12. Data & Safety Monitoring Plan .................................................................................................... 22 
13. Data Management ....................................................................................................................... 27 
14. Privacy, Data Storage & Confidentiality ....................................................................................... 27 
15. IRB .............................................................................................................................................. 30 
16. References.................................................................................................................................. 31 
17. Appendices ................................................................................................................................. 34 
a. Appendix 1: Study Workflow ........................................................................................... 34 
b. Appendix 2: Acute and Chronic Palliative Care Triggers ................................................. 36 
c. Appendix 3: Schedule of Events ..................................................................................... 38 
d. Appendix 4: Survey Timelines and Rules ........................................................................ 39 
e. Appendix 5: Data Collection and Timing.......................................................................... 40 
f. Appendix 6: Adverse and Serious Adverse Event Reporting Diagram ............................. 41 
g. Appendix 7: Study Contact Information ........................................................................... 42 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Abbreviations and Definitions 
• 
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 Raleigh Hospital (DRaH) 
o Study site in which eligible patients will be enrolled.  
• 
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. 
• 
Electronic Data Capture (EDC) 
o For this study, the EDC will be REDCap, which is a secure, Duke approved EDC 
platform in which relevant study data, such as screening, enrollment, and clinical 
variables 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).  
• 
Electronic Medical Record (EMR) 
o Used interchangeably with EHR; the EMR is the patient-specific medical record located 
in the secure MaestroCare (aka: EPIC).  
• 
Electronic Patient Reported Outcomes (ePRO) 
o ePRO can be used to describe study source, such as the patient-completed surveys 
(e.g., PTSS), or can refer to the system that houses patient-derived data. For this study, 
ePRO may refer to the surveys OR it may refer to the system which houses the patient-
derived data, which is the web application known as “PCplanner.”  
• 
General Anxiety Disorder-7 (GAD-7) 
o Anxiety symptoms 
• 
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.  
• 
Institutional Review Board (IRB) 
o Ethical and regulatory committee who provides approval and oversight of clinical trial at 
study site.  
• 
Manual of Operating Procedures (MOP) 
o A document detailing instructions for a specific task or set of tasks; often used to ensure 
consistency and accuracy among the study team.  
• 
National Institute of Aging (NIA) 
o Study Sponsor, branch of the National Institute of Health (NIH) 
• 
NEST (Needs at the End of life Screening Tool) 
o Needs assessment.  
• 
PCplanner  
o A novel web application developed by DHTS and external vendor, One Cow Standing, 
LLC (Durham, NC) that interfaces with the EMR on a daily basis, pulling relevant clinical 
data from patients admitted to an ICU setting that meet general study criteria. The web 

 
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application serves as the technological platform by which the study is to be conducted 
and the primary data (e.g., surveys) are completed by enrolled subjects.  
• 
Patient Health Questionnaire-9 (PHQ-9) 
o Depression symptoms 
• 
Post-Traumatic Stress Scale survey (PTSS) 
o 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.  
• 
System Usability Scale (SUS) 
o Usability scale used to measure usability of web-application.  
• 
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  
PCplanner: operationalizing needs-focused palliative care for older adults in intensive care units 
 
2.  Background 
The number of older adults who receive life support in an ICU (currently 2 million per year) is increasing 
while survival remains unchanged.  Yet the quality of ICU-based palliative care is highly variable across 
clinicians and hospitals. Namely, older adults often suffer from untreated symptoms in a technology-
focused setting; many caregivers (i.e., family members) report poor quality communication and decision 
making, and clinicians struggle to connect with each other in a shiftwork environment.  Additionally, 
there are process barriers to improving the delivery of high quality palliative care which include 
difficulties in efficiently identifying older adult patients and family caregivers with the greatest burden of 
unmet palliative care needs, engaging family decision makers, and coordinating care by ICU teams and 
palliative care specialists.  
 
To address these barriers, a mobile app platform prototype called PCplanner (Palliative Care planner) 
has been developed for patients, their family members, and clinicians.  PCplanner directly captures 
EHR data to automate the identification of older adults with palliative care needs based on clinical 
characteristics such as dementia and declining health status. The app engages families as partners in 
their loved one’s care by facilitating in a self-report of actual needs. Additionally, the app provides a 
scalable digital infrastructure for coordinating needs-targeted care from collaborating ICU teams and 
palliative care specialists.  In pilot work, PCplanner reduced unmet needs, psychological distress, and 
length of stay while increasing goal concordant care, communication, and hospice utilization.  While 
these data are promising, the intervention requires a rigorous evaluation of efficacy.1   
 
3.  Study Design 
This is a 5-year, randomized controlled trial (RCT) that aims to test a native, novel web application 
called “PCplanner” developed by an external technology vendor, One Cow Standing. PCplanner 
directly captures EHR data to automate the identification of older adults with palliative care needs 
based on clinical characteristics such as dementia and declining health status. The app engages 
families as partners in their loved one’s care by facilitating in a self-report of actual needs. Additionally, 
the app provides a scalable digital infrastructure for coordinating needs-targeted care from collaborating 
ICU teams and palliative care specialists. The project specifically intends to randomize 150 older 
patients aged ≥50years, their 150 self-described family members, plus their ICU clinicians to determine 
if the intervention can improve family-reported unmet palliative care needs compared to standard of 
care.  
 
Study Aims 
The project will operationalize this goal by completing three specific aims, which are described below:  
 
• 
Aim 1: Optimize the usability of the PCplanner mobile app, specifically for older adults.  
Approach and goal:  To optimize the PCplanner mobile app platform before Aim 2’s clinical trial, 
key features will be added, based on user testing feedback, compatible for older adult 
caregivers and clinicians.  Iterative revisions based on usability participant feedback will be 
performed until the app platform achieves ‘excellent’ usability (i.e., mean Systems Usability 
Scale (SUS) score >60).  
 
• 
Aim 2: Test the PCplanner intervention’s efficacy vs. usual care in a randomized clinical trial 
(RCT). Hypotheses: Compared to usual care at 8 days post-randomization, PCplanner-
augmented care will improve family-reported unmet palliative care needs.  It will also improve 
short-term and long-term (3-month) secondary outcomes among family caregivers 

 
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(psychological distress symptoms, quality of communication), patients (receipt of goal 
concordant treatment), and health systems (length of stay).  Approach and goal:  In academic 
and community medical center settings, the study team will test these hypotheses among the 
family caregivers of medical and surgical ICU patients with dementia, declining health status, 
poor functioning, and other characteristics common to the aging experience.  
 
• 
Aim 3: Explore family caregiver and clinician RCT experiences to characterize how these 
participants may have been impacted by intervention components in a variety of implementation 
contexts, with a goal of understanding intervention mechanisms and barriers to future 
implementation and dissemination. Approach and goal:  Using a mixed methods approach, we 
will integrate findings from both qualitative analysis of semi-structured interviews via telephone 
with family caregivers and clinicians as well as quantitative family caregiver, patient, and care 
process outcomes.  This will provide insight into mechanisms of action and highlight methods 
for future intervention optimization through enhanced personalization, replicability, and 
scalability—all factors that are critical to successful implementation and dissemination of the 
intervention. 
 
Primary and Secondary Outcomes  
All outcomes have been piloted by the Duke University study team and chosen based on the 
conceptual model, expert recommendations, and psychometrics (Table 1).2-4  Response burden will be 
minimized with short instruments and online data entry via ePRO.5  Pilot testing confirmed completion 
in 15-20 minutes and demonstrated that all outcomes were responsive at levels of clinical significance.1  
Data will be collected at pre-randomization baseline (T1 Data Collection) as well as 4 days (T2 Data 
Collection), 8 days (T3 Data Collection), and 3 months (T4 Data Collection) post-randomization. 
 
Primary Outcomes 
For Aim 1, usability will be assessed with the SUS 6 and analysis of semi-structured interview 
transcriptions, while  acceptability will be measured with the Client Satisfaction Questionnaire (CSQ-8).7   
 
For Aim 2, the primary RCT outcome will be unmet palliative care needs at T3 (8 days post-
randomization) as reported by family caregivers using the Needs; Existential concerns; Symptoms; and 
Therapeutic interaction (NEST) scale.1,8,9 The NEST, which assesses palliative care needs among both 
critically ill older adult patients and their family caregivers (and is completed by family caregivers), is the 
primary trial outcome and T3 is the primary timing of its measurement.9  The NEST’s 13 items (score 
range 0-130) sample each of the National Consensus Project’s eight domains of palliative care 
quality.10  The main patient-level outcome will be the receipt of goal concordant care at T2.11,12   
 
Secondary Outcomes 
Secondary outcomes will include family caregiver psychological distress symptoms measured with the 
PHQ-9 (depression),13 the GAD-7 (anxiety),14 and the PTSS (PTSD) at survey 3 (T3) (1 week post-
randomization) and survey 4 (T4) (3 months). Systems outcomes will include post-randomization length 
of stay (LOS), use of aggressive care, discharge disposition, and hospice use.15,16  Clinicians will 
complete a brief palliative care attitudes scale at the time of consent.17 Aim 3’s analysis of facilitators, 
barriers, and mechanisms will be based on transcribed semi-structured family and clinician interviews.   
 
Study Overview 
Aim 1  
The previous pilot showed compelling results, but also identified targets that could substantially improve 
app functionality. However, changes in an app’s user interface or function, regardless of intention, can 
influence intervention delivery, data validity (e.g., ePRO system), as well as usability—the quality of the 
user's experience across domains of ease of use, efficiency, memorability, error rate, and 

 
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satisfaction.18-20  Usability testing is a critical procedure because it can identify any problems 
proactively, using lessons learned to improve the software before its introduction in a clinical trial 
setting.1,19,21   Therefore, Aim 1, a cross-sectional refinement (not developmental) study involving 10-15 
participants, will aim to improve efficiency, memorability, satisfaction, and overall decrease error rate.  
Participants eligible for this portion of the study will be healthy volunteers, specifically Duke employees, 
at least 18 years of age or older. Aim 1, completed concurrently with Aim 2 startup tasks, will target 
three key areas: 
1. Engagement and personalization: the study team will enable a 'Recommender System' to 
improve user experience including reminders and notifications, dashboard views unique to study 
role (e.g., CRC vs. clinical teams), enhanced visualization of needs data, single-click ICU team 
approval for study team members to approach families, and hovering box feedback in response 
to user-completed tasks.   
2. Security:  The Duke Health Technology Support team will ensure that the app system’s security 
adheres to current standards throughout the course of the trial. 
3. Interoperability: Standards will be used for EHR triggers with the assistance of DHTS ACE team 
programmers.   
 
Aim 2 
The primary focus of the project is Aim 2, the RCT. Therefore, the majority of study activity will center 
on this particular aim.  The study workflow is shown in Appendix 1. 
 
As noted above, patients’ self-described family members will be enrolled in this project. The family 
members are the primary research subject of focus in that they will be asked to sign and date the 
informed consent for this study, undergo app registration, and complete a baseline survey (T1) for 
eligibility and subsequent randomization. If deemed eligible to continue in the study, as determined by 
their NEST score, each family member will be randomized to one of two study arms:  
 
• 
Arm 1—PCplanner intervention: individuals randomized to this arm are considered to be 
“intervention”. All individuals who are randomized to this arm will have their survey 1 (T1), 
survey 2 (T2), and survey 3 (T3) results shared with the attending ICU clinician (and possibly 
palliative care clinician for non-responder intervention participants) on service at the time of 
consent via an automatic, electronic notification from the web application. After the receipt of 
survey 1 (T1) results, the ICU clinician will conduct a one-on-one family meeting prior to survey 
2 (T2) completion by the family member. The purpose of this meeting is to discuss and attempt 
to address the needs reported by the family member. Should the family member continue to 
report high needs at the completion of survey 2 (T2), defined as a NEST score of ≥25 or T2 
NEST score > T1 NEST score, a formal Palliative Care team consult will be sought by the 
clinical team for the family member in an attempt to discuss and address the reported needs.  
• 
Arm 2—usual care control: Control family caregivers will receive usual ICU care that does not 
include a protocolized palliative care consult.  Data collection will be identical to the intervention 
group (email/text links with unique URLs integrated with the trial data system), though data 
reported by family members will not be visible in the PCplanner dashboard or otherwise 
available to clinicians.  Each usual care participant will be provided with telephone and email 
contacts for study staff to answer questions or address urgent distress.  A palliative care 
specialist consult is allowed for any control patient or family caregiver if ICU clinicians believe it 
is needed.  All such crossovers will be recorded (as will the total number of palliative care-family 
interactions).   
 
Randomization will be stratified by three variables:  

 
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• 
Department location at the time of ICU admission and informed consent (i.e., Medical versus 
Surgical) 
• 
Palliative Care Trigger type (i.e., Acute versus Chronic; see Appendix 2) 
• 
Baseline NEST score (i.e., ≥25 vs. <25 but ≥10) 
 
All family members, regardless of their randomization arm will be asked to complete a total of four 
surveys, as listed below (see Appendix 3 for survey timeline):  
• 
T1: to be completed within 72 hours of informed consent; study day 1  
• 
T2: to be completed on study day 4  
• 
T3: to be completed on study day 8  
• 
T4: to be completed on study day 90  
 
Surveys are completed remotely and electronically via the web application by the enrolled family 
member. Reminders are automatically provided by the PCplanner platform to the family members via 
email and/or text alerts to complete the surveys (Appendix 4). 
 
Patients enrolled into this study, at the consent of their legally authorized representative (LAR), will 
passively participate in the study. Passive participation includes allowing the study team to access and 
abstract relevant clinical data from the patient’s EMR. The clinical data abstracted for the purposes of 
this research project will be housed in the secure, EDC (REDCap). 
 
Clinicians, whether ICU attending or Palliative Care, will be asked to complete a baseline survey at the time 
in which informed consent is obtained. The baseline survey will collect relevant information from the 
clinician, such as sociodemographic and professional information, as well a contact information (e.g., email 
address and cell phone number). Clinicians, who are assigned to an intervention family, will receive 
automatic text and/or email alerts via the web application informing them of the completed survey(s), 
reported needs, and the need to complete a family meeting.  
 
Aim 3  
Each month during Aim 2’s RCT, we will purposefully sample up to 30 patient cases; a patient case 
being defined as 1 family caregiver and the associated clinician(s) from the intervention group.22,23 The 
sampling will be stratified to ensure variability in factors that may influence experiences relevant to 
patients (e.g., trigger type), family caregivers (i.e., gender, race, age, confidence with technology, 
baseline NEST), and clinicians (i.e., medical vs. surgical). Each patient case selected will be asked to 
undergo a single 30-minute semi-structured interview with each case participant conducted at T2 that 
focuses on exploring the participant’s experiences with core intervention components and palliative 
care processes.24,25 
 
4.  Study Population 
Eligibility apply to participants in all study Aims with the exception of Aim 1 in which healthy volunteers 
will be asked to test the usability of the web application. Healthy volunteers for Aim 1 will be recruited 
Duke employees. Briefly, inclusion criteria for patients and family caregivers, defined as the individual 
(related or unrelated) who provides the most support and with whom the patient has a significant 
relationship. Although only one family caregiver per patient is eligible, other family can participate in 
family meetings if they wish.  Patients’ bedside ICU clinicians on the day of family consent are eligible.  
Patient exclusions include previous palliative care consult.  Family caregiver exclusions are low need 
burden (NEST <10) and lack of English fluency (the app is not validated in other languages).  
 
Patients 
Inclusion Criteria (pre-consent, patients) 

 
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1. ≥50 years of age. 
2. Receiving care in an adult ICU for >24 hours. 
3. Meets >1 of 9 high risk phenotypes listed below: 
a. Dementia (e.g., Alzheimer’s, multi-infarct, other dementia etiology) 
b. Declining health status defined as EITHER: 
i. > 2 hospital admissions in 3 months preceding current admission 
OR 
ii. > 1 ICU admission in 3 months preceding current admission 
c. Poor functional status defined by EITHER: 
i. Admission from a skilled nursing facility (SNF) or long-term acute care (LTAC) 
facility. 
OR 
ii. > 3 activities of daily living (ADL) limitations at admission. 
d. Severe acute illness defined by EITHER: 
i. Cardiac arrest 
ii. Multi-system organ failure (> 3 of: lung, kidney, hematological, brain, cardiac, or 
liver) that has worsened over 48 hours (i.e., Sequential Organ Failure 
Assessment [SOFA] score increased during this time period) 
e. Severe acute stroke (e.g., acute intracranial hemorrhage, ischemic stroke, or traumatic 
brain injury). 
f. Acute respiratory failure, defined as any of the following: 
i. Mechanical ventilation > 24 hours 
ii. Any single use of O2 device, listed below, or combination of O2 devices used in 
> 24 hours from time of ICU admission: 
1. Nasal cannula with O2 flow > 6 liters per minute (LPM) 
2. Facemask oxygen (e.g., partial re-breather, non-rebreather) 
3. Non-invasive ventilation (BiPAP or CPAP) 
4. High flow nasal cannula 
g. Acute renal failure (new hemodialysis or continuous venovenous hemodiafiltration for > 1 
hour) 
h. Advanced cancer (Advanced/metastatic cancer diagnosis) 
i. 
Shock (use of vasopressor or inotrope for > 4 hours) 
 
Exclusion Criteria (pre-consent, patients) 
1. Palliative care consultation performed during the hospitalization before eligibility determination.  
2. Current admission to the ICU at the index hospital is >8 days. 
3. Patient is imprisoned.  
4. Patient has no known family or surrogate decision maker.  
5. Death is expected to occur within 24 hours.  
 
Exclusion Criteria (post-consent, patients) 
1. Patient dies before T1 completion.  
 
Family members 
Inclusion Criteria (pre-consent, family member) 
1. Family member is > 18 years of age.  
2. Self-described as the individual (related or unrelated) who provides the most support and with 
whom the patient has a significant relationship (per definition of ‘family’ described in the Society 
of Critical Care Medicine 2016 Guidelines for Family-Centered Care in the Neonatal, Pediatric, 
and Adult ICU).  
 

 
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Exclusion Criteria (pre-consent, family member) 
1. Lack of English fluency such that the potential participant and/or study team is not confident that 
they could complete study tasks (app viewing, surveys). 
2. Family member is imprisoned.  
3. Family member is unable to complete study surveys for any reason.  
 
Exclusion Criteria (post-consent, family member) 
1. Low need burden (NEST score < 10) at the completion of survey 1 (T1). 
 
Clinicians 
Inclusion Criteria (ICU Physicians) 
1. ≥18 years of age. 
2. Physician must be the attending or fellow physician of the eligible patient in the given study ICU.  
 
Exclusion Criteria (ICU Physicians) 
1. Not applicable; there are no factors excluding an ICU physician from participation.  
 
For aim 3, individuals who participated in aim 2 will be eligible for participation should they denote on their 
informed consent they are willing to be contacted for future research.  
 
5.  Study Procedures 
As noted above, this study is centered on Aim 2, therefore, study procedures detailed below are 
focused on Aim 2 of the project. However, for Aims 1 and 3; the study team will be expected to maintain 
screening and enrollment logs, complete informed consent, and also required to maintain relevant 
study documentation, as outlined in the study MOP(s).  
 
Screening, Recruitment and Informed Consent 
Screening for eligible patients will occur daily via the native web application, PCplanner by delegated 
study team members. PCplanner was developed to integrate with the EMR, MaestroCare, by “calling” 
to the EMR via an application programming interface (API) which retrieves patients’ clinical information 
that preliminarily meet study eligibility criteria. The study team will maintain a robust screening log of all 
patients reviewed and document the following (at a minimum): 
1. Date screening occurred. 
2. Whether or not the individual was eligible for the study. 
a. Reason for ineligibility, if applicable. 
3. If the individual was approached for consent. 
a. Reason not approached for consent, if applicable. 
4. Outcome of consent. 
a. Declined, reason for decline, and date of decline.  
b. Consent, date of consent, and consent version number.  
 
For those patients who are eligible to consent, the study team will either 1) release the patients, via the 
web application, to the attending ICU clinician (note: if the ICU clinician is not consented, the study 
team will be required to consent the ICU clinician prior to any further study activity) or 2) automatically 
approach the eligible patient/family dyad for consent if the clinician has opted out of reviewing the 
patient/family dyad prior to approach. If scenario 1 is being utilized, the ICU clinician will be asked to 
review the patient via the web application and determine if they are eligible for recruitment. If the ICU 
clinician denies the patient, the study team will not approach the patient’s family member for consent 
(unless otherwise discussed by the study team and the clinical care team). If the ICU clinician approves 
the patient, the study team will recruit the family member in-person using the traditional method of 
informed consent or remotely using an approved telephone script. If scenario 2 is utilized the study 

 
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team will mark the family automatically mark the family as “approved” and approach the patient/family 
dyad for consent. Regarding of the scenario for recruitment, all family members will be approached at 
the time of their loved one’s ICU admission. Also, physicians will be texted by the study team noting 
that they will approach a patient allowing them to say ‘no’ if they choose.. If a patient has decision-
making capacity at the time of recruitment, he/she will be approached for consent, in addition to the 
family member. All individuals approached for consent to the study 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 loved one’s care positively or 
negatively. If a family member chooses to not participate, he/she will be documented as a ‘declined’ 
individual and the date of decline, as well as reason (if available) will be documented. Should a family 
member be approached and opt to consent, they will be asked to complete the app registration and 
survey 1 (T1) within 72 hours of consent. Eligibility to continue study participation will be determined 
automatically via an automated, electronic scoring system built within the web application. Additionally, 
if the individual is eligible to continue study participation, randomization to one of the two study arms 
will occur automatically and simultaneously. The study team and the family member will be alerted of 
the family member’s study status and randomization arm assignment. As with screening, the study 
team will be required to maintain a robust enrollment log includes the following information (at a 
minimum): 
1. Patient Information (i.e., name, MRN, location of enrollment, race, gender, ethnicity) and Family 
Member Information (i.e., name, DOB, race, gender, ethnicity). 
2. Consent, date of consent, and consent version number.  
3. Study status (including randomization arm, assigned clinician, withdraw, lost to follow-up, study 
completion) 
4. Death (Patient and/or Family Member), including date 
 
It is important to note that for this study, there are several statuses a family member (and thus patient) 
can have. They are listed below:  
• 
Screened (in screening or screened): defined as any patient who’s EMR has been reviewed 
against protocol for eligibility purposes. Individuals who are assigned this status must be noted 
on the screening log.  
• 
Excluded: defined as any patient’s who’s EMR has been reviewed against protocol for eligibility 
purposes, but is found to not meet eligibility criteria, as determined by the study team. 
Individuals who are assigned this status must be noted on the screening log. 
• 
Released: defined as any patient’s who’s EMR has been reviewed against protocol for eligibility 
purposes and is determined to meet eligibility criteria, as determined by the study team. These 
individuals are sent to the ICU attending clinician to review and either APPROVE or DENY. 
Individuals who are assigned this status must be noted on the screening log. 
• 
Approved: defined as any patient who is RELEASED by the study team for clinician review and 
is ultimately determined to meet eligibility criteria and is appropriate for recruitment, as 
determined by the ICU attending clinician. Individuals who are assigned this status must be 
noted on the screening log. 
o Note: should the ICU attending opt out of approving each patient/family dyad for 
recruitment within the web application the study team will automatically “approve” the 
patient/family dyad and attempt consent.  
• 
Denied: defined as any patient who is RELEASED by the study team for clinician review and is 
ultimately determined to not meet eligibility criteria and is not appropriate for recruitment, as 
determined by the ICU attending clinician. Individuals who are assigned this status must be 
noted on the screening log. 
• 
Consented: defined as any patient who is both RELEASED and APPROVED, their family 
member is approached for consent, and voluntarily chooses to consent to the study, the 

 
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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. Family 
members who reach this status will be required to complete survey 1 (T1) within 72 hours of 
informed consent. Individuals who are assigned this status must be noted on the enrollment log. 
• 
Refused: defined as any patient who is both RELEASED and APPROVED, their family member 
was approached for consent, but opted to not consent and therefore participate in the study. 
Patients who are assigned this status must be noted on the screening log. 
• 
Randomized: defined as any family member who’s loved one has the statuses of RELEASED, 
APPROVED, and CONSENTED, the family member completes T1 survey, and continues to 
meet all eligibility criteria. Family members who reach this status will be required to interact with 
the app three additional times (i.e., completion of T2, T3, and T4). Additionally, if the family is 
randomized to Arm 1, they will be required to participate in at least one family meeting 
conducted by the ICU attending. Patients and family members who are assigned this status 
must be maintained on the enrollment log.  
o Responder: defined as any family member who is randomized to the intervention arm 
and upon completing survey 2 (T2) received a NEST score of <25 and their survey 2 
(T2) score is less than their survey 1 (T1) score. Individuals who are assigned this study 
status will not receive a Palliative Care consult by the Palliative Care clinician. Only the 
ICU attending will be able to view the survey results.  
o Non-responder: defined as any family member who is randomized to the intervention 
arm and upon completing survey 2 (T2) received a NEST score of >25 or their survey 2 
(T2) score is greater than their survey 1 (T1) score. Individuals who are assigned this 
study status are to receive a Palliative Care consult by the Palliative Care clinician. The 
family member’s survey results will be viewed by both the ICU attending and the 
Palliative Care clinician.  
• 
Screen Failed: defined as any family member who was consented to the study, completes 
survey 1 (T1), but DOES NOT receive a NEST score of ≥ 10 on completion of survey 1 (T1). 
Patients and their family members who are assigned this status must be maintained on the 
enrollment log.  
• 
Withdraw by PI or Self: defined as any family member who voluntarily consents to participate 
in the study, but is then withdrawn from the study. 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 
individual demonstrates lack of compliance with study protocol and study procedures. Family 
members who reach this status have no additional follow-ups or study requirements; no further 
clinical data will be abstracted from the patient’s EMR. Patients and family members who are 
assigned this status must be maintained on the enrollment log. 
• 
Lost to Follow-Up (LTF): defined as any family member 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 family member will be considered LTF. Patients and 
family members who reach this status have no additional follow-ups or study requirements. 
Patients and family members who are assigned this status must be maintained on the 
enrollment log. 
o A family member who returns the study team’s contacts within 1 week of last attempted 
contact may resume study participation.  
o A family member who has completed at least T1, T2, and T3 will be included in the 
overall target enrollment, even if deemed LTF for T4.  
• 
Completed: defined as any family member who both consented and randomized to the study 
and completed T1-T4 (or at least 75% of the surveys). Family members and patients who reach 
this status have no additional follow-up or study requirements. Family members and patients 
who are assigned this status must be maintained on the enrollment log. 

 
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Study data collection 
Each consented family member will be asked to complete four surveys, as well as up to two meetings 
(for intervention group participants).  Appendix 4 shows the timeline and acceptable time frames within 
which survey responses are allowed.  Note that some latitude is provided given the possibility for 
weekends, etc. 
• 
Baseline, Survey 1 (Day 1; up to 3 days allowed post-consent): this will occur generally on 
the day of consent. At this time, the following will occur: 
o App Registration 
o Survey 1 (T1) Completion 
o Randomization (if eligible) 
• 
ICU Family Meeting for intervention group: The ICU attending will initiate a one-on-one 
family meeting to discuss the reported family needs. This is to occur prior to the completion of 
Survey 2 (T2).  
• 
Survey 2: (Day 4; up to 4 days allowed post-randomization) 
• 
Need-focused Palliative Care Family Meeting for intervention group: As noted above, this 
meeting will be triggered by a family member’s T2 NEST score that is either ≥25 or higher than 
their T1 NEST score.  The ICU attending and the Palliative Care team will meet with the family 
member together if at all possible to discuss the reported family needs. This meeting is to occur 
prior to the completion of Survey 3 (T3).  
• 
Survey 3: (Day 8 up to 4 days allowed) 
• 
Survey 4: (Day 90; up to 28 days allowed) 
 
At each specified time point above, the study team will abstract, as needed, relevant clinical data, as 
defined in the study EDC manual of procedures (MOP) and enter into the EDC, REDCap.  
 
Compensation 
Compensation for study participation will be provided to each family member via Greenphire. Participants 
may receive up to a total of $60 for study completion:  
• 
T1: $15.00 
• 
T2: $15.00 
• 
T3: $15.00 
• 
T4: $15.00 
   
Compensation for study participants in aims 1 and 3 will also be provided. Participants who partake in 
aim 1 or 3 will receive a one-time payment of $15.00 for the completion of the single study visit.  
 
6.  Subject Participation Duration:  For those subjects enrolled in Aims 1 and 3, we anticipate their study 
participation consisting of only one study survey, which will last for 30-60 minutes. For the RCT (Aim 2), it 
will require 3 months for participants to complete the entire study from the time of randomization, including 
the intervention and all the follow up surveys. 
 
7.  Enrollment sites 
This study will be conducted at Duke University Health (DUH), Duke Regional Hospital (DRH), and Duke 
Raleigh Hospital—all sites within the Duke University Health System.  
 
8.  Statistical Design, Analyses, Sample Size and Power 
Statistical Design and Analyses Plan 
Aim 1 

 
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After programming is complete, the study team will determine PCplanner usability using a ‘system-user-
task-environment’ mixed-methods approach.1,5,19,26-28  The study team will interviews with healthy 
volunteers to determine app usability. During the single 30-minute sessions participants will complete: a 
‘think aloud’ protocol in which CRCs record comments as PCplanner is used;30 a semi-structured 
interview, and the 10-item (0 [lowest] to 100 [highest]) industry-standard Systems Usability Scale 
(SUS).31  App revisions that address the needs of all users.32  The study team anticipate 2-3 cycles of 
5-10 users each will achieve our testable hypothesis that PCplanner will attain a mean SUS score >60 
('excellent' usability). 33,34  
 
Aim 2 
We will test the primary study hypothesis that the NEST score is lower (i.e., fewer unmet needs) for 
intervention family caregivers compared to usual care at T3 (~1-week post-randomization).  All 
participants will be analyzed as part of the group they were assigned, regardless of adherence or 
crossover status (i.e., intention to treat).  We will use a general linear model to estimate mean NEST 
changes and corresponding confidence intervals over time using SAS PROC MIXED (SAS Institute, 
Cary NC).  Different correlation structures will be examined (e.g., unstructured, autoregressive) and 
model fit indices will be used to guide the choice of the final model’s structure. 
 
Analyses similar to those conducted for the NEST (primary outcome analyses) above will be performed 
for the secondary family caregiver hypotheses involving PHQ-9, GAD-7, and PTSS scores at T3 and 
T4.  While family caregivers will be interviewed at T4 regardless of patient survival, patient death could 
complicate the analyses in two key ways: (1) Presence of missing data due to family loss to follow up 
(i.e., non-random missing data) and (2) differences in family caregiver distress by patient survival status 
(i.e., heterogeneous effect).35  To address the impact of patient death on outcomes, after first exploring 
reasons for and predictors of dropout, we will conduct a 2-step supplemental analysis.  In Step 1, 
missing T4 data due to loss to follow up among family caregivers of survivors will be multiply imputed 
via SAS PROC MI.  In Step 2, we will account for T4 outcomes that are missing due to death via 
composite endpoint and principal stratification methods to estimate the causal effects of the intervention 
in the presence of these unidentified outcomes and complicated missing data patterns.36,37  For the key 
patient outcome, receipt of goal concordant care, we will use logistic regression models adjusting for 
the stratification variables, to examine if rates at T3 differ by treatment group.  The key healthcare 
systems outcome, post-randomization hospital length of stay (LOS), provides a unique challenge due to 
the high expected mortality rate (40-50%).  In addition to descriptive analyses, steps to examine 
treatment group LOS differences will include: (1) a proportional hazards model with death treated as a 
censoring event; (2) a chi-square test of mortality rate differences; and (3) a Brunner-Manzel rank test 
for the composite death-LOS outcome.  This last step implements a recently developed methodology of 
a composite outcome that incorporates a numerical value for death (i.e., coded as the worst possible 
outcome or the longest possible stay) in the observed LOS distribution.38,39 
 
Aim 3 
Transcribed interviews will be analyzed using a content analysis technique that combines structural 
(e.g., intervention component, palliative care process barriers) and magnitude coding (e.g., theme 
intensity) with inductive coding (e.g., variations in outcomes not captured by instruments).40  The study 
team will separately code 10 interviews, discuss the generated codes, and create an initial code book 
by consensus.  The code book will then be used by the study team for the next 10 transcribed 
interviews (with the PI coding each 5th interview).  The final code book will be organized into categories 
used to generate themes of mechanistic and process elements.  Narrative case summaries will be 
constructed and matrixed by patient case using qualitative analytic themes and quantitative data (e.g., 
triggers, needs, psychological distress, app use analytics).  Across-case comparisons will be made 
using meta-matrices to search for patterns in intervention mechanisms of action common across 
theoretically- and empirically-derived categories of cases.41  Next, process tracing will be used to 

 
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explore how particular outcomes (e.g., needs, distress, goal concordance) may have been related to 
intervention components and their effect on process barriers in our conceptual model.42,43   
 
Sample Size and Power   
Calculations were conducted via the mixed models with the differences in slopes option in PASS 2020 
(Kayesville, UT).  With a total of 130 participants at 8 days (n=65 per treatment arm), we will have 80% 
power to detect a differential NEST improvement between treatment groups of 8.80 units at 8 days 
(SD=21.1, ρ=0.64 between baseline and 8 days based on pilot data and an additional ongoing trial 
[NCT03506438]).  To account for 10% dropout by 8 days, we plan to consent and randomize 150 
participants (n=75 per treatment arm).  This sample size will also provide a power of 80% (Type-I error of 
5%, dropout rates as noted above) to detect a 2.33-unit PHQ-9 change (SD=5.3, ρ =0.6) at 8 days—far 
smaller even that it’s 5.0-unit MCID.  These estimates are based on our pilot work as well as an ongoing 
RCT (NCT03506438) we are conducting that uses the NEST 
 
9.  Study Duration:  As this project is centered around Aim 2, it is anticipated that from the time the clinical 
trial opens to enrollment it will require ~41 months to complete data collection (~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. 
 
10.  Risk-Benefit Assessment 
Potential risks   
Overall, this project is minimal risk. However, it is possible that participants could experience a breach 
of confidentiality should their records be accessed unlawfully by an outside party.  Also, it is possible 
that participants may experience mild anxiety when answering survey questions, though this has not 
been observed in similar interventions including the multiple pilot studies on which this trial is based.  It 
is believed 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 given that 
this project involves the use of a web application developed by external vendors, One Cow Standing, 
LLC located in Durham, NC.    
 
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 novel, Duke Health Technology Services (DHTS) and Office of Information 
Technology (OIT) developed, secured screening method that integrates the EMR and the novel web 
application. The API developed respects participant privacy and rights.  The study team will only approach 
those family members that are deemed appropriate for the study, which will be determined by individual patient 
EMR review and subsequent approval by the ICU clinician via the web application. The approach of family 
members, will be aided by a short IRB-approved recruitment video found at PCplanner.duke.edu. The study 
team will then ask the family member 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. 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 and other 
unanticipated problems related to research activity. 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.  This monitoring is facilitated by a telephone 

 
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number for the study team and an email address (pcplanner@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 
The study team will strive to create an environment free of any coercive practices for patients, the family 
members and the participating clinicians. The study team will stress that study involvement is absolutely 
voluntary and that choosing to participate or not participate will not affect their care in anyway. In addition, the 
study team 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 family members who have loved ones in an ICU environment, it is 
recognized that there is a slight risk that some participants may become distressed completing questionnaires 
or viewing study materials, as mentioned above.  Additionally, given the extreme stresses of the critical illness 
experience, participants may even endorse suicidal ideation (SI).   
 
The study team will take the following measures to effectively manage any serious distress that occurs:  
 
(1)  All of the in-person and telephone-based data collection sessions will be conducted by trained 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 also free to reschedule an interview or treatment session at any time within the week.   
 
(4)  There is also a potential risk for identifying underlying mental health issues through the 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.   
 
(5) As a safety measure, used in past and current ICU-based clinical research, the study team will monitor 
participants closely beyond just the parameters of questionnaire scores.  The study staff will monitor 
participants closely during any interviews performed and will refer those with any concerning level of emotional 
distress and/or relationship distress to the PIs to evaluate by phone or in person.  This will be done 
immediately, particularly if there is staff concern about a participant who indicates suicidality.  
 
All study participants will be informed of the suicidality response plan prior to signing the informed consent for 
their participation in the study. The PI or study team delegate(s) will complete the online Columbia Suicide 
Severity Rating Scale (C-SSRS) training, a 30-minute interactive slide presentation followed by a question-
answer session.  The C-SSRS is a scale that can delineate high, moderate, and low-risk levels.   
 
Suicidality Response Plan  
The Suicidality Response Plan can be activated if the study team have in-person or telephone interactions that 
concern them, deeming the participant as ‘high risk.’  Additionally, ‘high risk’ participants are defined as those 
who reply to the PHQ-9’s question #9 regarding suicidal ideation with any response indicating a frequency of 
such ideation measured in days other than ‘never’ PLUS responding ‘yes’ to a branching logic item that follows 
any such ‘positive’ response to item #9 that determines if the individual has an active suicidality plan.  
 

 
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If the participant is deemed to be at high risk of active suicidality, the app system will send an alert email and/or 
text message in real time to the study manager, the study coordinator(s) and the PIs (no PHI included, only 
study ID).   
 
One of these study staff will then contact the participant. Contact is to occur as soon as possible (and definitely 
within 24 hours of learning of the event).  Using the full C-SSRS, the trained staff will then help 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 participant is considered to be 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 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 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. 
 
• 
Situation 3:  
o If there are any active suicidal concerns in any of the surveys (e.g., PHQ-9 above), an email, or 
in a text message: 
 
The study data system will notify the PIs and Study Manager in real time of any PHQ-9 
suicidality item positively endorsed.  
 
The study personnel will then contact the honest broker to de-identify the participant 
information.  
 
Next, the study personnel (or a PI; whoever is able first) will contact the participant by 
telephone. 
 
The study personnel or PI will stay on the telephone with the subject participant 
 
The study personnel or PI will use a different telephone line to immediately contact 911 
to initiate an on-site rescue if action is clinically indicated. 
 
The study personnel or PI will stay on the telephone with the subject until EMS services 
have contacted the participant. 
 
If the participant if determined to be actively suicidal and require immediate medical therapy, they will be 
withdrawn from the study. 
 
If the family member is deemed not to be actively suicidal, they will be given a list of local mental health 
resources within the app platform’s screen as follows: 
 
• 
Duke:  Call Emergency Psychiatry at (919) 681-4410 or (919) 681-1316, available 24 hours a day, 7 
days a week. 

 
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• 
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. 
 
As described above, all concerns about participant safety will be discussed immediately with the PIs - including 
concerning severe distress that does not involve suicidality.   
 
For these situations, once an “alert situation” is known, the PIs 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, in previously completed similar studies, analysis has found that <5% of participants will require a call 
from the study team during some point in the study period.  Of those, none have required referral to acute 
psychiatric care after a detailed interview from the study team.  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.   
 
Patient Death While in Study 
Finally, it is recognized that this project targets patients who are critically ill and elderly, therefore, there is a 
risk of death. The study team will review the EMR to look for records of death, halting all study procedures, if 
applicable, and noting the date of death. Additionally, on phoning any family member, the study team will 
initiate a conversation to tactfully ascertain the patient’s vital status. If the patient has died, we will provide brief 
support.  If a family member 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. 
 
Vulnerable Populations 
The study team not enroll patients from vulnerable populations (e.g., imprisoned persons, minors). 
However, elderly patients will be targeted for enrollment into this project, and therefore, there is a 
potential risk of death due to their age and critical illness in < 3 months.  
 
Potential Benefits 
This randomized clinical trial will compare PCplanner to a usual care control condition. The PCplanner 
intervention may reduce unmet needs and psychological distress, increase goal concordance, and 
reduce length of stay. Therefore, this intervention could hold great promise for helping many others in 
similar situations in the future. However, this is not certain.  In fact, subjects in the usual care control 
condition may experience similar or even greater benefits to those described for PCplanner. Then 
again, they may receive no particular benefit. Nonetheless, study involvement puts subjects at low risk 
for any adverse physical or psychological risk. Therefore, the potential benefits for participation justify 
the minimal risk to those enrolled in the proposed study.  Financial compensation will not be 
emphasized as a benefit of participation in research. 
 
11. Adverse Events (AEs), Serious Adverse Events, (SAEs), Protocol Deviations (PDs) and 
Unanticipated Problems (UPs).   
As noted above, this is considered a minimal risk study. Since the project intends to enroll critically ill patients 
who are elderly, and therefore, at risk of multiple and significant comorbidities, hospitalizations, and even 
death, adverse and serious adverse events will be limited to events that directly affect the overall well-being 
and safety of the family member (research subject). Additionally, given that this is a self-directed, survey based 
study, it is anticipated that compliance of research subjects (family member or clinician) will be less than 100% 
and/or completed within the protocol window. As such, events related to incomplete or missed study 
procedures will not be considered a protocol deviation and therefore will not be reported to the institutional or 

 
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sponsor officials. Rather, events occurring outside of the study protocol will be documented and recorded by 
the study team in the web application, EDC, and/or study source documents as applicable.    
 
All participants will have access to the principal investigator’s contact information 24 hours a day (shown in the 
consent form).  If a telephone interview is required, it will be conducted by a trained study team member who 
has been trained to be sensitive to the nature of these issues.   
 
Adverse Events (AEs) and Serious Adverse Events (SAEs) 
Adverse events (AEs) generally would include extremely high distress levels (PHQ-9 score >25, GAD-7 
score >20, PTSS score >34) or active suicidal ideation (i.e., endorsement of PHQ-9 suicidal ideation 
item plus a positive response to a branching logic item signifying active planning that would follow 
inquiring about a plan).  A serious adverse event (SAE) would be a suicide attempt, a hospitalization, or 
death.   
 
It is anticipated, in this study, for AEs to be extremely uncommon as it is a behavioral study. However, it is 
possible that participants could exhibit signs of and/or experience suicidal ideations with intent or thoughts of 
intent to act on such ideations. No other event, outside of suicidal ideation with intent or thoughts of intent to 
act on ideations will be considered an AE for this trial.  
 
Like, AEs, it is not anticipated that SAEs will occur. However, for this study, an SAE would include a suicide 
attempt, a hospitalization (of family member), or death (of family member). 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.  
 
Protocol Deviations (PDs) and Unanticipated Problems (UPs) 
Protocol deviations are errors made by study staff or deviations from plan made by study clinicians 
such as failure to conduct a family meeting.  Unanticipated problems could consist of issues such as 
failure of the study staff to respond in a timely manner to suicidal ideation reported by a participant.  
 
Given the nature of this study, it is anticipated that most enrolled family members will not complete their 
study surveys within the assigned protocol window. Additionally, it is expected that surveys may be 
missed as these are self-reported outcomes. 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.  
 
The study team will record all reportable events with start dates occurring any time after informed 
consent is obtained until 7 days after the last day of study participation.  At each study survey, 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 survey.  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: 
• 
Definitely Related:  The definition of an AE/SAE that is definitely related would include episodic 
distress triggered by either a study survey or some study material (e.g., a video).   

 
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• 
Possibly Related:  The definition of an AE/SAE that is possibly related would include simply 
experiencing high levels of distress during the trial period.  That is, this could follow a 
reasonable temporal sequence from administration of the study intervention, but that could 
readily have been produced by a number of other factors. 
• 
Not Related:  An AE/SAE that is not related would include a hospitalization for a car accident, 
etc.  That is, it would be an adverse event that is clearly not related to the investigational 
agent/procedure - i.e. another cause of the event is most plausible; and/or a clinically plausible 
temporal sequence is inconsistent with the onset of the event and the study intervention and/or 
a causal relationship is considered biologically implausible.  
 
Expectedness  
• 
Unexpected – The definition of an unexpected AE/SAE will be one whose nature or severity of 
the event is not consistent with information about the condition under study or intervention in the 
protocol, consent form, product brochure, or investigator brochure. 
• 
Expected - There are no events known to be associated with the intervention. Psychological 
distress is expected given the severity of patients’ illnesses and their family members’ 
involvement in decision making about a life-threatening illness. 
 
Severity 
The following scale will be used to grade adverse events: 
1. Mild: no intervention required; no impact on activities of daily living (ADL).  For example, 
elevated distress levels (e.g., PHQ-9 score >25, GAD-7 score >20, PTSS score >34). 
2. Moderate: minimal, local, or non-invasive intervention indicated; moderate impact on ADL. For 
example, suicidal ideation endorsed (i.e., PHQ-9 item #9), though no plan endorsed. 
3. Severe: significant symptoms requiring invasive intervention; subject seeks medical attention, 
needs major assistance with ADL.  For example, suicide attempt, hospitalization due to distress 
symptoms, or death. 
 
Reporting Procedures 
Adverse and Serious Adverse Events 
We have a strong plan for AE/SAE reporting and follow up.  First, we have a very robust monitoring 
system for psychiatric and emotional symptoms.  We will know ‘alert’ values of depression, anxiety, and 
PTSD symptoms the second a questionnaire is completed via the mobile app.  For symptoms that are 
either great in total burden (i.e., total score is high), we will call the participant to check in.  For specific 
symptoms such as the suicidal ideation item in the PHQ-9 depression questionnaire, we will also call 
the participant and assess the severity of the situation, triaging them as appropriate to psychiatric 
support.  Last, we have broadly placed our email addresses and phone numbers in all study materials 
and will encourage people to contact us regarding any issues. 
 
Since this is a psychosocial intervention, we do not expect study related physical issues to occur.  
Furthermore, there is no lab work involved.   
 
All deaths will be reported to NIA Program Officer, the DSMB Chair, and the central IRB 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 
Days since enrollment 

 
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Brief description of circumstances surrounding death including expected or unexpected. 
 
All adverse events that are both serious (SAE) and unexpected (i.e., have not been previously 
reported for the study’s intervention) will be reported to the IRB, NIA PO, and to the independent data 
and safety monitoring body according to the timeframe displayed in appendix 6. The summary of all 
other SAEs should be reported to NIA PO and to the DSMB or a Safety Officer, if either is appointed, 
quarterly, unless otherwise requested by the DSMB or a Safety Officer.  
 
Serious (fatal or life-threatening) SAEs that are unanticipated (i.e., not listed in the Data and Safety 
Monitoring Plan) and that are related to the intervention will be reported to the NIH Program Officer and 
to the DSMB Chair according to the timeframe displayed in appendix 6.   
 
The summary of all other SAEs will be reported to NIH Program Officer and to the DSMB quarterly, 
unless otherwise requested by the DSMB.  Additionally, for SAEs, we will hold an all-investigator 
teleconference within 7 days.  The 
PIs will draft a description of the SAE 
and an action plan.  This will be 
passed on to the IRB, the NIH, and 
DSMB within 72 hours of the 
teleconference. See appendix 6 for 
identifying and reporting structure.   
 
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. 
 
12. Data & Safety Monitoring Plan 
Overall framework for safety monitoring and what information will be monitored 
The proposed trial will be monitored for safety using both automated / electronic means, as well as by 
human oversight.  The study data system will allow real-time monitoring of study participant distress 
levels, alerting study staff immediately with any participant report of suicidal ideation.  Human 
safeguards will include the study team, led by the experienced PIs, the Duke Institutional Review 
Board, and the study Data Safety Monitoring Board (DSMB).  All of these components are discussed in 
greater detail below.  The trial information monitored is shown in the Table. 
 
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. Also, 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. 
Table 
 
Information 
Timing 
Study operations:  Enrollment rate, 
refusals, dropouts 
Reviewed on a weekly basis 
Intervention adherence: Total app 
logins, number of pages viewed per 
use, surveys completed, total time 
spent per login 
Numerous dimensions via software 
analytics 
Distress:   
-Suicidal ideation 
 
 
-Psychological distress symptoms 
 
-Real-time monitoring with 
automated email alert sent to all 
study staff if suicidal ideation present 
-Every 6 months by DSMB and 
every year by IRB 
Unanticipated Problems, Adverse 
Events, and Serious Adverse 
Events:  hospitalizations, life-
threatening events, death 
Reviewed by PI and study staff 
immediately on discovery.   

 
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The PIs will supervise the study, including data management, data accuracy, and protocol compliance.  The 
study biostatistician and Study 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 Study Manager will 
review data system reports on a routine basis. These reports will show enrollment, missing data, and other 
values. Additionally, the Study Manager will process detailed reports to search for errors and generate basic 
reports for dissemination for regular staff meetings.   
 
Data Safety Monitoring Board (DSMB) 
This trial will be supervised by a single independent DSMB composed of professionals with significant 
experience in clinical trials, palliative care interventions, epidemiology, and biostatistics who are not 
directly involved in the study, its interpretation, or in current collaborative research 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 PCplanner intervention and usual care control, (b) ensure the validity 
and integrity of the data, and (c) make recommendations to the investigators and to the NIH about 
whether the trial 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 NIH 
staff), reviewing the protocol, and codifying a written DSMB charter.  The NIH'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 NIH; additionally, ClinicalTrials.gov registration will be finalized. 
 
The first DSMB data review will occur either after the first 50 participants have been enrolled—
representing approximately 25% of randomization target—or enrollment has occurred for 6 months, 
whichever is observed first.  Thereafter, the DSMB will review cleaned data reports (provided by the 
Study Manager 2 weeks before the DSMB meeting) every 6 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 (noting race & 
ethnicity of those enrolled), retention rate (noting race & ethnicity of those who drop out), PHQ-9 
scores, GAD-7 scores, PTSS scores, and Adverse Events.  The primary safety measures will be 
Adverse Events reports and PHQ-9’s suicidal ideation item.  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 retention, including women 
and minorities; (d) protocol adherence; and (e) presence of factors that could adversely affect study 
outcome or compromise data confidentiality.  Study patients 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 Manager, will provide written reports to DSMB members that do not name the treatment 
group.  The study biostatistician, will oversee any DSMB statistical requests and interpretations.  During 

 
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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 PHQ-9 
score is observed in any treatment group.  We do not plan interim analyses given the sample size of 
this trial.  If a specific group is found to have a statistically or clinically significant increase in mortality or 
PHQ-9 score, the DSMB scope of action may include recommendation for stopping the trial (see next 
paragraph).  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 Duke Institutional Review Board as well as to the project’s NIH 
Program Officer. 
 
As noted above, the DSMB will have the power to stop the trial at their discretion.  The following is a 
possible stopping plan that could be adapted by the study DSMB for inclusion in the final DSMB 
Charter.  Because this is an early phase trial, we will not have formal stopping rules based on efficacy 
or futility.  Criteria for intervention discontinuation and stopping based on safety concerns will be 
determined in partnership with the study DSMB and codified in the DSMB charter before enrollment 
begins.  We propose a strategy similar to that included in our past ICU-based RCTs that included family 
caregivers (e.g., R01 HL109823, PI: Cox).  Three-month all-cause mortality will be the primary adverse 
event for the patients in study.  We will examine the distribution of deaths by treatment arm three times 
during the trial:  at 15, 25, and 50 deaths.  At each of these interim looks, we will examine the 
distribution of deaths by study group and conducted either a non-parametric sign test or Wilcoxon 
signed-rank test to test the difference in median number of deaths between the arms.  We will use 
Haybittle-Peto guidelines and stringently set the p-value at 0.001 to flag a significant difference 
between arms at each of these interim looks.  If this difference is observed, this would then indicate a 
closer examination of related constructs, as well as proximate causes and circumstances surrounding 
death (e.g., timing and location of death, withdrawal of life support or not, comorbidities and illness 
severity, clinician expectations of survival).  We will use the Patient-Centeredness of Care Scale to 
provide additional information on the alignment of patient treatment and values at the time of death.  
Although past end of life interventions have not increased mortality, it is possible that by better focusing 
decision makers’ attention on patients’ values, higher mortality could be observed in the intervention 
group by identifying patients for whom prolonged life support would be a state worse than death 
(Patrick DL, et al. Ann Int Med. 139:410-415, 2003; Holloway RG, et al. JAMA. 298:802-804, 2007).  
Yet if PCplanner—a non-directive intervention—led to more decisions to forego life support, this would 
be ethically permissible if the treatments received reflected patient-centered care as assessed by the 
PCCS (Institute of Medicine, 2001; Lin GA, et al. Arch Intern Med. 169:1551-1553, 2009; Holloway RG, 
et al. 2007).  The primary adverse event for family caregivers will be symptoms of psychological 
distress as measured by the PHQ-9 and PTSS at T2 and T3.  We propose to examine the distribution 
of scores by treatment arm three times during the trial:  at 25, 75, and 100 caregivers.  Using methods 
similar to those above, we could examine circumstances more closely as per DSMB guidelines.   
 
Frequency of Data and Safety Monitoring  
The proposed trial will be monitored extensively.  In real-time, all study staff will be made aware of any 
study participant who reports any suicidal ideation.  Routine reports on enrollment, adherence, dropout, 
and study progress will be generated by the study data system and then reviewed by the study team.  
All primary outcomes will be reviewed as well in a summary view (for the PI; group-based data will not 
be included) and a group-based view (for the DSMB; treatment group name will be removed).  The 
study DSMB will view data every 6 months.  Interim analyses, though not planned, will be conducted at 
the behest of the DSMB.  Our approach to stopping rules is discussed below in the context of the 
DSMB. 
 

 
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Safety Review Plan  
Study progress and safety will be reviewed routinely. Progress reports, including recruitment, retention 
and attrition, and AEs will be provided to the DSMB semi-annually.  An Annual Report will be compiled 
and will include a list and summary of AEs.  In addition, the Annual Report will address (1) whether AE 
rates are consistent with pre-study assumptions; (2) reason for dropouts from the study; (3) whether all 
participants met entry criteria; (4) whether continuation of the study is justified on the basis that 
additional data are needed to accomplish the stated aims of the study; and (5) conditions whereby the 
study might be terminated prematurely.  The Annual Report will be sent to the Independent Monitors 
and will be forwarded to the IRB and the study sponsor.  The IRB and other applicable recipients will 
review progress of this study on an annual basis. 
 
Quality Assurance and Confidentiality 
First, the PCplanner electronic data platform “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 data 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.   
 
Safety Monitoring 
The proposed trial will be monitored for safety using both automated and electronic means, as well as 
by human oversight.  The study data system will allow real-time monitoring of study participant distress 
levels, alerting study staff immediately with any participant report of suicidal ideation.  Human 
safeguards will include the study team, led by the experienced PIs, the Duke Institutional Review 
Board, and the study Data Safety Monitoring Board (DSMB), as applicable per reporting criteria.  
 
Frequency of monitoring, including plans for interim analysis and stopping rules 
The proposed trial will be monitored extensively.  In real-time, all study staff will be made aware of any 
study participant who reports any suicidal ideation.  Routine reports on enrollment, adherence, dropout, 
and study progress will be generated by the study data system and then reviewed by the study team.  
All primary outcomes will be reviewed as well in a summary view (for the PI; group-based data will not 
be included) and a group-based view (for the DSMB; treatment group name will be removed).  The 
study DSMB will view data every 6 months. 
 
Safety Review Plan  
Study progress and safety will be reviewed monthly (and more frequently if needed).  Progress reports, 
including patient recruitment, retention/attrition, and AEs will be provided to the Independent Monitor(s) 
semi-annually.  An Annual Report will be compiled and will include a list and summary of AEs.  In 
addition, the Annual Report will address (1) whether AE rates are consistent with pre-study 
assumptions; (2) reason for dropouts from the study; (3) whether all participants met entry criteria; (4) 
whether continuation of the study is justified on the basis that additional data are needed to accomplish 
the stated aims of the study; and (5) conditions whereby the study might be terminated prematurely.  
The Annual Report will be sent to the Independent Monitors and will be forwarded to the IRB and NIA.  
The IRB and other applicable recipients will review progress of this study on an annual basis. 
 

 
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Study Report Outline for the Independent Monitors(s) (Interim or Annual Reports)  
The study team will generate Study Reports for the Independent Monitor and will provide information on 
the following study parameters:  NEST, PHQ-9, GAD-7, and PTSS scores; enrollment success; rate of 
consent; rate of successful randomization; retention rates; and AE/SAEs.  Study Report tables will be 
generated only from aggregate (not by group assignment) baseline and aggregate safety data for the 
study population. 
 
Submission of On-Site Monitoring/Audit and Inspection Reports 
The IRB, IMC, and NIA Program Officials will receive copies of all study monitoring/audit or inspection 
reports within 14 day of PI receipt.   
 
Table A 
 
Data management plan   
All study data will be entered by participants and delegated study team members via the PCplanner 
app and the REDCap data system, as applicable.  Participant data entry will primarily utilize our tested, 
highly secure ePRO system linked to the web application. The study team will abstract relevant clinical 
data from the EMR and input into the secure REDCap. The PCplanner mobile app backend will reside 
on a Duke University RHEL Server fronted by a ProxyPass pass through server within Apache HTTPD.  
The central REDCap database will run on a mirrored Duke University server system with automatic fail-
over features and transaction logs.  Data will be backed up hourly on the Duke University server and 
archived four times daily on a mirror server managed by Duke Health Technology System (DHTS). The 
app and data system will be built to security standards set by both the Duke Information Technology 
Security Office (ITSO) as well as DHTS; our programmatic partners, Duke ORI, have experience using 
this paradigm.  These standards enforce strict scheduled security patching of all digital resources. 
Weekly summative (i.e., not group-based) reports will be generated and reviewed by the study team to 
Data type 
Frequency of review 
Reviewer 
Subject accrual (including compliance 
with protocol enrollment criteria) 
Monthly 
PI, Internal QA Reviewer 
Semi-annually 
Independent Monitor(s) 
Status of all enrolled subjects, as of 
date of reporting  
Monthly 
PI, Internal QA Reviewer 
Semi-annually 
Independent Monitor(s) 
Data entry quality control checks on 
5% of charts 
Weekly 
QA Reviewer 
Adherence data regarding study visits 
and intervention 
Monthly 
PIs, Internal QA Reviewer 
Semi-annually 
Independent Monitor(s) 
AEs and rates (including out-of-range 
lab values) 
Monthly 
PIs, Internal QA Reviewer 
Semi-annually 
 
Independent Monitor(s) 
Annually 
NIA FDA (If Applicable) 
SAEs (unexpected and related) 
Per occurrence 
PIs, Independent  Monitor (s) 
NIA, FDA (if applicable) 
SAEs (expected or unrelated) 
Per Occurrence 
PIs, Internal QA Reviewer 
Annually 
Independent Monitor (s), NIH/NIA 
Unanticipated Problems 
Monthly 
PIs, Internal QA Reviewer 
Per Policy 
IRB, FDA (if applicable) 

 
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monitor enrollment and retention, safety indices, and missing data.   
 
Study Report Outline for the Independent Monitors(s) (Interim or Annual Reports)  
The study team will generate Study Reports for the DSMB and will provide information on the following 
study parameters:  NEST, PHQ-9, GAD-7, and PTSS scores; enrollment success; rate of consent; rate 
of successful randomization; retention rates; and AE/SAEs.  Study Report tables will be generated for 
baseline and aggregate safety data for the study population. 
 
Data handling and Record Keeping 
The study team is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the 
data reported.  All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data.  The study team will maintain adequate case histories of study subjects, including 
accurate case report forms (CRFs), and source documentation. The principal investigator will maintain 
overall oversight and responsibility of these activities.  
 
Personal identifiers, such as name, date of birth, MRN, diagnoses, dates of admission and discharge, 
and other relevant clinical information for both patients, family members and the clinicians may be 
stored in the REDCap study data system.  Data will be backed up hourly on the server and archived 
four times daily on a mirror server managed by the Duke Health Technology Solutions team.   
 
13.  Data management 
All study data will be input by participants and CRCs via the PCplanner app (noting that the usual 
control group will do the same via the private study webpage, directly linked to the study RedCAP data 
system, without access to the PCplanner content).  Participant data entry will primarily utilize our tested, 
highly secure ePRO system linked to our data system.  The PCplanner mobile app Ansible backend 
and the RedCAP study data system will reside on a Duke University RHEL Server fronted by a 
ProxyPass pass through server within Apache HTTPD.  The central RedCAP database will run on a 
mirrored Duke University server system with automatic fail-over features and transaction logs.  Data will 
be backed up hourly on the Duke University server and archived four times daily on a mirror server 
managed by Duke Health Technology System (DHTS), a technical partner in this R01 project. The app 
and data system will be built to security standards set by both the Duke Information Technology 
Security Office (ITSO) as well as DHTS; our programmatic partners, Duke ORI, have experience using 
this paradigm.  These standards enforce strict scheduled security patching of all digital resources.  
Routine summative (i.e., not group-based) reports will be generated and reviewed by the study team to 
monitor enrollment and retention, safety indices, and missing data.   
 
14. Privacy, Data Storage & Confidentiality  
Privacy  
We believe that risks to privacy associated with study participation will be low based on the steps we 
plan to take closely safeguard participant privacy, protected health information (PHI; see also next 
section), and personal information.  Study ID numbers, generated randomly at the time of enrollment, 
and are linked in a separate RedCAP subsystem patient names and medical record numbers.  Further, 
names, birthdates, telephone numbers, addresses, and medical record numbers are only viewable by 
the study team after entry of a unique username/password combination changed every 3 months.  The 
master list of study ID linkage to this personal data will be deleted after study completion.  The RedCAP 
system stores all data on a secure Duke University server with a sophisticated dual backup system.  No 
PHI is visible in any ePRO user interface (with the exception of the clinician user interface, which will 
show room number and patient last name—the minimal PHI that would still allow recognition).  Study 
participants cannot view data via the ePRO system, only enter data (a 'one-way view').  Participants 
access this one-way view ePRO system via secure, PHI-free email or text links sent from our study 
RedCAP data system.   

 
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Should participant privacy be compromised despite our attention to Duke Information Technology 
Security Office (ITSO) protocols, we will quickly assess the data exposed, disclose this immediately to 
all affected participants, and offer the assistance of the Duke ITSO in managing the breach.  The 
impact of a privacy breach is difficult to quantify, though could be distressing (phone number, address).  
For this reason, the study team will make every effort to first prevent such a breach first and foremost. 
 
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 
Duke 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.   
 
Protected Health Information (PHI) 
Duke University endeavors to build technological solutions that preserve the privacy, confidentiality, 
and security of protected health information (PHI) that may be part of health records or research 
datasets.  PHI is handled according to appropriate Health Insurance Portability and Accountability Act 
of 1996 (HIPAA) Privacy and Security Regulations.  Duke programmers and Duke Research staff who 
work with sensitive data are required to complete appropriate HIPAA training with periodic updates, 
complete human subjects and data privacy training, comply with site IT Security Policies, and agree to 
the provisions of the university Rules of Behavior and Sanction Policy.  Duke strives to implement 
reasonable security controls in its product builds guided by the Federal Information Security 
Management Act (FISMA), HIPAA, and Appendix III of the OMB Circular A-130.  
 
Of the 18 PHI elements, the study will collect the following at minimum: name (identification), address 
(to send surveys and/or remuneration), date of birth (to calculate age), telephone number and email 
address (to contact with surveys), social security number (collected only from those who wish to receive 
remuneration, as per Duke policy regarding payment reporting to Federal agencies), medical record 
number of patient (identification), and use of unique PCplanner web URLs through which data are 
collected in our ePRO system (per Duke / DHTS / ITSO security policy).  The study team will enter 
some of these data into our study data system, while family caregivers will enter others.  The PHI 
collected from clinicians includes, but may not be limited to, their name, area of medical focus, age, and 
relevant sociodemographic information. No PHI is ever visible in any app user interface seen by family 
caregivers. The PHI displayed in the PCplanner app includes the patient’s last name, bed number, 
MRN, date of admission, and palliative care trigger(s).   
 
Digital security  
The study digital infrastructure consists of a mobile web app browser with an integrated electronic 
patient reported outcomes (ePRO) function designed by One Cow Standing, LLC (Durham, NC), a 
research system ‘backend’ which interfaces with the EMR, and a REDCap study data system.  The 
security features are in line and supported by Duke’s Information Technology Security Office (ITSO), 
the Duke Health Technology Solutions (DHTS) frameworks, HIPAA, and Duke IRB standards.  Per 
DHTS standards, security updates and patches for the PCplanner web app will be required on a weekly 
basis.  Our digital systems are also protected up by the Duke University firewall system and monitored 
24 hours a day by DHTS digital security technicians. 
 
Private study website 
Study staff and participants will access the online elements through separate secure pathways hosted, 
monitored, and maintained by Duke University under the general domain of PCplanner.duke.edu.  

 
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Study staff will use their University credentials to login in a process identical in security strength to EHR 
login (i.e., Shibboleth multi-factor authentication).  The complete PCplanner system, after development 
by the Duke Office of Research Informatics (ORI) team and the study team, will be hosted within the 
secure Duke University Internal Digital Environment and will be composed of an app subserver (app 
interface, content, ePRO system), the study REDCap database, and system files (e.g., scripts, code, 
HTML, images).  
 
PCplanner Mobile Web Application 
The study team opted for a mobile web application versus a native app such as one downloads from an 
app store because of its enhanced security.  Web applications always have the most recent version, 
allowing security patches to be pushed out at any time.  In contrast, native apps require the user to 
update their app periodically—a process that many users simply do not do regularly, making the app 
more vulnerable to security breaches.  The programming service providers, One Cow Standing, 
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 
data privacy training, comply with site IT Security Policies, and agree to the provisions of the University 
Rules of Behavior and Sanction Policy.  Duke, and by extension Duke ORI, strives to implement 
reasonable security controls in its product builds guided by FISMA, HIPAA, and OMB Circular A-130, 
Appendix III. 
 
Data security is of the upmost importance for the study, particularly in providing a digital, online 
intervention for the participants.  Beyond the robust security that REDCap provides, One Cow Standing 
developers have implemented and maintains several security protocols and controls for apps as well.  
Duke ORI has developed a formal information security program, with a named individual responsible for 
its overall execution.  Duke ORI 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, Duke ORI evaluates and installs security patches in a timely 
fashion (generally weekly per DHTS guidelines), protects systems against self-propagating malware, 
maintains secure coding policies and practices, and utilizes standardized secure build processes to 
protect Duke hardware that accesses customer networks, protecting confidential data against attack.  
Duke does not use of off-shore service providers and/or data center facilities.  For our study, the web 
application and supporting backend system that Duke ORI develops will be hosted internally on a Duke 
University server behind two secure firewalls.  Thus, study data will be stored only on approved, secure 
University servers.  In fact, all development will be conducted at all times on a Duke University server 
under the strict monitoring of Duke ITSO and DHTS. 
 
REDCap 
REDCap, via Duke University’s secured platform, will serve as a central database for clinically relevant 
extracted data from each participant’s electronic medical record, as well as serve as an electronic 
source of secure storage for documentation of study visit completion, protocol deviations or 
unanticipated problems, adverse and serious adverse events, screening and enrollment logs, as well as 
the electronic informed consent. Only delegated study team members, such as the investigator(s), 
statisticians, and study team members will have access to the REDCap. 
 

 
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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 have login/password (reset every 3 months) 
credentialing for authentication of all study staff.  A University-approved plugin will be used to 
operationalize user-level permissions based on user roles to limit study staff access to authorized 
records and data fields alone.  
 
The central REDCap database will run on a mirrored Duke University server system with automatic fail-over 
features, daily backups, and transaction logs.  This system is physically located in a Tier II Data Center 
providing backup power sources, climate control, fire protection, and 24x7 surveillance.  Audit logs will be 
reviewed routinely by Duke Health Technology Solutions staff to verify that security measures are 
operational.  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 PIs (and approved by the NIH and 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.   
 
15.  IRB 
Duke University Health System (DUHS) IRB will be utilized as the IRB of record for this project pilot 
randomized, RCT and the future RCT.  
 
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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rating scale. Journal of usability studies. 2009;4:114-123 
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outcomes in randomized controlled trials with high mortality. BMJ. 
2018;360:j5748.PMC5751848 at www.icmje.org/coi_disclosure.pdf and declare: EC, AL, DOS, 
and DMN have support from National Heart, Lung and Blood Institute (R24HL111895) for the 
submitted work; CW and DOS were compensated for consultation services that motivated the 
composite outcome methods discussed in this paper, CW and DS were not paid for preparation 
of this manuscript. 
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Evaluation of Default Access to Palliative Services (REDAPS) Trial. Annals of the American 
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Appendix 1: Study Workflow 
 
 

 
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Appendix 1: Study Workflow Continued 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Appendix 2: Acute and Chronic Palliative Care Triggers 
 
Phenotypes 
Narrative description of 
‘positive’ trigger 
Time period relevant for 
screening by 
PCplanner 
Data source in EHR 
Acute phenotypes 
 
 
 
Mechanical ventilation  
 
Mechanical ventilation 
delivered via either an 
endotracheal tube or 
tracheotomy for ≥24 hours 
At any point 
during the first 48 
hours of the 
current ICU 
admission 
Respiratory care provider 
flowsheet 
Shock 
Defined as ANY use of ANY 
continuous intravenous 
vasopressor medication for ≥4 
hours 
At any point 
during the first 48 
hours of the 
current ICU 
admission 
• Medication list 
• Nursing flowsheet 
• Vital signs flowsheet 
Severe acute 
neurological injury  
• Acute intracranial hemorrhage 
• Ischemic stroke 
• Traumatic brain injury 
At any point in 
current 
hospitalization 
until time of 
screening( i.e., 
48 hours after 
ICU admission) 
• Physician billing 
• Problem list 
Cardiac arrest  
 
Has cardiac arrest managed 
in ED or during hospitalization 
At any point in 
current 
hospitalization 
(or preceding ED 
visit for out-of-
hospital cardiac 
arrests) 
Physician Billing 
 
Multisystem organ 
failure that is 
worsening 
 
Present if Sequential Organ 
Failure Assessment [SOFA] 
score on ICU day 2 (i.e., 
hours 25-48 after ICU 
admission) is greater than 
SOFA score on ICU day 1 
(i.e., hours 0-24 after ICU 
admission) 
ICU days 1 and 2 
(i.e., comparing 
first 24 hours of 
ICU admission to 
second 24 hours 
of ICU 
admission) 
• Lab 
• Medications 
• Respiratory care provider 
flowsheet 
Acute renal failure  
  
Use of continuous 
venovenous hemodiafiltration 
(CVVHD) for ≥1 hour during 
screening period 
on EITHER ICU 
day 1 (i.e., within 
24 hours of ICU 
admission) OR 
ICU day 2 (within 
48 hours of ICU 
admission) * 
• Medication list from nursing 
flowsheet 
• Dialysis flowsheet 
• Laboratory test 
 
 

 
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Chronic phenotypes 
 
 
 
Dementia  
• Alzheimer’s 
• Multi-infarct 
• Other dementia 
• 
Present before 
hospitalization 
(i.e., Problem 
List) 
• 
Present at any 
point in current 
hospitalization 
until time of 
screening (i.e., 
48 hours after 
ICU admission) 
• Physician billing 
• Problem list 
Admitted from facility   
 
Admitted from Skilled Nursing 
Facility (SNF) or Long-Term 
Acute Care (LTAC) facility * 
At any point in 
current 
hospitalization up 
until time of 
screening (i.e., 
48 hours after 
ICU admission)  
Intake flowsheet 
Declining health 
trajectory 
 
• ≥2 hospital admissions 
(includes Emergency 
Department visits) *  
• ≥1 ICU admission 
Within the 3 
months (or 90 
days, whatever is 
easier) that 
preceded the 
date of the 
current hospital 
admission 
Admission records 
Declining functional 
status 
≥2 activities of daily 
living (ADL) limitations * 
 
At any point in 
current 
hospitalization 
Nursing intake flowsheet 
 
Advanced cancer  
Cancer and/or metastatic 
cancer diagnosis 
At any point in 
current 
hospitalization 
• Physician billing 
• Problem list 
 
 

 
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Appendix 3: Schedule of Events 
 
 
Day 0 (In-Hospital, 
Baseline) 
 Family Meeting 
(Day 0, +3 days) 
Day 4 (+4 days) 
Family Meeting 
(Day 4, +3 days) 
Day 8 (+4) 
Day 90 (+28 days) 
Screening 
X 
 
 
 
 
 
Consent (a) 
X 
 
 
 
 
 
App Registration 
X 
 
 
 
 
 
T1 Survey (b) 
X 
 
 
 
 
 
Randomization (c) 
X 
 
 
 
 
 
T2 Survey (d) 
 
 
X 
 
 
 
T3 Survey (d) 
 
 
 
 
X 
 
T4 Survey (d) 
 
 
 
 
 
X 
ICU Physician Family Meeting (e) 
 
X 
 
 
 
 
Palliative Care Family Meeting (f) 
 
 
 
X 
 
 
Data Entry (g) 
X 
 
X 
 
X 
 
AE/SAE assessment (h) 
X 
 
X 
 
X 
X 
Survival Status (i) 
 
X 
 
 
 
X 
End of Study 
 
X 
 
 
 
X 
 
a) 
Study team is only able to approach family members (LARs) for consent once the ICU physician has marked the patient “approved” in the PCplanner web application (or if the 
ICU attending has opted out of approval for all patient/family dads).  
b) 
Survey 1, T1 is to be completed ideally on the day of consent, but within 72 hours.  
c) 
Family members are eligible for randomization to the study based on their NEST score at the completion of survey 1, T1 (> 10). Family members can be randomized to either the 
intervention or the control arm.  
d) 
The timing of completion of surveys T2, T3, and T4 are directly linked to the timing of completion of survey 1, T1. Family members will receive automated alerts notifying them of 
survey completion at each set time interval based on the completion of T1.  
e) 
The ICU Physician Family meeting occurs for any family member that is randomized to the intervention arm. The ICU physician in attendance will receive automated alerts 
notifying them of patient/family enrollment, the NEST score and associated results and daily reminders to complete the family meeting.  
f) 
Like the ICU Physician family meeting, the Palliative Care family meeting will occur for those individuals who are randomized to the intervention arm; however, only family 
members who receive a NEST score > 25 or > their T1 NEST score at the completion of T2 will illicit the Palliative Care family meeting. The ICU Physician is responsible for 
facilitating in the coordination of the Palliative Care family meeting.  
g) 
Data entry is to be completed within the study EDC, REDCap.  
h) 
AE/SAE assessment and survival status will be completed via EMR review and/or telephone interview.  
 
 
 
 
 
 
 

 
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Appendix 4: Survey timelines and rules 
 
 
 
 
 
 

 
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Appendix 5: Data Collection and Timing 
 
 
 
 
 
 
 
 
 
 
 
Table 1: Data collection and timing 
 
 
 
 
A. Clinical / patient information 
T1 
Baseline 
T2 
4 days post-
randomization 
T3 
8 days post-
randomization 
T4 
3 months post-
randomization 
Baseline 
General information 
Comorbidities 
Diagnoses 
APACHE II illness severity 
CPR information / baseline 
ICU type & admission source 
x 
- 
- 
- 
Across entire hospitalization 
CPR information / changes 
Palliative care consults 
Procedures and therapies 
Dates (mechanical ventilation, hospital, ICU) 
(x) 
- 
- 
- 
3 months 
3 month status 
- 
- 
- 
(x) 
Patient & family member information 
 
 
 
 
Contact info 
Gender 
DOB, race / ethnicity, gender, marital status, children 
Employment 
Relation to patient 
Social support 
Financial distress 
x 
- 
- 
- 
NEST  
x 
x 
x 
- 
Goal concordant care 
x 
x 
x 
- 
Quality of communication 
x 
x 
x 
- 
Patient-Perceived Patient-Centeredness (PPPC) scale 
- 
- 
x 
- 
PHQ-9 
x 
- 
x 
x 
GAD-7 
x 
- 
x 
x 
PTSS 
x 
- 
x 
x 
Relationship with physician 
x 
x 
x 
- 
Physician discussed needs 
x 
x 
x 
- 
Readmitted? 
- 
- 
- 
X 
Clinician information 
 
 
 
 
Gender 
Age 
Race / ethnicity 
Rank 
Service 
Study initiation 
- 
- 
- 
Physician responses 
 
 
 
 
I did family meeting  
- 
X 
X 
- 
CPR: cardiopulmonary resuscitation;  GAD-7: generalized anxiety disorder 7-item instrument; ICU: intensive care unit; NEST:  Needs; Existential 
concerns; Symptoms; and Therapeutic interaction scale; PHQ-9: patient health questionnaire 9-item depression instrument; PTSS: post-
traumatic stress scale 

 
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Appendix 6: Adverse and Serious Adverse Event Reporting Diagram 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Appendix 7: Study Contact Information 
 
Principal Investigator(s) 
Christopher E. Cox, MD, MPH 
Division of Pulmonary Allergy & Critical Care 
Box 102043 
Durham, NC 27710 
Phone: 919-681-7232 
Email: christopher.cox@duke.edu 
One Cow Standing, LLC 
Matthew Gauger, Programmer and Project Manager 
Email: matthew.gauger@onecowstanding.com 
 
 
Sharron Docherty, Ph.D. 
School of Nursing 
BOX 3322 
Durham, NC 27710 
Phone: 919-668-3836 
Email: sharron.docherty@duke.edu 
 
 
DSMB Members 
Keith Swetz 
Email: kswetz@uabmc.edu 
 
Gretchen Schwarze 
Email: SCHWARZE@surgery.wisc.edu 
 
Heather Bush  
Email: heather.bush@uky.edu 
 
Study team 
Katelyn Dempsey, CRC  
Clinical Research Coordinator 
Division of Pulmonary, Allergy & Critical Care 
Email: katelyn.dempsey@duke.edu 
 
Santos Bermejo, CRC  
Clinical Research Coordinator 
Division of Pulmonary, Allergy & Critical Care 
Email: santos.bermejo@duke.edu 
 
  
Study Sponsor 
Partha Bhattacharyya 
NIA Program Officer 
Email:  bhattacharyyap@mail.nih.gov 
 
Dennis Ongubo 
NIA Program Officer 
Email: dennis.ongubo@nih.gov 
 
 
Statistical Team 
Maren Olsen, Ph.D. 
Department of Biostatistics and Bioinformatics 
Email: maren.olsen@duke.edu 
 
Alice Parish, MSPH 
Department of Biostatistics and Bioinformatics 
Email: alice.parish@duke.edu