SPIRIT for Persons With Dementia and Complex Multimorbidity
Phase: NA
Conditions: End Stage Renal Disease
Sponsor: Emory University

An Effectiveness-Implementation Trial of SPIRIT in ESRD 
(Short title: SPIRIT Trial) 
Supplement Trial: SPIRIT in ESRD and Dementia 
 
NCT Number: NCT04108000 
 
Protocol Version Date: 8 April 2021 
 
 
 

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An Effectiveness-Implementation Trial of SPIRIT in ESRD 
(Short title: SPIRIT Trial)  
Supplement Trial: SPIRIT in ESRD and Dementia 
 
National Clinical Trial (NCT) Identified Number: NCT04108000 
Principal Investigator: Mi-Kyung Song 
Funded by: NIH/NINR, R01NR017018/5R01AG057714. 
Version Number:  v.13 
8 April 2021 
 
 
Summary of Changes from Previous Version: 
Affected Section(s) 
Summary of Revisions Made 
Rationale 
4.2 Scientific 
Rationale for Study 
Design 
5.1 Inclusion Criteria 
5.5 Recruitment 
10.1.1.2 Conflict of 
Interest Policy 
 
 
Inclusion of a new recruitment site.  
 
Expanding recruitment locations to meet 
target sample size.  
 
 

  
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Table of Contents 
STATEMENT OF COMPLIANCE ....................................................................................................................................... 1 
1 
PROTOCOL SUMMARY ...................................................................................................................................... 2 
1.1 
Synopsis .................................................................................................................................................. 2 
1.2 
Schema ................................................................................................................................................... 4 
1.3 
Schedule of Activities (SoA): Randomization occurs at the clinic level .................................................. 6 
2 
INTRODUCTION ................................................................................................................................................. 6 
2.1 
Study Rationale ...................................................................................................................................... 7 
2.2 
Background ............................................................................................................................................. 9 
2.3 
Risk/Benefit Assessment ...................................................................................................................... 14 
2.3.1 
Known Potential Risks ....................................................................................................... 14 
2.3.2 
Known Potential Benefits ................................................................................................. 14 
2.3.3 
Assessment of Potential Risks and Benefits ..................................................................... 14 
3 
OBJECTIVES AND ENDPOINTS ......................................................................................................................... 14 
4 
STUDY DESIGN ................................................................................................................................................. 17 
4.1 
Overall Design ...................................................................................................................................... 17 
4.2 
Scientific Rationale for Study Design .................................................................................................... 18 
4.3 
Justification for INTERVENTION............................................................................................................ 19 
4.4 
End of Study Definition ......................................................................................................................... 19 
5 
STUDY POPULATION ....................................................................................................................................... 20 
5.1 
Inclusion Criteria ................................................................................................................................... 20 
5.2 
Exclusion Criteria .................................................................................................................................. 21 
5.3 
Lifestyle Considerations ....................................................................................................................... 21 
5.4 
Screen Failures ..................................................................................................................................... 21 
5.5 
Strategies for Recruitment and Retention ........................................................................................... 21 
6 
STUDY INTERVENTION(s) ................................................................................................................................ 23 
6.1 
Study Intervention(s) Administration ................................................................................................... 23 
6.1.1 
Study Intervention Description ......................................................................................... 23 
6.1.2 
Dosing and Administration ............................................................................................... 24 
6.2 
Preparation/Handling/Storage/Accountability .................................................................................... 24 
6.2.1 
INTERVENTIONIST TRAINING and accountability ............................................................. 24 
6.2.2 
Formulation, Appearance, Packaging, and Labeling ......................................................... 25 
6.2.3 
Product Storage and Stability ........................................................................................... 25 
6.2.4 
Preparation ....................................................................................................................... 25 
6.3 
Measures to Minimize Bias: Randomization and Blinding ................................................................... 25 
6.4 
Study Intervention Compliance ............................................................................................................ 26 
6.5 
Concomitant Therapy ........................................................................................................................... 27 
6.5.1 
Rescue Medicine ............................................................................................................... 27 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT DISCONTINUATION/WITHDRAWAL ............. 27 
7.1 
Discontinuation of Study Intervention ................................................................................................. 27 
7.2 
Participant Discontinuation/Withdrawal from the Study .................................................................... 27 
7.3 
Lost to Follow-Up ................................................................................................................................. 27 
8 
STUDY ASSESSMENTS AND PROCEDURES ....................................................................................................... 28 
8.1 
OUTCOME Assessments ....................................................................................................................... 28 
8.2 
Safety and Other Assessments ............................................................................................................. 31 
8.3 
Adverse Events and Serious Adverse Events ........................................................................................ 31 
8.3.1 
Definition of Adverse Events (AE) ..................................................................................... 31 

  
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8.3.2 
Definition of Serious Adverse Events (SAE) ...................................................................... 31 
8.3.3 
Classification of an Adverse Event .................................................................................... 32 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up .................................. 32 
8.3.5 
Adverse Event Reporting .................................................................................................. 32 
8.3.6 
Serious Adverse Event Reporting...................................................................................... 32 
8.3.7 
Reporting Events to Participants ...................................................................................... 32 
8.3.8 
Events of Special Interest.................................................................................................. 32 
8.3.9 
Reporting of Pregnancy .................................................................................................... 33 
8.4 
Unanticipated Problems .......................................................................... Error! Bookmark not defined. 
8.4.1 
Definition of Unanticipated Problems (UP) ...................................................................... 33 
8.4.2 
Unanticipated Problem Reporting .................................................................................... 33 
8.4.3 
Reporting Unanticipated Problems to Participants .......................................................... 33 
9 
STATISTICAL CONSIDERATIONS ....................................................................................................................... 33 
9.1 
Statistical Hypotheses .......................................................................................................................... 33 
9.2 
Sample Size Determination .................................................................................................................. 35 
9.3 
Populations for Analyses ...................................................................................................................... 35 
9.4 
Statistical Analyses ............................................................................................................................... 35 
9.4.1 
General Approach ............................................................................................................. 36 
9.4.2 
Analysis of the Primary Endpoint(s) .................................................................................. 36 
9.4.3 
Analysis of the Secondary Endpoint(s) ............................................................................. 37 
9.4.4 
Safety Analyses ................................................................................................................. 38 
9.4.5 
Baseline Descriptive Statistics .......................................................................................... 38 
9.4.6 
Planned Interim Analyses ................................................................................................. 38 
9.4.7 
Sub-Group Analyses .......................................................................................................... 38 
9.4.8 
Tabulation of Individual participant Data ......................................................................... 38 
9.4.9 
Exploratory Analyses ........................................................................................................ 38 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ...................................................... 38 
10.1 
Regulatory, Ethical, and Study Oversight Considerations .................................................................... 39 
10.1.1 
Informed Consent Process ................................................................................................ 39 
10.1.2 
Study Discontinuation and Closure ................................................................................... 40 
10.1.3 
Confidentiality and Privacy ............................................................................................... 41 
10.1.4 
Future Use of Stored Specimens and Data ....................................................................... 41 
10.1.5 
Key Roles and Study Governance ..................................................................................... 41 
10.1.6 
Safety Oversight ................................................................................................................ 45 
10.1.7 
Clinical Monitoring ............................................................................................................ 46 
10.1.8 
Quality Assurance and Quality Control ............................................................................. 47 
10.1.9 
Data Handling and Record Keeping .................................................................................. 48 
10.1.10 
Protocol Deviations ........................................................................................................... 48 
10.1.11 
Publication and Data Sharing Policy ................................................................................. 48 
10.1.12 
Conflict of Interest Policy .................................................................................................. 49 
10.2 
Protocol Amendment History ............................................................................................................... 49 
11 
REFERENCES .................................................................................................................................................... 53 
 

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STATEMENT OF COMPLIANCE 
 
The trial will be carried out in accordance with International Conference on Harmonisation Good Clinical Practice 
(ICH GCP) and the following:  
 
• 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR Part 46, 21 CFR 
Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812)  
 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are responsible for 
the conduct, management, or oversight of NIH-funded clinical trials have completed Human Subjects 
Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials have been 
approved by the Institutional Review Board (IRB) at: 
Emory (Study No.: IRB0094859; approved on 3/3/2017) 
University of New Mexico (Study No: 17-357 approved on 10-27.17) 
University of Pittsburgh (Study No.: PRO07070106; approved on 09/08/17) 
University of North Carolina at Chapel Hill (Study #: 17-1295; approved on 7/28/2017) 
 
RRI Carolina Dialysis approval (08/03/2017) 
FMC approval 4.1.18 
DCI approval & IRBAA 1.22.18 
 
Any amendment to the protocol requires review and approval by the IRB before the changes are 
implemented to the study.  In addition, all changes to the consent form will be IRB-approved. 
 
 
 

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PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
Title: 
An Effectiveness-Implementation Trial of SPIRIT in ESRD 
Study Description: 
This multicenter, clinic-level cluster randomized trial will evaluate the effectiveness 
of SPIRIT, an advance care planning (ACP) intervention, delivered by dialysis care 
providers as part of routine care in free-standing outpatient dialysis clinics 
compared to usual care. Simultaneously, we will evaluate the implementation of 
SPIRIT, including its sustainability. 
Objectives: 
 
Primary Aim 1. Examine the effectiveness of SPIRIT compared to usual care on 
preparedness outcomes for end-of-life decision making (defined as dyad 
congruence on goals of care, patient decisional conflict, and surrogate decision-
making confidence) at 2 weeks post-intervention 
 
Aim 2. Evaluate the process outcomes of SPIRIT implementation: acceptability, 
fidelity, intervention costs, and sustainability during the initial and delayed 
implementation of SPIRIT (Descriptive aim to generate data for translation)  
Aim 3. Examine the effectiveness of SPIRIT and usual care on surrogates’ post-
bereavement distress (anxiety, depression, and post-traumatic distress 
symptoms) at 3 months after the patient’s death 
Aim 4 (exploratory): Examine the effectiveness of SPIRIT and usual care on end-of-
life treatment intensity (healthcare utilization; percentages of patients 
hospitalized, having ICU admission, and having intensive procedures and 
length of hospital stay) during the final month of life 
 
In a supplement study, we will pilot test SPIRIT adapted for patients with ESRD plus 
dementia as a model for determining whether patients with dementia 
superimposed on complex multimorbidity can fully participate in an advance care 
planning discussion. 
Supplement Aim 1. Estimate the effects of the SPIRIT-dementia intervention on 1) 
the preparedness outcomes 2-3 days post intervention, 2) care decisions assessed 
at 6 months post intervention or the patient’s death. 
Supplement Aim 2. Estimate the effects of the SPIRIT-dementia intervention on 
surrogates’ post-bereavement distress at 1 months after the patient’s death. 
Supplement Aim 3. Explore the relationships among patients’ cognitive status, 
decision-making capacity and their ability to express end-of-life wishes. 
 
 
A new supplement study is a longitudinal cohort study leveraging the parent 
study. The objective is to assess the effect of the pandemic on the stability of end-
of-life care preferences and on our key outcomes (dyad congruence on goals of 
care, patient decisional conflict, and surrogate decision-making confidence). 
Aim 1. Compare the stability of patients’ goals-of-care preferences over time, from 
pre-outbreak to during-outbreak, by group (SPIRIT vs control) and estimate 
effect by race (Blacks and Whites).  
Aim 2. Assess the stability in the preparedness outcomes (dyad congruence, patient 
decisional conflict, and surrogate decision-making confidence) comparing 
pre-outbreak to during-outbreak by group, and estimate race effect. 
Aim 3. Examine the associations of the COVID-19 Related Stress questionnaire, sex, 
race/ethnicity, and other sociodemographic characteristics (e.g., education 
level, income) to change in the outcomes and the stability of patients’ 
goals-of-care preferences after the COVID-19 outbreak. 

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Endpoints: 
Primary Endpoints (Aim 1):  
Dyad congruence on goals of care, patient decisional conflict, and surrogate 
decision-making confidence at 2 week post-intervention 
Secondary Endpoints (Aim 3):  
Surrogate HADS and PTSS scores at 3 months after the patient’s death;  
Exploratory (Aim 4): 
EOL treatment intensity 
 
Supplement Aim: 
Dyad congruence on goals of care, patient decisional conflict, and surrogate 
decision-making confidence at 2-3 day post-intervention 
Study Population: 
400 patients and 400 surrogates of the patients participate as pairs (400 patient-
surrogate dyads); adults (>=18 y); both genders; all race and ethnicity; ESRD/chronic 
dialysis population 
 
For the supplement aims: 
30 patients with ESRD + cognitive impairment, including early stages of dementia, 
who are not eligible for the parent study due to cognitive impairment, and 30 
surrogates of the patients as pairs 
 
Supplement cohort study: 
~100 dyads who completed the baseline assessment and post-intervention 
assessment prior to the pandemic lockdown. 
Phase: 
Phase III effectiveness trial 
 
For the supplement aims, NIH Stage 1 biobehavioral intervention research 
Description of 
Sites/Facilities Enrolling 
Participants: 
Participants recruited from outpatient dialysis centers located in GA (Emory), NC 
(UNC-CH), VA (UVA) and PA (U of Pitt).; dialysis centers owned and managed by 
Emory Healthcare, Fresenius Medical Care (FMC), Renal Research Institute (RRI), 
and Dialysis Clinic Inc (DCI).  
A total of 29 free-standing dialysis centers. 
 
For the supplement aims, only Emory dialysis centers will serve as study site. 
 
Supplement cohort study: no new participant recruitment from the clinic. Current 
study participants who are eligible for the cohort study will be contacted via phone.  
Description of Study 
Intervention: 
SPIRIT (Sharing Patient’s Illness Representation to Increase Trust), a patient and 
family-centered ACP intervention based on the Representational Approach to 
Patient Education, is to establish a testable model of how end-of-life care 
discussions could occur between a dialysis patient and his/her chosen surrogate 
(usually a spouse or adult child). The discussions, which are facilitated by a trained 
care provider, are framed around addressing each individual’s representations of 
(beliefs about) the illness and views of life-sustaining measures at the end of life. 
SPIRIT follows a six-step learning objective over two-sessions, which together take 
about 60 minutes. 
Study Duration: 
60 months 
 
For supplement aims, up to 2 years. 
 

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Supplement cohort study: 2 years 
Participant Duration: 
For patients, baseline and 2-week follow up (active participation), and then an 
observational period for 9 months (or until death). We will request extension of 12 
additional months at completion of 9 month time point. 
For surrogates, baseline and 2-week follow-up (active participation), and then a 9 
month observational period. We will request extension of 12 additional months if 
patient is still living. A post-death follow-up survey at 3 months after the patient 
death (if the patient death occurs during the observational period). 
 
For supplement aims, 
Patients: a brief survey at baseline and a follow-up at 2-3 days after the 
intervention, and then an observational period for 12 months. 
Surrogates: a brief survey at baseline and a follow-up at 2-3 days after the 
intervention, and then a post-death follow-up survey at 1 month after the patient’s 
death (if the patient death occurs during the observational period). 
 
Supplement cohort study: ~ 6 months once enrolled. 
1.2 
SCHEMA 

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1.3 
SCHEDULE OF ACTIVITIES (SOA): Randomization occurs at the clinic level 
Days offset 
Procedure 
Note 
Patients and 
surrogates 
Patient referralsa 
Screened and willing patients 
Patient screened (by research staff) b 
Linked to eligibility checklist  
Day -14 to Day -7 
Obtaining patient informed consent in personb 
Scan and upload signed consent pdf 
 
Obtaining contact informationb 
 
 
Medical record review: clinical characteristicsb 
To be linked to “pt consent”  
 
Usual care review 1b 
To be linked to “pt consent” & separate 
Every 6 months 
Day 0 
Surrogate verbal consentb 
 
 
Surrogate verbal consent receivedb 
 
 
Scheduling baseline (T1) appointment  
If control, schedule both T1 & T2  
 
Reminder call for T1 
 
Day 14 (+/- 7) 
Baseline (T1)-patient completion 
Link to the measures 
 
Baseline (T1)-surrogate completion 
Link to the measures 
 
Payment (T1) mailed to patient 
With thank-you note 
 
Payment (T1) mailed to surrogate 
With thank-you note 
 
Scheduling SPIRIT Session I & II and 2-wk F/Ub 
Need to coordinate with the care provider 
for SPIRIT sessions 
 
SPIRIT Session Ia 
 
 
SPIRIT Session II reminder callb 
Two days prior 
 
SPIRIT Session IIa 
 
 
SPIRIT Interview Guide Checklistb 
Care provider interventionist completes 
and the Site Coordinator enters to 
REDCap 
 
Reminder call for T2 
Central 
 
2-week follow-up (T2)-patient completion 
2 weeks from SPIRIT; including 
acceptability survey and SPIRIT 
components  
 
2-week follow-up (T2)-surrogate completion 
2 weeks from SPIRIT; including 
acceptability survey and SPIRIT 
components 
 
Payment (T2) mailed to patient 
With thank-you note 
 
Payment (T2) mailed to surrogate 
With thank-you note 
 
Monthly check-in call 1 
1 month from T2 
 
Monthly check-in call 2 
 
 
Monthly check-in call 3 
 
 
Monthly check-in call 4 
 
 
Monthly check-in call 5 
 
 
Usual care review 2a 
May need one more 
 
Monthly check-in call 6 
 
 
Monthly check-in call 7 
 
 
Monthly check-in call 8 
 
 
Monthly check-in call 9 
With note on study completion 
 
Mailing sympathy card 
Upon patient death 
 
Contacting surrogate & scheduling a 3-month post-death F/U 
 
 
Postcard reminder 2 weeks before the F/U 
 
 
Reminder call for 3-month F/U 
 
 
F/U 3 month post death 
 
 
Payment (F/U 3M) mailed to surrogate 
With thank-you note 
 
Clinic-level contextual datab 
At the end of each implementation 
Care providers 
Informed consentb 
At the end of each implementation 
 
Acceptability assessmentb 
Brief survey and interview 
 
SPIRIT care provider interview-sustainabilityb 
 
a Performed locally by the chosen care provider;  b Procedures performed locally by research personnel 
 
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INTRODUCTION 

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2.1 
STUDY RATIONALE  
 
End-stage renal disease (ESRD) currently affects nearly 662,000 people in the U.S.1 While dialysis is the treatment 
of choice for over 90% of patients with ESRD and is universally covered by Medicare regardless of patient age or 
means, the likelihood that dialysis can restore health or prolong life is limited; only 50% of dialysis patients are 
alive 3 years after the onset of ESRD.1 Thus many dialysis patients and their family members or surrogate decision-
makers have to face difficult end-of-life decisions. Although advance care planning (ACP), in which patients and 
surrogate decision-makers discuss future health states and treatment options, is a central tenet of dialysis care,2-5 
the vast majority of dialysis patients (>90%) report never engaging in ACP discussions with their care providers.6,7 
The lack of effective ACP to prepare patients and their surrogates for end-of-life decision making with sufficient 
time before death has deleterious consequences at all levels of society. Consequences have been well 
documented: prolonged use of futile treatment at the end of life, which misuses the healthcare system, high 
levels of surrogate distress during decision making, which emanates from not having a clear understanding of the 
patient’s wishes, and surrogates experiencing later sequelae of psychosocial morbidities, such as depression and 
family discord.8-14  
 
SPIRIT (Sharing Patient’s Illness Representation to Increase Trust), a patient and family-centered ACP intervention 
based on the Representational Approach to Patient Education,15,16 was designed by our team to establish a 
testable model of how end-of-life care discussions could occur between a dialysis patient and his/her chosen 
surrogate (usually a spouse or adult child). The discussions, which are facilitated by a trained care provider, are 
framed around addressing each individual’s representations of (beliefs about) the illness and views of life-
sustaining measures at the end of life. SPIRIT follows a six-step learning objective over two-sessions, which 
together take about 60 minutes. The care provider, who is value-neutral, guides the patient in examining his/her 
values related to end-of-life care, helps the surrogate understand the patient’s illness progression, and prepares 
the surrogate for his/her role as a surrogate in a highly emotionally charged medical setting. Over the last decade, 
we have iteratively tested SPIRIT to establish feasibility, patient-surrogate acceptability, and efficacy.17-20 In these 
explanatory trials carried out in dialysis clinics, SPIRIT was delivered by trained research nurses. Patients and 
surrogates in SPIRIT showed significant improvement in preparedness for end-of-life decision making, including 
the extent to which: a) the patient and surrogate agreed on end-of-life care goals, b) the patient had reduced 
conflict about the benefits and burdens of life-sustaining treatments, and c) the surrogate had increased 
confidence about the role of surrogate. Key to establishing the utility of this approach for broader generalizability, 
surrogates who received SPIRIT reported significantly improved post-bereavement psychological outcomes after 
the patient’s death compared to those who did not. The logical, critical next step is to ask: Will SPIRIT be effective 
as part of routine care in real-world clinical settings with less control? To address this very issue, we will conduct a 
real-world effectiveness-implementation study, an essential step prior to widespread implementation of SPIRIT.  
 
For Supplement Aims: 
Cognitive impairment, including dementia, is common among individuals with ESRD but is a poorly recognized 
problem. The prevalence ranges from 16-38% and up to 70% depending on the sample,5-8 but only less than 4% 
are formally diagnosed.7,9 Prevalence rates of dementia for dialysis patients are threefold higher than the age-
matched general population.7 The most common type of dementia among patients with ESRD is vascular 
dementia followed by Alzheimer’s disease.7   
 
ESRD is never a single disease but accompanied by other complex chronic conditions, such as diabetes, 
hypertension, coronary artery disease, congestive heart failure, and peripheral vascular disease.10 When dementia 
is superimposed on ESRD, the risk for poor outcomes, including disability, hospitalization and death, sharply 
increases.11,12  Similarly, initiating dialysis in older adults with multiple comorbidities, including dementia, does not 
offer survival benefit; a study of 3,700 nursing home residents found that half of the residents died within 6 

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months and more than 70% died by 12 months after the start of dialysis.13 Nevertheless, the vast majority of 
dialysis patients (>90%) across all age groups and comorbid conditions report never engaging in advance care 
planning (ACP) discussions with their care providers.14,15 The lack of ACP to prepare patients and their surrogates 
for end-of-life decision making is particularly problematic for those with dementia and complex multimorbidity 
given their poor prognosis and the limited window of opportunity before decision-making capacity is lost.  
 
In an on-going study (“SPIRIT in Dementia,” R01AG057714) which is now running in parallel to the parent SPIRIT in 
ESRD study, we carefully adapted SPIRIT for persons with mild to moderate dementia and their surrogates. As 
part of the NIH Stage I behavioral intervention development trial,16 we pilot tested the feasibility of the adapted 
SPIRIT intervention with 23 dyads (74% white; mean age = 74 years) recruited from the Emory Brain Health 
Center. The goal of SPIRIT is to promote cognitive and emotional preparation for end-of-life decision making for 
patients with a serious or life-threatening illness and their surrogates. SPIRIT is based on the Representational 
Approach to Patient Education.17,18 We demonstrated that, by using the adapted SPIRIT intervention, persons with 
dementia (PWD) were able to engage in an ACP discussion meaningfully and exchange authentic dialogue with 
their surrogates about experiences surrounding illness and values. While the sample was small, our team was able 
to conclude that meaningful ACP conversations were possible even for individuals with moderate dementia and 
that decision-making capacity might be the more important mental faculty than global cognitive functioning in 
ACP discussion. It is important to note that in most studies of ACP, including our own previous SPIRIT studies1-4 
and the current parent SPIRIT-ESRD study,19 PWD (regardless of their cognitive impairment level) are routinely 
excluded from clinical trials, largely because investigators assume that PWD do not have the cognitive capability 
to appreciate the complexity of ACP. 
 
As a next step we are now conducting a full-scale RCT of the adapted SPIRIT intervention for PWD and surrogates 
to examine preliminary efficacy on immediate outcomes, including preparedness for end-of-life decision making. 
In the SPIRIT-dementia study, we are targeting people with early stages of Alzheimer’s disease and related 
dementia. Therefore, in contrast to the patients in the ESRD study, PWD in the dementia study have a longer life 
expectancy (~10 years) and, for the most part, do not have complex multimorbidity. For patients with ESRD who 
have cognitive impairment, including dementia, the urgency for ACP is time sensitive because care decisions (e.g., 
discontinuation of dialysis, hospice enrollment) and surrogates’ bereavement are rather imminent. 
 
In this supplement study, we will pilot test the adapted SPIRIT intervention (SPIRIT-dementia) for patients with 
ESRD plus dementia as a model for determining whether patients with dementia superimposed on complex 
multimorbidity can fully participate in ACP discussion. The pilot randomized trial will include 30 dyads of patients 
with ESRD plus dementia and their surrogates from Emory dialysis clinics that are currently participating in the 
parent study. 
 
Supplement cohort study: 
For patients with complex multimorbidity (e.g., ESRD), COVID-19 infection results in much worse outcomes even 
after ICU admission and aggressive life-sustaining treatment.5,6 With the high risk of hospitalization and death in 
the context of scarce healthcare resources caused by the COVID-19 pandemic, experts in the field have urged the 
public to make their end-of-life wishes known especially if they have serious chronic illness and prefer to forgo 
prolonged life support measures.7 The COVID pandemic has brought fear and uncertainty to all aspects of life and 
to medical care in particular. Research has shown that after experiencing a natural disaster, people exhibit more 
risk averse behaviors, and that belief systems can change, i.e., people “update” their perception of background 
risk and perceive the world to be a much riskier place.8,9 
We have spent the past decade studying how to help individuals with a range of illnesses (and their caregivers 
/surrogates) clarify their end-of-life care preferences and prepare for end-of-life decision making to minimize 
unnecessary or unwanted end-of-life treatments in the face of life-limiting illnesses. We, through this body of 

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work, and others have shown that values and preferences for end-of-life care are stable over time especially after 
individuals made an effort to actively think about their end-of-life preferences, such as engaging in ACP.2,4,10 On 
the other hand, another body of literature suggests that abrupt and disturbing social changes, such as disasters, 
can affect the psychological mechanisms underlying cognitive performance.11 A disaster like the COVID-19 
pandemic evokes fear, anxiety, acute panic, and uncertainty surrounding access to resources, including medical 
care, which can cause irrational behaviors.12 The relationship between fear and demand for aggressive treatment 
has been debated since 1955.13 Generally, fear reinforces reflexive decision making in multiple domains.14 For 
instance, stockpiling toilet paper during COVID-19 is a behavior reflective of a need to regain a sense of control.15 
Lerner et al.9 found that experimentally induced fear caused people to express more pessimistic risk perceptions 
and to make more risk-averse choices in hypothetical scenarios. We are interested in assessing the effects of a 
disaster, such as the COVID pandemic, on the stability of end-of-life care preferences and outcomes of ACP in 
patients with ESRD so that we can gather evidence to revise/update our conceptual model to integrate best 
practices for ACP in the settings of disasters. 
 
2.2 
BACKGROUND  
 
Dialysis patients experience high end-of-life treatment intensity that may not reflect their wishes.   Despite 
advances in dialysis, adjusted all-cause mortality rates are 6-8 times greater for dialysis patients than for 
individuals in the general age-matched Medicare population.1 Only 50% of dialysis patients are alive 3 years after 
the onset of ESRD.1  End-of-life treatment intensity in this population is also substantially greater than that 
reported for other Medicare beneficiaries with life-limiting illnesses.21 For instance, in a study of older Medicare 
beneficiaries (≥ 65 years; N100,000) those on dialysis experienced significantly higher rates of hospitalization 
(76% vs 61% in cancer), ICU admission (48.9% vs 29% in cancer), and use of intensive procedures (29% vs 9% in 
cancer) during the final month of life.22  
 
Dialysis patients and their surrogates are not knowledgeable about the natural course of ESRD.  Although 
withdrawal of dialysis precedes 1 in 4 deaths of patients with ESRD,23 withdrawal from dialysis and aggressive 
treatment is very rarely (< 6%) discussed by patients and their surrogates with sufficient time to consider 
alternatives such as hospice or dying at home.23-26 In a study of over 530 chronic dialysis patients, only 19% 
indicated that they would want to continue dialysis if severely cognitively or functionally impaired, and 65% stated 
that they prefer to die at home or in hospice rather than in a hospital.27 Patients’ preferences for end of life care 
are significantly influenced by the patients’ illness representations (e.g., perceived illness severity).28 That is, when 
patients understand their illness severity and progression, they are likely to forgo futile end-of-life treatment, 
such as mechanical ventilation and CPR. In our work we have discovered that because so many dialysis patients 
are unaware that they are likely to die from an acute illness or complication (e.g., stroke, infection) rather than die 
from ESRD per se, they endorse the notion that with dialysis they can live as long as those without ESRD.18,29 
Similarly, surrogates are equally unaware of patients’ likely illness progression and comorbidities; surrogates 
report that prior to the time of end-of-life decision making they have not been told that the patient’s illness 
cannot be cured.9 Studies indicate that spouses' judgments about dialysis patients’ preferences for continuation 
of dialysis were only modesty correlated with patients’ preferences (r = .33),30,31 and spouses do not have intimate 
knowledge of whether or how long the patient would want to pursue life-sustaining measures.32,33 Our previous 
work demonstrated that surrogates are overly confident about their ability to act as a surrogate in that they have 
little understanding of the patient’s preferences and yet report confidence in understanding the patient’s wishes 
and their role as a surrogate.34 
 
Lack of preparedness for end-of-life decision-making can have a detrimental effect on patients and surrogates. 
There are predictable psychological and emotional consequences of lack of preparedness for end-of-life decision 
making. These include: high levels of conflict brought on by having to make life or death decisions (e.g., whether 
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futile); regrets over missed opportunities to benefit from palliative care or hospice; excessive distress for family 
members during decision making due to interfamily conflict, time pressure to make important decisions, lack of 
knowledge about options; and well documented psychosocial sequelae for family members (e.g., depression, 
anxiety, post-traumatic stress disorder) and complicated bereavement after the patient’s death.8,13,35-43 Numerous 
studies, including ours, indicate that families experience greater difficulty in decision making when they are 
uncertain about the patient’s wishes, when they feel unprepared for their role because they have never discussed 
it, and when they are called on to make decisions in a short period of time.29,37,43-48 Evidence shows that this 
distress contributes to a high prevalence of psychiatric illness among family decision makers: in one study nearly 
40% of bereaved families who experienced a loved one’s death in the ICU 3 to 12 months previously had at least 
one psychiatric illness meeting DSM-IV criteria, such as anxiety disorder or major depression.42 Even at 6-12 
months after the patient’s death, family members may experience intrusive thoughts of regret, guilt or search for 
evidence that they made the right decision.8,43,45,49,50 We will test the hypothesis that surrogates’ post-
bereavement psychosocial distress will be reduced by SPIRIT, a patient and family-centered ACP, in a real-world 
setting. 
 
Usual care does not prepare patients and surrogates for end-of-life decision making. Usual  ACP in free-standing 
dialysis facilities is based on the Centers for Medicare & Medicaid (CMS) requirements51 that written information 
on advance directives (ADs) is provided on a patient’s first day of dialysis, and a member of the dialysis team (e.g., 
social worker) reviews the written information with patients and encourages them to complete an AD. If 
completed, the AD is documented on the Plan of Care forms. If a patient expresses a desire not to be resuscitated 
in the dialysis unit, a do-not resuscitate (DNR) order is written by a nephrologist and placed in the clinic record. If 
there is no DNR order in the record, a full code is presumed. CMS has recently issued two new billing codes (CPT 
99497 and 99498) effective in 2016 that can be used to report the first 30 minutes and each additional 30 minutes 
of face-to-face services between a physician or other qualified healthcare professional and a patient, family 
member and/or surrogate in discussing ADs, with or without completing relevant legal forms.52 Although this is 
encouraging, CMS provides neither ACP tools nor guidance to ensure consistency and quality in ACP services. CMS 
recommends that ACP discussions be conducted during annual wellness visits at a doctor’s office to which these 
codes can be added; ACP discussions occurring outside of these visits are subject to patient co-pay or deductibles, 
which limits utility of the policy in other care settings. Further, ACP in these codes is narrowly defined as 
“including the explanation and discussion of ADs” and thus it may reinforce a common pitfall in ACP, i.e., a sole 
focus on AD completion.53   
 
SPIRIT, a patient and family-centered ACP, has beneficial effects on a range of psychosocial outcomes for 
dialysis patients and their surrogates. The goal of SPIRIT is to promote cognitive and emotional preparation for 
end-of-life decision making for patients with ESRD and their surrogates. SPIRIT is based on the Representational 
Approach to Patient Education.15,16 This approach melds two theories: Leventhal’s common sense model54 and the 
conceptual change model.55 The common sense model proposes that individuals have representations of their 
illness or health problems. Because representations are based on an individual’s everyday experiences, traditional 
or cultural information, or media, they may not be medically accurate. However, it is critical to understand the 
representations because they serve as the cognitive framework that affects whether or not individuals accept or 
reject new information,15 and whether knowledge is translated into behavior change.56,57 The conceptual change 
model proposes that the likelihood of learning increases when the individual has an opportunity to reflect and 
comment on current ideas and their consequences, when the individual is dissatisfied with current ideas or 
recognizes their limitations, and when alternative information is seen as beneficial.15,16,55,58 Learning/change can 
occur through integrating new information into existing representations to fill in gaps in understanding, through 
clarifying existing representations to reduce confusion, or through exchanging existing representations with new 
information.58,59 The Representational Approach to Patient Education requires a care provider to elicit the 
patient’s pre-existing illness representations before providing new information.15,16 Then, both the care provider 
and the individual have an opportunity to recognize gaps or confusions in the patient’s representations, and the 

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care provider can provide new information that is specific and relevant to the person. Thus, the patient is likely to 
understand and act on the new information. 
 
SPIRIT is a two-session, 60-minute, structured psychoeducational intervention, targeting both patient and 
surrogate. Using a provider manual, the care provider follows six steps: 1) assessing illness presentation, 2) 
identifying gaps and concerns, 3) creating conditions for conceptual change, 4) introducing replacement 
information, 5) summarizing, and 6) setting goals and planning (See Appendix).60 SPIRIT first establishes an 
understanding of the cognitive, emotional and spiritual aspects of the patient’s representation of his/her illness. 
This understanding enables the care provider to provide individualized medical information and to assist the 
patient in examining his/her own values related to life-sustaining treatment at the end of life. In this way, the 
patient can more readily express his/her treatment preferences to the surrogate. SPIRIT also enables the 
surrogate to understand the patient’s illness experiences and values and to be prepared for the responsibility and 
emotional turmoil that can arise during decision making at the end of life. Each element of SPIRIT is designed to 
enhance the quality and authenticity of exchanges between patient and surrogate about experiences surrounding 
illness and values. During the process, the patient discovers his/her own representations about illness and dialysis 
and examines thresholds and/or conditions for (dis)continuing life support measures. The surrogate gains an 
understanding of the patient’s illness experience and begins to see his/her limited life expectancy. The surrogate 
also validates similarities or differences with the patient in regard to life support measures and examines his/her 
own ability to follow the patient’s wishes. This process is critical to preparation for end-of-life decision making.20,60 
To deliver SPIRIT sessions, care providers are trained in communication skills and end-of-life planning. Over 12 
years of conducting iterative trials of SPIRIT with diverse dialysis patient populations, we have developed a 
structured protocol to assist providers in addressing the unique challenges and complexities in ACP with dialysis 
patients and surrogates. This evidence-based guide promotes quality, consistency, and fidelity in ACP delivery60 in 
this pragmatic trial of SPIRIT.  
 
Preliminary data to support feasibility of the proposed cluster randomized trial in dialysis clinics. 
Three RCTs testing SPIRIT18-20 were conducted in free-standing outpatient dialysis settings and established the 
feasibility, patient and surrogate acceptability, preliminary effects (R21NR009662), and efficacy of SPIRIT 
delivered in those settings by trained research nurses. Dialysis facilities varied in type, including profit and non-
profit ownership, urban and rural, and academic affiliation and community. The PI (Dr. Song) has the intimate 
knowledge of implementing SPIRIT in these complex health care systems. Recruitment rates have consistently 
been over 80% with a very low dropout rate (<4%). Throughout these trials, we have tested strategies and 
procedures related to recruitment, retention, data collection, and SPIRIT training, fidelity, and measurement. 
 
In a full-scale multicenter RCT (R01NR011464), we formally tested the efficacy of SPIRIT compared to 
usual care in preparation for end-of-life decision-making: Measured at 2, 6, and 12 months, primary outcomes 
were dyad congruence, patient decisional conflict, and surrogate decision-making confidence.20 We also tested 
whether SPIRIT reduced post-bereavement distress for surrogates (at 2 wks., 3 and 6 months).  For the RCT, 210 
dyads of seriously ill dialysis patients and their surrogates from 20 free-standing dialysis facilities (mean age 62, 
57% women, 67% African Americans, 96% on hemodialysis) were randomized to SPIRIT or usual care.  Intention-
to-treat analysis showed that, adjusting for time and baseline values, dyad congruence on goals of care (OR=1.89 
[95% CI, 1.1 to 3.3]; p=.029) and surrogate decision-making confidence (β=0.13 [CI, 0.01 to 0.24]; p=.027) were 
significantly better in SPIRIT. Patient decisional conflict was significantly lower in SPIRIT at 12 months (β=-0.19 [CI, 
-0.33 to -0.04]; p=.011). We also created a composite outcome combining dyad congruence and surrogate 
decision-making confidence because surrogates can feel highly confident even if they misunderstand patients’ 
wishes.18,34 Thus, to differentiate surrogates who understand the patient’s wishes and feel confident in their role 
from those who do not (i.e., understand the wishes but lack confidence, misunderstand the wishes but feel 
confident, or neither understand nor feel confident), dyads were grouped as congruent in both scenarios and 
surrogate decision-making confidence ≥ 3 (“confident” to “very confident”), or not.18 SPIRIT’s effect on the 
composite outcome was also significant (OR=1.82 [95% CI, 1.0 to 3.2]; p=.041).  
 

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Mortality rates between the groups were 
similar. Among 45 bereaved surrogates, adjusting 
for time and baseline values, those in the SPIRIT 
had less anxiety (β=-1.13 [CI, -2.23 to -0.03]; 
p=.044), depression (β=-2.54 [CI, -4.34 to -0.74]; 
p=.006), and post-traumatic distress (β=-5.75 [CI, 
-10.9 to -0.64]; p=.027) than did controls.  
 
Our qualitative thematic analysis of post-
bereavement interviews with surrogates (Box 1) 
helps explain how SPIRIT reduced surrogates’ 
post-bereavement distress.61 Our data revealed 
that surrogates reported gaining insight about 
the life-limiting nature of the patient’s illness and that death might be near; notably, no prognostic information 
was provided during the SPIRIT sessions. An important outcome 
was that the steps of SPIRIT helped raise prognostic awareness for 
participants without prognostic estimates having been conveyed.61   
 
For Supplement Aims: 
Adaptation of SPIRIT for dementia and pilot testing: In contrast to 
people with ESRD, participants in the ongoing parallel trial (“SPIRIT 
in Dementia,” R01AG057714) do not have complex multimorbidity 
and are expected to live for ~10 years after a diagnosis of 
dementia. We have completed the iterative process of adaptation for persons with mild to moderate dementia 
and their surrogates and recently pilot tested the adapted SPIRIT with a sample of 23 PWD (a Montreal Cognitive 
Assessment [MoCA] score, M=17.7, SD=4.0, range, 13-25; 74% non-Hispanic white; 50% male; mean age=74 
years) and their surrogates (65% female, 74% spouse). The PWDs also were assessed for their decision-making 
capacity using a screening test, the University of California San Diego Brief Assessment of Capacity to Consent 
(UBACC),38 at enrollment (M=13.2, SD=2.1, range 9-16 out of 18). As part of the analysis, using a “quantitizing” 
technique of qualitative data analysis,39 we reviewed SPIRIT session transcripts focusing on the values of 
treatment outcomes and the goals of care discussions, and rated the level of PWD’s articulation of end-of-life care 
preferences on a 3-point scale (from 3=expressed wishes very coherently to 1=unable to express wishes 
coherently). 
 
Preliminary findings: Of the 23 PWD, 14 PWD (60.9%) had moderate dementia (MoCA=13-17). Of note, all 
23 PWD were able to articulate their values and end-of-life wishes somewhat or very coherently; 20 of them 
expressed their wishes very coherently (rating=3). While MoCA (global cognitive functioning) scores did not differ 
by the level of articulation of wishes, the UBACC (decision-making capacity) scores did, Kruskal-Wallis H = 5.57, df 
= 1, p = 0.02, with a mean rank score of 3.50 for a rating of 2 (somewhat coherent, n = 3) and 13.28 for a rating of 
3 (very coherent, n = 20).  
 
Our finding that meaningful ACP conversations were possible even for those with moderate dementia and limited 
decision-making capacity is an important finding because Hirschman et al40 found that as PWD’s cognitive 
impairment becomes advanced, family members use the best interest standard (what a reasonable person would 
do) more often than substituted judgement (what my loved one would have wanted). The primary reason for 
using the best interest standard was that there had been no previous discussion about the PWD’s preferences.41 
Our data also show that decision-making capacity may be the more important mental faculty than global cognitive 
functioning in ACP discussion, particularly for eliciting end-of-life wishes. However, the relationships among 
cognitive functioning, decision-making capacity, and ability to express wishes need future evaluation. As part of 
the supplement, we propose to replicate the examination of one’s ability to express wishes about end-of-life care 
in a sample of patients with ESRD plus dementia to assess 1) if these patients have more severe cognitive 
Box 1. Perceived impact of SPIRIT: Themes 
SPIRIT… 
a) was an eye-opening experience, acquiring 
knowledge and understanding of the patient’s 
illness, prognosis, and end-of-life care 
b) helped strengthen relationships between 
patients and surrogates 
c) helped surrogates feel prepared during the 
time leading up to end-of-life decision-making 
d) helped surrogates have peace of mind during 
and after actual end-of-life decision-making 

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impairment and how that impacts the ACP conversations, and 2) if complex multimorbidity, i.e., ESRD, impacts the 
ACP conversation across a range of dementia severity. The supplement also gives us the opportunity to evaluate 
the adapted SPIRIT with a largely African American sample who are disproportionately represented in conditions 
with multimorbidity and dementia.  
 
The adapted SPIRIT intervention (SPIRIT-dementia) sessions lasted 100 minutes on average (range, 51-122). The 
main reasons for the longer duration compared to earlier SPIRIT studies (on average 82 minutes) were that the 
interventionist was required to: a) speak slowly, b) repeat questions for the PWD, and 3) ask clarifying questions 
whenever the PWD’s response was vague. As is typical with PWD there is slowing of speech and the PWDs often 
paused to come up with words or collect their thoughts, and the interventionist was prohibited from rushing, 
interrupting, or finishing the sentence for the PWD. Although the intervention could have been broken down to 
two sessions, as in previous SPIRIT with other patient populations, we determined that a single session approach 
would be more appropriate due to PWD’s limited or absent short-term memory. 
 
Supplement Cohort Study: 
End-of-life preferences of patients with serious illnesses are generally stable. A recent systematic review10 of 
evidence on the stability of end-of-life preferences over time found that more than 70% of patients’ preferences 
for end-of-life care were stable over time, and preference stability was generally greater among inpatients and 
seriously ill outpatients than among older adults without serious illnesses (p<.002; N=55 studies; 24 studies for 
metanalysis). Further, patients who completed advance directives had more stable preferences than those who 
did not, suggesting that efforts to engage patients in actively thinking about these decisions can augment stability 
of preferences for treatment over time. These findings support that previously stated preferences for end-of-life 
care may be sufficiently stable to guide current care. 
Disasters, psychosocial impact, and decision making behaviors: According to the National Oceanic and 
Atmospheric Administration,19 over the past 4 decades, the U.S. has been affected by 219 natural disasters where 
the overall damage costs exceeded in inflation-adjust $1 billion, and 10,000 lives were lost. Recently, the COVID-
19 pandemic, one of the most devastating disasters, has killed 100,000 Americans in less than 4 months (as of 
May 2020)20 and caused 4 million job losses nationwide.21 
Because disasters are typically unexpected, sudden, and overwhelming, it is common for people who have 
experienced one to have strong psychological responses, and their behaviors are affected in the short and 
possibly longer term.22,23 Studies24,25 have shown that following disaster, people frequently feel disoriented or 
unable to integrate distressing information, and once these initial reactions subside, people can experience a 
variety of thoughts and behaviors, such as intense or unpredictable feelings of nervousness or grief, disruptive 
sleep and eating patterns, strained interpersonal relationships with increased conflict and disagreements with 
family members, and disengagement from seeking social support. Shortly after the 9/11 terrorist attack, a 
national survey26 found that heightened levels of posttraumatic stress were not limited to New York city and 
surrounding areas but across the country, suggesting that the psychological impact of a disaster may not require 
direct exposure to the disaster.  
There is great interest in elucidating the effects of disaster for different racial groups especially in light of the 
disproportionate health disparities in COVID-related hospitalization rates and deaths in Blacks across the US.  We 
briefly discuss 2 studies that did not concern disasters but that sheds light on why race is an important 
consideration in our proposed aims. Rosen et al.27 found that Blacks, compared to Whites, were more risk tolerant 
even after adjusting for educational status. Specifically, Blacks were more willing to live with the risks of their 
underlying disease and undergo fewer procedures and that Blacks would accept much larger risks to avoid an 
invasive procedure compared to Whites. They also found that White race, lower education, and female sex were 
associated with a higher likelihood of risk aversion. On the other hand, from a different study, Blacks and 
Hispanics are far less likely to invest in the stock market (more risk averse in terms of investing behaviors) than 

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Whites, and low-income Whites are far more likely to invest in the stock market than Blacks or Hispanics 
regardless of income.28 
Although the literature on economical and psychosocial impact of disasters is growing, we have very little 
empirical data to guide ACP with our sickest patients during a disaster. Via this new research, we seek to learn 
whether a disaster would make patients with a serious chronic illness more or less likely to want aggressive 
treatment. We posit that the effects of a disaster bring doubt to clinicians as well as families regarding how to 
interpret an advance directive or end-of-life care preferences expressed some time ago before the pandemic. We 
will generate empirical data on the impact of the COVIDE-19 pandemic on patients’ end-of-life preferences, to 
address whether the stability of preferences is disrupted by the pandemic, and to identify patient characteristics, 
including race/ethnicity, associated with pre-/post-pandemic changes. 
 
2.3 
RISK/BENEFIT ASSESSMENT   
 
2.3.1 KNOWN POTENTIAL RISKS  
 
As the SPIRIT intervention has proven to be safe and efficacious, this Phase III pragmatic trial involves very 
minimal or low risk. Patient and surrogate participants may experience an emotional reaction (e.g., anxiety) or 
fatigue during the intervention or data collection. In our previous studies,17-20 intervention dyads were less 
apprehensive and more satisfied with the quality of communication than control dyads. It is expected that 
psychological burden caused by the SPIRIT intervention will be less than or equal to that of usual care.  
 
2.3.2 KNOWN POTENTIAL BENEFITS  
 
Findings from our previous studies indicate benefits of the SPIRIT interventions for participants in the intervention 
group, including meeting needs to plan for future medical care and sharing values and beliefs. In addition, in our 
recent study, surrogates in the intervention group perceived the intervention to be highly beneficial during end-
of-life decision making for their loved ones and surrogates showed significantly lower post-bereavement distress 
symptom scores.  
 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
 
As described above, it is expected that psychological burden caused by the SPIRIT intervention will be less than or 
equal to that of usual care. Previous studies have demonstrated the potential benefits of SPIRIT.  
 
3 
OBJECTIVES AND ENDPOINTS 
 
The objective of this multicenter, clinic-level cluster randomized trial is to evaluate the effectiveness of SPIRIT 
delivered by dialysis care providers as part of routine care in free-standing outpatient dialysis clinics compared to 
usual care plus delayed SPIRIT implementation. Simultaneously, we will evaluate the implementation of SPIRIT, 
including sustainability. We will use a Type I effectiveness-implementation hybrid approach62,63 that combines 
testing intervention effectiveness and gathering information about implementation of an efficacious intervention 
in a real world setting. The short-term goal is to generate sufficient evidence to accelerate the integration of 
SPIRIT into dialysis practice and policy. We will recruit 400 dyads of patients at high risk of death in the next year 
and their surrogates from 30 dialysis clinics in 4 states. 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR ENDPOINTS 
Primary 
 
 

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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR ENDPOINTS 
Examine the effectiveness of SPIRIT 
compared to usual care on 
preparedness outcomes for end-of-life 
decision making (defined as dyad 
congruence on goals of care, patient 
decisional conflict, and surrogate 
decision-making confidence) at 2 
weeks post-intervention. 
 
 
Dyad congruence on goals of care 
(binary); 
Patient decisional conflict (scale); 
Surrogate decision-making confidence 
(scale) 
Composite outcome (goals-of-care 
congruence with confident surrogate; 
binary) 
The primary goal of SPIRIT is to 
prepare the patient and surrogate 
for end-of-life decision making. The 
preparedness outcomes will indicate 
whether or to what extent SPIRIT 
accomplished the goal.  
Secondary 
 
 
Examine the effectiveness of SPIRIT 
and usual care on surrogates’ post-
bereavement distress  
Anxiety symptom score (HAS-anxiety); 
Depression symptom score (HAS-
depression); 
Post-traumatic distress symptom score 
(PTSS) 
 
Surrogate prepared by SPIRIT for EOL 
decision making should experience 
less post-bereavement distress.  
Evaluate the process outcomes of 
SPIRIT implementation: during the 
initial and delayed implementation of 
SPIRIT  
 
Acceptability, fidelity, intervention costs, 
and sustainability 
Descriptive aim to generate data for 
translation 
Tertiary/Exploratory  
 
 
Examine the effectiveness of SPIRIT 
and usual care on EOL treatment 
intensity 
Health care utilization (percentages of 
patients hospitalized, having ICU 
admission, and having intensive 
procedures, and LOS) 
To examine whether SPIRIT reduces 
aggressive EOL treatment 
Supplement 
 
 
Estimate the effects of the SPIRIT-
dementia intervention on the 
preparedness outcomes and care 
decisions 
Dyad congruence on goals of care 
(binary); 
Patient decisional conflict (scale); 
Surrogate decision-making confidence 
(scale) 
Composite outcome (goals-of-care 
congruence with confident surrogate; 
binary) 
 
Care decisions (withdrawal from dialysis, 
Do-Not-Resuscitate order, hospice 
enrollment)  
The primary goal of SPIRIT is to 
prepare the patient and surrogate for 
end-of-life decision making. The 
preparedness outcomes will indicate 
whether or to what extent SPIRIT 
accomplished the goal. 
 
 
Care decisions will reflect the effects 
of SPIRIT on end-of-life decision 
making. 
Estimate the effects of the SPIRIT-
dementia intervention on surrogates’ 
post-bereavement distress 
Anxiety symptom score (HAS-anxiety); 
Depression symptom score (HAS-
depression) 
 
Surrogate prepared by SPIRIT for 
EOL decision making should 
experience less post-bereavement 
distress. 
Supplement cohort study (non-clinical 
trial) 
 
 
Assess the effect of the pandemic on the stability of end-of-life care preferences and on our key outcomes (dyad 
congruence on goals of care, patient decisional conflict, and surrogate decision-making confidence). 
 
 

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Measurement and data collection time points 
 
Outcome 
Measure 
Completed by 
Time points 
pt 
srgt 
prov 
Effectiveness outcome evaluation 
 
 
 
 
Preparedness 
 
 
 
 
 
Dyad congruence 
Goals-of-Care Tool (2 end-of-life scenarios) 
 
 
 
Baseline and 2 wks 
Patient decisional 
conflict 
Decisional Conflict Scale (range, 1-5) 
 
 
 
Baseline and 2 wks 
Surrogate decision-
making confidence 
Decision Making Confidence Scale (range, 0-4) 
 
 
 
Baseline and 2 wks 
Overall preparedness 
Preparedness for End-of-Life Decision Making (range, 26-
104) 
 
 
 
Baseline and 2 wks 
Post-bereavement 
distress 
HADS (each subscale range, 0-21) 
PTSS-10 (range, 10-70) 
 
 
 
Baseline and 3 mo. 
after patient death 
End-of-life care intensity 
Percentages of patients hospitalized, having ICU 
admission, and having intensive procedures and length of 
hospital stay 
 
 
 
Medicare claims data 
after patient death 
Initial implementation process evaluation 
 
 
 
 
Care provider  
acceptability 
Dialysis care provider’s perceived acceptability (range, 7-
28); 
Semi-structured interview 
 
 
 
 
End of the initial 
implementation  
Patient & surrogate 
acceptability 
Patient and surrogate acceptability (range, 10-40 each) 
 
 
 
2 wks  
Fidelity 
SPIRIT provider’s coverage of the SPIRIT components and 
durations;   
Brief patient and surrogate survey 
 
 
 
SPIRIT provider after 
each SPIRIT 
completion 
Patient and surrogate 
at 2 wks 
Intervention costs 
The actual time the care provider spent in carrying out 
SPIRIT, multiplied by hourly wage (+benefits), plus costs 
of materials 
 
 
 
End of the early 
implementation 
Sustainability  
Brief semi-structured interview 
 
 
 
End of 12 mo.post 9-
month follow-up 
Delayed implementation process evaluation 
 
 
 
 
Care provider 
acceptability 
Dialysis care provider’s perceived acceptability (range, 7-
28); 
Semi-structured interview 
 
 
 
 
 
End of the delayed 
implementation  
Fidelity 
SPIRIT provider’s coverage of the SPIRIT components 
durations 
 
 
 
SPIRIT provider after 
each SPIRIT 
completion 
Intervention costs 
The actual time the care provider spent in carrying out 
SPIRIT, multiplied by hourly wage (+benefits), plus costs 
of materials 
 
 
 
End of the delayed 
implementation 
Descriptors and potential covariates 
 
 
 
 
   Sociodemographics 
Sociodemographic Profile 
 
 
 
Baseline for patients 
and surrogates  
 
 
 
End of the initial 
implementation for 
clinicians 
   Clinical characteristics 
Medical Profile  
 
 
 
Baseline  
   Clinic-level contextual  
      data 
Contextual Data Collection Form 
 
 
 
End of each 
implementation 
   Usual care  
Documented AD completion on the Plan of Care form; 
presence of DNR, POLST, or MOST (from EMR) 
 
 
 
Baseline and  6 mo. 
Pt, patient; Srgt, surrogate; Pro, care provider 
Data collection highlighted in yellow is performed locally. 
 
 

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For supplement aims: 
 
Measurement and data collection time points 
 
Outcome 
Measure 
Completed by 
Time points 
pt 
srgt 
Estimating the effects of SPIRIT-dementia 
 
 
 
Preparedness 
 
 
 
 
Dyad congruence 
Goals-of-Care Tool (2 end-of-life scenarios) 
 
 
Baseline and 2-3 days 
Patient decisional 
conflict 
Decisional Conflict Scale (range, 1-5) 
 
 
Baseline and 2-3 days 
Surrogate decision-
making confidence 
Decision Making Confidence Scale (range, 0-4) 
 
 
Baseline and 2-3 days 
Overall preparedness 
Preparedness for End-of-Life Decision Making (range, 26-
104) 
 
 
Baseline and 2-3 days 
Post-bereavement 
distress 
HADS (each subscale range, 0-21) 
 
 
Baseline and 1 mo. 
after patient death 
Care decisions 
Percentages of patients hospitalized, having ICU 
admission, and having intensive procedures and length of 
hospital stay 
CMS form 2746 
After patient death 
 
4 
STUDY DESIGN  
 
4.1 
OVERALL DESIGN 
 
We will conduct a dialysis clinic-level cluster randomized trial with two groups, SPIRIT versus usual care followed 
by delayed SPIRIT. We will recruit 400 dyads of patients on chronic (“prevalent”) dialysis who are at high risk of 
death in the next year and their surrogate decision-makers (total 800 individuals) from 30 free-standing dialysis 
clinics in 4 states. The primary outcomes are patient and surrogate self-report preparedness for end-of-life 
decision making. The implementation evaluation data will be obtained throughout the study course. Upon patient 
death (anticipate 20% of patients; n = ~ 80), we will assess surrogates’ post-bereavement distress. Patient 
participation will end at 9 months (to allow for obtaining Medicare claims data during the study period) or death, 
whichever occurs first; surrogate participation will end at 9 months or at the completion of 3-month post-death 
follow-up. If patient is still living at 9 months, we will ask for an extension of follow up period to include 12 more 
months. Medicare claims data for end-of-life treatment intensity will be obtained quarterly. Clinics assigned to 
usual care will receive the delayed implementation, SPIRIT, in Year 4, Q1. This is a Phase III trial of an intervention 
that involves minimal risks and has proven to be efficacious, and thus no interim analysis is planned.  
 
For Supplement Aims: 
 
Consent
at the clinic
Baseline
Preparedness 
outcomes
SPIRIT
Usual 
care
Follow-up
Preparedness 
outcomes
R
Care decisions 
(withdrawal
from dialysis;
hospice
enrollment)
1-2 weeks
~2 weeks
2-3 days
6 months
Figure 1. Design Overview
Care decisions 
and
Surrogate
post-
bereavement 
distress
If patient dies

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We will use a randomized controlled trial design with two groups: SPIRIT-dementia and usual care. From the pool 
of screened but excluded ESRD patients, we will recruit 30 dyads of patients with mild to moderate dementia and 
their surrogates. The groups will be stratified by race (white vs non-white). Patient and surrogate self-reported 
preparedness for end-of-life decision making will be measured at baseline and shortly after the intervention (by 
phone in the next 2-3 days) as done in the pilot test of SPIRIT-dementia. Additionally, we will review the patient’s 
medical record to examine care decisions at 6 months or after the patient’s death, whichever occurs first. In the 
case of patient death, we will also assess surrogates’ post-bereavement outcomes (anxiety and depression 
symptoms) at 1 month after the patient’s death. Based on previous research,13 we anticipate about 50% of the 
supplement sample will die within 12 months of enrollment. All data collection from study participants will be 
telephone-based. 
 
Supplement cohort study: 
 
 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
 
We chose cluster over individual randomization for the benefits of increased efficiency and decreased risk of 
experimental contamination, while recognizing potential loss in statistical precision from the effects of variance 
inflation.64 However, cluster effects are usually small and can be controlled in analysis. Cluster randomization is 
also a favorable design strategy for the Type I hybrid effectiveness-implementation approach to test clinical 
effectiveness while gathering information on implementation.62 Hybrid designs are increasingly used to expedite 
the sequential process, “efficacy to effectiveness to preliminary implementation63 and are recommended when 
there is strong evidence of the intervention effects and the intervention is low risk for participants.62. To maximize 
data on the implementation process and sustainability, we chose a delayed intervention design65 in which clinics 
are randomized either to implement SPIRIT immediately after randomization (i.e., initial implementation) or to 
maintain usual care for a comparison condition and then implement the intervention in Year 4 (i.e., delayed 
implementation). The delayed implementation group will effectively serve as control for effectiveness evaluation. 
The process outcomes from the initial implementation of SPIRIT will be used to determine if any modifications to 
SPIRIT are necessary. We anticipate that we will make clinic-specific adaptations to improve implementation in 
the delayed implementation phase. Clinics in the delayed implementation phase will be evaluated on the process 
outcomes, which will provide data on the iterated version of SPIRIT without having to conduct another trial. The 
Clinics 
rando-
mized
SPIRIT
Usual care
Baseline 
(T1)
(by 
phone)
Follow-up 
at 2 
weeks
(T2)
(by 
phone)
SPIRIT 
Sessions 
I & II 
(in 
person)
Monthly 
check-in 
call x 9 or 
more
(by 
phone)
Parent study
(T3)
(by 
phone)
Before March 13, 2020
Supplement  
study
6 months 
after T3
(T4) 
(by 
phone)
Consent for
supplement study
during monthly 
check-in call
Patient 
death or 
study end
After March 13

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delayed implementation is more ethical than not providing SPIRIT at all because its demonstrated efficacy would 
preclude equipoise.     
 
Virtually no trials are purely pragmatic or explanatory; based on the PRECIS Tool and key characteristics of 
pragmatic trials,66,67 the proposed study is more pragmatic than explanatory in the pragmatic-explanatory  
continuum because it will include diverse patient populations, multiple heterogeneous settings, few inclusion and 
exclusion criteria, and the comparison condition is a real-world alternative (i.e., usual care), not a placebo. 
Further, the study is built around normal dialysis care operations as much as possible with flexible study protocols 
that minimize intrusion in daily work flow at the dialysis facilities. Of direct relevance to dialysis care, the 
intervention will be implemented by dialysis care providers, such as nurses and social workers. 
 
For Supplement Aims: 
As in our previous studies of SPIRIT, we chose individual randomization because intervention spillover to the 
control condition is very unlikely. The intervention will be delivered by a trained interventionist, not a care 
provider, in a private room at the clinic, or virtually due to the COVID-19 pandemic, and thus it is nearly 
impossible for care providers to obtain the knowledge and skill related to SPIRIT to change their ACP practice. We 
chose race (white vs non-white) as a stratification factor to ensure equal allocation of race to each condition to 
control for race as a confounding variable.49  
 
The follow-up time point (2-3 days post intervention) is to evaluate the impact of SPIRIT on preparedness 
outcomes while minimizing the potential influence of the patient’s impaired ability to recall what was discussed 
during the SPIRIT session. We considered measuring the outcomes immediately following the intervention, but 
this would increase subject burden as SPIRIT sessions tend to last longer with PWDs than those without cognitive 
impairment. The time point for care decision reviews (6 months post intervention) was chosen to help maximize 
the number of patients whose conditions progress within the study period so that we can explore the impact of 
SPIRIT-dementia on care decisions. As in earlier SPIRIT trials and the parent study with ESRD patients and the 
parallel study with dementia patients, we will use telephone-based data collection to reduce participants’ travel 
burden. 
 
Supplement cohort study: 
We posit that reflexive decision-making in response to the pandemic could discount previously expressed 
preferences for end-of-life care, thereby affecting the stability of those preferences. We postulate that such 
alterations in decisions may be more prevalent among patients and families who have not had ACP to explore 
own values and beliefs about end-of-life care (such as dyads in the control group in the parent study), and also 
among Blacks, a racial group that is thought to embrace more aggressive treatment at the end of life.29 This is 
especially important now in light of recent findings30 that counties in the U.S. with higher Black populations 
account for more than half of all COVID-19 cases and almost 60% of deaths even though Blacks represent only 
13.4% of the American population. We have an opportunity to address these complicated but urgent questions 
about end-of-life decision making when people fear a dangerous virus and are alarmed about scarce lifesaving 
resources, such as ICU beds and ventilators. 
 
4.3 
JUSTIFICATION FOR INTERVENTION 
 
The SPIRIT intervention is a one-time advance care planning intervention that has been rigorously tested and has 
demonstrated its efficacy. The details about the intervention, including the rationale, are described above (2.2 
Background). 
 
4.4 
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Because the study uses a delayed intervention design to maximize implementation data collection, the end of the 
study will be the completion of care provider acceptability, fidelity and cost data collection.  
 
For Supplement Aims: 
We will review the patient’s medical record to examine care decisions at 6 months or after the patient’s death, 
whichever occurs first. In the case of patient death, we will also assess surrogates’ post-bereavement outcomes 
(anxiety and depression symptoms) at 1 month after the patient’s death. Based on previous research,13 we 
anticipate about 50% of the supplement sample will die within 12 months of enrollment. 
 
Supplement cohort study: 
Completion of 6 month follow-up (T4) after T3. 
 
5 
STUDY POPULATION 
 
5.1 
INCLUSION CRITERIA 
 
Patient eligibility criteria:  
a) 18 years or older  
b) on either hemodialysis or peritoneal dialysis  
c) able to understand and speak English.  
 
Surrogate eligibility criteria: 
a) 18 years or older (to serve as a surrogate decision-maker, the individual must be an adult) 
b) being chosen by the patient.  
 
Roughly 76 providers at the 29 clinics, including all medical directors, nurse managers, social workers, and those 
who are selected to conduct SPIRIT sessions will participate in the implementation evaluation. 
 
For Supplement Aims: 
 
Patient eligibility criteria:  
a) Receiving in-center hemodialysis at Emory or UVA dialysis clinics.   
b) Diagnosed with dementia of any etiology (or those for whom their care providers, either MD or APRN, are 
suspicious of dementia) with having mild to moderate cognitive impairment based on a Montreal 
Cognitive Assessment (MoCA) score of 13 or higher,54,55 or a Saint Louis University Mental Status (SLUMS) 
score of 21 or higher (high school education) or 20 or higher (less than high school education)56  
c) Able to understand and speak English 
d) A UBACC (decision-making capacity screening test) score  11. Because dementia is largely under-
diagnosed in the clinical setting for patients with ESRD, to identify additional patients with possible 
dementia, a trained research assistant will administer the MoCA or SLUMS to patients who are suspected 
(by dialysis clinicians) of having dementia. MoCA or SLUMS will take about 10 minutes to complete. 
 
Surrogate eligibility criteria: 
a) 18 years or older (to serve as a surrogate decision-maker, the individual must be an adult) 
b) being chosen by the patient.  
 
 
For supplement cohort study: 

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Dyads who completed the parent study’s baseline (T1) and 2-week follow-up (T2) before March 13, 
2020. 
 
5.2 
EXCLUSION CRITERIA 
 
Patient exclusion criteria:  
a) lack of an available surrogate,  
b) too ill or cognitively impaired to participate based on clinicians’ judgment*,  
c) already enrolled in hospice. 
 
Surrogate exclusion criterion: 
a) Those who cannot complete questionnaires due to physical or cognitive limitations will be excluded. 
 
For Supplement Aims: 
Patient exclusion criteria:  
a) lack of an available surrogate,  
b) uncompensated hearing deficits,  
c) already enrolled in hospice. 
 
*Patients who are excluded from the parent study will be considered for the supplement study.  
 
5.3 
LIFESTYLE CONSIDERATIONS 
 
Not applicable 
 
 
 
 
5.4 
SCREEN FAILURES 
 
Because patients are approached first at the dialysis center, it is possible that patients provide written consent to 
participate in the study with the assumption that their surrogates would be willing to participate with them 
(however, patients cannot complete the baseline without willing surrogates), and then the surrogate actually 
declines to participate. Because randomization occurs at the clinic level, not the individual level, these cases will 
be reported under “not eligible” with reason.  
 
5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
 
Recruitment and Consent procedures: 
The dialysis care provider who has been selected by the clinic as one responsible for SPIRIT delivery at each clinic 
(so-called, “SPIRIT clinician champion”) in both groups will generate a list of patients each quarter who meet the 
inclusion criteria. Depending on the clinic’s structure and workflow, the care provider who determines patients 
meeting these criteria may not be the same care provider, i.e., SPIRIT clinician champion who is responsible for 
SPIRIT delivery.  
 
From this list, the care provider will then assess the patient’s willingness to meet with a recruiter from the 
research team. The recruiter will then approach willing patients during their scheduled dialysis clinic appointment 
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patient after the study is reviewed and understanding is established.  The recruiter will then provide the patient 
with a study brochure and encourage him/her to talk to the surrogate regarding the study within the next 2-3 
days (to avoid a cold call). Several days later, the recruiter will telephone the surrogate to assess his/her 
willingness to participate. Using a Surrogate Verbal Consent script and form, the site coordinator will document 
time and date. Upon this verbal consent, the research staff at the Emory Study Coordination Center will 
conduct baseline data by phone. For surrogates in the SPIRIT implementation clinics, the recruiter (at each study 
site) will schedule the first SPIRIT session to take place at the clinic 2 weeks hence, as is possible.  
 
Recruitment will occur over 24 months beginning at the end of Year 1. We are highly experienced in recruiting 
seriously ill ESRD patients and their surrogates for research. Consent rates in our previous studies have been 
consistent at approximately 84% despite the studies’ focus on end-of-life, the requirement that both patient and 
surrogate participate, and long-term follow-up. We expect a similar if not higher consent rate because the study 
involves a shorter follow-up time and minimal data collection directly from patients and surrogates. Based on our 
previous studies,18-20 we conservatively anticipate that 427 patients (20%) will be eligible and willing to 
participate. To reach 400 dyads, we expect to enroll 21-22 dyads per cluster on average. These clinics each accept 
10-70 new patients each year (total 700 additional patients), and thus our recruitment goal is readily achievable. 
 
To Maximize Participant Retention, strategies found effective in retaining dyads over 12 months (dropouts, 3.8%) 
in our efficacy trial20 will be used: we will  
a) obtain two backup contacts from each member of the dyad in the event that we cannot reach them by 
telephone and mail 
b) make confirmation phone calls 2 days prior to each follow-up 
c) make monthly check-in calls 
d) send holiday cards 
e) assign the same data collector whenever possible 
f) compensate each member of the dyad with gift cards ($15 at baseline, $15 at 2 weeks for the 
preparedness outcome assessment; $20 at 3 months for the post-bereavement outcome assessment). 
Consistent with a pragmatic trial, participants will not be compensated for participating in the 
intervention. The Emory Study Coordination Center will be responsible for disbursement.  
 
For Supplement Aims: 
Participants will be recruited from the Emory dialysis centers and the UVA dialysis centers . First, patients who 
have been diagnosed with an early stage of dementia (mild to moderate) or are suspected of having cognitive 
impairment by a care provider will be referred by the dialysis APRN. The medical records of those patients will be 
reviewed to preliminarily determine eligibility by a research staff member. During the patient’s dialysis treatment 
session at the center, the patient’s care provider will gain permission for the staff member to explain the study. 
With the patient’s permission, the staff member will approach the patient, briefly explain the study, obtain verbal 
consent to conduct the MOCA or SLUMS and UBACC screening. If the patient has met the criteria for both early 
stages of cognitive impairment and decision-making capacity, the research staff member will provide detailed 
study information and confirm his/her surrogate decision-maker. Written consent will then be obtained from the 
patient. The research staff member will obtain the name and phone number of the surrogate (or confirm with the 
medical record as necessary) and call the surrogate in 2-3 days to assess the surrogate’s willingness to participate. 
Verbal consent will be obtained from the surrogate. At the time of surrogate consent, the staff member will 
schedule a telephone-based data collection session for baseline assessment in about 2 weeks. 
 
To minimize in-person contacts, we will screen patients remotely/via phone whenever possible. Patients who are 
deemed eligible will be approached by a social worker during their dialysis treatment session or by phone to ask 
them about their willingness to be contacted via telephone by Emory research staff. Patients who agree to be 
contacted, a research staff member will call the patient, briefly explain the study, obtain verbal consent to 
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patient if screening occurred over the phone. The research staff member will obtain the name and phone number 
of the surrogate (or confirm with the medical record as necessary) and call the surrogate in 2-3 days to assess the 
surrogate’s willingness to participate. Verbal consent will be obtained from the surrogate. At the time of 
surrogate consent, the staff member will schedule a telephone-based data collection session for baseline 
assessment in about 2 weeks.  
 
For supplement cohort study: 
At the next monthly check in phone call (as part of the parent study protocol), the research staff member will 
proceed with the procedures for the parent study and then introduce the participant to the supplement study, 
including the purpose and procedures and obtain verbal consent. After both members of the dyad have 
consented, the recruiter will schedule two data collection calls (T3 within 1 week and T4 at 6 months). If 
additional subjects are needed, we will contact those who already completed the study before the pandemic. 
 
To Maximize Participant Retention, we will  
a) obtain two backup contacts from each member of the dyad in the event that we cannot reach them by 
telephone and mail 
b) make confirmation phone calls 2 days prior to the baseline and/or the SPIRIT session (intervention group) 
c) make scripted monthly check-in calls 
d) send holiday cards 
e) assign the same data collector whenever possible 
f) provide transportation support ($20) for the SPIRIT session in person at the center (intervention group)  
g) compensate each member of the dyad with gift cards ($20 at baseline; $25 at post-intervention follow-up; 
and surrogates who complete post-bereavement assessment will receive $30 at 1 month after the 
patient’s death). 
For supplement cohort study, each member of the dyad will receive an additional $20 at the completion 
of T3 and $30 at T4. 
 
Recruitment of Care Providers for Implementation data collection, we will obtain a list of dialysis care providers 
from each dialysis center, who are willing to be contacted by the study staff for participating in implementation 
related data collection. This data collection is to obtain inputs from the care providers regarding SPIRIT 
implementation as part of routine dialysis care. Research study staff at the study site will contact care providers 
on the list using their preferred contact numbers or emails. Verbal Care Provider Informed Consent will be used in 
consenting process. Survey/Interviews will be scheduled to be conducted over the phone or in person at the 
convenience of the Care Provider. There will be no compensation for care provider’s participation. 
 
 
 
 
6 
STUDY INTERVENTION(S) 
 
6.1 
STUDY INTERVENTION(S) ADMINISTRATION 
 
6.1.1 STUDY INTERVENTION DESCRIPTION 
 
SPIRIT Intervention:  
All care providers responsible for SPIRIT delivery will follow the structured SPIRIT Interview Guide. All sessions will 
be conducted in a private room in the clinic. The goals of SPIRIT are to assist patients clarify their end-of-life 
preferences and to help surrogates understand the patient’s wishes and prepare for the surrogate role. SPIRIT has 
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software (Zoom) when surrogate decision makers live or work outside a 50-mile radius of patient’s clinic. We 
project the monthly caseload for SPIRIT delivery will be 1-2 dyads per cluster on average. 
During the first session (~45 min.), the care provider will assess the patient’s and surrogate’s cognitive, 
emotional, and spiritual/religious representations of the patient’s illness, prognosis, and end-of-life care. This will 
allow the care provider to provide individualized information about topics, such as the effectiveness of life-
sustaining treatment for people with end-organ failure, and assist the patient to examine his/her values about 
life-sustaining treatment at the end of life. The care provider will help the surrogate prepare for end-of-life 
decision-making and for the emotional burden of decision-making by actively involving the surrogate in the 
discussion. If the surrogate is someone out of the order of the hierarchical compensatory model71 (e.g., a sibling is 
chosen instead of a spouse), the care provider will explore potential family conflicts and encourage the dyad to 
talk with other family members and complete a healthcare power of attorney. A Goals-of-Care document will be 
completed at the end of the session to indicate the patient’s preferences.   
A brief second session (~15 min.) will be delivered about approximately 2 weeks later, if possible. For PD 
patients who scheduled dialysis is varying, the second session of the SPIRIT Intervention can be scheduled to 
occur approximately 2-4 weeks hence, if possible. This session is a follow-up to address remaining or new 
concerns and questions raised after the first session. The patient’s Goals-of-Care document will be reviewed and 
assessed for the need for clarification or correction. The provider will document the patient’s end-of-life 
preferences and the surrogate’s name and relationship to the patient in the medical record. If the patient desires 
a DNR order, POLST, or MOST, the care provider will discuss with the patient’s nephrologist and arrange a meeting 
to complete a treatment order form. We will track completion of these forms.  
 
For Supplement Aims: the SPIRIT intervention will include one session only due to the patient’s limited or absent 
short-term memory.  During the COVID-19 pandemic, all SPIRIT sessions will be done via zoom whenever possible. 
 
Usual Care 
As required by CMS,51 written information on ADs is provided to a patient on the first day of dialysis, and a social 
worker reviews this information with patients and encourages them to complete an AD. This typically takes about 
10 minutes. If completed, the presence of an AD is documented on the Plan of Care form. If a patient expresses a 
desire not to be resuscitated in the dialysis unit, a DNR order is written by a nephrologist and placed in the clinic 
record. If there is no DNR order in the record, a full code is presumed. A social worker or charge nurse reviews 
code status and updates it annually. Currently, all four states endorse the physician orders for life-sustaining 
treatment (POLST) paradigm; NM MOST (medical orders for scope of treatment), NC MOST, PA POLST, VA POST 
and GA POLST; these forms may be completed to complement ADs. None of the clinics employ routine 
identification of patients at high risk for death or structured ACP sessions targeting those patients. 
6.1.2 DOSING AND ADMINISTRATION 
 
Described above (6.1.1). 
 
 
6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
 
6.2.1 INTERVENTIONIST TRAINING AND ACCOUNTABILITY 
 
Care Provider Training for SPIRIT 
The ideal individual to conduct ACP discussions is still unknown, but we believe it is not the profession per se but 
rather the willingness and appropriate training that make an individual suitable for conducting the discussions. 
Each dialysis clinic has identified a care provider designated to conduct SPIRIT sessions (e.g., ANP, RN, MSW). 
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the delayed implementation clinics. The SPIRIT trainers, trained and certified by the PI at the Study Coordination 
Center (at Emory), will conduct SPIRIT training for all four sites based on the manualized curriculum.  
 
Care provider training will consist of a 1½-day, competency based program that has been used in our previous 
trials:  
• 
Module 1 (1/2 day) to ensure understanding of end-of-life care issues and communication as key to 
improving end-of-life care and the Representational Approach (theoretical underpinnings of SPIRIT);  
• 
Module 2 (1/2 day), as skill-base session to gain understanding of the SPIRIT intervention and delivery, 
including role plays. A 2-week practice period will be scheduled for integration of skills and exploration of 
additional learning needs; and  
• 
Module 3 (1/2 day) for skill-demonstration and certification. These training sessions will be conducted in 
collaboration with the Emory Nursing Professional Development Center. 
 
For Supplement Aims: 
An RN who has been trained and certified for SPIRIT-dementia will deliver the intervention, who is currently 
working as the interventionist for the SPIRIT-AD study (IRB #00099738). SPIRIT sessions will be conducted in a 
private room at the dialysis center or virtually with ZOOM. At the beginning, the interventionist will administer 
the MoCA or SLUMS (depending on which test was used at enrollment), which should take about 10 minutes. The 
interventionist will begin the SPIRIT session by assessing the patient’s and surrogate’s cognitive, emotional, and 
spiritual/religious representations of the patient’s illness, prognosis, and end-of-life care. This will allow the 
interventionist to provide individualized information about topics, such as the effectiveness of life-sustaining 
treatment for people with end-organ failure, and assist the patient to examine his/her values about life-sustaining 
treatment at the end of life. The interventionist will help the surrogate prepare for end-of-life decision-making 
and for the emotional burden of decision-making by actively involving the surrogate in the discussion. If the 
surrogate is someone out of the order of the hierarchical compensatory model59 (e.g., a sibling is chosen instead 
of a spouse), the care provider will explore potential family conflicts and encourage the dyad to talk with other 
family members and complete a healthcare power of attorney. A Goals-of-Care document will be completed at 
the end of the session to indicate the patient’s preferences. The delivery of SPIRIT-dementia incorporates so-
called “enhanced consent techniques,” such as reducing information load by proceeding in manageable segments 
or chunks, offering repetition of material, opportunity for rehearsal, and using targeted questioning to verify 
adequate comprehension prior to eliciting preferences for goals of care.60-62 All sessions will be audio-recorded 
and transcribed. At the end of the session, the dyad will receive $20 to compensate travel costs. The 
interventionist will schedule a follow-up call for the outcome assessment in the next 2-3 days. 
 
6.2.2 FORMULATION, APPEARANCE, PACKAGING, AND LABELING 
 
Not applicable. 
 
6.2.3 PRODUCT STORAGE AND STABILITY 
 
Not applicable. 
 
6.2.4 PREPARATION 
 
Not applicable. 
 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
 

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Clinics covered by the same care provider who will deliver SPIRIT sessions will be combined to one cluster to avoid 
risk of contamination; this results in clusters (4 in GA, 3 in NC, 8 in NM, 5 in PA and 8 in VA). Because the numbers 
of available patients substantially vary across the clusters, to minimize group imbalance clusters will be stratified 
to three sizes: small (patient census ≤ 52), medium (53-105), and large (≥ 106). We will randomize clusters to 
either SPIRIT or usual care plus delayed SPIRIT, with randomly permuted blocks (sizes of 2 and 4) within cluster 
size stratum nested in each state, using a pseudo-random-number generator, by the Study Coordination Center.  
 
Before the study starts, the Study Coordination Center will inform the group assignment for each cluster to the 
site PIs, with a unique ID consisting of abbreviations for state and cluster size stratum. While the heterogeneity in 
minority race/ethnicity across clusters improves the study’s generalizability, stratification or pairing clusters by 
race/ethnicity is not feasible because some clinics uniquely serve one race with no comparable clinics within state. 
Group imbalances on race/ethnicity and other potential confounding factors will be examined and adjusted for in 
the analyses. The cluster randomized design prevents blinding patient-surrogate dyads and dialysis care providers 
to group allocation. However, research staff assessing effectiveness outcomes will be blind to group assignment. 
 
For Supplement Aims: 
Dr. Paul (biostatistician/Co-I) will generate a randomization scheme using stratified (by race), permuted block 
randomization with block size 5, using a random-number generator. Dyads will be randomized with equal 
allocation (1:1) to SPIRIT or usual care. Due to the nature of the intervention, blinding dyads to their group 
allocation is impossible, but the research staff assessing outcomes will be blind. Immediately after the completion 
of the baseline assessment by phone, the data collector will open a sealed envelope to identify group assignment 
and schedule an intervention session to take place ~2 weeks hence for SPIRIT as well as a follow-up data 
collection session in the next 2-3 days. 
 
6.4 
STUDY INTERVENTION COMPLIANCE 
 
To maintain internal validity, certain components of the intervention will be standardized: standardized care 
provider training using the training modules (described above); Session 1 will be delivered via face-to-face; the 
SPIRIT Interview Guide will be used during each session to promote consistency and quality of intervention 
delivery. We will develop a template of procedures related to SPIRIT implementation for each clinic to customize 
and use as a resource.  
 
To assess fidelity, we will use two independent data sources.  
1) The SPIRIT Interview Guide will direct the care provider to document performance data after each 
patient-surrogate dyad encounter (the data will be entered into REDCap by each site coordinator). The 
Guide has a checklist of SPIRIT components, including start and finish times and brief self-evaluation.  
2) At the 2-week post-intervention follow-up, a research assistant will query patients and surrogates about 
the SPIRIT sessions using the checklist of SPIRIT components. After the first 50 dyads (~first 4 months) 
have been seen, clinics with <80% adherence on both data sources will receive feedback and another 
orientation meeting by the Site PI and the SPIRIT trainer.  
 
We considered replacing clinics with <80% adherence, but this approach would not be consistent with the 
pragmatic nature of the study to test SPIRIT in a real-world setting. We also considered recording a sample of 
SPIRIT sessions, but this approach would likely be considered intrusive by the dialysis care providers and is 
unrealistic in a pragmatic trial.  
 
For Supplement Aims: 
To promote consistency and quality of intervention delivery, the SPIRIT Interview Guide will be used during each 
session. To monitor fidelity, we will use two data sources. 1) The SPIRIT Interview Guide will direct the 
interventionist to document performance data after each patient-surrogate dyad encounter; these data will be 

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entered into the Research Electronic Data Capture (REDCap) by the research coordinator. The Guide has a 
checklist of SPIRIT components, including start and finish times, and brief self-evaluation. 2) All intervention 
sessions will be audio-recorded. Every 2 months, 50% of sessions randomly selected will be reviewed by the PI. 
Using the Treatment Fidelity Assessment Tool, the interventionist’s adherence to intervention content, process, 
and duration will be evaluated on a 3-point scale (1=appropriate, 3=skipped). Problems detected including drift 
from protocol will be discussed with the interventionist and re-training will be provided if adherence is <80% 
based on the Fidelity Assessment Tool. 
 
6.5 
CONCOMITANT THERAPY 
 
Not applicable (all patients receive usual care related to advance care planning). 
 
6.5.1 RESCUE MEDICINE 
   
Not applicable. 
 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
 
7.1 
DISCONTINUATION OF STUDY INTERVENTION 
 
SPIRIT is a one-time intervention with two sessions. If patient-surrogate dyads is not able to complete Session I or 
II, the reason or circumstances (e.g., the patient became too ill) will be documented and reported. Session II 
cannot be offered without Session I completed; that is, it is possible that a patient-surrogate dyad completes 
Session I but not Session II. Dyads who never complete Session I and dropout will be replaced by enrolling a new 
dyad.  
 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
 
Participants are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue or withdraw a participant from the study for the following reasons: 
• 
If the participant meets an exclusion criterion that precludes further study participation. 
 
The reason for participant discontinuation or withdrawal from the study will be recorded on the study REDCap. 
Subjects from the dialysis center randomized to initial SPIRIT who sign the informed consent form but do not 
receive the study intervention may be replaced.  Subjects in the initial SPIRIT who sign the informed consent form 
and receive the study intervention, and subsequently withdraw, or are withdrawn or discontinued from the study 
will not be replaced. 
 
7.3 
LOST TO FOLLOW-UP 
 
Patients lost to follow-up will not be applicable in this trial since all patients must come to the dialysis center for 
their treatment and thus can be contacted at the center.  
 
A surrogate participant will be considered lost to follow-up if he or she fails to complete the scheduled 2-week 
follow-up (after the receipt of the intervention) and is unable to be contacted by the study site staff until the end 
of the 9-month follow-up period. Or, a surrogate participant will be considered lost to follow-up if he or she fails 

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to complete the scheduled 3-month follow-up (after the patient’s death) and is unable to be contacted by the 
study site staff.  
 
The following actions must be taken if a participant is determined to be lost to follow-up: 
• 
The site will attempt to contact the participant and reschedule the missed appointment for 4 weeks and 
ascertain if the participant wishes to continue in the study. 
• 
Before a participant is deemed lost to follow-up, the investigator or designee will make every effort to 
regain contact with the participant (where possible, 3 telephone calls and, if necessary, a certified letter 
to the participant’s last known mailing address or local equivalent methods, or speak to the patient at the 
dialysis center). These contact attempts will be documented in the participant’s record in REDCap.  
• 
Should the participant continue to be unreachable, he or she will be considered to have withdrawn from 
the study with a primary reason of lost to follow-up. 
 
8 
STUDY ASSESSMENTS AND PROCEDURES 
 
8.1 
OUTCOME ASSESSMENTS  
 
Collecting effectiveness outcome data will be centralized; research staff at the Study Coordinating Center will 
collect the data from patients and surrogates by phone. Telephone-based collection minimizes participants’ travel 
burden. Centralized data collection maintains data collectors being blind to group assignment. The preparedness 
outcomes will be assessed at 2 weeks post-intervention, as in our R21 trial.18  We expect roughly 40% of study 
patients (~160) to die by the 9-month follow-up; deaths are readily identifiable through dialysis clinics and will 
trigger post-bereavement surveys with surrogates at 3 months and staggered CMS data collection. Post-
bereavement assessment at 3 months is based on our efficacy data showing that distress symptoms sharply rose 
in both groups 2-weeks post-bereavement and then stabilized at 3 months. 
 
Effectiveness Outcomes 
Preparedness for end-of-life decision making (measured at baseline and 2 wks post-Session II):   
• 
Dyad congruence will be assessed using the Goals-of-Care Tool,18,20 which includes two scenarios 
describing medical conditions commonly occurring in ESRD patients. In the first, the patient develops a 
severe complication and cannot speak for himself/herself; the medical team believed recovery unlikely 
and continuing life-sustaining treatment, including dialysis, would no longer be beneficial. In the second 
scenario, the patient develops advanced dementia. Each scenario has three response options: “The goals 
of care should focus on delaying my death, and thus I want to continue life-sustaining treatment”, “The 
goals of care should focus on my comfort and peace, and thus I do not want life-sustaining treatment, 
including dialysis”, and “I am not sure”. Patients and surrogates complete this tool independently and 
their responses are then compared to determine dyad congruence -- either congruent in both scenarios 
or incongruent. If both members of the dyad endorse “I am not sure”, they are considered incongruent.   
• 
Patient decisional conflict will be measured using the 13-item Decisional Conflict Scale (DCS), a validated 
measure in the context of end-of-life decision making17; higher scores indicate greater difficulty in 
weighing benefits and burdens of life-sustaining treatments and decision making (range 1-5; Cronbach’s  
= 0.8 – .9317,18,20,72).  
• 
Surrogate decision-making confidence will be measured using the 5-item Decision Making Confidence 
(DMC) scale (Cronbach’s  = 0.81-0.9018,34) on which higher scores reflect greater comfort in performing 
as a surrogate (range 0, not confident at all-4, very confident). DMC is a self-report of a surrogate’s 
confidence in: knowledge of the patient’s wishes, ability to make treatment decisions even in a highly 
stressful situation, ability to seek information about risks and benefits of medical choices, ability to handle 
unwanted pressure from others, and ability to communicate with health care providers about the 
patient’s wishes.  

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• 
Composite outcome: We will also create a composite outcome combining dyad congruence and surrogate 
DMC to differentiate surrogates who understand the patient’s wishes and feel confident in their role from 
those who don’t (understand the wishes but lack confidence, misunderstand the wishes but feel 
confident, neither understand nor feel confident).18,34  
• 
We will also assess the overall preparedness for end-of-life decision making using the 26-item 
investigator-developed measure. The measure assesses the level of preparedness for end-of-life decision 
making in the cognitive, emotional, and behavioral dimensions on a 4-point scale (4=strongly agree to 
1=strongly disagree) with higher scores indicating higher levels of preparedness. Patient and surrogate 
each will complete this measure separately.    
 
During the supplement cohort study, the participating dyads will complete the same measures above twice, at 
enrollment and 6 months after.  
In addition, they will complete the COVID-19 Stress Scale. COVID-19 Stress Scale35 is a 35-item measure to assess 
pandemic related emotional responses (i.e., COVID-19 stress and anxiety symptoms) on a 5-point scale ranging 
from 0 (not at all) to 4 (extremely). The subscales are (1) danger and contamination fears, (2) fears about 
economic consequences, (3) xenophobia, (4) compulsive checking and reassurance seeking, and (5) traumatic 
stress symptoms about COVID-19. The scale has demonstrated excellent internal consistency reliability 
(Cronbach’s >.8 for all subscales) and convergent and discriminant validity. We will also add an overall rating to 
assess how much respondents worry about COVID-19, which recently was used by Wang et al.,36 “Please rate the 
level of your current worry toward COVID-19” on a scale ranging from 1 (very mild) to 10 (very severe). 
 
Surrogates’ post-bereavement psychological distress (at baseline and 3 mo. post patient death):   
Symptoms of anxiety, depression, and post-traumatic distress42,73 will be measured using the Hospital Anxiety and 
Depression Scale (HADS)74; subscale scores range from 0 to 21 with higher scores indicating greater symptom 
severity. Internal consistencies and test-retest reliabilities are 0.88–0.90 and 0.84–0.94, respectively.75 Intensity of 
post-traumatic distress symptoms will be assessed using the Post-Traumatic Symptoms Scale-10 (PTSS-10).76 
Higher scores indicate more intense symptoms (range 10-70).77 The PTSS-10 has been shown to have high 
sensitivity and specificity.76,78,79   
 
Implementation Process Outcomes   
For the initial SPIRIT intervention, after the final dyads have completed the SPIRIT sessions (~Year 3, Q1), care 
providers will complete a survey and an interview.  
• 
Care provider acceptability will be evaluated using the 7-item Care Providers’ Perceived Acceptability 
Survey to assess their perceptions about SPIRIT implementation, including the time required, impact on 
interactions with patients, and whether they would recommend SPIRIT to other clinics.80  Response 
options range from 1=strongly disagree to 4=strongly agree; higher scores indicate greater acceptability.  
• 
A brief (~15 min.) semi-structured interviews (face-to-face or by telephone; audio-recorded) will obtain 
providers’ perspectives on whether the implementation of SPIRIT is compatible with their setting and the 
workflow, it’s perceived utility, their willingness to continue using it after the study, factors influencing 
implementation (barriers, logistical constraints, and facilitators), and suggestions for improvement.  
• 
Patient and surrogate acceptability will be assessed using the 10-item ACP Acceptability Questionnaire 
developed from our previous trial,24  Participants are asked how strongly they agree or disagree  (4 to 1) 
with statements about their experience with SPIRIT sessions, including duration, interactions with the 
care provider, level of comfort and satisfaction. Higher scores indicate greater acceptability. Each patient 
and surrogate will complete this survey at the 2-week post-intervention follow-up.  
• 
Fidelity/adherence will be assessed using two independent data sources, (a) the SPIRIT Interview Guide, 
Checklist, and self-evaluation completed by the care provider after each SPIRIT session and (b) patient and 
surrogate responses to the SPIRIT components coverage during the 2-week post-intervention follow-up as 
described above. The number of SPIRIT components covered, the minutes required for the care provider 

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to complete the sessions, the number of dyads who complete SPIRIT sessions, and the number of 
incomplete or interrupted sessions will be aggregated.  
• 
Intervention costs will be estimated based on the actual time the care provider spent in carrying out 
SPIRIT, multiplied by hourly wage (+benefits), plus costs of materials. Overhead (e.g., facility) costs and 
research staff’s time will not be included.  
• 
We define sustainability as the extent to which a newly implemented intervention is maintained within a 
service setting’s ongoing, stable operations.81 In Y4, Q4, we will conduct a brief interview with SPIRIT care 
providers to ask about sustainability: (a) Is SPIRIT on-going (and at what frequency)? (b) What 
components of the SPIRIT protocol have been retained? and (c) Has SPIRIT implementation been 
evaluated at the clinic level? If so, how?82   
 
For the delayed SPIRIT implementation, the process evaluation will involve care providers only since patient and 
surrogate study participation will have ended at the end of 9-month follow-up or patient death. Care provider 
acceptability, fidelity, and intervention costs will be determined as described above.  
 
End-of-life treatment intensity (upon patient death)  
We will link study data to publicly available USRDS data. The USRDS captures inpatient and outpatient Medicare 
claims on all treated U.S. ESRD patients and releases these data annually free of charge. Medicare claims data are 
the most complete and reliable source of data on end-of-life care intensity because patients on dialysis are 
Medicare beneficiaries. The USRDS data are far superior to that which could be obtained through individual 
hospitals because data collection at the latter is extremely difficult and highly likely to result in missing data. From 
the inpatient and outpatient claims data, we will obtain dates and attributed causes of death; dates of hospital, 
skilled nursing facility, and hospice admissions and discharges; dates of outpatient encounters (including dialysis 
sessions and ED visits); and diagnostic and procedure codes for all inpatient and outpatient encounters. Thus, we 
will be able to determine hospitalization, ICU days, days hospitalized, use of intensive procedure, 
(dis)continuation of dialysis (also from CMS Form 2746), and hospice use during the final month of life. We will 
consider the following to be intensive procedures: mechanical ventilation, feeding tube placement, dialysis, and 
cardiopulmonary resuscitation.22 These intensive procedures will be identified using HCPCS and ICD-9-CM codes 
(e.g., ICD-9 codes for intubation and mechanical ventilation: 96.04, 96.05, 96.7X).83  
 
Descriptors and Potential Covariates 
• 
Patients and surrogates will complete a Sociodemographic Profile which includes age, gender, race and 
ethnicity, type of relationship between patient and surrogate, marital status, religious affiliation, 
education, household income, previous end-of-life decision-making experience, and previous participation 
in an ACP discussion or AD completion.  
• 
To describe the sample, the patient’s clinical characteristics, including dialysis modality, years on dialysis, 
comorbid conditions will be abstracted from the patient’s EMR.  
• 
Care providers’ sociodemographic data will include age, gender, race and ethnicity, education, and years 
of practice.  
• 
At baseline, we will collect clinic-level contextual data84 that could facilitate understanding study results, 
including staffing, patient census, rural-urban status,85-89 palliative care and hospice availability, and 
proximity of hospitals.  
 
For Supplement Aims,  
 
• 
The preparedness outcomes measures will be assessed at baseline and 2-3 days after the intervention. 
• 
Surrogates’ post-bereavement psychological distress will be assessed using the HADS, which will be 
completed at baseline and 1 month post patient death. 
• 
Patients’ level of articulation of end-of-life wishes: Using a “quantitizing” technique of qualitative data 
analysis,39 two raters will independently review SPIRIT session transcripts focusing on the values of 

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treatment outcomes and the goals of care discussions and rate the level of patient’s articulation of end-
of-life care preferences on a 3-point scale (3=expressed wishes very coherently, 2=somewhat coherently, 
1=unable to express wishes coherently). Inter-rater reliability (percent agreement) will be established, 
targeting  90%. 
• 
Care decisions (assessed at 6 months post intervention or after the patient’s death, whichever occurs 
first): Stopping dialysis, DNR order, and hospice enrollment are major care decisions that must involve the 
treating physician (or APRN) and social worker. These decisions are also required to be documented in the 
CMS Form 2746 in the event of a dialysis patient’s death. On a monthly basis, the research coordinator 
will check in with the outpatient dialysis APRN to track these care decisions and will be aggregated at 6 
months.  
• 
Descriptors and Potential Covariates (collected at baseline): Patients and surrogates will each complete a 
Sociodemographic Profile which includes demographic information and previous end-of-life decision-
making experience. Patients’ clinical characteristics (e.g., date of dementia diagnosis, etiology of 
dementia, and comorbid conditions) will be abstracted from the patient’s medical records.  
 
8.2 
SAFETY AND OTHER ASSESSMENTS 
 
SPIRIT is a one-time psychoeducational intervention. The study involves very low risk and the potential risk may 
include fatigue or emotional upset during the session.  
 
Fatigue  
 
As part of outcome assessment, HADS and PTSS-10 will be completed. Although these measures are not 
diagnostic tools, if a surrogate’s HADS-Depression is high (≥ 15), the data collector will ask the surrogate if she/he 
is aware of the mood state and encourage to speak to his/her primary care provider. If a surrogate expresses 
suicidal ideation, the data collector will immediately notify the local site coordinator who will confer with the Site 
PI. This Site PI will determine if referral to the local mental health clinic (during hours) or the 24-hour Emergency 
Psychiatry Service (after hours) for evaluation of mental health or emergency intervention is necessary. 
   
8.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
 
8.3.1 DEFINITION OF ADVERSE EVENTS (AE) 
 
SPIRIT is a one-time psychoeducational intervention. The study involves very low risk and the potential risk may 
include fatigue or emotional upset during the session, neither of which is a “medical occurrence”. SPIRIT has been 
extensively tested in previous trials and no safety concerns have ever arisen. The present trial is to generate data 
to accelerate translation of the intervention into clinical practice. 
 
8.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE)  
 
The trial targets ESRD patients on dialysis who already have serious life-threatening medical conditions and are 
likely to die within a year (by clinician’s judgment). SPIRIT is an advance care planning intervention to prepare 
these patients and their surrogates for end-of-life decision making. SPIRIT’s safety and beneficial effects (e.g., 
reducing psychological distress) have been consistently demonstrated. Participants’ deaths or hospitalizations (or 
other events described above) during the trial are expected (and needed to answer the scientific questions) and 
will occur as part of the illness course. These events will not be considered as SAE in this trial. However, any 
participant’s death will be reported to IRB through annual progress report and included in the NIH annual 
progress report.  

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8.3.3 CLASSIFICATION OF AN ADVERSE EVENT 
8.3.3.1 SEVERITY OF EVENT 
 
Not applicable. 
 
 
8.3.3.2 RELATIONSHIP TO STUDY INTERVENTION 
 
Not applicable.  
 
8.3.3.3 EXPECTEDNESS  
 
There are no known expected adverse reactions. SPIRIT has been tested in 5 RCTs with various patient 
populations with serious chronic conditions and in 3 different regions and settings. Although possible adverse 
reactions to the intervention may include fatigue or emotional distress during the intervention session, no such 
reactions have been observed in the previous studies. Thus, these reactions are very unlikely to occur and will be 
considered “unexpected.” Intervention sessions will stop if any of these events occurs.   
8.3.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
 
Not applicable. 
 
8.3.5 ADVERSE EVENT REPORTING  
 
The possible adverse reactions (fatigue, emotional distress during the intervention session), if ever occurs, will be 
tracked (documented in the study REDCap) and the aggregated numbers will be reported at the upcoming 
biannual DSMB meeting.  
 
Any disease-related events (DREs) common in the study population (e.g., expected) such as death will not be 
reported per the standard process of reporting but will be monitored so that surrogates’ post-bereavement 
outcomes and end-of-life treatment intensity data (Medicare claims data) can be collected timely.  However, any 
participant’s death will be reported to IRB through annual progress report and included in the NIH annual 
progress report.  
 
8.3.6 SERIOUS ADVERSE EVENT REPORTING  
 
Not applicable. 
 
8.3.7 REPORTING EVENTS TO PARTICIPANTS  
 
Not applicable. 
 
8.3.8 EVENTS OF SPECIAL INTEREST  
 
Not applicable. 
 

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8.3.9 REPORTING OF PREGNANCY  
 
Not applicable. 
 
 
8.4 
SUBJECT SAFETY 
 
Any unexpected problem related to the Research that negatively affects the rights, safety or welfare of subjects 
and is not described as such in the materials describing risks associated with the study.  
 
8.4.1 DEFINITION OF UNANTICIPATED PROBLEMS (UP) 
 
Unanticipated problems are defined by DHHS 45 CFR part 46 as any incident, experience, or outcome that meets 
all of the following criteria: 
• 
unexpected, in terms of nature, severity, or frequency, given (a) the research procedures that are 
described in the protocol-related documents, such as the IRB-approved research protocol and informed 
consent document; and (b) the characteristics of the study population;  
• 
related or possibly related to participation in the research (in this guidance document, possibly related 
means there is a reasonable possibility that the incident, experience, or outcome may have been caused 
by the procedures involved in the research);  
• 
suggests that the research places participants or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized. 
It will be extremely unlikely in this study that the events of fatigue and emotional distress would meet the all of 
the criteria above. 
 
8.4.2  UNANTICIPATED PROBLEM REPORTING  
 
If we encounter any adverse event that meets the definition above and that is related to the intervention, the PI 
will notify the Emory IRB and NINR Program Official and the DSMB within 24 hours of the event being reported to 
the PI. The expedited report will be followed by a detailed, written SAE report as soon as possible. 
 
8.4.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
 
Not applicable. 
 
9 
STATISTICAL CONSIDERATIONS  
 
9.1 
STATISTICAL HYPOTHESES 
 
• 
Primary Endpoint(s):  
1) The number of SPIRIT dyads who are congruent on goals of care at 2 weeks post-intervention will be 
significantly higher than that of control dyads. 
2) Patient decisional conflict scores at 2 weeks post-intervention will be significantly lower than those of 
control dyads. 
3) Surrogate decision making confidence (DMC) scores at 2 weeks post-intervention will be significantly 
higher than those of control dyads. 

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4) The number of SPIRIT dyads who are congruent on goals of care and confident surrogate (DMC=3 or 
higher) at 2 weeks post-intervention will be significantly higher than that of control dyads. 
 
• 
Secondary Endpoint(s): 
1) HAD-anxiety scores in SPIRIT surrogates will be significantly lower than those of control surrogates at 
3 months after the patient’s death. 
2) HAD-depression scores in SPIRIT surrogates will be significantly lower than those of control surrogates 
at 3 months after the patient’s death.  
3) PTSS-10 scores in SPIRIT surrogates will be significantly lower than those of control surrogates at 3 
months after the patient’s death. 
 
• 
Exploratory: Among patients who have died, 
1) The percentage of patients hospitalized during the final month of life in the SPIRIT group will be 
significantly lower than that in the control group. 
2) The percentage of patients admitted to an ICU during the final month of life in the SPIRIT group will 
be significantly lower than that in the control group. 
3) The percentage of patients having intensive procedures during the final month of life in the SPIRIT 
group will be significantly lower than that in the control group. 
4) The length of hospital stay during the final month of life in the SPIRIT group will be significantly 
shorter than that in the control group. 
 
For Supplement Aims: 
• 
Aim 1:  
1) The number of SPIRIT dyads who are congruent on goals of care at 2-3 days post-intervention will be 
higher than that of control dyads. 
2) Patient decisional conflict scores at 2-3 days post-intervention will be lower than those of control 
dyads. 
3) Surrogate decision-making confidence (DMC) scores at 2-3 days post-intervention will be higher than 
those of control dyads. 
4) The number of SPIRIT dyads who are congruent on goals of care and confident surrogate (DMC=3 or 
higher) at 2-3 days post-intervention will be significantly higher than that of control dyads. 
5) The proportion of decisions made at 6 months (e.g. stopping dialysis, DNR order, and hospice 
enrollment etc.) follow-up or death of patient will be higher in the intervention dyads than that of 
control dyads. 
 
• 
Aim 2: 
1) HAD-anxiety scores in SPIRIT surrogates will be lower than those of control surrogates at 1 month 
after the patient’s death. 
2) HAD-depression scores in SPIRIT surrogates will be lower than those of control surrogates at 1 months 
after the patient’s death.  
 
Supplement cohort study: 
Aim 1. Changes in patient’s goals of care preferences over time (T2-T3 and T2-T4) in the intervention group will be 
smaller than those in the control group. 
Aim 2. Changes in the preparedness outcomes over time in the intervention group will be smaller than those in 
the control group. 
Aim 3. The COVID-19 Related Stress and race/ethnicity will be significantly associated with changes in goals of 
care stability and the preparedness outcomes. 
 
 

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9.2 
SAMPLE SIZE DETERMINATION 
 
We have an adequate sample size  to detect 
clinically meaningful differences between 
SPIRIT and usual care for our primary 
outcomes. Statistical power is based on a 
random effects models: a generalized linear 
mixed model for binary outcomes (e,g., dyad 
congruence) and a linear mixed model for 
continuous outcomes (e.g., patient decisional 
conflict). 
 
We conducted a simulation study to estimate 
power with 2-sided significance level 
alpha=.05, corrected for anticipated dropout 
and potential intraclass correlations (ICCs) 
ranging .01-.04, based on ICCs observed in our 
prior work. To estimate the power more 
conservatively, we used the effect sizes 
observed at 2 months20 rather than those at 2 
weeks,18 which are larger (e.g., for the composite outcome, OR=1.8 at 2 months, OR=4.4 at 2 weeks). The overall 
power to detect clinically meaningful differences is excellent for the primary outcomes and good for the post-
death outcomes. 
 
For Supplement Aims: 
Because this is a pilot study, prior estimates of effect sizes were not available; thus a traditional sample size 
calculation was not performed. Instead we focused on calculating the minimum effect size that can be detected 
with adequate power (>=80%). Based on preliminary calculations, we found that a sample size of 30 will achieve 
80% power to detect an effect size (Cohen’s f2) of 0.28 (moderate-high), attributable to the treatment group 
indicator using an F-test at a 5% significance level. We will use the estimates of effect sizes obtained from this 
study for sample size calculations in future larger studies. 
 
Supplement cohort study: 
Due to the exploratory nature of the study, a traditional sample size calculation was not performed. Instead, our 
goal was to provide estimates of effect sizes (standardized mean differences between pre- and during- COVID-19 
study points) for the outcomes in aims 1-3. Preliminary power calculations based on a two-sample t-test, indicate 
that a sample size of 72 in the SPIRIT intervention and 35 in the usual care group achieve 80% power to detect a 
difference in mean changes of 0.5 between the groups. This calculation assumes a repeated measures design with 
a standard deviation of 1.0 at both time points, a between measurement correlation of 0.2 and a 5% significance 
level. 
 
9.3 
POPULATIONS FOR ANALYSES 
 
Patient-surrogate dyads will be the primary unit of analysis; all analyses will be intent to treat with all available 
data from all participants. 
 
9.4 
STATISTICAL ANALYSES 
Power for comparing SPIRIT and usual care with 19 clusters 
 
 
Aim 1 
Percent or 
min. 
difference 
OR or 
variance 
ICCa 
Estimated 
power 
Dyad congruence 
48% 
OR=2.0 
0.02 
0.92 
0.04 
0.84 
Patient DCS 
d=0.24 
0.23 
0.01 
0.98 
0.10 
0.81 
Surrogate DMC 
d=0.22 
0.20 
0.01 
0.99 
0.10 
0.80 
Composite 
outcome 
47% 
OR=2.0 
0.02 
0.93 
Aim 3 
 
 
 
 
Anxiety 
d=1.35 
7.0 
0.01 
0.84 
0.03 
0.80 
Depression 
d=1.60 
10.0 
0.01 
0.85 
0.03 
0.79 
PTSS-10 
d=4.75 
90.0 
0.01 
0.85 
0.03 
0.78 
a observed ICCs in our prior work; d=1/2 SD. 
DCS, decisional conflict scale; DMC, decision-making confidence. 

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9.4.1 GENERAL APPROACH 
 
The preliminary analysis will include summarizing variables with standard descriptive statistics and graphical 
displays or frequency tables. Distributional assumptions will be assessed and the data will be transformed as 
necessary. Clinic characteristics (e.g., rural-urban status) will be compared using 2 tests for categorical variables 
and t-tests for continuous variables. We will compare SPIRIT and usual care participants on baseline 
characteristics (e.g., age, race/ethnicity) to explore possible between-group differences using generalized 
estimating equation (GEE) methods, accounting for the observed correlation within the same cluster.90,91  In our 
previous work SPIRIT has no effect on patient mortality20; however, we will compare survival time between SPIRIT 
and usual care using Cox proportional hazards models, adjusted for cluster effects. If imbalanced, we will consider 
adjustment for the group difference. 
 
9.4.2 ANALYSIS OF THE PRIMARY ENDPOINT(S) 
 
SPIRIT effectiveness on the preparedness outcomes: Dyad congruence and the composite outcome (binary 
variables) will be analyzed by fitting a generalized mixed effects model for each, where the binary outcome is 
modeled in terms of a logit link90 with both a random intercept and random slope to control for variation within 
and between subjects and clusters. The model also includes the intervention SPIRIT, cluster size and their 
interaction. For patient DCS and surrogate DMC scores, we will replace the logit link by the identity link with an 
additional error term. These models will allow us to examine whether SPIRIT was superior to usual care in the 
primary outcomes at 2 weeks and whether the effect of SPIRIT varies by cluster size. The analysis will be adjusted 
for potential covariates, such as race/ethnicity, and rural-urban status, in the model, including interaction 
between treatment and race/ethnicity.  
 
For Supplement Aims: 
To account for small sample size, resampling methods will be used for all analyses and 95% bootstrap confidence 
intervals of the differences in outcome scores will be reported. 
 
1) Aim 1. SPIRIT effects on the preparedness outcomes: For testing the effect of the intervention on dyad 
congruence, a paired binary outcome (congruent or not congruent), Mcnemar’s test will be used. In addition, a 
logistic regression model will be used to test for differences in post-intervention outcomes by groups after 
adjusting for potential covariates. The adjusted ratio of odds of congruence in the intervention group versus the 
control group will be evaluated and reported as an effect size estimate. 
 
2) Aim 1. SPIRIT effects on care decisions:  Differences in proportion of decisions made (e.g. stopping dialysis, 
DNR order, and hospice enrollment etc.) at 6-month follow up or death of patient will be described across groups 
and used as effect size. We will also explore time to event analysis to assess the difference in rate of risks between 
the two groups using non-parametric and semiparametric methods. 
 
3) Aim 2. Surrogate post-bereavement distress (HADS scores): Differences in the HADS subscale scores between 
the intervention and control groups will be assed using t-tests. Because, we estimate a 50% rate of death during 
the study, the number for this analysis would be n=15. A standardized difference between groups will be used as 
an effect size estimate. 
 
4) Aim 3. Relationships among patients’ cognitive status, decision-making capacity and their ability to express 
end-of-life wishes:  For patients in the SPIRIT intervention arm (n=15), associations between patients’ cognitive 
status (continuous), decision-making capacity (continuous) and their ability to express end-of-life wishes 
(categorical) will be analyzed using one-way analysis of variance (ANOVA). We will also explore ordinal logistic 
regression to obtain the proportional odds ratios defined by the odds of “expressing wishes very coherently” or 

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“expressing wishes somewhat coherently” versus the odds of “unable to express wishes coherently” for a unit 
increase in cognitive status or decision-making capacity. 
 
Supplement cohort study: 
As in the parent R01, we will use the Research Electronic Data Capture (REDCap) to create and update study 
participants’ data. During data entry, automated checks will be performed that will immediately flag problematic 
data (e.g., missing, out of range, inconsistent). Preliminary analyses will include summarizing variables with 
descriptive statistics and graphical displays. We will assess distributional assumptions of the outcomes and apply 
appropriate transformations to remedy any violations. Any differences in patient characteristics (e.g. age, sex, 
education level, household income) across groups will be adjusted when modeling the outcomes. As observed in 
the parent R01 (< 1% missing data), we expect very little missing data. Nonetheless, we plan to use restricted 
maximum likelihood (REML) method for estimating the repeated measures analysis to minimize the impact of 
missing data. This will make it possible to retain cases with partial data while making less restrictive assumptions 
about missing data patterns.  
Aim 1. Compare the stability of patients’ goals-of-care preferences over time, from pre-outbreak to during-
outbreak, by group and estimate effect by race: We will use mixed effects modeling to assess differences in 
patients’ goals of care over time, from pre- to post-lockdown time points. We will sequentially build a longitudinal 
model that will include time, treatment group and race as fixed effects; then 2-way interactions of time x group, 
time x race, treatment x race, and finally a 3-way interaction of time x group x race, if the sample size permits. We 
will select the most parsimonious model using Akaike information criterion (AIC) and Bayesian information 
criterion (BIC). We will use contrasts to test whether participants demonstrated significant change in goals-of-care 
preferences across different combinations of treatment and race. 
Aim 2. Assess the stability in the three preparedness outcomes, from pre-outbreak to during-outbreak by 
group, and estimate race effect: We will perform analyses similar to those described in Aim 1. In addition, for 
non-normal outcomes (binary, count) a generalized mixed effects model will be used. Appropriate contrasts will 
be used to assess differences in the outcomes over time by treatment groups, race and groups x race. 
Aim 3. Examining the associations of the COVID-19 Related Stress, sex, race/ethnicity, and other 
sociodemographic characteristics to the level of changes in the preparedness outcomes and patient’s goals-of-
care preference stability: We will use analysis of covariance to assess the relationship between COVID-19 related 
stress and changes in outcomes from T2 to T3 and T3 to T4, after controlling for the corresponding baseline values 
of the outcomes (i.e., T2 and T3 respectively). Using similar methods, we will evaluate whether there are 
disparate effects of sex, race/ethnicity and other sociodemographic factors on outcome changes and goals-of-care 
preference stability from T2 to T3 and T3 to T4, respectively 
 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
 
Analysis of secondary endpoints are not dependent on findings of primary endpoints. 
 
SPIRIT effectiveness on surrogates’ post-bereavement psychological distress: We will use the same approach as 
in the analysis of the primary endpoints to compare anxiety, depression, and post-traumatic distress symptoms in 
SPIRIT vs usual care among surrogates of patients who die during the initial implementation and 9-month (or 
extended) follow-up. 
 
Implementation process outcomes: Quantitative data on acceptability, fidelity, and costs of SPIRIT will be 
summarized using descriptive statistics. SPIRIT will be determined to be acceptable to care providers and patients 
and surrogates if over 75% of responses exceed an average summative score ≥ 3 (of 4) on the acceptability 
measures. Cost estimates will be used to ascertain resources needed to implement or replicate SPIRIT in the 

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future.92 We will also explore the relationships of these quantitative data with characteristics of settings and 
stakeholders. Transcripts of acceptability interviews will be transferred to ATLAS.ti for analysis. Content analysis 
techniques93 will be used without preconceived categories.94 Open coding will be applied95 and disagreements on 
coding will be resolved by consensus. We will examine the data for patterns or differences in themes between 
those with acceptability scores >=3 and scores <3 and setting characteristics. This analysis will be facilitated by 
creating matrixes that organize textual and numeric data for comparing and contrasting96 so that what 
contributed to acceptability scores that are positive and less than positive may be identified. We will use a similar 
approach, content analysis, to evaluate the sustainability data.  
 
 
9.4.4 SAFETY ANALYSES 
 
Not applicable. 
 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
 
See 9.4.1 General Approach. 
 
9.4.6 PLANNED INTERIM ANALYSES  
 
Not applicable. 
 
9.4.7 SUB-GROUP ANALYSES 
 
In order to evaluate whether the SPIRIT has differential effects according to demographic factors such as age, sex, 
race/ethnicity we consider the same generalized mixed effects model in the context of protocol design, 
mentioned in Section 9.4.1.  Our approach is first to consider each factor one at a time.  We will fit the same 
generalized mixed model by additionally including a subject level factor (e.g., race) and its’ interaction with the 
SPIRIT.  If the interaction is significant the analysis will indicate that SPIRIT effect changes according to race.  We 
will report p-values and importantly, standard errors and confidence intervals by recognizing the fact that we may 
not have power to detect significant interaction effects for examining all demographic factor combinations. 
 
For Supplement Aims: no subgroup analyses will be possible due to the small sample size. 
 
Supplement cohort study: no subgroup analyses will be possible due to the small sample size 
 
9.4.8 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
 
Individual participant data will be listed by measure and time point.  
 
9.4.9 EXPLORATORY ANALYSES 
 
SPIRIT effectiveness on end-of-life treatment intensity: Among patients who die during the initial SPIRIT 
implementation and follow-up, percentages of patients hospitalized, having ICU admission, having intensive 
procedures and length of hospital stay in the final month of life will be summarized using descriptive statistics, 
95% CIs, and graphical displays. The exploratory examination of SPIRIT’s effectiveness on improving these 
outcomes, we will use the same analytic approach as in the analysis of the primary endpoints (See 9.4.2).  
 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 

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10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
 
10.1.1 INFORMED CONSENT PROCESS 
 
10.1.1.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO PARTICIPANTS 
 
Consent forms describing in detail the study intervention, study procedures, and risks are given to the participant 
and written documentation of informed consent is required prior to starting intervention/administering study 
intervention.  The following consent materials are submitted with this protocol. 
• 
Patient Consent Form-SPIRIT 
• 
Patient Consent Form-Usual Care 
• 
Surrogate Verbal Consent Form –SPIRIT 
• 
Surrogate Verbal Consent Form – Usual Care 
• 
Care Provider Verbal Consent Form 
• 
VERBAL Consent Addendum – Patient 
• 
VERBAL Consent Addendum - Surrogate 
 
For Supplement Aims, the following consent materials will be used: 
• 
Patient Verbal Consent for Screening (cognitive impairment level) 
• 
Patient Consent Form 
• 
Surrogate Verbal Consent Form  
 
Supplement cohort study: 
• 
Verbal Consent Addendum for Cohort – Patient 
• 
Verbal Consent Addendum for Cohort - Surrogate 
 
 
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
 
Participating dialysis centers/clinics will be randomized first (see the study flow diagram). The care team member 
who has been selected by the clinic as a care provider responsible for SPIRIT delivery at each clinic in both groups 
(e.g., nurse or social worker) will generate a list of patients each quarter based on the inclusion criteria. This staff 
member may differ from clinic to clinic depending on who is qualified, comfortable and able to assess each 
potential participant. The medical director of the dialysis unit (and/or the attending physician as required) 
approves the list if required by the dialysis center.  From this list, one of the care providers will then assess the 
patient’s willingness to meet with a recruiter from the research team. The recruiter (e.g., site coordinator) will 
then approach willing patients during their scheduled dialysis clinic appointment.  
 
Consent forms have been Institutional Review Board (IRB)-approved and the participant will be asked to read and 
review the document. In a private room, a verbal explanation will be provided in terms suited to the patient’s 
comprehension of the purposes, procedures, and potential risks of the study and of their rights as research 
participants.  Patient participants will have the opportunity to carefully review the written consent form (including 
HIPAA authorization from) and ask questions prior to signing. The patient participants should have the 
opportunity to discuss the study with their family or surrogates or think about it prior to agreeing to participate. 
The patient participant will sign the informed consent document prior to any procedures being done specifically 
for the study. Patient participants must be informed that participation is voluntary and that they may withdraw 
from the study at any time, without prejudice. A copy of the informed consent document will be given to the 

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participants for their records. The informed consent process will be conducted and documented in the source 
document (including the date), and the form signed, before the participant undergoes any study-specific 
procedures. The rights and welfare of the participants will be protected by emphasizing to them that the quality 
of their medical care will not be adversely affected if they decline to participate in this study. The recruiter will 
then provide the patient participant with a study brochure and encourage him/her to talk to the surrogate 
regarding the study within the next 2-3 days (to avoid a cold call).  
 
Several days later, the recruiter will telephone the potential surrogate participant to assess his/her willingness to 
participate. Following the Surrogate Verbal Consent Form, a verbal explanation will be provided in terms suited to 
the surrogate’s comprehension of the purposes, procedures, and potential risks of the study and of their rights as 
research participants.  Upon the surrogate’s verbal consent using the IRB approved script/form, the research staff 
at the Emory Study Coordination Center will schedule and conduct a baseline data collection session. All 
surrogates will provide verbal consent only with a waiver of written consent and a Surrogate Verbal Consent form 
will be signed by the recruiter.  
 
For Supplement Aims: 
Participants will be recruited from the Emory dialysis centers and UVA dialysis centers. First, patients who have 
been diagnosed with an early stage of dementia (mild to moderate) or are suspected of having cognitive 
impairment by a care provider will be referred by the dialysis APRN. The medical records of those patients will be 
reviewed to preliminarily determine eligibility by a research staff member. During the patient’s dialysis treatment 
session at the center, the patient’s care provider will gain permission for the staff member to explain the study. 
With the patient’s permission, the staff member will approach the patient, briefly explain the study, obtain verbal 
consent to conduct the MOCA or SLUMS and UBACC screening. If the patient has met the criteria for both early 
stages of cognitive impairment and decision-making capacity, the research staff member will provide detailed 
study information and confirm his/her surrogate decision-maker. Written consent will then be obtained from the 
patient. The research staff member will obtain the name and phone number of the surrogate (or confirm with the 
medical record as necessary) and call the surrogate in 2-3 days to assess the surrogate’s willingness to participate. 
Verbal consent will be obtained from the surrogate. 
 
Supplement cohort study: 
At the upcoming scheduled monthly check-in call with the participant (in the parent study, a check-in telephone 
call [scripted] is made to each member of the dyad after the 2-week follow-up call), the research staff member 
will proceed with the procedures for the parent study and then introduce the participant to the supplement 
study, including the purpose and procedures and obtain verbal consent. After both members of the dyad have 
consented, the recruiter will schedule two data collection calls (baseline/T3 and 6 months/T4).  
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
 
It is very unlikely that this study may be suspended or prematurely terminated sine the SPIRIT intervention has 
been extensively tested, including its safety and efficacy. Also, this study aim includes collecting implementation 
data and no planned interim analysis and stopping rules. Nonetheless, if suspension or termination occurs, 
written notification, documenting the reason for study suspension or termination, will be provided by the 
suspending or terminating party to study participants, investigator, dialysis organizations, and regulatory 
authorities.  If the study is terminated or suspended, the Principal Investigator (PI) will promptly inform study 
participants, the Institutional Review Board (IRB), and sponsor and will provide the reason(s) for the termination 
or suspension.  Study participants will be contacted, as applicable, and be informed of changes to study 
appointment schedule. 
  
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• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Insufficient compliance to protocol requirements 
 
Study may resume once concerns about safety, protocol compliance, and data quality are addressed, and satisfy 
the sponsor and IRB. 
 
10.1.3 CONFIDENTIALITY AND PRIVACY  
 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their staff, and the 
sponsor. The study documentation, data, and all other information generated will be held in strict confidence. No 
information concerning the study or the data will be released to any unauthorized third party without prior 
written approval of the sponsor.  
 
All research activities will be conducted in as private a setting as possible. 
 
The study monitor, other authorized representatives of the sponsor, representatives of the Institutional Review 
Board (IRB), regulatory agencies may inspect all documents and records required to be maintained by the 
investigator, including but not limited to, medical records (office, clinic), for the participants in this study. The 
clinical study site will permit access to such records. 
 
The study participant’s contact information will be securely stored in REDCap study database for internal use 
during the study. At the end of the study, all paper records will continue to be kept in a secure location for as long 
a period as dictated by the reviewing IRB, Institutional policies, or sponsor requirements. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will be directly 
entered into and stored in REDCap study database. Individual participants and their research data will be 
identified by a unique study identification number.  All information collected during the study will be secured and 
password protected. At the end of the study, all study databases will be de-identified and archived at the Emory 
Study Coordination Center. 
 
10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA  
 
Data collected for this study will be analyzed and stored at the Emory Study Coordination Center. After the study 
is completed, the de-identified, archived data will be transmitted to and stored in the REDCap study archive for 
use by other researchers including those outside of the study. When the study is completed, access to study data 
will be provided through the Emory Study Coordination Center. 
 
 
10.1.5 KEY ROLES AND STUDY GOVERNANCE 
 
Study Coordination Center 
Principal Investigator 
Mi-Kyung Song, PhD, RN 
Professor 
Emory University, School of Nursing 
1520 Clifton Rd NE, Atlanta, GA 30322 
404-727-3134 
mi-kyung.song@emory.edu 
Project Director 
Mary Laszlo 
Project Manager 
Emory School of Nursing 
404-727-2882 
Mary.laszlo@emory.edu  
Study Site 
Site PI 
Site Coordinator 
Emory University  
Mi-Kyung Song 
 
Mary Laszlo 
Project Manager 

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University of North Carolina at Chapel 
Hill 
Abhijit Kshirsagar, MD, MPH 
Associate Professor 
Chief Medical Director, UNC Dialysis 
Care 
UNC Kidney Center 
CB 7155 Burnett-Wormack 
Chapel Hill, NC 27599 
919-445-2684 
abhijit_kshirsagar@med.unc.edu 
 
University of Pittsburgh 
Manisha Jhamb, MD, MPH 
Assistant Professor 
UPMC Presbyterian 200 Lothrop St 
Suite C1100, Rm C1103 
Pittsburgh, PA 15213 
412-647-7062 
jhambm@upmc.edu 
 
University of New Mexico 
Mark Unruh, MD, MS 
Professor and Chair 
UNM, Internal Medicine 
DoIM MSC10-5550 
1 University of New Mexico 
Albuquerque, NM  87131 
505-272-0407 
MLUnruh@salud.unm.edu  
 
University of Virginia 
Maureen Metzger, RN, PhD 
Associate Professor 
University of Virginia School of Nursing 
PO Box 800782 
5038 McLeod Hall 
Charlottesville, VA 22908-0782 
434-924-0112 
Mjm9cd@virginia.edu 
 
Emaad Abdel-Rahman, MD PhD, FASN 
(Co-Investigator) 
Prof. Internal Medicine/Nephrology 
Division of Nephrology 
UVA 
PO Box 800133 
Charlottesville, VA 22908 
434-243-2671 
ea6n@virginia.edu 
 
Other study co-investigators: 
Laura Plantinga, PhD 
Assistant Professor 
Emory University School of Medicine 
Renal Division 
laura.plantinga@emory.edu 
 
Janice I.P. Lea, MD, MSc 
Professor of  Medicine 
Chief Medical Director Emory Dialysis 
Clinical Specialist in Hypertension 
Emory University School of Medicine 
Renal Division 
550 Peachtree St. 7th floor, MOT 
Atlanta, GA 30308 
404-686-5038 
jlea@emory.edu 
Amita Manatunga, PhD 
Professor 
Rollins School of Public Health 
Emory University 
1518 Clifton Rd NE 
Atlanta, GA 30322 
404-727-1309 
amanatu@sph.emory.edu  
Sandra Ward, PhD, RN, Professor Emerita 
University of Wisconsin-Madison 

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608-257-0119 
sward@wisc.edu 

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Study organization and coordination 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
For Supplement Aims: 
Principal Investigator 
Mi-Kyung Song, PhD, RN 
Professor 
Emory University, School of 
Nursing 
1520 Clifton Rd NE, Atlanta, 
GA 30322 
404-727-3134 
mi-kyung.song@emory.edu 
 
Coordinator 
Taylor Adkins, MPH 
Research Coordinator 
Emory University 
404-727-1978 
tradkin@emory.edu 
 
Co-
Investigator/Statistician 
Sudeshna Paul, PhD 
Assistant Professor 
Emory University, School of 
Nursing 
sudeshna.paul@emory.edu 
 
Co-Investigator 
Linda Turbevill-Trujillo, MSN, 
ANP 
Emory Healthcare 
linda.turberville-
trujillo@emoryhealthcare.org 
Co-Investigator 
Drenna Waldrop-Valverde, 
PhD 
Professor 
Emory University, School of 
Nursing 
drenna.waldrop-
valverde@emory.edu 
 
Co-Investigator 
Janice I.P. Lea, MD, MSc 
Professor of Medicine 
Chief Medical Director 
Emory Dialysis 
Clinical Specialist in 
Hypertension 
Emory University School of 
Medicine 
Renal Division 
550 Peachtree St. 7th floor, 
MOT 
Atlanta, GA 30308 
404-686-5038 
jlea@emory.edu 
 
 

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Supplement cohort study: 
 
 
 
10.1.6 SAFETY OVERSIGHT 
 
Safety oversight will be under the direction of a Data and Safety Monitoring Board (DSMB) composed of 5 
individuals with the appropriate expertise, including dialysis care, advance care planning, palliative care, clinical 
trials, intervention testing, and biostatistics. Members of the DSMB are independent from the study conduct and 
free of conflict of interest (see signed disclosure forms).   
 
The DSMB will meet bi-annually to evaluate the study progress, including assessment of data quality, timeliness, 
participant recruitment, rates of eligibility and ineligibility across study clinics and sites/states, accrual and 
retention, participant risk versus benefit, performance of trial sites, patient deaths, and any adverse events or 
care providers’ concerns that can affect study outcome. Consistent with prior end-of-life communication 
interventions, including our prior trials, we do not expect that the intervention will alter mortality rates. 
Nonetheless, this will be one of the measures monitored by the DSMB. The DSMB will compare recruitment rate 
and sample characteristics to assumptions used for power calculations. The DSMB will monitor the design factor, 
intra-cluster correlation coefficient, to assess whether the study will have expected power. Formal interim 
analyses are not planned for several reasons: (a) the SPIRIT efficacy has been established, (b) risks associated with 
SPIRIT are very minimal, (c) the control condition is usual care, not a placebo, and (d) the proposed study also 
aims to gather implementation data, including sustainability, that are critical for widespread implementation. 
Finally, the DSMB will not monitor fidelity/adherence data and make recommendations for ways to improve 
adherence because of the pragmatic nature of the proposed trial (i.e., seeking real world answers). The DMSB will 
operate under the rules of an approved charter that will be written and reviewed at the organizational meeting of 
the DSMB.  
 
See DSMB Charter. 
 
For Supplement Aims: 
Although the proposed study involves minimal risk, we will implement a data and safety monitoring plan at 
multiple levels to ensure the safety of participants and the validity and integrity of the data: 
 
(1) The PI/Dr. Song will convene weekly meetings with staff to review progress, subject accrual, and any 
anticipated and unanticipated problems. The weekly progress information will be aggregated for reports 
and presented at bi-monthly or monthly all investigators meetings. 
(2) The PI/Dr. Song will convene a videoconference with the study investigators monthly. At these meetings 
the investigators will assess study performance related to subject recruitment, review the quality of the 
data, and discuss any adverse events. The investigators will determine any need for re-training of study 
staff. 
Principal Investigator 
Mi-Kyung Song, PhD, RN 
Professor 
Emory University, School of 
Nursing 
1520 Clifton Rd NE, Atlanta, 
GA 30322 
404-727-3134 
mi-kyung.song@emory.edu 
 
Coordinator 
Mary C Laszlo 
Research Project Manager 
Emory University, School of 
Nursing 
404-727-2882 
mlaszlo@emory.edu 
 
Co-
Investigator/Statistician 
Sudeshna Paul, PhD 
Assistant Professor 
Emory University, School of 
Nursing 
sudeshna.paul@emory.edu 
 
Co-Investigator 
Sandra Ward, PhD, RN, 
Professor Emerita 
University of Wisconsin-
Madison 
608-257-0119 
sward@wisc.edu 

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(3) We will set up a Data and Safety Monitoring Committee (DSMC) responsible for reviewing trial data on 
an ongoing basis to ensure the safety of study participants and validity and integrity of the study data. 
The DSMC will include 3 experts who are independent, with no vested interest in SPIRIT or trial outcomes 
(to-be-named; e.g., investigators in the field and academic institutions, and biostatistician).  
 
The DSMC will meet with the PI twice during the study or as needed to evaluate the study progress, 
including informed consent procedures, participant recruitment, rates of eligibility and ineligibility, 
assessment of data quality, timeliness, and retention, participant risk versus benefit, breaches in 
confidentiality, patient deaths, and any adverse events or care providers’ concerns that can affect the 
protection of human subjects and study outcome.  
 
The first meeting will occur at the beginning of the trial. At this meeting, the committee will review the 
study protocols, including consenting procedures, recruitment and retention procedures for practicality 
and protection of human subjects and make recommendations as needed. At the subsequent annual 
meetings, the DSMC will review: 
a. Timeliness in meeting the goals for recruitment and retention 
b. Adherence to the study protocols 
c. Adherence to the intervention protocol 
d. Data related to adverse events 
e. Quality, completeness, and timeliness of the data collected 
f. 
Factors that could affect the outcome or compromise data or confidentiality 
g. Other factors outside the study, such as therapeutic developments, agency related to policies 
that could impact the safety of participants or the ethical conduct of the study 
 
In general, recommendations the DSMC may make include: 
a. Continue the study without change 
b. Modifications to the study protocol 
c. Suspension or early termination  
d. Alternative approaches to consider (e.g., if there is a failure to accrue participants as planned) 
 
The information about adverse events that occur during the study will be sent to the DSMC chairperson, who will 
distribute it to the other members of the committee. The relatedness of the event to the study would be provided 
at the time of presentation of the information. In addition, the Emory University IRB and the NIH Program Officer 
will be notified within one week of the event by the PI.  
 
10.1.7 CLINICAL MONITORING 
 
Clinical site monitoring is conducted to ensure that the rights and well-being of trial participants are protected, 
that the reported trial data are accurate, complete, and verifiable, and that the conduct of the trial is in 
compliance with the currently approved protocol/amendment(s), with International Conference on 
Harmonisation Good Clinical Practice (ICH GCP), and with applicable regulatory requirement(s).  
 
All study data will be directly entered into REDCap. The data entry forms in REDCap will be set up such that out-of-
range values are not accepted, which will minimize data entry error.  Although HADS (anxiety and depression 
symptom scales) and PTSS-10 (post-traumatic distress symptom screening) are not diagnostic tools, when a 
surrogate’s HADS score is abnormal (Depression score ≥15), the REDCap data entry form will flag the research 
staff to notify the surrogate that the local research staff member may confer with the Site PI so that the 
participant can be referred to a local mental health if necessary. 
 

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• 
The PI and Project Director will conduct centralized monitoring quarterly throughout the study. A random 
review of 10% primary endpoint data and secondary endpoint data (HADS and PTSS-10) will be 
performed. A monitoring report will be generated at completion of review and will be shared with the 
study site teams.   
• 
Independent audits will not be conducted as this trial does not collect clinical data after baseline (as 
descriptors).  
 
10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
 
We will use centralized training of research staff for recruitment and data collection activities as appropriate. The 
PI and Project Director will train staff in all study procedures. All project staff will complete university sponsored 
research integrity training, including modules on the protection of human subjects, HIPAA, and Good Clinical 
Practice. All roles, responsibilities, and a protocol with scripted subject contacts will be clearly delineated in the 
study Standard Operating Procedures (SOPs). These SOPs will be accessible via REDCap.  
 
Data collectors/recruiters will attend a competency based, one-day training session that the PI and Project 
Director will convene. Following a demonstration by the PI or Project Director on how to recruit participants and 
obtain informed consent, the recruiters will be expected to perform three satisfactory practice recruitment 
sessions before actual performance. The final practice sessions will be audio- or video-recorded and reviewed for 
adherence to the protocol. After demonstrating satisfactory performance of consenting sessions, the recruiters 
will be authorized to recruit and enroll participants.  
 
Training for data collection will include scripted data collection techniques with special attention to assessing 
participant fatigue or discomfort during the data collection session. Data collectors will conduct a series of three 
practice baseline and follow-up data collections using volunteers. After demonstrating satisfactory performance 
on data collection, they will be authorized to perform data collection activities with enrolled participants. They 
will also need to demonstrate completeness of data collection activities using REDCap.  
 
Each study site will perform internal quality management of study conduct, data collection, documentation and 
completion. In general the following strategies will be employed: 
• 
Use of data collection and data entry SOP 
• 
Before ending the data collection session, review the data entry form in REDCap for any missing data 
• 
Each data collector signs his/her work 
• 
Audit research staff members’ performance (e.g., consenting and data collection) Biannually. 
 
We will also employ systematic checking of data quality: The project director at the Emory Study Coordination 
Center will run quality control checks on the database quarterly; any missing data or data anomalies will be 
reported to the PI and communicated to the site(s) for clarification/resolution.  
 
The PI/Dr. Song will convene weekly meetings with staff to review progress, subject accrual, and any 
unanticipated problems at the Emory site. Site PIs will do the same at their respective study sites. The weekly 
progress information will be aggregated for reports and presented at bi-monthly or monthly all study sites 
meetings. 
 
To ensure compliance with the monitoring plan and reporting requirements across study sites, the PI/Dr. Song at 
the Study Coordination Center will convene a videoconference (using Adobe Connect or Zoom) with the study 
investigators, project director, SPIRIT trainer, and site coordinators monthly. At these meetings the investigators 
will assess study performance related to subject recruitment across the study sites (at least 1 dyad per month in a 
small cluster and 3 dyads in a larger cluster), review the quality of the data, and discuss any adverse events.  
 

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10.1.9 DATA HANDLING AND RECORD KEEPING  
 
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
 
The School of Nursing at Emory University, the Emory site, will be the Study Coordination Center and will maintain 
close contact with every entity within the study and will monitor study activities. All study sites will use a common 
study web-portal using the Research Electronic Data Capture (REDCap) created and managed in Emory SON. Each 
site will create and update study participants’ data through REDCap. During data entry, automated checks will be 
performed that will immediately flag problematic data (e.g., missing, out of range, inconsistent), allowing for the 
sites to address any discrepant data promptly thus increasing data quality. Data entered into the web-based form 
are immediately stored in a study database and tracked through a journaling process where they are accessible 
for review by the study team. Social Security numbers are entered directly into REDCap and not listed on paper 
forms. Suspicious data can be flagged through a query management system, and automated alerts provided to 
the sites. A complete audit trail is stored for each database modification. Any discrepant data identified through 
analytic manipulations will be communicated to the sites. Once all queries have been resolved and the database 
has been deemed “clean”, it will be officially locked. All permissions to make changes (append, delete, modify or 
update) to the database by the sites will be removed at that time.  
 
Record keeping and data collection (recruitment data, patient medical record review at enrollment, clinic-
contextual data, SPIRIT implementation data) are the responsibilities of the research staff at the site under the 
supervision of the site investigator. The investigator is responsible for ensuring the accuracy, completeness, 
legibility (if hardcopies of worksheets are used), and timeliness of the data reported. 
 
10.1.9.2 STUDY RECORDS RETENTION  
 
All study’s written records will be stored in a locked cabinet for 5 years. Study data will be de-identified and 
shared with future researchers per written request and IRB approval (Resource and Data Sharing Plans). 
 
10.1.10 
PROTOCOL DEVIATIONS  
 
A protocol deviation is any noncompliance with the clinical trial protocol, International Conference on 
Harmonisation Good Clinical Practice (ICH GCP), or Manual of Procedures (MOP) requirements. The 
noncompliance may be either on the part of the participant, the investigator, or the study site staff. As a result of 
deviations, corrective actions are to be developed by the site and implemented promptly.  
 
It is the responsibility of the site investigator to use continuous vigilance to identify and report deviations within 7 
working days of identification of the protocol deviation.  See Protocol Deviation/Violation Report Form and the 
related SOP.  All deviations will be addressed in study source documents, reported to the Study Coordination 
Center.  The site investigator is responsible for knowing and adhering to the reviewing IRB requirements.  
 
10.1.11 
PUBLICATION AND DATA SHARING POLICY 
 
This study will be conducted in accordance with the following publication and data sharing policies and 
regulations: 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access to the published 
results of NIH funded research. It requires scientists to submit final peer-reviewed journal manuscripts that arise 
from NIH funds to the digital archive PubMed Central upon acceptance for publication. 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical 
Trial Information and the Clinical Trials Registration and Results Information Submission rule. As such, this trial has 

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been registered at ClinicalTrials.gov, and results information from this trial will be submitted to ClinicalTrials.gov. 
In addition, every attempt will be made to publish results in peer-reviewed journals.   
 
Authorship determination: Authorship confers credit and has important academic, social, and financial 
implications. Authorship also implies responsibility and accountability for published work. We will follow the 
recommendations by the International Committee of Medical Journal Editors (ICMJE) to determine authorship (vs. 
non-author contributors). http://www.icmje.org/recommendations/browse/roles-and-responsibilities/defining-
the-role-of-authors-and-contributors.html   
Authorship will be based on the following 4 criteria: 
1. Substantial contributions to the conception or design of the work or the acquisition, analysis, or 
interpretation of data for the work; AND 
2. Drafting the work or revision it critically for important intellectual content (simply participating in writing 
or technical editing of the manuscript is insufficient for authorship); AND 
3. Final approval of the version to be published; AND 
4. Agreement to be accountable for all aspects of the work in ensuring that questions related to the 
accuracy or integrity of any part of the work are appropriately investigated and resolved.  
Those who do not meet all 4 of the above criteria will be acknowledged as non-author contributors.  
 
Data sharing:  
We will make the final data from the study, including a codebook, available to researchers after acceptance for 
publication of the main findings from the final dataset. The final data will be a complete and cleaned data set free 
of identifiers. We will make the research data available to users with a data-sharing agreement that includes: (1) a 
commitment to using the data only for research purposes, (2) a commitment to securing the data using 
appropriate computer technology, (3) a commitment to destroying the data after analyses are completed and not 
redistributing to third parties, and (4) IRB approval and clear research questions. Data request and sharing 
procedures, data request forms, and a data-sharing agreement will be accessible through the website of Center 
for Nursing Excellence in Palliative Care, Nell Hodgson Woodruff School of Nursing. The requester will be able to 
download final dataset and codebook. Also, care providers or administrators who wish to use the SPIRIT 
intervention in their practice and care setting can place a request through the Center’s website and will be able to 
download the SPIRIT intervention manual. 
 
10.1.12 
CONFLICT OF INTEREST POLICY 
 
Any actual conflict of interest of persons who have a role in the design, conduct, analysis, publication, or any 
aspect of this trial will be disclosed and managed. Furthermore, persons who have a perceived conflict of interest 
will be required to have such conflicts managed in a way that is appropriate to their participation in the design 
and conduct of this trial.  The study leadership in conjunction with the NINR has established policies and 
procedures for all study group members to disclose all conflicts of interest and will establish a mechanism for the 
management of all reported dualities of interest. 
 
10.2 PROTOCOL AMENDMENT HISTORY 
 
Version 
Date 
Description of Change  
Brief Rationale 
1 
29-June-2017 
Original draft 
 

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2 
25-
September-
2017 
From: waiver of written consent for 
surrogates from the control clinics 
To: waiver of written consent for all 
surrogates  
 
From: audio-recording surrogate verbal 
consent 
To: no audio-recording surrogate verbal 
consent 
To make the consent process 
consistent between the 
intervention and control groups 
and the intervention’s safety has 
been proven, involving no greater 
than minimal risk. This change will 
also reduce the risk of breach of 
confidentiality by only mailing 1 
copy signed by coordinator. 
From: the SPIRIT clinician champion will 
determine whether the patient meets 
the SQ criterion 
To: 
Procedure for dialysis clinic 
identification of potential 
participants with “no” to SQ 
question will be determined by the 
staff who is thought to be most 
qualified and suitable in making 
assessment by the clinic. The 
culture and workflow of the 
dialysis clinic should be respected. 
 
For PD patients who have to travel far to 
visit the clinic, SPIRIT Session II may be 
scheduled to occur approximately 4 
weeks after Session I.  
To coincide with the next monthly 
clinic visit and thus reduce the 
travel burden. 
 
Severe depression symptom scores 
(HADS-Depression ≥ 15) score given 
procedure for referral. 
Add response to suicidal ideation 
With a high HADS-depression score, the 
surrogate should be informed and 
encouraged to consider talking to the 
primary care provider. 
If suicidal ideation is expressed, site 
coordinator is notified and he/she will 
address with Site PI. 
Subject safety  
3 
25 January- 
2018 
Remove: copy of verbal consent will be 
mailed. 
Changed name of Site Coordinator at 
Univ. of Pittsburgh  
Unnecessary according to IRB 
policy. 
For information purposes only.  
4 
31 July 2018 
Addition of DCI  and Emory Decatur to 
Emory University Sites 
In order to meet recruitment goals 
5 
 
4 December 
2018 
Deletion of Surprise Question inclusion 
criterion and addition of 
teleconferencing for SPIRIT session 
Broadening the recruitment base 
in order to meet recruitment goal 
by proposed timeframe.  
 
Delete: Surprise Question- “would I be 
surprised if the patient died in the next 
year?” 
 
 
 
 
 
 
 
 
Renal community has been 
promoting timely advance care 
planning for every patient on 
dialysis regardless of their current 
health condition because of their 
high comorbidity and 
unpredictable prognosis. Because 
the SPIRIT intervention has 
extensively tested and 
demonstrated its safety and 
efficacy, the investigators have 

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Allow for teleconferencing for 
Intervention delivery (Using Zoom, LITS 
approved platform) 
 
decided to broaden the inclusion 
criteria by not using the SQ any 
longer. This change will also help 
ensure the study meets the target 
sample size within the proposed 
timeline. 
 
Chosen Surrogates may not live 
locally and this would allow their 
participation in a secure and 
private setting and alleviate 
transportation and schedule 
demands. 
 
 
6 
21 January 
2019 
Add: University of Virginia as study site 
Additional University site added to 
increase recruitment to meet study 
milestones and targets. 
7 
27 February 
2019 
1.1 Synopsis 
4.1 Overall study design 
9.4.3 analysis of secondary endpoint(s) 
9.4.9 Exploratory analysis 
10.1.1.1 Consent/Assent 
 
Study Duration: Patients & Surrogates 
participation duration of 9 months post 
data collection; we will request an 
extension of 12 months by Informed 
Consent addendum for both patients 
and surrogates 
We have had very few patient 
deaths (less than 4% of recruited 
population) and we run the risk of 
not meeting secondary aims unless 
we can extend the follow up 
period. This will be done by 
informed consent addendum for 
both patient and surrogate at 
completion of 9 month time point 
8 
05 August 
2019 
Note: Below revisions are all related to 
the supplement study, and the parent 
study is not affected. 
 3 Aims, endpoint, phases, Emory only 
sites, duration ~ 2 years 
Supplement study to include dementia 
patients 
Preliminary study results from SPIRIT-AD 
for the supplement study 
Objectives, endpoints, justification and 
measures. 
 
Randomization to two groups 
 
Single SPIRIT session 
Follow up period up to 12 months 
ESRD plus dementia – use of MoCA, 
SLUMS and UBACC 
Same; patients previously excluded will 
have opportunity under supplement 
Transportation support offered 
 
Single session due to patients limited 
short-term memory 
Addition of MoCA and SLUMS 
We request approval for a 
modification to the current 
protocol to evaluate the effects of 
SPIRIT in patients on dialysis who 
have an early stage of cognitive 
impairment or dementia and thus 
would be ineligible for the current 
parent study. This additional 
evaluation of SPIRIT added to the 
current protocol has been funded 
by the NIH. Dialysis patients will 
continue to be assessed for their 
eligibility for the parent study. If 
they meet the inclusion criteria for 
the current parent study, they will 
move along with the existing 
pathway. If they are determined to 
be ineligible due to cognitive 
impairment, those patients may be 
qualified for this sub-study. Having 
these two pathways, patients who 
are excluded from the parent study 
but still able to consent for study 
participation and able to express 
their wishes will have an 

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Randomization by dyad into one of two 
groups; SPIRIT or usual care. 
 
Addition: Audio recording of sessions 
and sequent qualitative analysis 
1 month post-death HADS for surrogate, 
medical records review at 6m or death 
 
AIMS 1 & 2, sample size = 30 
 
AIM 1: Preparedness and Care decisions; 
AIM 2: Srgt post-bereavement distress: 
AIM3: Decision making capacity 
 
Pt written consent, Srgt verbal consent 
and Screening HIPAA. Limit to Emory 
Sites. Use of MoCA and SLUMS 
 
Add: Dr. Paul, biostatisitian, Linda 
Turberville-Trujillo ANP, and Drenna 
Waldrop-Valverde, PhD 
opportunity to participate. This 
sub-study will involve Emory 
dialysis centers only. If patients are 
eligible for the pathway of the sub-
study, they will be randomized 
either to receive usual care only or 
to receive SPIRIT adapted for those 
with cognitive impairment. We 
have brought in additional 
investigators who have expertise in 
neuroscience and cognition. 
 
9 
July 29, 2020 
Changes in 5.5. Strategies for 
recruitment and retention and 6.0 Study 
intervention  
Supplement study procedures to be 
done remotely/via phone 
During the pandemic, SPIRIT sessions 
will be conducted via zoom whenever 
possible. 
To avoid or minimize in-person 
contacts. 
 
 

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5.5. Strategies for 
recruitment and 
retention 
 
6.0 Study 
intervention 
July 29, 
2020 
Supplement study procedures to be done 
remotely/via phone 
 
 
During the pandemic, SPIRIT sessions will be 
conducted via zoom whenever possible. 
 
To minimize in-person contacts 
10 
 
1.1 Synopsis 
2.1 Study rationale 
2.2 Study 
background 
4.1 Overall study 
design 
4.2 Scientific 
rationale for study 
design 
4.4 End of study 
definition 
5.1 Inclusion 
criteria 
5.5 Strategies for 
recruitment and 
retention 
8.1 Outcome 
assessments 
9.1 Statistical 
hypotheses 
9.2 Sample size 
determination 
9.4 Statistical 
analyses 
10.1 Regulatory, 
ethical, and study 
oversight 
considerations 
 
8/12/20 
New Changes are related to a new supplement, 
COVID-19 related, study and do not affect the 
parent study. 
A new supplement study is a 
longitudinal cohort study 
leveraging the parent study. 
 
The objective is to assess the effect 
of the pandemic on the stability of 
end-of-life care preferences and on 
our key outcomes (dyad 
congruence on goals of care, 
patient decisional conflict, and 
surrogate decision-making 
confidence). 
 
11 
10-
.22.2020 
5.1 Inclusion Criteria: *Changes are related to 
supplemental aim (SPIRIT in ESRD plus 
ADRD),  and do not affect the parent study. 
 
Supplement study: Adjusting the 
MoCA and SLUMS criterion to 
meet target sample size.  
 
12 
 
1/8/2021 
5.5 Recruitment: Care Providers recruitment and 
consent procedures  
 
 
Recruitment involves email 
contacts and phone calls. 
Current informed consent for Care 
Providers is not changing.  
 
 
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