Addressing Palliative Care Needs Among Intensive Care Unit Family Members
Phase: NA
Conditions: Critical Illness, Family Members, Psychological Distress, Informal Caregivers, Palliative Care
Sponsor: Duke University

NCT03506438 
Full Title: Addressing Palliative Care Needs Among Intensive Care Unit Family Members 
Document Date: 04/28/2021 
Protocol (Pro00090202) 

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Research Abstract
Please type your Research Abstract here:
The Research Abstract should summarize the main points of your study in one paragraph. The following 
guidelines may help you:
1. Purpose and objective (1-2 sentences)
2. Study activities and population group (2-4 sentences)
3. Data analysis and risk/safety issues (1-2 sentences)
This 5-year project funded and conducted under Duke's REACH Equity Center, run by PI Kimberly Johnson. 
The blanket protocol number for the REACH Equity Center is Pro00090554.
The purpose of the study is to test and develop a web application (ICUconnect) that will improve racial 
disparities and unmet palliative care needs among ICU family members using a randomized clustered 
clinical trial (RCT). An ancillary study will be conducted simultaneously to determine if the presence of 
‘palliative care triggers’ among patients is associated with greater unmet needs among patients’ family 
members.
We anticipate that our total study population across both the RCT and ancillary studies will include, in 
total, 360 patients, 395 family members, and 60 physicians. The clinical trial group will consist of 160 
family members of patients (80 white and 80 black) in Duke ICUs (medical, surgical, cardiac, cardio-
thoracic and neurological, including DRH ICU). A total of 200 family members will participate in the 
ancillary study, 130 of whom will be enrolled as the control group in the clinical trial (including up to 30 
who otherwise would have been deemed ineligible after T1 based on a low needs score i.e., NEST survey) 
and 70 others. 10 family members will complete app user testing alone and will not be trial participants 
(Aim 1 Usability) and up to 25 family members previously enrolled in aim 2 of the RCT and ancillary 
studies will be asked to participate in Aim 4 of the RCT (or Aim 3 of the ancillary study). 
For the families enrolled in Aim 2 of the RCT or the ancillary project, study activities include the completion 
of 4 surveys: T1, T2, T3, and T4. Should a family member be enrolled into the RCT under an ICU clinician 
who has been randomized to intervention, a family meeting will occur between the randomized clinician 
and the family member to discuss the reported needs from T1. This family meeting will occur after T1 is 
completed but prior to T2 survey completion. Clinicians enrolled into the RCT and randomized to the 
intervention arm will be able to view the family needs data.
This study represents minimal risk. We have specific plans to address potential distress occurring during 
the study, as well as plans to protect against the potential loss of data confidentiality.
Research Summary
State your primary study objectives
The primary objective of the RCT is to compare the web app (ICUconnect) to usual care on unmet needs 
and perceptions of quality of care. The secondary objective is to determine the effect of the web app 
(ICUconnect) as an intervention on racial disparities in both unmet needs and in the quality of patient-
centered care within the Duke University Hospital Intensive Care Units (ICUs) and Durham Regional ICUs. 
The ancillary study aims to understand how ICU patients’ and their families’ palliative care needs in an ICU 
setting evolve over time and develop a needs-targeted, ICU-based palliative care collaborative delivery 
model.
Using a multi-aim approach, we hypothesize that by conducting the RCT and ancillary studies 
simultaneously that we will be able to:
Optimize the usability of the ICUconnect web app intervention (Aim 1, RCT)
Find that the intervention (web app, ICUconnect) will improve:
Unmet needs in both Black and White patients and families in the ICUs (Aim 2, RCT).

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Quality of patient-centered care in both Black and White patients and families in the ICUs 
(Aim 2, RCT).
Find that the intervention (web app, ICUconnect) will improve:
Reduce racial disparities in unmet needs and quality of patient-centered care for patients 
and families in the ICUs (Aim 3, RCT)
Understand the type, severity and burden of the needs of patients and families and thereby develop 
a method to decrease psychological distress and develop a collaborative care delivery model for ICU 
clinicians (Aim 1 and 2, Ancillary)
Understand previously enrolled family members’ unique experiences of having a loved one in an 
ICU—before or during COVID. (Aim 3, Ancillary and Aim 4 RCT).
State your secondary study objectives
N/A
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your protocol fits under the other research summary templates in this category).  Use of these instructions is 
helpful for ensuring that the research summary contains all necessary elements.
Standard Research Summary
Purpose of the Study
Objectives & hypotheses to be tested
The purpose of the study is to test and develop a web application (ICUconnect) that will improve racial 
disparities and unmet palliative care needs among ICU family members using a randomized clustered 
clinical trial (RCT). An ancillary study will be conducted simultaneously to determine if the presence of 
‘palliative care triggers’ among patients is associated with great unmet needs among patients’ family 
members.
The primary objective of the RCT is to compare the web app (ICUconnect) to usual care on unmet needs 
and perceptions of quality of care. The secondary objective is to determine the effect of the web app 
(ICUconnect) as an intervention on racial disparities in both unmet needs and in the quality of patient-
centered care within the Duke University Hospital Intensive Care Units (ICUs) and Durham Regional ICUs. 
The ancillary study aims to understand how ICU patients’ and their families’ palliative care needs in an ICU 
setting evolve over time and develop a needs-targeted, ICU-based palliative care collaborative delivery 
model.
The RCT will consist of 4 aims:
Aim 1:  Optimize the usability of the ICUconnect app intervention in preparation for Aim 2's RCT.
Approach & goal:  We will optimize the usability of ICUconnect using focus group 
interaction-response testing. We will add key features based on a short series of iterative 
revisions with clinicians and families until it achieves ‘excellent’ usability (mean Systems 
Usability Scale score >85). 
Aim 2:  In a cluster RCT, determine the effect of the ICUconnect intervention versus usual care on 
unmet needs(primary outcome) and perceptions of the quality of patient-centered care(secondary 
outcome) in the ICU, both overall and within Black and White patients and families.  
Hypothesis 2a:  As compared to usual care, the intervention will improve unmet needs in 
both Black and White patients and families in the ICU.  
Hypothesis 2b:  As compared to usual care, the intervention will improve quality of patient-
centered care in both Black and White patients and families in the ICU.
Aim 3:  Determine the effect of the ICUconnect intervention versus usual care on racial disparities 
in both unmet needs (primary outcome) and in the quality of patient-centered care (secondary 
outcome).

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Hypothesis 3a: Racial disparities in unmet needs will be reduced among patients and 
families in the ICU in the intervention group as compared to usual care.
Hypothesis 3b:  Racial disparities in the quality of patient-centered care will be reduced 
among patients and families in the ICU in the intervention group as compared to usual 
care.      
Aim 4 (exploratory): Using mixed methods (semi-structured interviews and quantitative process 
measures), characterize the impact of ICUconnect across a variety of family-and patient-
implementation contexts, with a goal of understanding intervention mechanisms and family 
members’ unique experiences of having a loved one in an ICU—before or during COVID.
Approach & goal: We will integrate content analysis via a semi-structured interview with 
previously enrolled family members as well as quantitative family, patient, and care process 
outcomes. The content analysis will provide insight into ICUconnect’ mechanisms of action, 
relate outcomes to unique case contexts, and help lead to future intervention optimization, 
replicability, and scalability. It is hoped that this aim may also provide meaningful 
information to field regarding the effects of COVID-19 on family members who have had a 
loved one in an ICU setting.
The Ancillary Study, conducted simultaneously with the RCT, will consist of 3 aims:
Specific Aim 1: To understand ICU patients’ and families’ palliative care needs in an ICU setting—
and how they evolve over time.
Goal: To understand the type, severity, and burden of need as measured with a framework 
of palliative care quality domains and derive clinically relevant ‘need typologies’ from these 
dat
Exploratory hypothesis 1a:  Family members with needs that remain unmet 
across the ICU stay will report greater 3-month psychological distress compared to 
those whose needs were met. 
Exploratory hypothesis 1b:  Family member need burden will be higher based on 
patient trigger status (present vs. absent), even after adjustment for 
sociodemographic and patient characteristics.
Specific Aim 2:  Develop a need-targeted, ICU-based palliative care collaborative care delivery 
model.
Goal 2a:  Develop a provisional collaborative ICU-based palliative care model based on Aim 
1’s need typologies, clinician skill in addressing needs, clinician attitudes, and published 
guidelines.  The algorithm-based model will display recommendations for addressing needs 
(ICU team or ICU team plus specialist palliative care) on a mobile app viewable on any 
electronic device. 
Goal 2b: Test the care model’s acceptability among clinicians, using qualitative analysis of 
focus groups and quantitative satisfaction metrics.  Model improvements will be made in an 
iterative process.
Aim 3 (exploratory): Using mixed methods (semi-structured interviews and quantitative process 
measures), characterize the impact of ICUconnect across a variety of family-and patient-
implementation contexts, with a goal of understanding intervention mechanisms and family 
members’ unique experiences of having a loved one in an ICU—before or during COVID.
Approach & goal: We will integrate content analysis via a semi-structured interview with 
previously enrolled family members as well as quantitative family, patient, and care process 
outcomes. The content analysis will provide insight into ICUconnect’ mechanisms of action, 
relate outcomes to unique case contexts, and help lead to future intervention optimization, 
replicability, and scalability. It is hoped that this aim may also provide meaningful 
information to field regarding the effects of COVID-19 on family members who have had a 
loved one in an ICU setting.
Background & Significance
Should support the scientific aims of the research
Currently, the quality of ICU-based palliative care is highly variable. Patients suffer from unmet symptoms 
in a technology-focused setting, family members report poor quality communication and decision making, 
and clinicians struggle to identify needs and connect with families in a shiftwork environment. These 
factors disproportionately impact Black patients and their families.  Compared to Whites, Blacks report 
lower satisfaction with the quality of ICU care and studies document disparities in multiple domains of 
patient-centered care in the ICU, including communication. Process barriers to improving the quality 
palliative care for this high-risk population include difficulty identifying high risk patients and families with 

unmet palliative care needs, coordinating care by ICU teams, and engaging diverse family decision makers 
as partners in the care process.  The field needs better ways to meet the palliative care needs of families 
in an ICU setting. 
 Figure 1 outlines the project's conceptual model.
Design & Procedures
Describe the study, providing detail regarding the study intervention (drug, device, physical 
procedures, manipulation of the subject or the subject’s environment, etc.). Discuss justifications for 
placebo control, discontinuation or delay of standard therapies, and washout periods if applicable. 
Identify procedures, tests and interventions performed exclusively for research purposes or more 
frequently than standard of care. Include alternative therapies, concurrent therapies discontinued per 
protocol, risk benefit ratio, and use of tissue/specimens. Discuss monitoring during washout periods if 
applicable. Include brief description of follow-up, if any.
This study is a randomized clustered clinical trial (RCT) that will be conducted within the Intensive Care 
Units (ICUs) at Duke University Hospital (DUH) and Durham Regional Hospital (DRH). An ancillary study 
will be conducted simultaneously within the same locations as the RCT.
The RCT, as noted in the “Purpose of the Study” section above, will consist of 4 aims.
Aim 1 of the RCT will consist of three phases. The first phase will involve conducting 1-2 very informal 
focus groups in community gatherings at the Durham AME Zion Health Equity Advocates and Liaisons 
(HEAL) Partnership Meeting. During the meetings, the study team will obtain informal feedback 
surrounding the study surveys and the proposed subject handouts. Written informed consent will not be 
obtained because participants are aware of our participation in the meeting. The study team will preface 
the purpose of the presentation (and note that participants of the meeting do not have to participate or 
even remain in the room if they do not wish to do so). Feedback will be recorded by the study team via 
simple note taking. The study team will not record names of participants and no written questionnaires will 
be distributed. The study team will ask participants if they would be willing to participate in a more formal, 
future usability testing procedure and then record their contact information. The second phase of Aim 1 
will involve web application (ICUconnect) improvements based on feedback received. These improvements 
include, but may not be limited to: simpler, secure login for Duke clinicians via shibboleth authentication, 
user-friendly interface, automated alerts to staff related to task completion, and enhanced dashboard 
views unique to the study role (e.g., CRC vs. clinical teams vs. family members). During this process, 
enterprise-level security features will be integrated to meet Duke’s standard requirements. The third and 
final phase of Aim 1 is the evaluation of usability of the web application after phase 2 enhancements have 
been completed. During this phase a mixed methods approach will be utilized to complete usability testing. 
We intend to enroll 10-15 community-based laypersons (sampled geographically and racially). To complete 
user testing, each participant will receive an email with a brief explanation of the task (open ICUconnect, 
view information, complete ICUconnect survey) and a link to the System Usability Scale (SUS). Using this 
survey link, participants will have the opportunity to write free text feedback. No identifiers will be 
collected. Similarly, the study team will evaluate the physician-facing elements of ICUconnect among 8-12 
purposively sampled ICU and palliative care clinicians. From both types of participants, data will be 
organized with the Nielsen usability heuristics model and revisions will be made to the web application as 
needed.
Aims 2 and 3 of the RCT will be completed simultaneously. The total targeted population for Aims 2 and 3 
of the RCT are 240 enrolled patient/family dyads and a maximum of 60 randomized clinicians. To be 
considered “enrolled” for this study, a patient/family dyad must meet all eligibility criteria and receive a 
NEST score of 
 15.
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For aims 2 and 3, the study team will conduct a randomized clustered clinical trial. Randomization occurs 
at the ICU clinician level versus that of the patient/family level. Clinicians are identified as eligible if they 
are the current attending on service for the particular ICU. Clinicians are randomized to one of the two 
arms based on the following:

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Gender (male/female)
Clinical Experience (<10 years vs 
 10 years)
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Discipline (medical vs. surgical)
Consented, enrolled clinicians are expected to complete the following survey(s):
Baseline Demographics Survey (on the day of consent)
For those clinicians who are randomized to intervention, they will be required to complete the following:
Review patient/family needs score and survey results within ICUconnect (at the completion of T1 by 
patient/family dyad)
Schedule and conduct a family meeting (after T1 completion but before T2 completion)
Review patient/family needs score and survey results within ICUconnect (at the completion of T2 by 
patient/family dyad)
Complete the Clinician Survey via ICUconnect (after Family Meeting and completion of T1 and T2 by 
patient/family dyad).
Patient/family dyads will be identified at the time of ICU admission and approached for consent based on 
meeting study inclusion/exclusion criteria (see Selection of Subjects). Each patient/family member, if 
enrolled into the RCT will be asked to complete an ICUconnect profile and survey (T1). This survey is to be 
completed within 24 hours of consent to the study. Given that this study’s intent is to address unmet 
needs, eligible participants must receive a NEST score of 
 15 (see Study Eligibility Workflow).
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If a participant receives a NEST score of < 15 and they are assigned to a randomized intervention 
clinician, the participant is considered a screen failure.
If a participant receives a NEST score of < 15 and is assigned to a randomized control clinician, the 
participant is considered a screen failure for the RCT but is allowed to continue participation within 
the ancillary study.
Assuming that a participant receives a NEST score of 
 15, regardless of clinician randomization, the 
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participant will continue with the following study procedures:
Survey 2 (T2) to be completed within 3 days (0/+1 day) of T1 completion.
Survey 3 (T3) to be completed within 7 days (0/+3 days) of T1 completion
Survey 4 (T4) to be completed within 3 months (90 days, 0/+3 days) of T1 completion.
Should a participant receive a NEST score of 
 15 and be randomized to an intervention clinician, the 
>
participant will be contacted by the intervention clinician have a family meeting. Family meetings are to 
occur after the completion of T1 but prior to the completion of T2. Given the short timeframe between T1 
and T2, the clinician can conduct the family meeting in a variety of settings: in the ICU at bedside, in a 
private conference room and/or location within the waiting room (at the choice of the participant), and/or 
over the phone.
In conjunction with Aims 2 and 3 of the RCT, the study team will simultaneously enroll patient/family 
dyads into the ancillary study. The ancillary study will include a total of 250 enrolled patient/family dyads. 
Eligible participants will be approached for consent at the time of the ICU admission. Participants enrolled 
into the ancillary study will be those participants whose current attending clinician is not enrolled in the 
RCT and/or their identified primary race and ethnicity is something other than White or African American
/Black and Non-Hispanic. Participants enrolled in the ancillary study, like the RCT, must meet study 
eligibility criteria.
Participants enrolled into the ancillary study will complete an ICUconnect profile and then be asked to 
complete the following surveys:
Survey 1 (T1) to be completed within 24 hours of consent.
Survey 2 (T2) to be completed within 3 days (0/+1 day) of T1 completion.
Survey 3 (T3) to be completed within 7 days (0/+3 days) of T1 completion
Survey 4 (T4) to be completed within 3 months (90 days, 0/+3 days) of T1 completion.
Given that the targeted patient population involves individuals who are seriously ill and/or injured, the 
study team expects that there is a high likelihood that death could occur while the patient/family dyad’s 
participation is ongoing. Should a patient pass away while study participation is ongoing, the following will 
occur:
If the patient passes after the completion of T1 but prior to the completion of T2, the patient/family 
dyad will be withdrawn from the study.
If the patient passes after the completion of T1 and T2 but prior to T3 completion, the patient
/family dyad will remain eligible to continue study participation; however, the study team will be 
mindful and sensitive regarding approach and may skip T3. It is not considered a deviation if the 
family completes T3 prior to the study team enabling the “skip” option within ICUconnect.

If the patient passes after the completion of T1, T2, and T3 but prior to completion of T4, the study 
team may wait 1 month before asking the family to complete the fourth and final study survey. It is 
not considered a deviation if the family completes T4 1 month late.
In regards to survey completion, it is understood, given the nature of the study design (self-directed 
participant survey completion), that surveys may not be completed in the specified protocol windows. The 
study team will provide participant education at the time of consent regarding the importance of 
completing surveys in a timely manner. In addition, the study team will follow-up with participants (patient
/family dyads and clinicians) via phone, email, and in-person to complete study surveys and/or family 
meetings, as applicable.
The study consists of the following statuses for patient/family dyads:
Consented: an individual(s) who meets all eligibility criteria and has voluntarily agreed to 
participate in the study (RCT or ancillary).
Enrolled: an individual whom, after consent is obtained, completes the first survey.
Nte: if a participant is enrolled in the RCT study and receives a NEST score of < 15, he/she 
is deemed a screen failure and is therefore no longer enrolled. If a participant is enrolled in 
the ancillary study, he/she does not need to meet a NEST threshold for enrollment.
Screen Fail: any participant who is enrolled into the RCT and receives a score of < 15.
Withdrawn by PI: any participant who does not comply with study specific requirements (i.e. such 
as timely completion of study surveys, specifically T1 and/or T2) or is found to be by the principal 
investigator no longer appropriate for this study due to current state of being (physical, mental and
/or emotional).
Withdrawn by Self: voluntary withdraw of participant from study for any reason.
Completed: any participant (RCT or ancillary) who completes 75% of study visits.
The study consists of the following statuses for clinicians:
Consented: an individual clinician who is on service at the time of the eligible patient/family dyad 
admission and has agreed to voluntarily consent to the study.
Randomized: a clinician who has been randomized to one of the two study arms:
Interventin: a clinician wh receives the patient/family dyad T1 and T2 survey results, 
conducts a family meeting to discuss results, and completes a clinician survey post family 
meeting and survey results review. 
Cntrol: a clinician wh neither receives patient/family dyad T1 and T2 surveys nor conducts a 
family meeting to discuss results.
Given the nature of the targeted population under study and that the goal of this study is to address 
unmet needs and racial disparities among ICU family members, we do not anticipate adverse events and
/or serious adverse events. However, it is possible that the patient/family dyad could become distressed in 
an ICU setting, especially as the patient becomes more ill and/or dies. As a result, the study team will 
monitor, document and report suicidal ideation (SI) as an Adverse Event (AE). The monitoring of SI is 
operationalized by the participant responding to one of the survey questions (PHQ-9; #9: Thoughts that 
 An automated alert is triggered and an 
you would be better off dead or of hurting yourself in some way).
email is sent to the Principal Investigator, the Study Manager, and the Clinical Research Coordinators. The 
PI will be the primary responsible party for addressing the SI alert; however, the Study Manager may also 
serve in the PI’s absence. Both are trained on the Columbia Suicide Severity Rating Scale (C-SSRS).
A serious adverse event (SAE) for this trial would include a suicide attempt. Again, given the nature of the 
targeted population under study, it is not unexpected that the patient would experience hospitalization and 
subsequent ICU admission (or even repeat hospitalization, if discharged), therefore, the study will not 
document and/or report hospitalizations and/or deaths for the patients. However, if the enrolled family 
member and/or clinician were to be hospitalized and/or pass away, the study team would consider this an 
SAE and would document and report appropriately.
All protocol defined AEs and SAEs will be reported to the appropriate agencies (NIH) and the institutional 
review board, as appropriate and in line with guidelines and policies.
In addition, given that this study is short term, participant-driven, and survey-based, it is not anticipated 
that protocol deviations, violations, and or other unanticipated problems will occur at any great frequency. 
Should a protocol deviation, violation, or other unanticipated problem occur, the following reporting 
process will be adhered to: the study team will notify the PI of the error/issue(s). The event will be 
reviewed, documented and reported per institutional policies and NIH guidelines, as appropriate. As 
previously stated, this study does lend itself to the likelihood that the self-directed surveys will be 
completed outside of defined protocol window. These are not to be considered deviations and will not be 
reported as such given the likely frequency and benign nature of the event itself.
Characteristics of an Adverse Event(s)Relationship to Study Intervention
To assess relationship of an event to study intervention, the following guidelines are used:

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Related (Possible, Probable, Definite)
The event is known to occur with the study intervention.
There is a temporal relationship between the intervention and event onset.
The event abates when the intervention is discontinued.
The event reappears upon a re-challenge with the intervention.
Not Related (Unlikely, Not Related)
There is no temporal relationship between the intervention and event onset.
An alternate etiology has been established.
Expectedness of SAEs
The Study PI will be responsible for determining whether an SAE is expected or unexpected.  An adverse 
event will be considered unexpected if the nature, severity, or frequency of the event is not consistent with 
the risk information previously described for the intervention. 
Severity of Event
The following scale will be used to grade adverse events:
Mild: no intervention required; no impact on activities of daily living (ADL)
Moderate: minimal, local, or non-invasive intervention indicated; moderate impact on ADL
Severe: significant symptoms requiring invasive intervention; subject seeks medical attention, 
needs major assistance with ADL
For Aim 4 (or Aim 3 for the ancillary study), delegated study team members will review the list of 
previously enrolled patient/family dyads and select individuals for recruitment based on their already 
collected information from study participation in aims 2 and 3 in the following categories: 
-Study (R21 vs. ICUconnect intervention arm)
-Gender
-Trigger (present vs. absent)
-Race
-Age
-Medical vs Surgical ICU (place of eligibility and recruitment)
-NEST at T1 and T2 (responder vs. non-responder)
-Technology confidence
-Status (completed)
Families who meet the criteria listed above will be contacted via telephone and/or email and asked to 
participate in this portion of the project using the approved telephone and/or email consent template. Each 
individual will be asked to read, review, and sign/date an eConsent attesting to their willingness to 
participate. 
As part of this aim, families who choose to participate will be asked to complete a 15 minute audio 
recorded interview in which the family member will be asked a series of questions pertaining to their loved 
one's hospitalization and ICU admission, the status of their loved one (alive or deceased), and then their 
overall experience related to their loved one's care in the ICU and their interactions with the clinical care 
team. 
Selection of Subjects
List inclusion/exclusion criteria and how subjects will be identified.
To identify eligible patient/family dyads for consent in both the RCT and the ancillary study, the study 
team will utilize the electronic medical record (EMR) known as EPIC for screening purposes. The study 
team will complete a daily review of the EMR, specifically reviewing each ICU unit and associated beds for 
patients who meet study criteria.

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For both the RCT and the ancillary study, eligible participants are those patients who are at least at 
moderate risk of death or disability. In addition, while patients will not be excluded based on diagnosis, it 
is anticipated that most patients will predominantly be diagnosed with cardiorespiratory failure, stroke, 
trauma, and/or septic shock.
Eligible clinicians will be identified by the Principal and sub investigators. Clinicians must meet the criterion 
listed below. In addition, the selected clinician for consent and subsequent randomization should be 
scheduled to be on service at least 8 weeks per year (or the equivalent in terms of 12-hour shifts).
Inclusion Criteria (Patients, Pre-Consent)
≥18 years of age
Patients must be on mechanical ventilation in a study ICU for ≥ 24 hours
For those patients whose mechanical ventilation is interrupted for <72 hours, they will 
remain eligible for study participation.
If a patient is intubated on the day of eligibility but then subsequently extubated the same 
day, the patient remains eligible for the study as long as consent and T1 are completed 
within 8 hours of extubation. 
Death must not be imminent (< 24 hours)
Inclusion Criteria (Family Members, Pre-Consent)
One family member per patient is eligible.
The family member must be ≥ 18 years old.
The family member must be self-described as the individual (related or unrelated) who provides the 
most support and with whom the patient has a significant relationship.
Inclusion Criteria (Clinician, Pre-Consent)
Patients’ bedside ICU attending physicians on the day of family consent are eligible.
Exclusion Criteria (Patients, Pre-Consent)
Patients who are admitted to an ICU at the index hospital >14 days will be ineligible for 
participation.
Patients who are on comfort care or are planned to undergo withdrawal of treatment within the 
following 48 hours of enrollment will be excluded.
Prisoners
Patients who have no known family or surrogate.
Patients who are transferred to a non-study ICU or non-study clinician will be excluded if they are 
enrolled into the RCT only.
Exclusion Criteria (Family Members, Pre-Consent)
Family members will be excluded if they lack English fluency or have other limiting factors that 
inhibit their ability to use the app (e.g. literacy, blindness, etc).
Family members will be excluded if they are not directly involved in decision making, are 
unreachable or unavailable.
Family members will be excluded if they are <18 years of age.
Family members will be excluded if they are unable to consent (e.g., dementia, cognitive 
impairment).
Prisoners.
For the RCT only: family members who self-identify as Hispanic and/or self-identify most with a 
racial group other than White or Black will be excluded.
Ethnic and racial exclusions do not apply to the ancillary study.
Exclusion Criteria (Patient/Family Dyad Post-Consent)
Patient dies before T2 is completed. 
Family members will be excluded from the RCT, but not the ancillary study, who have a very low 
need burden (NEST < 15) after the completion of T1.
For the primary RCT, participants are also excluded if the randomized physician leaves ICU service 
or is replaced by a non-participating ICU physician < 2 calendar days after family completes T1.
For Aim 4 RCT (or Aim 3 Ancillary Study) Only:
Inclusion Criteria (Family Member)
1. Must have been previously consented and enrolled in the ancillary and/or RCT study, meaning that all
eligibility criteria noted above was met both pre and post consent.
Exclusion (Family Member)

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1. Inability, in the opinion of the study team, to complete the single study visit.
Subject Recruitment and Compensation
Describe recruitment procedures, including who will introduce the study to potential subjects. Describe 
how you will ensure that subject selection is equitable and all relevant demographic groups have access 
to study participation (per 45 CFR 46.111(a) (3)). Include information about approximately how many 
DUHS subjects will be recruited. If subjects are to be compensated, provide specific prorated amounts 
to be provided for expenses such as travel and/or lost wages, and/or for inducement to participate.
All eligible patient/family dyads, regardless of RCT or ancillary study, are recruited from within the 
participating ICU. Recruitment of eligible patient/family dyads can occur in 1 of 3 ways, depending on the 
patient/family dyad at the time of consent:
Traditional research introduction and in-person consent: the study team will approach a member of 
the clinical team who is facilitating in the care and communication with the eligible patient/family 
dyad. The study team will inform the clinical team member (typically the registered nurse in charge 
of the patient’s room) that the patient/family dyad are eligible for participation in a research study. 
A brief explanation of the research study will be provided to the clinical team member. Given the 
sensitive nature of the targeted study population (at risk for death and/or disability), the study 
team will ascertain from the clinical care team member if it is an appropriate time to speak with the 
patient/family dyad. If the clinical care team member says that it is okay, the clinical care team 
member will be asked to provide a research introduction to the patient/family dyad. Assuming that 
a verbal “okay” to approach is provided, the study team will approach and provide a brief review of 
the study (verbally and/or utilizing the brief study infomercial) and ask if they would like to review 
the informed consent. Should the patient/family dyad be interested, the study team member will 
proceed with either eConsent or traditional paper consent, at the request and preference of the 
patient/family dyad.
Traditional research introduction and remote consent utilizing eConsent: in many instances family 
members of patients admitted to the ICU are not able to be present at the patient’s bedside during 
normal business hours. In addition, many patients’ family members are located out of state. The 
family members are still communicating with the clinical care team about their loved one after 
normal business hours or remotely (via phone, email and MyChart); however, this makes obtaining 
an in-person consent nearly impossible. As a result, when this type of scenario occurs, the study 
team will speak with the clinical care team and request a research introduction. Assuming that the 
family member provides verbal or written affirmation that they are okay to be approached by 
research, the study team will email the eConsent(s) to the family member and then follow-up via 
phone to review the informed consent with the family member in the same manner that they would 
review the consent if in person.
Utilization of the DUHS Recruitment and Engagement Policy: As noted above, many eligible family 
members of patients admitted to the ICU are not present at bedside. In addition, the clinical care 
team is often busy and have a number of different topics to discuss with the family members. As a 
result, research introductions for those families who are remote and/or visit the ICU after regular 
business hours often go uncompleted. To ensure enrollment for both the RCT and the ancillary 
studies remain successful, the study team would like to utilize an approved script to speak with 
family members without a traditional research introduction by a member of the clinical care team. 
Should this approach be utilized, the study team will utilize the eConsent to obtain informed 
consent unless the family member requests an in-person meeting for the purpose of consenting via 
paper. Prior to utilizing the policy, the study team will first review any potential participant's 
indication in MaestroCare to ensure they have not opted out of being contacted for research prior to 
contacting them. If the patient has opted out of being contacted for research no contact will be 
made utilizing the Recruitment and Engagement Policy.
Please note that for all scenarios described above, a research introduction may also be completed by the 
investigators of this study, as they all are routinely physicians on service and dually serve as members of 
the clinical care team. Research introductions for eligible patient/family dyads provided by investigators 
will be used as infrequently as possible and only when necessary. This will ensure that coercion to 
participate in the study is minimized as much as possible.
Eligible clinicians will be introduced to the research study by the investigators of the study. All eligible 
clinicians will be approached and provided a brief research introduction. If the clinician is interested in 
participation, he/she will provide verbal or written affirmation to the investigators. The investigators will 
then inform the study team of the clinician’s interest in the study and confirm that it is okay to approach 
for research. The study team will then contact the clinician, due to their busy schedule, electronically and 
provide the eConsent (unless otherwise requested by the clinician, in which case paper consent would be 
utilized).

For the RCT, specifically, the study includes only those participants who self-identify as non-hispanic and 
either white or black. The purpose of this design is to determine racial disparities experienced among black 
patients and their families.  However, the ancillary study is open to all races and ethnicities and will 
therefore ensure that the subject selection for this entire project is equitable and all relevant demographic 
groups have access to study participation.
To meet the statistical power needs for data analysis, the RCT intends to consent approximately 320 
patient/family dyads to ensure that 240 patient/family dyads meet all study criteria and are subsequently 
enrolled. In order to enroll 240 patient/family dyads, 30-60 clinicians will be consented, enrolled and 
randomized to the study with a relatively equitable split between those clinicians assigned to intervention 
and those assigned to control.
In the same manner, the ancillary study intends to consent approximately 300 patient/family dyads to 
ensure that 250 patient/family dyads meet all study criteria and continue with subsequent study 
enrollment. The study team does not anticipate as high a screen fail rate among the ancillary study 
population as compared to the RCT given that participants do not need to meet a high needs threshold as 
defined by their completed NEST score at T1. No clinicians or other clinical care team members will be 
enrolled as part of this study.
All participants who consent and complete at least T1 will receive $20.00 for their time. For those 
participants who are enrolled into the RCT and remain eligible after T1, they will receive up to a total of 
$70.00 for the completion of all four surveys. For those participants who are enrolled into the ancillary 
study and remain eligible after T1, they will receive up to a total of $70.00 for the completion of all four 
surveys.
Compensation for participants is based on the completion of each study survey:
T1: $20.00
T2: $20.00
T3 (mini survey): $10.00
T4: $20.00
All compensation is received via check to the participant’s provided mailing address on the completed IRB 
Data Disclosure Form (DDF).
Clinicians are not compensated for their study participation. This is to ensure and mitigate any potential 
research bias and/or coercion.
As noted above, Aim 4 RCT (or Aim 3 Ancillary), will recruit families from those individuals who already 
consented to the study for aims 2 or 3. Individuals will be approached via telephone and/or email and 
asked to consider study participation. They will be informed that research is 100% voluntary and that they 
are being asked to participate as they previously opted to participate in another portion of this study 
project. All willing participants will be asked to read, review, sign and date the eConsent attesting to their 
willingness to participate in the study. 
Compensation will be provided to family members who choose to participate. Each individual will receive 
$20.00 for their time via check.
Subject’s Capacity to Give Legally Effective Consent
If subjects who do not have the capacity to give legally effective consent are included, describe how 
diminished capacity will be assessed. Will a periodic reassessment occur? If so, when? Will the subject 
be consented if the decisional capacity improves?

Given the nature of the targeted patient population (i.e. those who are mechanically ventilated in an ICU), 
it is expected that they will not have the capacity to legally give effective consent. As a result, the family 
member (primary caregiver) and legally authorized representative (LARD) will be asked to consent on their 
behalf.
For those patients who have decision making capacity (DMC), they will not be excluded from participating. 
The family member (primary caregiver) of the patient will still be asked to consent and will be the primary 
responder for the study surveys; however, the patient who has DMC will be asked to consent on their own 
behalf to allow the study team to collect necessary medical information from their EMR for data analysis 
instead of the patient’s LAR.
Study Interventions
If not already presented in #4 above, describe study-related treatment or use of an investigational 
drug or biologic (with dosages), or device, or use of another form of intervention (i.e., either physical 
procedures or manipulation of the subject or the subject’s environment) for research purposes.
The intervention under study is the novel web application known as ICUconnect. The primary purpose of 
ICUconnect is to develop an accessible, automated, and present application that proactively address needs 
(i.e. physical, mental, emotional, spiritual, and racial) and improves communication between ICU families, 
patients and the clinical care team members.
All participants, regardless of study enrollment into to the RCT or ancillary study, will be given access to 
ICUconnect and asked to complete surveys T1, T2, T3 and T4.
For those patient/family members enrolled into the RCT, they will specifically be assigned to a clinician 
who has been randomized to one of two study arms: “intervention” or “control”. For those patient/family 
members who are randomized to an “intervention” clinician, the following will occur:
T1 completed within 24 hours of consent.
Assuming a NEST scre of 
 15, the T1 survey results will be emailed r texted to the 
>
randomized clinician.
Clinician will review the T1 survey results and then, based n results, conduct a family 
meeting with the family member. The family meeting is to occur prior to T2.
T2 completed 3 days after the completion of T1.
Clinician will receive T2 survey results and will be able t visualize the “change” in score post 
their family meeting. The purpose of this is to provide feedback to the clinician regarding 
how well they addressed the patient/family reported needs.
After the clinician has viewed the secnd survey results and “change” in score from the first 
survey to the second survey, the clinician will be asked to complete a 3 question survey 
regarding the patient’s prognosis, the completion of the family meeting, and general 
impression of the family relationship.
T3 completed 7 days after the completion of T1.
T4 completed 90 days after the completion of T4.
For those patient/family dyads who are enrolled into the RCT and assigned a “control” clinician, they will 
receive “standard of care” as follows:
T1 completed within 24 hours of consent.
Assuming a NEST scre of 
 15, the patient/family dyad remains eligible fr the RCT and 
>
continues with study enrollment. If they receive a score of < 15, they are no longer eligible 
for the RCT but will roll into the ancillary study.
T2 completed 3 days after the completion of T1.
T3 completed 7 days after the completion of T1.
T4 completed 90 days after the completion of T4.
For those patient/family dyads enrolled into the ancillary study, they will not be assigned a clinician and 
will receive “standard of care” as follows:
T1 completed within 24 hours of consent.
T2 completed 3 days after the completion of T1.
T3 completed 7 days after the completion of T1.
T4 completed 90 days after the completion of T4.

1.  
2.  
a.  
3.  
For both the RCT patient/family dyads who are assigned to a “control” clinician and the ancillary patient
/family dyads, their survey results will not be visible to a clinician and a family meet will not be conducted 
for research purposes.
Risk/Benefit Assessment
Include a thorough description of how risks and discomforts will be minimized (per 45 CFR 46.111(a) (1 
and 2)). Consider physical, psychological, legal, economic and social risks as applicable. If vulnerable 
populations are to be included (such as children, pregnant women, prisoners or cognitively impaired 
adults), what special precautions will be used to minimize risks to these subjects? Also identify what 
available alternatives the person has if he/she chooses not to participate in the study. Describe the 
possible benefits to the subject. What is the importance of the knowledge expected to result from the 
research?
Participants may experience some degree of stress due to the critical illness itself, and it is possible that 
they could experience anxiety when answering survey questions.  When necessary, participants who 
experience psychological distress related to filling out self- report questionnaires will be referred for 
appropriate psychiatric or psychological care as described below. 
Additionally, given the extreme stresses of the critical illness experience, participants may even endorse 
suicidal ideation (note the PHQ-9 has a suicidal ideation item).  The study team will take the following 
measures to prevent any negative reactions as well as effectively manage any serious distress that occurs:
Participants will be told that they can discontinue survey completion at any time and revisit the 
survey when they feel they are able to complete it.
The study team will remain sensitive when discussing psychological distress among ICU family 
members.
There is a potential risk for identifying underlying mental health issues through interactions, 
telephone calls, and survey responses.  If issues, such as passive suicidal ideation or 
symptoms of depression, anxiety, or PTSD are suspected, the study team will alert the 
principal investigator. The principal investigator will follow-up with the patient/family dyad’s 
treating clinician and/or case manager within the ICU and ask for clinical follow-up, as 
needed.
The study team has developed a specific protocol to manage any study participant who expresses 
suicidal thoughts in person, by telephone, or via the app at any point during the study. The PI and 
other delegated study team members, as needed, are required to complete the online Columbia 
Suicide Severity Rating Scale (C-SSRS) training, a 30-minute interactive slide presentation followed 
by a question-answer session. Once completed, they are able to administer the C-SSRS. The C-
SSRS is scale that can delineate high, moderate, and low-risk levels. 
Our Suicidality Response Plan can be activated in two main ways.  First, study staff (coordinators, 
investigators, PI) may have in-person or telephone interactions that concern them.  Second, the 
study data system will automatically detect any endorsement of the PHQ-9's suicidality item, 
sending an alert email in real time to the Study Manager and the PI.  An example of this alert 
system in the context of using the Hospital Anxiety and Depression Scale (HADS) questionnaire in 
the CSTEP RCT is shown in the screenshot below.
If the participant is deemed to be at high risk based on direct interaction or the PHQ-9 item 
response, then the PI and study manager will be notified immediately.  Using the C-SSRS, the PI 
will then help to assess the participant to determine if they endorse active suicidal ideation.  The 
PI will also determine of the participant is currently being treated by a mental health professional.
If the patient is deemed not to be actively suicidal, they will be given a list of local mental health 
resources as follows:
Duke: Call Emergency Psychiatry at 681-4410 or 681-1316, available 24 hours a day, 7 days a 
week.
Backup: The National Suicide Prevention Lifeline - 1-800-273-TALK (8255) is a free, 24-hour 
hotline available to anyone in suicidal crisis or emotional distress.
If the participant is considered 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. If the participant is with one of the study personal:
a. The study personnel will notify the PI immediately
b. The study personnel will either physically walk the subject to the emergency
department, or call a Psychiatric Emergency services number.
Situation 2. If the participant is on the telephone:
a. The study personnel will notify the PI immediately.
b. The study personnel will stay on the telephone with the subject participant.
c. The study personnel will immediately contact 911 to initiate an on-site rescue if such
action is clinically indicated.
d. The study personnel will stay on the telephone with the subject until EMS services have
contacted the participant.
Situation 3. If there are any active suicidal concerns in any of the surveys (e.g., PHQ-9 above):
a. The study data system will notify the PI and Study Manager immediately.
b. Next, the study personnel will contact the participant by telephone.
c. The study personnel will stay on the telephone with the subject participant.
d. The study personnel will use a different telephone line to immediately contact 911 to
initiate an on-site rescue if action is clinically indicated.
e. The study personnel will stay on the telephone with the subject until EMS services have
contacted the participant.
If the participant is determined to be actively suicidal and requires immediate medical therapy, 
they will be withdrawn from the study.
Finally, there is a theoretical risk of loss of confidentiality of data given known limitations of data 
systems and human inputs. The study team will closely safeguard participant privacy regarding 
protected health and personal information. Study ID numbers, generated randomly at the time of 
enrollment, are linked to a separate Duke DHTS-maintained database, known as Study Tracking, 
that contains patient and family member names, as well as to a separate RedCAP subsystem that 
contains patient names and medical record numbers.  Further, names, birthdates, telephone 
numbers, addresses, and medical record numbers are only viewable by the study team after 
authenticating into the webapp backend dashboard via Duke’s shibboleth gate with two factor 
authentication. The webapp backend will store all study data on a Duke DHTS hosted, secured, 
and maintained SQL database. In addition, study data will be exported daily to a REDCap 
database via the REDCap API. Both databases store all data on secure Duke University servers 
with a sophisticated dual backup system.  No PHI is made visible in any study participant 
interface. Study participants cannot view data via the webapp, only enter data (a 'one-way view') 
via one-time unique URLs to surveys. Participants access this one-way survey via PHI-free email 
or text links sent from the webapp backend system.
The study digital infrastructure consists of a central backend study management application, 
known as Study Tracking, hosted on a Duke secure server. This backend system manages three 
portals, one for study participant, one for ICU clinicians, and one for study management. Access 
to the study participant portal is through HTTPS and is designed to take in survey responses and 
serve up static content on the study and on asking questions while in the ICU via a proxy server 
that will serve as a hard wall between the web portal and the backend system. Access to the ICU 
clinician portal and the study management portal will only occur through Duke’s Shibboleth two-
factor authentication. The central backend system will house study data on a separate Duke DHTS 
hosted, secured, and maintained database, and will export study data daily to a separate REDCap 
database via the REDCap API. The central backend system will also utilize Duke’s secure SMTP 
mail server to send out notifications.
Clinicians and intervention families will access the online elements through separate secure 
pathways hosted, monitored, and maintained by Duke University via the study webapp HTTP 
portals. Study staff will use their University credentials to login in a process identical in security 
strength to EHR login. The complete ICUconnect system is hosted on a secure Duke University 
and will be composed of a central webapp backend system, the separate HTTP portals 
(participant, clinician, study management) that will be served from the backend, a separate DHTS 
secured and maintained study database, and the study REDCap database.

Smashing Boxes has built technological solutions that preserve the privacy, confidentiality, and 
security of protected health information that may be part of health records or research datasets. 
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.
Any and all storage of confidential participant data on Smashing Boxes’ hardware is strictly 
prohibited. For both the RCT and ancillary study, the web application and supporting backend 
architecture that Smashing Boxes developed is hosted internally on a secure Duke University 
server, established behind Duke’s PHI firewall system. Thus, no patient data will be stored on 
Smashing Boxes’ hardware and only on approved, secure University servers.
Study data imported into the REDCap database will be delivered via the ICUconnect web app 
backend via the REDCap API.  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 project leader as described in the Resource Sharing Plan.  User 
authentication is based on user passwords as described earlier.  Password creation requirements 
are in place to guarantee “strong passwords” as defined by the CERT security 
recommendations.  The lead systems administrator is GIAC Security Essentials certified through 
May 2018.
To the study team’s knowledge, this is the first study proposed to address the psychological 
distress of both ICU survivors using a telephone-based or mobile web platform-based behavioral 
intervention. The targeted population faces enormous but common disability as a result of critical 
illness and its sequelae. Therefore, the implications of this research, designed to mitigate this 
stress and suffering, are significant for the approximately one million such patients and their 
families treated each year in an ICU setting in the US.
It is hypothesized that that the intervention could greatly improve participants’ well-being in the 
future, and we therefore believe that important knowledge could come of this proposed study. 
Specifically, the ICUconnect intervention may reduce psychological distress.  Additionally, subjects 
in the control condition may experience similar or even greater benefits to those described for 
ICUconnect.  At this time; however, direct benefit cannot be guaranteed.
Study involvement does place subjects at low risk for any adverse physical or psychological 
risk.  Therefore, the potential benefits justify the minimal risks associated with the study.
Costs to the Subject
Describe and justify any costs that the subject will incur as a result of participation; ordinarily, subjects 
should not be expected to pay for research without receiving direct benefit.
There are no costs to any participant (patient/family dyad or clinician) for participating in the RCT or 
ancillary study.
Data Analysis & Statistical Considerations
Describe endpoints and power calculations. Provide a detailed description of how study data will be 
analyzed, including statistical methods used, and how ineligible subjects will be handled and which 
subjects will be included for analysis. Include planned sample size justification. Provide estimated time 
to target accrual and accrual rate. Describe interim analysis including plans to stop accrual during 
monitoring. Phase I studies, include dose escalation schema and criteria for dose escalation with 
definition of MTD and DLT.

Aim 1 Analyses:  Aim 1 is designed to optimize ICUconnect usability. Verbal and free-text feedback from 
families and physicians, along with SUS scores examined across purposively sampled strata after each 
iteration until the goal is reached (mean SUS >85), will ensure app revisions adequately address the needs 
of low technology / low health literacy users. 14
Aim 2 Analyses:
General considerations:  The primary analyses will be conducted on an intention-to-treat basis; clinicians 
and patients will be analyzed in the group to which they were randomized, regardless of clinician 
intervention adherence, using all available data. The main conclusions drawn from this trial will be based 
on the pre-specified hypotheses outlined below and will be tested with two-sided p-values at the standard 
0.05 level. For all study outcomes, we will interpret differences between groups over time with reference 
to prior literature regarding clinically meaningful changes.  Results from exploratory analyses will be 
interpreted with appropriate consideration for their exploratory nature.  Statistical analyses will be 
performed using the latest release SAS for Windows (Cary, NC) and R/Rstudio.
Approach to statistical models: The goal of the primary hypothesis (2a) is to determine the efficacy of the 
ICUconnect intervention versus usual care on reduction in unmet needs from T1 to T2.  Additionally, we 
are interested the intervention effect within Black families and White families separately. Unmet needs will 
be assessed at T1 and T2 with the total NEST score, a continuous, normally distributed measure. Because 
each family member is surveyed at multiple time points and the same ICU physician sees several patients, 
outcome variable measurements will not be independent. We, therefore, plan to use hierarchical linear 
models as our primary analytic strategy because they appropriately account for the multiple types of 
correlation inherent in our study design.45  The hierarchical linear model will have the following form: 
Yijk= b0+ b1(T2) + b2(T2*intk) + b3(racek)+ b4(servicetimek) + b5(ICUtypek)+ bik+ ck+ eijk, where 
Yijkis the total NEST score for family iat time jand physiciank. In this model, T2and intare indicator 
variables for the post-treatment and intervention group, respectively.  Additionally, we include indicators 
for the randomization stratification variables. The multiple levels of correlation are captured via the 
physician-level random effect, ck, and the family-level random effect, bjk.  Both random effects and the 
residual error (eijk) are assumed to be independent and normally distributed.  PROC MIXED in SAS (SAS 
Inc., Cary, NC) will be used to fit the hierarchical linear models and test the primary hypothesis 
(2a).  Specifically, if b2is negative and significantly different than zero, this provides evidence families in 
the intervention group have reduced unmet needs as compared to usual care group families. The 
secondary outcome, quality of patient-centered care, is also a continuous measure assessed at T1 and T2. 
A similar hierarchical linear model will be used to test Hypothesis 2b; in this model, if b2is positive and 
significantly different than zero, this provides evidence families in the intervention group have improved 
quality of patient-centered care as compared to usual care group families. Both analyses for Hypotheses 
2a and 2b will be repeated within Black and White patients separately, with the goal to ensure that the 
intervention is effective in both subgroups (as an overall treatment effect can sometimes mask important 
heterogeneity).  Aim 3 addresses relative differences in the intervention effect on reducing disparities.
Aim 3 Analyses:  A hierarchical linear model will again be the primary modeling strategy for the Aim 3 
analyses.  For this Aim, however, the model will include patient-race interaction terms and will have the 
following form: Yijk= b0+ b1(Blacki) + b2(T2) + b3(T2*Blacki) + b4(T2*intk) + b5(T2*Blacki*intk) + b6
(racek)+ b7(servicetimek) + b8(ICUtypek)+ bik+ ck+ eijk, where Yijkis the NEST score for family iat time 
jand physician k.  In this model, Blackiis the indicator variable for whether a patient is Black (value of 1) or 
White (value of 0). Racial disparities in unmet needs at baseline are represented by the estimated value of 
b1. That is, the estimated baseline mean for White families is b0 and the estimated baseline mean for 
Black families is b0 + b1, so if the estimate of b1is positive, this indicates that prior to the intervention, 
Black patients have more unmet needs than White patients. Post-treatment, the Black-white mean 
difference among usual care group families is BWuc = (b0 + b1+ b2 + b3) – (b0 + b2), and among 
intervention group families is BWint = (b0 + b1+ b2 + b3 + b4 + b5) - (b0 + b2+ b4).  Hypothesis 3a will 
be tested by the difference between BWint and BWuc, indicating that racial disparities unmet needs are 
reduced in the intervention group as compared to the control group.  The estimated difference, p-value, 
and 95% confidence intervals will be calculated via estimate statements in PROC MIXED.  Additionally, 
estimated values and confidence intervals will be calculated for BWint as compared to b1 to quantify the 
magnitude of reduction from baseline.  A similar hierarchical linear model will be used to examine the 
reduction in racial disparities of quality of patient-centered care and test Hypothesis 3b.
Missing Data: The survey data may contain missing values in any of the clinician-level and patient-level 
variables due to drop-out, death, or item non-response.  Our primary analysis technique, hierarchical 
models, allow for unbalanced or incomplete data and will be fit with maximum-likelihood methods to 
preserve the missing at random assumption.  Additionally, we will thoroughly explore reasons for dropout, 
and depending upon the type and scope of missing data, variables may be multiply imputed as 
recommended by guidelines.46Note that if needed, we will utilize imputation methods that account for the 
multiple levels of correlation inherent in the clustered data structure.
Aim 4’s mixed methods analyses will explore and describe user experiences with the intervention to 
understand both mechanisms of action and how outcomes may be related to unique case contexts. 
Additionally, Aim 4 intends to understand the effects COVID-19 may have had on the family member and 

their loved one's ICU admission as it relates to their needs.  This knowledge can guide future intervention 
optimization through enhanced personalization, replicability, and scalability. Interview transcripts will be 
analyzed using a content qualitative analysis technique that combines structural (e.g., intervention 
component, care process barriers) and magnitude coding (e.g., theme intensity) with inductive coding (e.
g., variations in outcomes not captured by instruments).50  Drs. Docherty and Cox will separately code the 
same 5 family members, discuss the generated codes to create an initial code book by consensus. Next, 
they will each code 5 different interviews with further refinements made to the code book which will then 
be used by the investigators to code remaining 15-20 family member transcripts. While the final code book 
will be organized into categories used to generate themes of mechanistic and process elements from 
across all participants, within-case themes generated from family member and clinician interviews will be 
used to write case profiles. Case profiles will merge data from case context descriptors (family and clinician 
race, patient illness, etc), within-case qualitative themes, and quantitative process measures.  A visual 
‘ethnoarray’ matrix will be constructed to display key case findings in relation to every other case.  The 
ethnoarray, loosely adapted from a graphical heat map approach, is a powerful way to present complex 
data and is a flexible method for blending narrative and quantitative data to facilitate the discovery of 
patterns, relationships and understand the contextual richness of the data. These procedures will enhance 
comparative analyses and theoretical interpretation.  For example, case comparisons could be made by 
needs (needs met vs. needs unmet) or patient-centeredness of care (high vs. low).  Process tracing will be 
used to explore how particular case outcomes (e.g., need, distress, goal concordance) may have been 
related to intervention components (e.g., needs assessment, family meeting) and to their effect on 
barriers in our conceptual model (Figure 1). Dr. Docherty will use ATLAS.ti qualitative data analysis 
software for analyses. 
Power and sample size considerations.  For Aim 1, to reach a target of ‘excellent’ usability (mean SUS 
score >85), we expect 1-2 iterative revision cycles of 8-15 family members and 8-10 clinicians—a sample 
similar in size to that needed to reach thematic saturation in qualitative analysis (e.g., the 30 patient-level 
cases (total n=90) we expect will allow us to recognize theme saturation in Aim 4). The effect of interest 
for Aims 2 and 3 is essentially the T1 – T2 difference between the intervention and usual care groups.  Aim 
2 focuses on the overall difference and the difference within Black and White patients separately, while 
Aim 3 focuses on the difference within Black families compared to White families. Therefore, we base our 
sample size calculations on the mean difference score using tests for two means in a cluster randomized 
design. The sample size requirements are greatest for Aim 3; as discussed by Leon and Heo (2009), the 
needed sample size for the family race by intervention group interaction is 4 times that needed for the 
overall test. Based on preliminary studies, the standard deviation of the change in NEST score is estimated 
as 12 units and a reasonable range of intraclass correlation coefficients is 0.01 to 0.1.  For all calculations, 
the type I error is 5% and power is 80%.  With a sample size of 160 families (4 per each of 40 physicians, 
20 per treatment arm), we will be able to detect differences of 4.0 to 5.0 NEST units for Hypothesis 2a in 
the overall test, 5.4 to 6.1 for Black or White patients separately, and 7.6 to 8.0 units for Hypothesis 
3a.  For Aim 4, we expect that up to 25 cases comprised of family members will be sufficient to reach 
informational redundancy—the point at which no new themes emerge.
Ancillary study:  Needs and triggers: improving intensive care unit-based palliative care deliveryStatistical 
methods:
Aim 1:  The primary goal of the cohort study (Aim 1) is to derive 3-5 clinically rational palliative care need 
typologies, or subgroups with a phenotypic homogeneity of need severity and type, to inform Aim 2’s 
derivation of a care delivery model. These analyses will be conducted within the framework of latent class 
analysis (LCA), a statistical methodology that uses contingency table analyses to discern response patterns 
across a series of categorical variables.  LCA will be applied to the dichotomized (high vs. low need) NEST 
item scores to identify latent (i.e., unobservable) subgroups of need classes within family members at T1 
via maximum likelihood estimation (SAS PROC LCA).  Study investigators will iteratively develop more fully 
formed needs typologies resulting from these analyses in a series of face-to-face investigator meetings 
using a decision-rule process.  We will provisionally classify need typologies as ‘simpler’ (ICU team can 
address) or ‘complex’ (specialist care advised).
Exploratory hypotheses: Hypothesis 1aexplores the potential value of a novel intervention target—‘unmet 
needs,’ defined as a NEST summary score at T2 that is greater than T1 for those completing both 
interviews.  This hypothesis will be confirmed if the unmet needs coefficient is statistically significant after 
regressing PHQ-9 scores at T4.  Hypothesis 1bwill tested via a multivariable regression model with NEST 
summary score as the outcome and trigger status (present / absent) as the coefficient of interest, 
adjusted for sociodemographic and clinical variables. We anticipate < 10% missing data between T1 and 
T2. 
Aim 2:  This Aim’s primary goal is to develop a provisional collaborative model of ICU-based palliative care 
using a mixed methods approach in which qualitative focus group data from family members, self-reported 
skills confidence data from clinicians, and expert guidelines will be integrated with Aim 1’s need 
typologies.  Step 1: validate needs typologies.  3 focus group interviews with family members purposively 
sampled from each of Aim 1’s needs typologies subgroups will be conducted to validate the needs 
typologies in participants’ own voices, verify the complexity of needs, and allow us to look beyond 
socioemographic variables for other common factors shared by subgroup members.  Transcripts will be 

analyzed using a content analysis technique that will combine structural and magnitude coding (a 
deductive form using a set of codes derived from the needs domains) with inductive coding (which 
identifies text of meaningful units and creates a label for the new category).  Drs. Docherty and Cox will 
separately code an initial set of 5 interviews, discuss generated codes, and use a consensus procedure to 
create an initial code book, subsequently coding the remaining interviews. Final categories of codes will be 
used to generate themes.  Step 2: assess confidence vs. expected skills.  We will next survey 30 ICU 
physicians and 55 ICU nurses to evaluate their attitudes about and confidence in addressing each of the 
NEST need domains using 10-point Likert scales; scores >7 will reflect ‘high’ confidence. Step 3: assess 
acceptability. We will conduct 2 focus groups of 8-10 clinicians sampled purposively by stratifying across 
reported confidence levels (low vs. high), job type (physician vs. nurse), and discipline (ICU vs. palliative 
care).  Clinicians will provide feedback on the clinical use of the derived need typologies. We anticipate 
discussions about how to sensibly use need type (i.e., NEST domains), need burden (i.e., NEST summary 
score), and need change over time (T2 > T1 NEST scores) to facilitate triage. Step 4: finalize model. Using 
data from Steps 1-3, investigators, expert Advisory Committee, and consultants (see letters of support), 
site palliative care and ICU leaders, and past guidelines relevant to expected basic palliative care skills, we 
will finalize the care model using an iterative, consensus-building approach.
Aim 2’s secondary goal is to optimize model acceptability.  Dr. Cox will facilitate 2-3 focus groups of 8-10 
clinicians diverse in ICU type and role; a number sufficient to hold an active discussion and allow each 
participant to be heard.  We will assess model acceptability using open-ended feedback and quantitative 
satisfaction metrics.  Our targets will be a mean CSQ-8 score >15, with no scores < 5. A series of iterative 
revisions and retesting will be performed until the acceptability target is met.  ‘Member checking’ of all 
past clinician participants will be performed using a 5-item Likert-scaled approval rating for the final model.
Aim 3’s mixed methods analyses will explore and describe user experiences with the intervention to 
understand both mechanisms of action and how outcomes may be related to unique case contexts. 
Additionally, Aim 3 intends to understand the effects COVID-19 may have had on the family member and 
their loved one's ICU admission as it relates to their needs.  This knowledge can guide future intervention 
optimization through enhanced personalization, replicability, and scalability. Interview transcripts will be 
analyzed using a content qualitative analysis technique that combines structural (e.g., intervention 
component, care process barriers) and magnitude coding (e.g., theme intensity) with inductive coding (e.
g., variations in outcomes not captured by instruments).50  Drs. Docherty and Cox will separately code the 
same 5 family members, discuss the generated codes to create an initial code book by consensus. Next, 
they will each code 5 different interviews with further refinements made to the code book which will then 
be used by the investigators to code remaining 15-20 family member transcripts. While the final code book 
will be organized into categories used to generate themes of mechanistic and process elements from 
across all participants, within-case themes generated from family member and clinician interviews will be 
used to write case profiles. Case profiles will merge data from case context descriptors (family and clinician 
race, patient illness, etc), within-case qualitative themes, and quantitative process measures.  A visual 
‘ethnoarray’ matrix will be constructed to display key case findings in relation to every other case.  The 
ethnoarray, loosely adapted from a graphical heat map approach, is a powerful way to present complex 
data and is a flexible method for blending narrative and quantitative data to facilitate the discovery of 
patterns, relationships and understand the contextual richness of the data. These procedures will enhance 
comparative analyses and theoretical interpretation.  For example, case comparisons could be made by 
needs (needs met vs. needs unmet) or patient-centeredness of care (high vs. low).  Process tracing will be 
used to explore how particular case outcomes (e.g., need, distress, goal concordance) may have been 
related to intervention components (e.g., needs assessment, family meeting) and to their effect on 
barriers in our conceptual model (Figure 1). Dr. Docherty will use ATLAS.ti qualitative data analysis 
software for analyses.
Power calculations and sample size: Based on Dziak’s series of simulation studies examining statistical 
power in latent class models, 200 family members will provide > 80% power to detect a 3-class vs. a 2-
class latent class model.   Based on data from previous studies (estimated SD=12, type-I error of 5%), 
enrolling 184 family members (92 met/unmet needs) will provide 80% power to detect a 5-point 
difference.  We conservatively plan to enroll 200 family members to protect against deviations from our 
assumptions and to account for dropout >25%.
Data & Safety Monitoring
Summarize safety concerns, and describe the methods to monitor research subjects and their data to 
ensure their safety, including who will monitor the data, and the frequency of such monitoring. If a 
data monitoring committee will be used, describe its operation, including stopping rules and frequency 
of review, and if it is independent of the sponsor (per 45 CFR 46.111(a) (6)).

The study team will report all applicable adverse and serious adverse events, protocol deviations, protocol 
violations, and other unanticipated problems as defined by the Study Design & Procedures section and per 
Institutional Review Board (IRB) and NIH policies. In addition, all adverse and serious adverse events, 
protocol deviations, violations and other unanticipated problems will be reported as part of the semi and 
annually progress reports in the non-competitive and competitive renewals.
Dr. Cox will supervise this study at all times but will be in close and frequent contact with other 
investigators, including Dr. Olsen, the study biostatistician and the chief data manager.  Investigators will 
adhere to established federal and institutional patient safety and protection guidelines.  To assure data 
accuracy, Drs. Cox and Olsen will review the computer data files on a monthly basis.  Additionally, 
coordinator staff will process the RedCap database routinely to search for errors and generate basic 
reports for dissemination at regular meetings. Protocol compliance will be reviewed during weekly 
meetings between clinical research coordinators and Dr. Cox.
Aim 2's RCT will be supervised by a single independent central DSMB due to its interventional nature.  The 
DSMB will include professionals with significant experience in clinical trials, mind-body interventions, and 
biostatistics who are not directly involved in the study, its interpretation, or any study institution.  DSMB 
members will be chosen with the assistance and approval of the NIH.  The main responsibilities of the 
DSMB will be to (a) assess for the presence of potential harms and unintended consequences of the 
intervention, (b) ensure the validity and integrity of the data, and (c) make recommendations to the NIH 
about whether the study should be continued without modification, continued with modification, or 
terminated.  The initial DSMB meeting will occur before the initiation of subject enrollment for the purpose 
of updating members on the study, ensuring agreement on the review process, and establishing the 
review methodology and procedures.  The first DSMB data review will then occur either after the first 10 
patients (5 per treatment group) have been enrolled or enrollment has occurred for 3 months, whichever 
is observed first.  Thereafter, the DSMB will review cleaned data pulled from the RedCap database system 
every six months during enrollment and will prepare a report with any recommendations within the 
following month.  While this is an intensive DSMB engagement schedule, the short enrollment period will 
demand greater oversight. 
The specific study functions and outcomes that the DSMB will review at each meeting include:  dropout 
rate, randomization rate, NEST, PHQ-9, GAD-7, and Post-Traumatic Stress Scale (PTSS) scores.  The 
primary safety measures will be Adverse Events reports and post-intervention PHQ-9 scores.  Other items 
reviewed by the DSMB at each meeting will include: (a) data quality, completeness, and timeliness; (b) 
performance of the Duke center; (c) adequacy of compliance with goals for recruitment and retention, 
including women and minorities; (d) protocol adherence; and (e) presence of factors that could adversely 
affect study outcome or compromise data confidentiality.
During the review process, formal statistical tests for examining the differences in Adverse Event or 
outcome rates between study groups may be performed under DSMB supervision if requested.  However, 
this is unlikely given the exploratory pilot study design.  For differences in study dropout rates, appropriate 
changes to the protocol will be made by investigator consensus after DSMB member input.  Additionally, 
the DSMB may request a formal statistical assessment if a suspicious increase in PHQ-9 score is observed 
in either group. If the intervention group is found to have either a statistically significant increase in PHQ-9 
score, the DSMB scope of action will include recommendation for cessation of the trial.  Dr. Olsen, the 
biostatistician, will oversee any DSMB statistical requests and interpretations.  Any protocol changes, as 
well as any adverse events, will also be reported to the Institutional Review Boards of all study sites, as 
well as to the NIH.
Privacy, Data Storage & Confidentiality
Complete the Privacy and Confidentiality section of the iRIS submission form.
Describe Role of External Personnel:
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