Palliative Care to Improve Quality of Life in CHF and COPD
Phase: NA
Conditions: Heart Failure, Pulmonary Disease, Chronic Obstructive, Emphysema, Pulmonary Fibrosis, Interstitial Lung Disease
Sponsor: VA Office of Research and Development

 
Palliative care to improve quality of life in CHF and COPD_Protocol_v_05.08.2018 
w 
COMIRB Protocol 
COLORADO MULTIPLE INSTITUTIONAL REVIEW BOARD 
CAMPUS BOX F-490    TELEPHONE:  303-724-1055   
Fax:  303-724-0990 
 
Protocol #: 
 
 
15-1891 
Project Title:  
 
Palliative care to improve quality of life in CHF and COPD 
Principal Investigator:  
David Bekelman, MD, MPH 
Version Date: 
 
 05.08.2018 
I. Hypotheses and Specific Aims:   
 
We will conduct a two site randomized clinical trial (VA Eastern Colorado Health Care System [VA ECHCS] 
and VA Puget Sound [PSVAHCS]) to determine whether an intervention to improve symptoms and to help 
Veterans adjust to living with Chronic Heart Failure (CHF), Chronic Obstructive Pulmonary Disease (COPD) 
and Interstitial Lung Disease (ILD) improves quality of life. The intervention will also help Veterans 
communicate preferences for treatment with their providers. The intervention involves routine clinical care and 
no experimental drugs or devices.  The results will be directly relevant to Veterans who suffer with these 
illnesses and their families, as well as to providers, leaders in VA Central Office, and other researchers. 
Furthermore, this study will generate information that supports the broader dissemination and implementation 
of the intervention and informs the development of future palliative care and team-based interventions in the 
VA.  Specific aims include: 
 
Aim 1: Determine the effect of the intervention on (a) quality of life as a primary outcome, and (b) 
depression, symptom burden, advance care planning communication and documentation, disease-  
specific health status, emergency department visits, hospitalizations, and mortality as secondary 
outcomes. 
Aim 2: Examine the implementation of the intervention. 
Aim 2a: Assess the degree, barriers, and facilitators of implementation of various intervention 
components.  Identify which intervention components and processes are most critical from the 
perspectives of patients, intervention team members, and primary care providers whose 
patients received the intervention. 
Aim 2b. Evaluate the resources (e.g., personnel time and other costs) associated with the 
intervention, and estimate the resources needed for implementation and maintenance of the 
intervention in other VA settings. 
The brief study title is Advancing Symptom Alleviation with Palliative Treatment (ADAPT) and will 
be used with participants as it provides a simple acronym.  
 
 
II. Background and Significance:  
 
Among Veterans, CHF and COPD are top causes of poor quality of life, hospitalizations, mortality, and health 
care costs.  While not as common, ILD also leads to poor quality of life, has few effective treatments, and has a 
poor prognosis.  While palliative care is effective in advanced cancer, it has not been adequately studied in 
CHF, ILD, or COPD.  Commonalities in CHF, ILD, and COPD make them priorities for a palliative care 
intervention to improve quality of life in both populations.  CHF and COPD commonly co-occur: there is a 20% 
chance a patient with COPD will have CHF, and a 30% chance a patient with heart failure will have COPD. 1  
Despite disease-specific treatments CHF, ILD, and COPD, Veterans with these illnesses still suffer from the 
burdens of persistent, diverse symptoms and depression that reduce quality of life.  These burdens are 
remarkably similar in CHF, ILD, and COPD despite different organ systems and pathophysiology.   
 
Palliative care need #1: Poor quality of life in CHF, ILD and COPD is due to similar persistent, diverse 
symptoms and depression. This is illustrated in the study conceptual model (Figure 1), which is based on 

 
Palliative care to improve quality of life in CHF and COPD_Protocol_v_05.08.2018 
integrating elements of Lenz’ unpleasant symptom theory2 into an adaptation of the Wilson and Cleary model 
of health related quality of life.3  As illustrated in the conceptual model, in CHF, ILD, and COPD, the symptom 
experience and depression exert major influences on health-related quality of life. 
1. Symptom experience: persistent, diverse symptoms.  Patients who have CHF, ILD or COPD are 
burdened by the same disease-related symptoms of breathlessness (44-85%) and fatigue (66-85%) as 
well as pain (38-58%) and other non-disease related symptoms that reduce quality of life and persist 
over time.4-11  In CHF, a mean of 15 physical and emotional symptoms are experienced concurrently. 12  
Diverse symptoms reduce quality of life in patients with CHF,12 ILD,10, 13 COPD.7 
 
2. Depression.  Depression in CHF, ILD and COPD is a key determinant of the experience of 
symptoms12, 14-16 and quality of life.14, 17, 18  Between 20-30% of patients with CHF,19 ILD16 or COPD20 
have depressive disorders.  Between 50-60% have clinically significant depressive symptoms.19, 21  VA 
studies demonstrate that the prevalence and severity of depression in Veterans with CHF and COPD 
increases with disease severity.20, 22, 23 
 
Combining palliative symptom 
management with psychosocial 
care to reduce depression and 
help patients adjust to illness is 
an innovative approach.  This 
approach is based on the strong 
correlation between depression 
and symptoms12 and evidence 
showing that combined 
treatment of depression and pain 
is the most effective approach 
for both.24   
 
Diverse symptoms and 
depression are not only major 
contributors to quality of life in 
Veterans, but they are also 
associated with numerous other 
adverse outcomes (Figure 1).  In 
both HF and COPD, symptom 
severity and depression 
independently predict health 
care utilization (e.g., emergency department visits and hospitalizations) and mortality19, 25-29 and contribute 
substantially to high care costs.30   
 
Palliative care need #2: Few Veterans with CHF, ILD or COPD engage in advance care planning.  Advance 
care planning is the process of considering and communicating healthcare values and goals.31  An advance 
directive is a legal document describing preferences for future care and appointing a surrogate to make health 
care decisions in the event of incapacity.  While the benefits of completing an advance directive are 
controversial,32, 33 recent studies demonstrate advance care planning can reduce health care costs; increase 
the likelihood of dying at home and receiving care aligned with one’s wishes; decrease rates of hospital 
admission; and increase rates of hospice admission.34, 35  Advance care planning also improves patient and 
family satisfaction and reduces stress, anxiety, and depression in surviving relatives.36  Despite these benefits 
and professional heart and lung organization recommendations,37-40 few Veterans with CHF, ILD or COPD 
engage in advance care planning.41  In addition, patients with CHF, ILD and COPD are often hospitalized at 
the end of life, although many say they would prefer to die at home.42, 43 
 
 

 
Palliative care to improve quality of life in CHF and COPD_Protocol_v_05.08.2018 
By addressing diverse symptoms and depression to improve quality of life, and implementing a 
successful advance care planning intervention, this study will overcome limitations of prior studies  
Despite disease-specific care in CHF, ILD, and COPD, patients experience poor quality of life.  Disease 
management interventions in either illness have not consistently improved quality of life because they have not 
simultaneously addressed diverse symptoms and depression (Figure 1).  In COPD, intensive pulmonary 
rehabilitation improves quality of life, but has limited reach as most veterans cannot access or receive 
pulmonary rehabilitation.   
 
Prior palliative care interventions to improve quality of life in CHF, ILD, or COPD are sparse, have mixed 
results, and did not use high quality randomized study designs.44-46  Furthermore, these studies did not 
evaluate advance care planning outcomes, a key component of palliative care.  In the most promising study, 
common symptoms including depression and pain did not improve because providers often did not follow the 
palliative care consult recommendations.44  By using a collaborative care model that integrates palliative care 
into primary care, our intervention will address this barrier.   
 
By complementing disease-specific care with the addition of palliative and psychosocial care to address 
diverse symptoms and depression simultaneously, we hypothesize the proposed intervention will succeed in 
improving quality of life.  In addition, the intervention will implement an advance care planning intervention that 
successfully improved advance care planning communication in COPD (see Preliminary Studies).  Because 
both CHF, ILD and COPD have common barriers to advance care planning,47-50 our advance care planning 
intervention is likely to succeed. 
 
Limitations of palliative care delivery models will be addressed in this proposal to increase the reach 
and potential for dissemination of palliative care 
1. Need to integrate palliative care into primary care.  The predominant care delivery model in palliative 
care is inpatient, consultative care focused on the end of life.  However, both patients with CHF and 
providers believe palliative care should be provided earlier in CHF and integrated into chronic 
outpatient care.51, 52  Most of the care of Veterans with CHF or COPD takes place in primary care, and 
both primary care providers (PCPs) and specialists believe palliative care should be provided through 
primary care.53  The intervention integrates palliative care into primary care through (1) a nurse who 
provides palliative care and collaborates with the Veteran’s PCP, and (2) once a palliative care plan is 
approved by the PCP, palliative care orders are written for the PCP to review and sign 
2. Specialist, consultative model of palliative care cannot be scaled-up to CHF and COPD.  Given the 
difficulty assessing when end of life is near and talking to patients about palliative care, as well as 
concerns about professional control, providers avoid referring patients for palliative care. 53  
Furthermore, there is an inadequate palliative care workforce to provide care for the large numbers of 
Veterans with advanced CHF or COPD.54  Patients with advanced CHF prefer not to see additional 
providers for their care, including palliative care specialists.52  Rather than using a consultative model, 
the study uses population-based identification of patients.  A nurse and social worker are trained to 
provide basic palliative care and are supervised by a palliative care specialist. 
3. Prior palliative care interventions are not structured and thus are difficult to replicate or disseminate.  
The proposed palliative care intervention is structured and operationalized in a treatment manual which 
will facilitate replication and dissemination. 
 
Study innovation and rationale for Aim 2: within the context of an effectiveness trial, examine 
implementation issues 
Blending the efficacy and effectiveness stages of intervention testing can (1) reduce the time delay between 
the discovery of health care innovations and their implementation;55 (2) produce additional knowledge for 
researchers; and (3) increase the operations and policy relevance of clinical research.56  VA researchers have 
emphasized the importance of understanding challenges to implementation early in intervention studies.57  In 
the context of an effectiveness trial, VA QUERI has recommended blending by testing the effects of a clinical 
intervention while simultaneously observing and gathering information on implementation.  QUERI has termed 
this a “hybrid effectiveness-implementation” (type 1) study design.56 
 

 
Palliative care to improve quality of life in CHF and COPD_Protocol_v_05.08.2018 
The proposed study is innovative in that it is a “pragmatic” or “practical” (i.e., “effectiveness”) clinical trial58 that 
uses a type 1 hybrid design to generate information on implementation of team-based and palliative care 
interventions.  It is an effectiveness trial because (1) population-based sampling is used to identify a “real 
world” population of veterans; (2) the intervention “dose” is allowed to vary with Veteran needs as would occur 
in the clinical setting; and (3) the analysis includes all patients regardless of compliance with the intervention 
and missing data.  As a type 1 hybrid, the study will include collection of data on valuable intervention content 
and processes from the perspectives of patients, intervention team members, and PCPs whose patients 
received the intervention (Aim 2a).  This data will yield information about barriers and facilitators of intervention 
delivery that will be important to plan subsequent implementation if the intervention is successful.  If the 
intervention is not successful, this aim will inform subsequent implementation of other team-based, palliative 
care, or specialty/primary care interventions. 
 
The operational partners contributing to this study recommended we determine the personnel time and other 
costs to implement and maintain the intervention (Aim 2b).  This information, combined with an understanding 
of whether the intervention improves quality of life or advance care planning outcomes, was most important to 
them in considering intervention implementation and dissemination. 
 
Research staff at VA ECHCS will assist PSVAHCS in some aspects of recruitment, follow-up data collection 
and the process evaluation.  The Intervention SW and RN at each site will interact with participants at both 
sites. 
 
III. Preliminary Studies:   
Preliminary studies demonstrate study and intervention feasibility and likelihood of success:   
1) The Principal Investigator (PI, Bekelman) developed and conducted initial pilot-testing of the CASA 
palliative symptom management component, which includes evaluations and treatments for fatigue, 
breathlessness, and pain, as Director of outpatient CHF palliative care programs at the University of Colorado 
Hospital (published sample of patients)59 and the Denver VAMC.    
2) The psychosocial care component of the intervention was developed by Carolyn Turvey, PhD (see letter of 
support) through grants from the NIMH (R34MH73566) and the American Heart Association (AHA 
0555699Z).60  In a randomized pilot study of the intervention (n=37), the mean Beck Depression Inventory-II 
(BDI-II, scale range 0-63) scores for the intervention patients improved from 21.1  to 11.8, while those in the 
usual care remained approximately the same, 17.8 to 16.2 (mixed effects model, treatment assignment by time 
interaction F=5.45, p=0.009).   Defining treatment response as a 50% or greater decline in BDI-II score, 9/19 
(47%) responded in the intervention group as compared with 1/18 (5.5%) in the usual care group.   
3) In a single arm pilot study of 15 patients with advanced stage (GOLD III/IV) COPD, depression (Patient 
Health Questionnaire-9), anxiety (Generalized Anxiety Disorder-7), and overall quality of life (St. George 
Respiratory Questionnaire) improved with CASA over three months (effect sizes of 0.64, 0.54, and 0.22 
respectively).  The nurse was able to continue the intervention after the study concluded, and 10 patients 
(67%) elected to continue the intervention.   
4) In a single arm pilot study of 17 patients with CHF (15 Veterans at the Denver VAMC), 16 completed the 
study, and symptom distress, depression, anxiety, and quality of life improved with CASA over three months 
(using the same measures as in the proposed IIR study, effect sizes of 0.64, 0.12, 0.57, and 0.27 
respectively).61  This study was funded by VA QUERI RRP 11-239 (PI: Bekelman).  As planned in the 
intervention protocol, the CASA intervention team met weekly, and the nurse and social worker each provided 
a mean of 6 phone visits per patient. 
5) In a RCT of 376 Veterans with COPD conducted by Co-I David Au (VA HSR&D IIR 02-292), advance care 
planning communication increased from 11% to 30% using the patient-completed preference form.62   
6) For the proposed study, collaborating with the VA Office of Analytics and Business Intelligence, we 
electronically identified the number of potentially eligible patients with CHF and COPD.  There were a total of 
10,860 Veterans with CHF or COPD (Denver VAMC, n=5301; Seattle VAMC, n=5550).  Of these, we identified 
5,951 who were at high risk of hospitalization and death (see Table 1, Eligibility). 
7) Drs. Bekelman (PI) and Au (Co-I) have expertise conducting multi-site behavioral and health delivery 
clinical trials. 
 

 
Palliative care to improve quality of life in CHF and COPD_Protocol_v_05.08.2018 
IV. Research Methods 
 
A. Outcome Measure(s):   
 
Aim 1: The measures were chosen to reflect domains of the conceptual model (Figure 1) as follows 
(instrument abbreviations defined below):  
• 
Antecedents: Demographics; CHF factors (e.g., left ventricular ejection fraction); COPD factors (e.g., 
spirometry) 
• 
Symptom Experience: GSDS (symptom distress), Symptom assessments 
• 
Depression: PHQ 
• 
Health-Related Quality of Life: FACT-G (primary outcome measure), QUAL-E, KCCQ-12, CCQ, K-BILD 
• 
Health Care Utilization: Hospitalizations 
• 
Advance care planning communication, documentation: patient-reported advance care planning 
communication, advance directive documentation in Electronic medical record review 
1. FACT-G (primary outcome):  The Function Assessment of Chronic Illness Therapy-General is a widely used, 
valid, reliable (alpha range, 0.88-0.92), and responsive 27 item self-report measure of health-related quality of 
life that includes domains of physical, social/family, emotional, and functional well-being.35, 63-65  Norms for the 
general population allow FACT-G scores to be measured and compared across study populations.66  Validity in 
CHF and COPD has been demonstrated through FACT-G correlations with disease severity.64 
2. QUAL-E: The Quality of Life at the End of Life is a valid and reliable self -report measure of several domains, 
each scored separately, of quality of life in advanced illness.67   
3. GSDS:  The General Symptom Distress Scale is a single item measure of overall symptom distress that is 
reliable and valid68  and asks, “In general, how distressing are all of your symptoms to you?” It is rated on 0 
(“not at all distressing”) to 10 (“extremely distressing”) on a numeric rating scale.   
4. PHQ-8: The Patient Health Questionnaire-8 is an 8-item valid and reliable instrument that provides a 
continuous measure of depressive symptoms and is sensitive and specific for a diagnosis of major depressive 
disorder.69 
5. GAD-7:  The Generalized Anxiety Disorder-7 is an 7-item valid and reliable screening instrument for four 
common anxiety disorders in primary care (post-traumatic stress disorder, generalized anxiety disorder, panic 
disorder, and social anxiety disorder.79,80 It provides a continuous measure of anxiety symptoms. 
6. PEG: The PEG is a reliable and valid 3-item scale of pain intensity and interference.70 Patients rate the 
pain’s intensity and interferences with their enjoyment of life and general activity on a numeric rating scale 
ranging from 0 (“no pain” or “does not interfere”) to 10 (“pain as bad as you can imagine” or “completely 
interferes”).  
7. PROMIS Fatigue: The Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue 
Scale is a 4-item scale that measures fatigue impact and fatigue experience.71 Patients rate how much fatigue 
they have experienced and how much fatigue has bothered them on a 5-point Likert-type scale ranging from 0 
(“not at all”) to 5 (“very much”). 
8. ISI: The Insomnia Severity Index is a 7 item reliable and valid instrument to quantify perceived insomnia 
severity.72   
9. Constipation and Numbness/Tingling: These symptoms will each be assessed by one question asking how 
much the symptom distressed or bothered the respondent in the last week using a 6 point Likert-type scale 
from no symptom to very bothersome. 
10. KCCQ-12:  The Kansas City Cardiomyopathy Questionnaire is a 12-item self-administered validated 
questionnaire (administration time 5-10 minutes) that measures CHF-specific health status.73  it is a shortened 
version of the KCCQ 23 item measure which is reliable, sensitive to clinical change, and predicts 
hospitalization and mortality.74, 75  Additionally, we will ask two questions assessing how bothersome symptoms 
are. It will be administered to Veterans with CHF. 
11. CCQ:  The Clinical COPD Questionnaire is a self-administered 10-item measure of COPD symptoms, 
functioning, and emotional well-being.  It is well-validated, reliable, and responsive.76, 77  It will be administered 
to Veterans with COPD. 

 
Palliative care to improve quality of life in CHF and COPD_Protocol_v_05.08.2018 
12. K-BILD:  The King’s Brief Interstitial Lung Disease is a 15-item self-completed health status measure for 
ILD. It is validated and can be used to assess ILD from the patient’s perspective.  It will be administered to 
Veterans with ILD78.  
12. Demographics/Study Form:  Age, gender, race and ethnicity, education level, and clinical variables will be 
determined at the enrollment visit from the electronic medical record and patient self-report.  For example, 
spirometry results (COPD), NYHA classification (CHF), etiology of CHF or COPD, most recent ejection fraction 
(CHF), and BNP or NT-pro BNP (CHF) will be documented.  Medical history (including comorbidities), current 
medications, number of hospitalizations in the previous year will also be collected at the time of the enrollment 
visit. Patients’ current care, including palliative care, mental health, cardiology, pulmonology, hospice and 
specialist pain care will be ascertained at baseline and 6 months.  At the 6 and12 month study visit, patients 
will be asked to relate interim events, including hospitalizations, the reasons for them, and for permission to 
obtain medical records relevant to such events from VA and non-VA facilities.  Medications from the medical 
record will be documented again at the six month visit. 
13. Advance care planning communication will be measured using patient report questions at the baseline and 
6 month study visits. Advance directive documentation will be defined by the presence of any of the following 
notes in the electronic medical record at baseline and 6 months: advance directive discussion; scanned 
advance directive (either a living will or durable power of attorney for health care); or medical orders for life-
sustaining treatment. 
14. Hospitalizations/emergency room visits, mortality and risk of hospitalization and/or death:  The following 
events will be assessed during the study period through VA and non-VA facility medical record review to 
supplement patient report: hospitalization (with cause) and mortality.  We will also review medical records for 
intensive care use and end of life care patterns. We will also assess risk of hospitalization and/or death for 
participants during the study. Vital status will also be ascertained via the VA Vital Status File and the National 
Death Index.  
15.Telephone Interview for Cognitive Status (TICS): The Telephone Interview for Cognitive Status is an 11-
item verbally administered test of cognitive status. The TICS takes approximately 4 minutes to administer and 
assesses memory and other cognitive functions. The TICS was originally developed to discriminate between 
cognitive normals and dementia patients79 and has demonstrated good sensitivity and specificity when 
discriminating between normals and individuals with mild cognitive impairment. 80 The TICS will be used as a 
covariate in the analyses. 
16.  Satisfaction surveys: Satisfaction with health care and the study will be assessed.  Questions were 
adapted from the CANHELP Questionnaire.81 
  
 
Aim 2a: We will conduct a mixed method (i.e., combination of quantitative and qualitative) evaluation to assess 
intervention implementation.   
Intervention database:  The intervention database will be used to track intervention content and processes.   
Brief patient interviews: After the 6 month outcome measurement, we will conduct interviews with Veterans 
randomized to the intervention arm to ask for their feedback on the intervention.   
Intervention Close Out Summary:  The intervention team will complete an Intervention Team Intervention Close 
Out Summary on each Veteran once they complete the intervention. 
Focused Group Discussion with Intervention Team:  We will conduct structured group discussions with 
intervention team members at the completion of the project intervention period to debrief about how the 
intervention was implemented.   
Surveys of PCPs:  We will administer a brief survey to all PCPs who have patients who have completed the 
intervention. 
 
Aim 2b: We will evaluate the resources and costs to implement and maintain the intervention.  Data for the 
costs to implement (i.e., start-up costs) and the cost to maintain the intervention will be collected separately. At 
a minimum, the costs to implement will include personnel training, database development; the costs to 
maintain will include identification of eligible Veterans and personnel time to provide the intervention (e.g., 
patient visits/phone calls; team meetings; communication/coordination with PCPs). 

 
Palliative care to improve quality of life in CHF and COPD_Protocol_v_05.08.2018 
 
B. Description of Population to be Enrolled:   
Settings   
The study will be conducted at the VA Eastern Colorado Health Care System (VA ECHCS) and Puget Sound 
VA Health Care (PSVAHCS) systems.  Each health care system includes a tertiary care medical center and 
seven community-based outpatient clinics (CBOCs).   
 
Study population: 
 
Aim 1: A total of 400 adult subjects will be randomized in a 1:1 ratio to one of 2 treatment arms: 1) enhanced 
usual care or 2) team-based palliative care intervention plus usual care. A component of the study intervention 
involves speaking to study subjects’ informal (family) caregivers.  The eligibility criteria (Table 1) aim to enroll 
Veterans with a diagnosis of CHF, ILD, or COPD who are at risk of hospitalizations or death, have poor quality 
of life, and are able to participate in the intervention. 
 
Patients with CHF, ILD, or COPD in both the PSVAHCS and VA ECHCS will be identified electronically by staff 
at the VA ECHCS site using validated combinations of diagnostic codes.82, 83  The Care Assessment Need 
Table 1.  Eligibility Criteria 
 
Inclusion Criteria 
Definition 
• CHF: Diagnosis of CHF in 2 years 
prior to enrollment 
• Inpatient hospital diagnosis or ≥2 outpatient visits*  
• COPD:  Diagnosis of COPD in 2 years 
prior to enrollment 
• Inpatient hospital diagnosis or ≥2 outpatient visits* 
• ILD: Diagnosis of ILD in 2 years prior 
to enrollment 
• Inpatient hospital diagnosis or ≥ 2 outpatient pulmonary visits ** 
• Among those with CHF or COPD, 
high risk for hospitalization and death 
• Care Assessment Need score ≥ 80 
• Poor quality of life 
• FACT-G score ≤ 70 
• Symptomatic 
• Bothered by at least one of the target symptoms: pain, fatigue, 
depression, shortness of breath, trouble sleeping 
• Primary care or other provider who is 
willing to facilitate intervention medical 
recommendations 
• PCP listed in  Electronic medical record review or self-report 
• Able to read and understand English 
• Consistent access to and able to use 
a standard telephone 
• Self-report 
• Self-report 
 
 
Exclusion Criteria 
 
• Previous diagnosis of dementia 
• Inpatient or outpatient diagnostic code† 
• Active substance abuse 
• Electronic medical record review for substance abuse in the previous 6 
months 
• Comorbid metastatic cancer 
• Electronic medical record review 
• Diagnosis of obesity hypoventilation 
syndrome 
• Nursing home resident 
• Inpatient or outpatient diagnostic code (ICD9 278.03, ICD10 E66.2) or 
(BMI >=45 and diagnostic codes for COPD) 
• Electronic medical record review  or self-report 
• Heart or lung transplant or LVAD 
• Participation in the intervention arm of 
the CASA trial, COMIRB 11-0969 
• Electronic medical record review  or self-report 
• Electronic medical record review 
• Enrolled in palliative care, hospice or 
home based primary care 
• Prisoner 
• Pregnant 
• Electronic medical record review or self-report 
 
• Electronic medical record 
• Electronic medical record or self-report 
* ICD-9 code definitions for CHF (428.XX) validated in Go et al82; ICD-9 code definitions for COPD (491.XX, 492.XX, 
493.2, 496.XX) validated in Au et al83  and the corresponding ICD-10 codes 
**ICD-9 code definitions for ILD: 515, 516.30, 516.31, 516.32, 516.34, 516.37 and the corresponding ICD-10 codes 
† ICD-9 codes for dementia (290.0-290.43, 291.2. 046.1, 294.0, 294.1x, 294.2x, 294.8, 331.0, 331.1x, 331.2, 331.6, 
331.7, 331.82, 331.89, 331.9) from Taylor et al84 and Bharmal et al85  and the corresponding ICD-10 codes  

 
Palliative care to improve quality of life in CHF and COPD_Protocol_v_05.08.2018 
(CAN) score will be used to define a population at increased risk for hospitalizations or death that is likely to 
need the palliative care intervention because of increased illness severity. 86 The CAN is a VA-developed 
prognostic tool that was created to help primary care proactively identify and manage at risk Veterans on a 
population level.  We will collect the CAN score on all potential subjects with a diagnosis of CHF, COPD, or ILD 
as defined in Table 1.  A CAN score of ≥ 80 for those with CHF or COPD was chosen in consultation with the 
VA Central Offices of Primary Care and Palliative Care.  Preliminary studies identified 5,951 Veterans total at 
both sites with CHF or COPD and a CAN score of ≥ 80. The CAN score may not be as valid for the small 
number of patients with ILD, thus we will not use it as an eligibility criterion. 
 
To enroll a sample with poor quality of life who is appropriate for the intervention, potential participants will 
need to report a Functional Assessment of Chronic Illness Therapy-General (FACT-G) score ≤ 70 and be 
bothered by one of the intervention target symptoms.  The FACT-G is a widely-used, valid, reliable quality of 
life measure that is the primary outcome in this study.  It measures physical, social/family, emotional, and 
functional well-being.  A score of ≤ 70 identifies poor quality of life as validated by declining performance status 
and increasing disease burden.87   
 
Given the intervention delivery model whose purpose is to integrate palliative care into chronic care, a provider 
(ideally the PCP) must be willing to work with the intervention team. In prior studies, 61,72 all PCPs were willing 
to work with the team. The intervention was developed in English for adults and the majority of the study 
instruments have been validated only in English. As the intervention is provided by phone, participants must 
have phone access. Potential participants who have a previous diagnosis of dementia will be excluded 
because the intervention requires participation in counseling that was not developed for people with dementia, 
and most of the questionnaires were not validated in persons with dementia. Subjects who have problems with 
active substance abuse, defined as a substance abuse documented in EMR in the previous 6 months 
(cannabis will be allowed) are unlikely to participate in the regular follow up phone calls or respond to the 
intervention and will be excluded. Subjects with comorbid metastatic cancer are excluded because this study 
focuses on CHF, ILD, and COPD rather than cancer palliative care. Those with a diagnosis of obesity 
hypoventilation syndrome, or those at high risk for obesity hypoventilation syndrome (BMI >= 45 and diagnostic 
codes for COPD), are excluded as we do not think this intervention will be helpful to them.  Those with a heart 
or lung transplant or left ventricular assist device (LVAD) will be excluded because they already receive 
substantial psychosocial care and resources. Those receiving palliative care, hospice and home-based primary 
care will be excluded as they are likely to be receiving services similar to what is provided in the intervention. 
We will exclude those who participated in the intervention arm of the CASA trial (COMIRB #11-0969) as they 
have received some components of the intervention in this trial.  Finally, nursing home residents will be 
excluded since this study is focused on outpatient care. Competence for study participation will be evaluated 
by potential participants’ ability to explain to study personnel the goals of the study, requirements of study 
participation, and potential risks and benefits. 
 
Patient interviews: After the outcome measurement at 6 months, we will conduct interviews with Veterans 
randomized to the intervention arm to ask their opinions on the helpfulness of the intervention. We will 
interview a subset of patients completing the intervention every 6 months in order to account for potential 
differences over time (e.g., intervention provider experience).   
 
Intervention personnel: All intervention personnel will be invited to participate. 
 
Primary care providers whose patients have received the intervention: Providers who have patients who have 
completed the intervention will be invited to complete a brief survey.   
 
 
C. Study Design and Research Methods.   
Timeline 
 
Table 2. Timeline 
Year 
Activity 
1 
2 
3 
4 
Study start-up 
x  
 
 
 
 
 
 
Patient recruitment 
 
x x x x  
 
 
Outcomes measurement, 
implementation data collection 
 
x x x x x x  
Analysis and write-up 
 
 
 
 
 
 
 
x 

 
Palliative care to improve quality of life in CHF and COPD_Protocol_v_05.08.2018 
The proposed study will be completed within a 4 year timeline (Table 
2).  Collection and analysis of medical record information will 
continue for up to ten years after a patient’s active study participation 
concludes.   
The table illustrates timing for completion of the main study tasks 
using 6-month increments.  We will try to complete recruitment over a 
19 month period, but have budgeted for completing recruitment over 
25 months. 
 
 
Recruitment Targets and Tracking 
 
Aim 1: 
The estimated flow of patients and overall accrual goals are 
displayed in Figure 2.  We will aim to randomize 8 patients per month 
at each site (16 total) over a 19 month period.  This will yield one 
intervention patient per week per site on average.  If enrollment is 
slower than anticipated, we will still be able to complete the study on 
time if 6 Veterans per month are randomized at each site over a 25 
month period.  
 
Aim 2a: 
 
Patient interviews: We anticipate at most 120 eligible patients of the 
200 receiving the intervention will participate, as they have already 
participated in the intervention and would be likely to offer feedback.   
 
Intervention personnel: We expect all intervention team members to 
participate as they are invested in the intervention and would be likely 
to want to provide feedback. 
 
Primary care providers whose patients have received the 
intervention: We expect approximately 100 providers will participate. 
 
Recruitment Process 
Aim 1:  
1. We are requesting a HIPAA waiver to allow us to screen administrative databases and review medical 
records of Veterans seen at each study site to identify Veterans who may be appropriate for the study. 
Data sources for screening include CDW Production, CDW Raw, CAN Score, PACT Implementation 
Index, Real SSN, Scrambled SSN, CAPRI, and VSSC web reporting. 
2.  Administrative data will be pulled according to the inclusion/exclusion criteria outlined in section “Study 
population.” We will also use a research database of veterans who consented to be contacted for future 
research studies as part of the VA CASA trial (COMIRB #11-0969) and meet eligibility requirements. 
Providers within the VA system can also choose to tell potential study participants about the study and 
provide them with a flyer for the patient to write in patient contact information and either return to study 
staff or call study staff directly for more information about the study. 
3. Study staff will review medical records to confirm eligibility criteria.   
4. Veterans who meet initial eligibility screening will be mailed a letter that describes the study and gives 
them the opportunity to call the recruitment team if they are interested or decline by returning a postage 
paid letter and envelope.  The letter will also say that the Veteran will be contacted by phone if the 
study team does not receive communication from the Veteran.  Veterans can also opt out during the 
phone call.   
5. Interested Veterans will be asked to verbally consent to further phone screening to verify eligibility (see 
included script).   
Initial Eligibility Screening 
CHF, ILD, or COPD; CAN ≥ 80 
120 medical record reviews per month 
Contacted by Mail 
90 per month 
Enrolled 
12-16 per month 
Baseline assessment 
Randomization 
Usual Care 
N=6-8/month 
Intervention 
N=6-8/month 
Palliative Symptom 
Management 
Psychosocial Care 
Advance care 
planning 
Outcomes Assessment 
4 , 6 and 12 month follow-up 
Figure 2. Study Population Flow 
Contacted by Phone 
70 per month 

 
Palliative care to improve quality of life in CHF and COPD_Protocol_v_05.08.2018 
6. Patients who are eligible after screening will be asked to provide informed consent (study and 
evaluation interview) and to complete HIPAA B forms. Informed consent will be conducted in-person, 
whenever possible.  If geographic distance prohibits an in-person visit, the patient will be mailed the 
consent forms and a member of the study team will contact the patient via telephone to conduct the 
informed consent process.  If amenable, the patient will sign the consent form and return it to the study 
team. Patients will be offered a $10 incentive for participation, provided at the baseline, 4m and 12 
month visits and $15 at the 6 month visit. Participants may decline payment.   
 
Patients will be assigned a study identifier, a number unrelated to any personal identifying information.  
Data will be kept on a secured server (see Protocol Application for details).  No surveys will be labeled 
with the subject’s name or identifying information. The surveys will be coded with the patient’s study 
identification number. 
 
VA providers may refer their patients to the study. 
 
The research coordinator, research assistant, study social worker and the study nurse may contact and 
conduct study procedures with patients according to the protocol at both sites.   
 
Prior to the start of the study, all research staff will be trained and will practice the screening and consent 
process.  The training will include the process of fully explaining the study and consent procedures, 
explaining the possible risks and inconveniences, answering patient questions and assessment of the 
patient’s understanding of the study and consent process.  
  
Randomization - Aim 1: 
Randomization will occur at the patient level with 1:1 randomization of patients to intervention or control 
groups.  Randomization will be computer generated using random block sizes and stratified by site and 
disease CHF, ILD, or COPD, or both CHF and COPD.   
 
Sample Size 
The sample size was planned to detect a clinically significant 
change on the primary outcome, quality of life.  We plan to enroll 
400 Veterans and anticipate 5% will die and 15-20% will have 
missing outcome data because they did not complete surveys or 
dropped out.  Thus approximately 115 Veterans per arm will 
complete the study.  With this sample size, we will have 85% 
power to detect a moderate effect size of 0.4 (two-sided test, 
alpha=0.05).  The minimal clinically important difference on the FACT-G is 4-6 points,88 and with a standard 
deviation of 15, a Cohen’s d effect size of  0.4 will be on the high end of clinical significance.  We believe 
this is appropriate as this is a personnel-intensive intervention.  Table 3 illustrates a range of sample sizes 
per study arm with different power and effect size assumptions. 
 
 
Aim 2a: 
Patient interviews: Patients will consent to participant in interviews when they provide informed consent for Aim 
1.   
 
Intervention personnel: All intervention personnel will be asked to participate in the focused group discussion.   
Recruitment and consent: Those who agree will be asked to provide verbal consent to the following at the 
beginning of all focus group: 
• 
Full disclosure that the session will be digitally recorded and detailed notes taken; 
• 
Statement that responses will be kept confidential and names will not be linked with responses in the 
summary;  
• 
An opportunity for them to excuse themselves   
 
Table 3.  Sample sizes per study arm 
for different assumptions 
 
Power 
Effect size 
80% 
85% 
90% 
0.35 
130 
148 
173 
0.40 
100 
114 
133 
0.45 
79 
90 
105 

 
Palliative care to improve quality of life in CHF and COPD_Protocol_v_05.08.2018 
Primary care providers whose patients have received the intervention: Providers will be invited to complete the 
survey via email, phone or in-person.  By completing in the survey, they will provide consent for this portion of 
the study.  We will request a waiver 
of written consent for providers who 
complete the survey because the 
surveys are minimal risk, and it is 
impractical to obtain written consent 
from busy health care providers.  
 
Description of the Intervention 
Overview:  The intervention is 
Veteran-centered, multidisciplinary, addresses palliative and psychosocial issues, and integrates with PCP 
care (Table 4).  A nurse (Registered Nurse, RN) and a social worker (Master’s level, e.g., MSW) will be the 
primary intervention personnel. The nurse and social worker will meet weekly for approximately 60 minutes 
with a collaborative care team (“Team”) including a representative PCP and palliative care specialist.  Each site 
(VA ECHCS, PSVAHCS) will have a Team.  The Team will provide caseload supervision and write notes and 
orders for patient’s clinical providers to sign. 
Team collaborative care model:  The Team will provide symptom-based care by integrating palliative symptom 
management with CHF, ILD, and/or COPD disease-specific care plans37, 38 based on the intervention team 
interviews/evaluations of patients and medical record review.  Study staff will record the Team’s 
recommendations in a progress note in the Veteran’s electronic medical record.  The psychosocial care and 
other non-pharmacological recommendations (e.g., pacing) will be implemented immediately by the 
intervention team.  Orders for medications or tests will be written for patient’s clinical providers to review & sign 
at their discretion.  This integration into ongoing primary care both informs patient’s clinical providers of the 
intervention care plan and provides an extra level of safety for patients by asking clinical providers to sign 
medical orders.  The team will have phone access to a cardiologist and pulmonologist for specialist support 
and will re-review patients if their symptoms are not improving as assessed by the study staff. 
Visits:  The intervention team will make an initial in-person, phone or VA telehealth equipment visit with 
patients and informal caregivers.  At the initial visit, a history and examination will be conducted and the patient 
will be offered the option of choosing which initial symptom (fatigue, breathlessness, pain, depression, trouble 
sleeping) on which to focus. With participants’ permission, these visits may be audiorecorded. If an informal 
(family) caregiver is present, s/he will be invited to participate in the discussion. Follow-up visits will be by 
phone or in-person to accommodate patient preferences, and the number and duration will be tracked.  The 
nurse will provide approximately 6 visits (2/month) to check on symptoms and provide education, and the 
social worker will provide approximately 6 visits (2/month) to complete the psychosocial intervention.  This will 
be allowed to vary dependent on patient and staffing needs. In the unexpected situation that study nurse or 
social worker are unavailable to contact participants, study physicians will contact study participants to 
administer the intervention as needed. 
 
Algorithm-guided symptom management:  The nurse will assess patients’ symptoms and, based on the 
symptom algorithms, discuss an initial management plan with the collaborative care team.  Algorithms for 
breathlessness, fatigue, and pain have been previously developed and studied. An algorithm for trouble 
sleeping was developed for this study. To facilitate patient commitment and activation, we will suggest patients 
choose one of the symptoms to work on initially, although they will have the option of choosing other symptoms 
in subsequent visits (e.g., constipation).  In our previous studies, the overwhelming majority seek help for 
fatigue, breathlessness, pain or depression,52, 61 which will be addressed by the social worker.  The nurse is 
responsible for following up on medical orders, disease and health care system navigation education, advance 
care planning discussions, assessing changes in patients’ symptoms and progress on behavioral changes 
(e.g., increased physical activity), and communicating with patients’ PCPs. The social worker will assist the 
nurse as needed for this part of the intervention. 
Structured psychosocial care:  The social worker will conduct a psychosocial assessment,89 and provide 6 
phone-based counseling sessions.  This counseling was specifically developed and tested in patients with CHF 
or COPD to improve depression60 (see Preliminary Studies).  The purpose is to help veterans adjust to living 
Table 4. Intervention Overview 
Intervention Component 
Personnel 
Algorithm-guided symptom management: 
breathlessness, fatigue, pain, trouble sleeping 
Registered Nurse (RN) 
Structured psychosocial care, targeting 
depression and adjustment to illness; advance 
care planning 
Social Worker  
Team collaborative care model: 30-60 minute 
weekly team meetings 
RN, LCSW, palliative and 
primary care providers 

 
Palliative care to improve quality of life in CHF and COPD_Protocol_v_05.08.2018 
with CHF, ILD, or COPD and to activate/empower them to discuss issues related to their illness with their care 
providers. The counseling will be supplemented with antidepressant medication if the Team agrees providing 
antidepressant medication is an appropriate, evidenced-based recommendation.  The social worker will also 
follow up on the patient-completed advance care planning preference form to help patients clarify health care 
goals and complete written advance directives.  The nurse will assist the social worker as needed for this part 
of the intervention. 
 
Advance Care Planning: The intervention team will meet with the patient one time to discuss care goals.  Using 
a structured guideline,90 participants understanding of their illness will be assessed.  Questions about what is 
important, goals, concerns and fears will be asked.  If a caregiver is present, s/he will be invited to participate 
in the discussion. The discussion will be documented in the medical record. 
 
 
Control Group (treatment as usual plus information from baseline surveys and self-care materials) 
Patients in the control group will continue to receive care at the discretion of their providers, which may include 
referrals to and ongoing care from cardiology, pulmonary, palliative care, or mental health.  They will also have 
the same amount of interaction with research assistants as the intervention patients, completing questionnaires 
and participating in study visits at the same frequency.  Patients’ providers will be given the results of all 
baseline depression surveys if screen positive for depression.  For example, patients in the usual care arm 
who have significant depressive symptoms will be notified of this and their providers will also be contacted.  
Referring providers will then assume responsibility for depression care at their discretion, with no constraints 
on treatment or referrals.  Therefore, the usual care patients may benefit from self-care materials or the 
feedback of screening instruments to their referring providers.  This sets a high but appropriate standard by 
which to judge the effectiveness of the intervention.  We considered a control group that included time with a 
nurse or social worker to match the intervention patients’ time (“attention control”).  However, this is not 
feasible as the intervention “dose” of nursing and social work care varies according to patient needs and 
symptoms.  It would not be possible to match the “dose” of provider time in both groups. 
 
 
D.   Description, Risks and Justification of Procedures and Data Collection Tools: 
 
Aim 1:  Study personnel will administer measures four times: enrollment (baseline), 4 months, 6 months and 
12 months (Table 5). The baseline and 6-month measures which are comprised of approximately 120 
questions and are expected to last 45 minutes, will be obtained during an in-person visit, by mail and phone or 
by video teleconference.  We will allow patients to complete 4 month and 12 month measures by mail or phone 
if they prefer Veterans will be offered an incentive for completing each of the 4 study visits ($10 at baseline, 
$10 at 4 months, $15 at 6 months, $10 at 12 months).  Patient reported survey data is necessary to achieve 
study aims as the primary outcome is quality of life which is patient perceived.  Demographic data and 
information from medical record review is necessary to determine secondary outcomes.  We have 
implemented the following protections:  
 
Table 5.  Study Visits and 
Assessments 
Baseline 
Month 4  
Month 6 
Month 12 
Demographics/study form 
X 
 
 
 
FACT-G (primary outcome) 
X 
X 
X 
X 
PHQ-8, GAD-7 
X 
X 
X 
 
KCCQ-12, CCQ, K-BILD  
X 
X 
X 
 
QUAL-E,Symptom Assessment, GSDS 
X 
 
X 
 
Advance care planning communication,  
assess for advance directive 
documentation 
X 
 
X 
 
Medications 
X 
 
X 
 
Heath care utilization, vital status, risk 
of hospitalization/death  
 
 
X 
X 
Use of other medical services 
X 
 
X 
 

 
Palliative care to improve quality of life in CHF and COPD_Protocol_v_05.08.2018 
 
Medical record data will be gathered for up to ten years after each participant concludes active study 
participation.  The purpose of this is to determine the effect of the intervention on long-term health and health 
care use.  This could include but is not limited to hospital discharge summaries, progress notes, operative 
notes, laboratory results, and diagnostic tests.  
 
 
Protection against loss of confidentiality. 
To protect against loss of confidentiality, all research materials will be inaccessible to anyone other than the 
investigators and research staff. All source documents will be identified by study identification (ID) number, and 
the key to that ID will be kept in a locked file cabinet in a locked office of the site PI, study coordinator, or 
research assistant. All personally identifiable information also will be kept separately from data forms and in a 
locked file cabinet. No results will be entered into our data collection system or reported in a personally 
identifiable manner.  Any non-VA healthcare records will be faxed to a fax machine in a restricted access room.   
 
We will use the Research Electronic Data Capture (REDCap) system for electronic entry of deidentified 
outcome data. All tracking system data will be password-protected with several levels of protection. The first 
will allow access to the operating system of the computer. The second will allow access to the basic menus of 
the integrated system; within certain menu options, such as database browsing, a third password will be 
required. All user interaction with the web-based system, from transmission of access passwords to sensitive 
patient data, is done via 128-bit encryption using the secure HTTPS protocol. REDCap is also HIPAA-
compliant. Data will be downloaded from VINCI REDCap to the local VA Server for analysis. Data for 
intervention patients will be stored on VA secure research servers designated for storage of protected health 
and identifiable information. 
 
Protection against loss of privacy.  
The majority of the interactions with study subjects will occur over the phone. Study personnel will make these 
phone calls from a private office or cubicle. At the beginning of any phone calls, study personnel will ask 
subjects if it is an acceptable time to talk and if privacy can be assured. We will accommodate study subjects 
by calling on different dates or times. For the recruitment visit and initial study visit that takes place in the 
hospital or clinic setting, we will also attempt to enhance privacy as much as possible if study subjects do not 
have a private room. For example, we will use a family conference room on the hospital unit or clinic and close 
curtains or doors. 
 
Satisfaction 
X 
 
X 
 
Table 6.  Intervention implementation (Aim 2a) objectives, data collection, and analytic frameworks 
Objective 
Data Source 
Sample Size 
Analytic Framework 
Assess intervention 
component 
implementation 
Intervention database 
150 
Quantitative: descriptive statistics by site 
and illness of the variability in “dose” and 
content of the delivered intervention 
 
 
Identify critical 
intervention 
components and 
processes and 
facilitators/barriers to 
intervention 
implementation 
Brief patient interviews 
100 
Qualitative analysis of data using the 
following CFIR* Domains, Constructs, 
allowing for emergence of new codes/ideas 
Intervention Characteristics 
Relative advantage, complexity, cost, 
design quality and packaging 
Characteristics of Individuals 
Knowledge & beliefs about Intervention 
Outer Setting 
Patients’ Needs and Resources 
Inner Setting 
Implementation climate, relative priority, 
readiness for implementation 
Intervention close out 
summary  
150 
Focused group 
discussion with 
intervention team 
1-2 
Survey of PCPs whose 
patients have received 
the intervention 
150 
*CFIR, Consolidated Framework for Implementation Research 

 
Palliative care to improve quality of life in CHF and COPD_Protocol_v_05.08.2018 
Staff Training, Supervision and Quality Assurance.  
The intervention manual and protocol, procedures for medical or psychological emergencies, procedures for 
protection of human subjects, and HIPAA requirements will be reviewed in detail in a pre-study meeting. The 
importance of adherence to intervention protocol will be stressed. The social workers will be trained in the 
intervention and how to provide psychosocial care. This will include training to review the theory underlying the 
counseling, a review of the treatment manual and patient materials, and role-playing to show the appropriate 
application of the counseling.  Study training will also include training for the study nurse who is conducting the 
palliative symptom management algorithms and coordinating the collaborative care team. This training will 
review the symptom management algorithms and procedures for unanticipated events (e.g., a subject 
complains of chest pain while on the phone). Day-to-day supervision and study fidelity and quality assurance 
will be maintained by the PIs. 
 
Data management/Data quality 
To ensure data integrity, the study protocol manual will include a section on data collection with descriptions of 
each data element or measure and instructions for its accurate collection or acceptable source.  Several 
strategies will be used to avoid missing data and dropout, such as follow-up phone calls and letters.  The study 
will use VA research servers for building and managing online databases.   
 
Monitoring plan 
Monitoring will focus on recruitment, baseline comparability of treatment groups, protocol adherence, 
completeness of data, accrual of primary endpoint data, safety, and follow-up rates.  This monitoring will 
provide the basis for reporting to a Data Safety and Monitoring Board and quarterly review by the study 
investigators.   
 
In the event we discover a serious medical or psychological problem in the usual care group, a referral will be 
made to appropriate medical and/or psychological professionals. Participants will be encouraged to access 
resources provided by their personal health team as well as community resources. 
 
Study Procedures for Positive Depression Screening:  
The outcome measures administered to all subjects include a screen for depression (a score of greater than 10 
on the PHQ-869). Because the intervention focuses on depression, these issues will be addressed in 
intervention subjects as part of the intervention. Subjects in the usual care group who score above the 
screening cutoff for moderate depression will be advised of this and given resources for depression care, 
including advice to discuss these results with a health care professional. In addition, the results will be 
forwarded to their health care professional. 
 
Aim 2a: To understand why particular intervention components and processes were most critical from the 
perspectives of patients, intervention team members, and PCPs, we used the Consolidated Framework for 
Implementation Research (CFIR) to guide data collection (Table 6).  CFIR, which is well-established in VA, 
was chosen as it provides a useful framework for considering contextual facilitators and barriers to intervention 
implementation.91 Specific domains and constructs from CFIR were chosen to reflect the areas that were 
important to patients, intervention team members, and providers in the CASA pilot study.61  The following data 
sources will be used for Aim 2a: 
Intervention database:  The following data will be collected: (1) team meeting duration, number of patients 
discussed and time spent per patient, medical orders (e.g., tests, medications) written and completed; (2) 
nurse and social worker visit duration, number, and content (using a brief checklist) for each patient. 
Brief patient interviews: After the outcome measurement at 6 months, we will conduct brief in-person or 
telephone interviews with Veterans randomized to the intervention arm. Interviews will be conducted to elicit 
patient views about different parts of the intervention (e.g., nurse vs. social worker); how to improve the content 
and value of the intervention; communication and coordination; and to what extent they continue to su stain 
their use of the intervention after the study. We will continue to interview as staff time permits or until no new 
information emerges from continuing interviews, a principle known in qualitative research as “saturation.” 92  We 
will interview a subset of patients completing the intervention every 6 months in order to account for potential 

 
Palliative care to improve quality of life in CHF and COPD_Protocol_v_05.08.2018 
differences over time (e.g., intervention provider experience).   We will seek variability in the sample we 
interview (e.g., by sampling from both study sites and sampling patients who benefit the most and least from 
the intervention based on changes in the FACT-G score at 6 months or participant ratings of helpfulness). 
Interviews will be audio-recorded using a secure recording mechanism or an audio recording device. Detailed 
notes will be taken during the interviews.  Interviews will be transcribed verbatim by VA contracted transcription 
service or a member of the study team.  All interviews will be de-identified and all PHI/PII will be removed 
before transcribed.  
 
Intervention Close Out Summary:  This 1-page summary form will capture information from intervention 
providers on what worked well and not so well with components of the intervention, what was missing, and 
whether the patient engaged in and followed up with behavioral changes.   
 
Focused Group Discussion with Intervention Team:  The goal of this discussion is to elicit intervention team 
views about what worked well; what parts of the intervention might be streamlined, dropped or enhanced; and 
their views about patient, family caregiver, and PCP receptivity and responsiveness.  A qualitative researcher 
will lead these focused group discussions which will be recorded and transcribed  
Surveys of PCPs: Using a combination of rating scales and a few open-ended questions, the goal of these 
surveys is to efficiently identify strong positive or negative opinions about the usefulness of different 
intervention components, integration of the intervention into work flow, and the perceived impact of the 
intervention on quality of care.  We will also ask for their insights into ways to sustain and spread the 
intervention to other urban and rural VA sites.  The questions were selected to explore specific CFIR 
constructs of importance. Providers will complete the survey via phone, in-person, or via e-mail.     
 
Aim 2b: In addition to the above data collected for Aim 2a that are associated with the intervention content and 
processes, we will also use methods and instruments described in Ritzwoller et al 200993 to evaluate the 
resources and costs to implement and maintain the intervention.  These resources and costs will be measured 
from the perspective of each VA health care system site.  The rationale for this perspective is that each health 
care system (ECHCS and PSVAHCS) has budgetary and administrative authority over implementing programs 
such as the proposed intervention.  Resources associated with the program will be classified as labor (e.g., 
nurse intervention time) or non-labor (e.g., supplies, printing of patient materials) and recorded using Excel 
spreadsheets.  Costs for research (e.g., grant administration, IRB approvals, informed consent, analysis) will 
not be included. 
 
E.   Potential Scientific Problems:   
 
1.  Recruitment problems.  The recruitment goals are modest, reasonable for each site, and were planned 
based on the investigators experience with similar prior trials.  If necessary, resources can be diverted to 
increase efforts at one of the recruitment sites.  We can also add recruitment of inpatients at the sites’ VAMCs 
using the same enrollment criteria and conduct a sensitivity analysis to determine if outcomes are different for 
those recruited in this setting. 
2.  Limits of administrative data for the diagnosis of CHF, ILD, or COPD.  While the administrative codes used 
to identify patients with CHF or COPD have been validated, they are not perfect and some Veterans will be 
enrolled who do not have these illnesses.  However, all enrolled Veterans will be appropriate for the 
intervention because they will (1) be at high risk of hospitalization and death, (2) have poor quality of life, and 
(3) be symptomatic.  The team will recommend appropriate evaluation and management for all Veterans.  For 
example, this may include a spirometry test to evaluate for COPD if it was not previously done. 
3.  Palliative care elements such as spiritual care are not explicitly mentioned.  The palliative care specialist is 
on the team to bring all aspects of palliative care to patient care.  In addition, social workers have basic 
spiritual assessment and management skills.  If spiritual distress is identified, for example, the team can enlist 
assistance from a chaplain or the Veteran’s religious community.   

 
Palliative care to improve quality of life in CHF and COPD_Protocol_v_05.08.2018 
4.  If the intervention is not successful in showing improvements in any of the outcome measures, this will be 
an important, if undesired result, but study will still contribute to the evidence base regarding models of 
palliative care delivery.  The process monitoring will inform future interventions. 
5.  This is a personnel intensive intervention.  Compared to a traditional palliative care consultation in which a 
specialist palliative care team (physician, nurse, social worker, chaplain) all provide direct patient care, the 
intervention was designed to use much less personnel time.  Most of the intervention is delivered by phone.  
We will track the personnel time and other costs associated with the intervention (Aim 2b).   
 
 
 
F.   Data Analysis Plan:   
 
Aim 1 Data Analysis 
Descriptive Statistics and Basic Comparisons.  All analysis variables, including predictors, covariates, and 
outcomes, will be examined carefully prior to any formal statistical analysis. Standard graphical methods, 
including histograms and boxplots, will be used to examine overall distributions and identify potential outliers, 
which will be confirmed prior to inclusion in analysis. Internal consistency of multi-item scales will be examined 
using Cronbach’s alpha, and whenever possible, items and scales will be compared to existing findings on 
their psychometric properties to ensure appropriate performance.  Data transformations will be considered, 
such as log transformations for highly skewed data, to meet model assumptions. Each measure will be 
summarized using standard descriptive statistics, including means and standard deviations, medians, and 
ranges for continuous measures and proportions for categorical measures.  Baseline characteristics will be 
compared between groups using appropriate tests, such as Chi-square and t-tests.  
 
Primary/Secondary Analyses.  Data from all participants will be included regardless of level of participation 
using an intent-to-treat approach.  The primary outcome measure, FACT-G, will be analyzed as a continuous 
variable, while the secondary outcomes will be either continuous (disease-specific health status, depression, 
symptom burden, emergency department visits, hospitalizations) or binary (advance care planning 
communication and documentation; mortality).  Due to the short follow-up period, time-to-event analyses will 
not be used.  Analyses of the repeated measures, including primary and secondary endpoints, will be 
performed with SAS 9.4 using maximum likelihood estimation (MLE) for incomplete data using linear mixed 
models for continuous outcomes and generalized linear mixed models with a logit link for binary endpoints. 
This approach has several advantages: 1) all available data on eligible subjects can be included in the analysis 
even when there are missing data at follow-up, 2) MLE estimates the correlation between related measures 
and adjusts test statistics appropriately, 3) time-varying covariates can be incorporated into the model, if 
desired, and 4) the assumptions about missing data are relaxed from missing completely at random to missing 
at random.94  The primary analyses will not consider the pre-randomization variables, but the effect of these 
variables on outcomes will be investigated as secondary analyses.  We will add a random intercept for PCP to 
the analytic models to account for clustering of outcomes by practice patterns.   
 
The primary outcome will be the difference in FACT-G score at 6 months.  Because of the anticipated high 
correlation of baseline FACT-G with follow-up FACT-G (r>0.5), we will include the baseline FACT-G as a 
precision variable in the mixed model.95  To describe the treatment by disease interaction, we will estimate the 
treatment effect and its confidence interval within each of the disease groups (CHF, ILD, COPD) using 
disease-specific health status measures (KCCQ, K-BILD, CCQ) at the 6 month endpoint.  In exploratory 
analyses, we will estimate treatment effect within illness subgroups (CHF, ILD, and COPD) on the primary 
outcome, and within subgroups of illness, including CHF (preserved vs. reduced ejection fraction) and COPD 
(defined by spirometry and imaging).  Missing data will be reviewed to identify potential patterns and examined 
to assess how these patterns impact our results.  Specifically, we will examine plots of group means over time 
stratified by the time of the last completed observation to determine if biases are evident due to missing data.  
When data are missing at random, unbiased results can still be obtained from the likelihood method used in 
the analysis.  To account for the possibility of data missing not at random, sensitivity analyses will be 
performed using pattern mixture models96 and results will be presented to assess the impact of missing data 
on the reported conclusions.  Among those who were hospitalized or died, we will examine for differences in 

 
Palliative care to improve quality of life in CHF and COPD_Protocol_v_05.08.2018 
intensive care utilization and patterns of care at the end of life.  We will also examine for intervention effect on 
longer term health care utilization (e.g., hospitalization, intensive care utilization).  
 
Aim 2a Data Analysis 
The quantitative data on intervention component implementation will be examined using descriptive statistics.  
For example, for team meetings, the number and type of medical orders written and completed will be 
summarized.  For social worker visits, the median, range, interquartile range, and types of modules completed 
will be displayed.  This type of analysis was completed for the pilot study61 and will show what components of 
the intervention were actually done.  It will characterize the true “dose” and content of the intervention that was 
provided.  This will contribute information about what may have led to intervention success or failure. 
 
The data on intervention components and processes will be analyzed using a combination of inductive and 
deductive methods.  We will create an evolving set of codes linked to units of text (fragments, sentences or 
paragraphs) using the Atlas.ti software package.  A qualitative analyst and the research assistant will serve as 
primary coders for qualitative data, and PI will review coding and codebooks as they are developed.  We will 
follow a systematic process to enhance coder agreement in assigning codes and a peer debriefing process 
that requires regular meetings with a qualitative analyst, the PI, and the research assistant to review and refine 
codes, code definitions and conceptual boundaries for our analysis.97  The iterative analysis will begin by using 
the a-priori codes based on the CFIR model (Table 6), supplemented by codes reflecting intervention content 
and structure and questions used for data collection.  Codes will be refined and new codes added as new 
insights emerge.  Through systematic coding we will quickly develop working themes and hypotheses about 
critical intervention components and processes that will be examined (and inform any minor changes in data 
collection interview guides/survey).  These themes will also describe facilitators and barriers to intervention 
implementation.  We will both audio-record and take detailed notes during all data analysis meetings in order to 
document proposed codes and code revisions, proposed themes and their descriptions, and other decisions 
made during these working meetings.   
 
We will use several recommended strategies to enhance the validity or credibility of qualitative findings:92 (1) 
structured interview guides administered by well-trained interviewers, (2) coding templates and detailed 
descriptions of codes, coding decisions and analysis strategies to document all phases of the data analysis 
(audit trail); and (3) team approaches (at least two analysts) to develop coding templates and independently 
code subsets of transcripts/notes to determine their agreement and application of codes and code definitions.  
 
In addition to analyzing and summarizing quantitative (implementation tracking database and provider surveys) 
and qualitative (patient interviews and intervention team focus groups) findings separately, we will also merge 
findings to draw overarching lessons learned from multiple methods used.  In this process, findings will be 
summarized in a table placing qualitative themes side by side with the quantitative findings to show the extent 
to which the data converges.  Merging these findings will provide “triangulation”:  findings from each data 
source will be used to validate and confirm findings from the other data sources.  With the combination of 
qualitative and quantitative data, we expect to provide a more complete explanation of why certain intervention 
components and processes are more critical than others, as well as facilitators and barriers to the 
implementation of the intervention. 
 
Aim 2b Data Analysis 
We will first calculate the resources (personnel hours or FTE, and other costs) to implement and maintain the 
intervention during the study.  Personnel costs associated with the program will be calculated based on actual 
VA nurse (and other staff) wage and benefit rates.  Total intervention costs and costs per intervention 
participant at each site will be calculated.  Actual salaries and benefits will be used when calculating personnel 
costs.  Second, we will estimate the resources and costs to implement and maintain the program in a variety of 
VA settings.   
 
Several sensitivity analyses will estimate the range of intervention costs using alternative assumptions for 
costs that may vary in different implementation contexts.  Three sensitivity analyses are planned: (1) variable 
labor costs with more or less experienced nurses or physicians; (2) variable efficiency of the nurse and social 

 
Palliative care to improve quality of life in CHF and COPD_Protocol_v_05.08.2018 
worker in part-time vs. full-time intervention roles; this will be done using actual data that reflect the range of 
time spent per patient early in the study vs. later in the study; (3) variable patient case mix using the range of 
time spent per patient.  In exploratory analyses, we will estimate which patient-level predictors (e.g., cardiac 
ejection fraction, spirometry, quality of life) are associated with time spent per patient (outcome) using linear 
regression models. 
 
G. Summarize Knowledge to be Gained 
The proposed study is significant because it aims to improve quality of life and provision of care according to 
Veterans’ goals and preferences in common, burdensome illnesses. The study is innovative because it (1) 
tests the effectiveness of palliative care in CHF, ILD, and COPD, leading causes of death among Veterans; (2) 
combines palliative and disease-specific care for symptoms with psychosocial treatment for depression to 
improve quality of life; and (3) leverages the skills of affiliate health providers (nurses, social workers) to 
provide basic palliative care, with physician supervision; and (4) uses an hybrid effectiveness/implementation 
design to increase the relevance to operations leaders and future research. The research team has expertise 
in behavioral and health care delivery clinical trials, CHF, ILD and COPD, and implementation science. 
 
H. References: 
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