Comparative Effectiveness of Early Integrated Telehealth Versus In-Person Palliative Care for Patients With Advanced Lung Cancer
Phase: NA
Conditions: Lung Cancer
Sponsor: Massachusetts General Hospital

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Comparative Effectiveness of Early Integrated Telehealth versus In-Person Palliative 
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FINAL PROTOCOL 
 
Comparative Effectiveness of Early Integrated Telehealth versus In-Person Palliative 
Care for Patients with Advanced Lung Cancer 
DF/HCC SOCIAL-BEHAVIORAL RESEARCH PROTOCOL 
 
Lead Site: 
Massachusetts General Hospital (Boston, MA) 
Overall PI: Jennifer Temel, MD – MGH 
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01/30/2024 

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Section 1: Protocol Schema 
 
Patients with advanced NSCLC (N=1250) 
[and their caregivers] 
 
Baseline participant-reported measures 
 
Randomization 
Telehealth 
early palliative 
care (monthly 
telehealth 
visits) 
In-person 
early palliative 
care (monthly 
in-person 
visits) 
12, 24, 36, and 48 week participant-reported 
measures while patient is living 
 
Caregiver after death assessment three months 
after patient’s death 

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Section 2: Body of Protocol 
 
Contents 
Section 1: Protocol Schema .................................................................................................2 
Section 2: Body of Protocol .................................................................................................3 
1.0 
Introduction .......................................................................................................................6 
1.1 
Overview ....................................................................................................................6 
1.2 
Background and Rationale .........................................................................................6 
2.0 
Objectives ..........................................................................................................................9 
2.1 
Primary Aim ...............................................................................................................9 
2.2 
Secondary Aims .........................................................................................................9 
3.0 
Research Subject Selection ................................................................................................9 
3.1 
Patient Eligibility Criteria ........................................................................................10 
3.2 
Caregiver Eligibility Criteria ....................................................................................10 
4.0 
Research Subject Entry ....................................................................................................10 
4.1 
Patient Screening ......................................................................................................10 
4.2 
Participant Recruitment and Enrollment ..................................................................11 
4.3 
Informed Consent Process ........................................................................................11 
4.4 
Baseline Completion and Registration .....................................................................12 
5.0 
Study Design and Methods ..............................................................................................13 
5.1 
Study Design ............................................................................................................13 
5.2 
Selection of Instruments ...........................................................................................13 
5.3 
Description of Intervention ......................................................................................16 
5.4 
Data Collection .........................................................................................................19 
5.4.1 
Data from Electronic Health Record: .......................................................................20 
5.4.2 
Data on PC Visits and Resource Utilization: ...........................................................20 
5.4.3 
Data Storage .............................................................................................................21 
5.5 
Description of Study Processes ................................................................................21 
5.6 
Adverse Reactions and their Management ...............................................................26 
6.0 
Ethical and Legal Issues ..................................................................................................27 
6.1 
Confidentiality ..........................................................................................................27 
7.0 
Statistical Analysis ..........................................................................................................27 
7.1 
Primary Endpoint .....................................................................................................27 
7.2 
Secondary Endpoints ................................................................................................28 
7.3 
Exploratory Endpoints ..............................................................................................28 
7.4 
Sample Size and Power Calculation .........................................................................28 
7.5 
Analysis Plan ............................................................................................................29 
7.6 
Handling of Missing Data ........................................................................................32 
8.0 
Disseminating the Study Results .....................................................................................32 

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9.0 
References ...................................................................................................................... 34 
10.0 Appendices ..................................................................................................................... 37 
10.1 
Instruments for Patients in English ..................................................................... 37 
10.2 
Instruments for Caregivers in English ................................................................ 51 
10.3 
Instruments for Patients in Spanish .................................................................... 61 
10.4 
Instruments for Caregivers in Spanish ............................................................... 75 
10.5 
Suggested Clinician Permission Email ................................................................ 84 
10.6 
Suggested Voicemail for Contacting Participants to Offer Enrollment ........... 84 
Suggested ................................................................................................................ 84 
10.7 
Verbal Telephone Conversation for Questionnaire Administration ................ 84 
10.8 
Suggested Paper Cover Letter when Mailing the Baseline Questionnaire to 
Prospective Participants ..................................................................................................... 85 
10.9 
Suggested Paper Cover Letter when Mailing the Follow Up Questionnaires to 
Participants .......................................................................................................................... 85 
10.10 
Suggested Email Cover Letter when Emailing the Baseline Questionnaire to 
Prospective Participants ..................................................................................................... 86 
10.11 
Suggested Email Cover Letter when Emailing the Questionnaires to 
Participants .......................................................................................................................... 87 
10.12 
Suggested Email Cover Letter when Contacting the Caregiver ....................... 87 
10.13 
Suggested Email Cover Letter when Emailing Patients in Telehealth Group 87 
10.14 
Suggested Email for Caregivers Joining the Video Visit Remotely .................. 88 
10.15 
Suggested Email with 3rd Party Appointment Link for Caregivers Joining the 
Video Visit Remotely ........................................................................................................... 89 
10.16 
Data Safety and Monitoring Plan ........................................................................ 90 
10.17 
REACH PC Study Overview ................................................................................ 93 
10.18 
REACH PC Study Overview – Spanish .............................................................. 94 
10.19 
Dana Farber Cancer Center Data Safety Monitoring Plan .............................. 95 
1. 
INTRODUCTION ................................................................................................... 96 
1.1 
Purpose ........................................................................................................................... 96 
1.2 
Multi-Center Data and Safety Monitoring Plan Definitions ........................................... 96 
2. 
GENERAL ROLES AND RESPONSIBILITIES ................................................... 97 
2.1 
DF/HCC Sponsor ............................................................................................................ 97 
2.2 
Coordinating Center ....................................................................................................... 97 
2.3 
Participating Institution .................................................................................................. 98 
3. 
DF/HCC REQUIREMENTS FOR MULTI-CENTER PROTOCOLS ................... 98 
3.1 
Protocol Distribution ...................................................................................................... 98 
3.2 
Protocol Revisions and Closures .................................................................................... 99 
3.3 
Informed Consent Requirements .................................................................................... 99 
3.4 
IRB Documentation ........................................................................................................ 99 
3.5 
IRB Re-Approval .......................................................................................................... 100 
3.6 
Participant Confidentiality and Authorization Statement ............................................. 100 
3.7 
DF/HCC Multi-Center Protocol Registration Policy .................................................... 100 
3.8 
DF/HCC Protocol Case Number .................................................................................. 101 
3.9 
Safety Assessments and Toxicity Monitoring .............................................................. 102 

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3.10 Data Management .......................................................................................................... 102 
4. 
MONITORING: QUALITY CONTROL .............................................................. 103 
4.1 
Ongoing Monitoring of Protocol Compliance ............................................................... 103 
4.2 
Monitoring Reports ....................................................................................................... 103 
4.3 
Accrual Monitoring ....................................................................................................... 104 
5. 
AUDITING: QUALITY ASSURANCE ................................................................ 104 
5.1 
DF/HCC Internal Audits ................................................................................................ 104 
5.2 
Audit Notifications ........................................................................................................ 104 
5.3 
Audit Reports................................................................................................................. 104 
5.4 
Participating Institution Performance ............................................................................ 104 

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1.0 
Introduction 
1.1 
Overview 
Early and longitudinal involvement of palliative care (PC) in the outpatient management 
of patients with advanced cancer improves patient-reported and end of life (EOL) care 
outcomes. While recommended by national organizations as the standard of care, this 
early integrated care model utilizes substantial PC resources, which has limited its 
dissemination across care settings. Telehealth (i.e., the use of information and 
communication technology in health care delivery) is an effective strategy to increase 
patients’ access to health care services when the numbers of specialty-trained clinicians 
are limited.1 We seek to perform a multi-site comparative effectiveness trial of early 
integrated telehealth versus in-person PC in patients with advanced lung cancer. By 
demonstrating the equivalence of the telehealth delivery modality, we seek to define a 
role for this more accessible, scalable and patient-centered approach to PC. 
 
1.2 
Background and Rationale 
Early Integrated PC Improves Patient-Reported and End of Life Care Outcomes 
Over the past decade, a growing body of evidence has supported a new role for PC 
clinicians in the outpatient management of patients with advanced cancer.2-9 For example, 
Bakitas conducted a randomized trial comparing a telephone-administered PC psycho- 
educational intervention with usual care in patients with newly diagnosed poor prognosis 
cancers, which demonstrated improvements in quality of life (QOL) and mood.3 In two 
additional trials, investigators evaluated in-person interventions administered by PC- 
trained clinicians. Specifically, Zimmermann evaluated a four-month intervention 
involving monthly outpatient PC visits in patients with poor prognosis cancers, 
demonstrating improvements in QOL, symptom burden and satisfaction, compared with 
usual care.6 Similarly, in our trial of patients with newly diagnosed advanced non-small 
cell lung cancer (NSCLC), monthly visits with PC throughout the course of illness 
(“early integrated PC”) improved patient-reported QOL and depression, compared with 
usual care.7 Notably, this study also demonstrated improvements in the delivery of EOL 
care with early integrated PC including greater documentation of EOL care preferences, 
longer length of stay in hospice, and less chemotherapy administration near death.10 More 
recently, we completed a larger efficacy trial of the early integrated PC model in patients 
with advanced cancers, which confirmed prior findings and also demonstrated that the 
intervention led to an increase in patient-clinician communication about EOL care 
preferences.11 While both telephone-based and brief duration in-person PC interventions 
improve patient-reported outcomes, only early integrated PC enhances communication 
and decision-making about EOL care. 
 
Early Integrated PC also Improves Outcomes in Caregivers of Patients with 
Advanced Cancer 
The practice of PC encompasses the psychosocial, emotional, and spiritual care needs of 
both patients and their caregivers. In our recent trial of early integrated PC in patients 
with advanced lung and gastrointestinal cancers, we invited caregivers of enrolled 
patients to participate in a secondary study evaluating the impact of this care model on 
caregiver-reported outcomes. The results showed that the caregivers of patients assigned 
to early PC had improvements in several QOL domains and lower depression.12 

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Moreover, even in the months closer to the patient’s death, the caregivers of patients 
receiving early PC reported lower depression and anxiety compared to those receiving 
usual care.12 Thus, early integrated PC improves the experience and outcomes of not only 
patients with advanced cancer but also their caregivers. 
 
Most Cancer Care Settings Lack Capacity to Provide Guideline-Concordant, 
Patient-Centered Early Integrated PC 
Based largely on the data described above, the American Society of Clinical Oncology 
(ASCO) published an Opinion Statement in 2012 recommending early PC for any patient 
with advanced cancer.13 Similarly, the Institute of Medicine and the National 
Comprehensive Cancer Network recommend consideration of early PC for patients with 
advanced cancers.14,15 By recognizing the value of PC for patients with advanced cancer, 
these recommendations represent significant progress in the delivery of comprehensive 
cancer care. However, the early integrated PC model studied to date included at least 
monthly visits with a PC clinician. Currently, most cancer care settings have insufficient 
outpatient PC services to provide this level of care to all patients with advanced cancer. 
Additionally, many individuals receiving cancer care in remote, resource-poor, and rural 
settings have no access to PC services.16 Therefore, to provide guideline-concordant care, 
further research is critically needed to evaluate novel PC delivery models that increase 
patients’ access to PC services in a patient-centered fashion.17 
 
Patients with advanced cancer and their caregivers are burdened by frequent visits for 
oncology care, chemotherapy and radiation treatment, and radiographic studies. To 
address this, patients receiving early integrated PC typically meet with both their 
oncology and PC clinicians on the same day to help minimize additional trips to the 
cancer clinic. Yet, few institutions have sufficient numbers of PC clinicians, outpatient 
clinic space or support staff to provide such care in accordance with recommended 
guidelines.17,18 If PC is to be delivered in a patient-centered fashion, novel models of 
service delivery are needed to reduce the burden of additional clinic visits, given 
transportation costs and disruptions to home and work schedules of both patients and 
their caregivers. While home-based PC models are being developed as an alternative to 
in-person clinical services, home care requires an even greater number of clinicians and is 
generally not feasible for remote areas where travel time would be prohibitive.19 
Therefore, the study of innovative service delivery models has the potential to increase 
access and efficient utilization of limited PC resources in a patient-centered fashion. 
 
Telehealth Increases Access and Efficiency with Limited Health Care Clinicians and 
Resources 
Telehealth (i.e., the use of information and communication technology in health care 
delivery) is an effective strategy to increase patients’ access to health care services when 
the numbers of specialty-trained clinicians are limited.1 Initially developed as a means to 
provide specialized care to patients with acute conditions such as stroke, telehealth 
services are expanding to the care of patients with chronic health conditions, especially 
given the growing interest among health care stakeholders such as physician 
organizations, health care systems, and insurance providers.20,21 To date, telehealth for 
patients with chronic conditions has focused predominantly on asynchronous monitoring, 

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such as collecting vital signs of patients with congestive heart failure in the home setting 
and transmitting the information to clinicians.22 However, health care stakeholders now 
recognize the need for the practice of medical care by clinicians through telehealth as a 
means to provide patient-centered care for patients in their homes.23 A recent Cochrane 
review concluded that further research is needed to evaluate the effectiveness, efficiency 
and appropriateness of telemedicine.24 
 
Telehealth enables clinicians to perform virtual house calls to provide patients “the care 
they need, the convenience that they desire, and the comfort they want.”25 Studies of 
telemedicine using video house calls with clinicians for patients with chronic health 
conditions, such as Parkinson’s disease and diabetes, have demonstrated the feasibility, 
acceptability and preliminary efficacy of this delivery model.26,27 While the use of video 
house calls has yet to be studied in the context of PC, Bakitas and colleagues evaluated 
telephone-based, psycho-educational interventions, delivered by PC-trained advanced 
practice nurses, for patients with advanced cancer and their caregivers.3-5 The 
investigators observed an improvement in QOL and lower depression among patients 
with newly diagnosed poor prognosis cancers as well as lower depression in caregivers; 
however, the intervention did not increase rates of advance care planning or utilization of 
PC and hospice services.3 Although these studies demonstrate the feasibility of providing 
such services via telehealth, the intervention failed to improve salient PC outcomes, 
including communication about EOL care preferences or the delivery of high quality 
EOL care. In contrast, the in-person early integrated PC model, which could be 
efficiently adapted to a video telehealth platform, is associated with improved patient- 
clinician communication and EOL care outcomes. 
 
Lung Cancer is an Ideal Population in which to Study Early PC Models 
The strongest evidence base supporting early integrated PC is among patients with 
advanced lung cancer, with two randomized trials demonstrating significant 
improvements in QOL, mood, and EOL care.7,28 However, treatment paradigms for 
patients with advanced lung cancer are changing rapidly.29 Approximately one-third of 
patients with metastatic lung cancer have gene mutations or fusions that predict responses 
to targeted oral therapies or express PDL1 and have tumor shrinkage with immune 
checkpoint inhibitors, both of which can portend a prognosis of several years.30-35 Despite 
these advances, the majority of patients with advanced lung cancer do not respond to 
novel therapies and have a median survival of approximately one year.36 Moreover, these 
patients often experience a high symptom burden and poor QOL at diagnosis, which 
intensifies throughout their illness course.37 
 
Scientific Premise of the Project 
We propose to transform the delivery modality of our proven efficacious in-person early 
integrated PC model to a telehealth platform, thereby enabling PC clinicians to provide 
virtual house calls and increase access to services in a patient-centered manner. If the 
proposed study demonstrates that telehealth is as effective as (or superior to) in-person 
PC, such findings would address a major evidence gap between the data supporting early 
integrated PC and lack of data regarding how to disseminate this care model most 
efficiently, equitably, and effectively. The 2016 ASCO Clinical Practice Guideline 

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Update on the integration of palliative and oncology care highlights this evidence gap by 
not only making a strong recommendation for early PC for patients with advanced 
cancer, but also acknowledging that PC resources are currently lacking to provide this 
essential care.38 
 
2.0 
Objectives 
2.1 
Primary Aim 
To determine whether telehealth PC is equivalent to in-person PC for improving patients’ 
QOL. 
 
Hypothesis: Patients assigned to telehealth PC will report QOL that is equivalent to 
patients receiving in-person early integrated PC, with an equivalence margin of 4.0 points 
on the Functional Assessment of Cancer Therapy-Lung (FACT-L). 
 
2.2 
Secondary Aims 
2.2.1 To determine whether telehealth PC is equivalent to in-person PC with 
respect to patient-clinician communication about EOL care preferences 
and length of stay in hospice. 
 
Hypothesis 1: Telehealth will be equivalent to in-person PC in the rate by 
which patients communicate their EOL care preferences to their clinicians, 
with an equivalence margin of 8%. 
Hypothesis 2: Telehealth PC will be equivalent to in-person PC with 
respect to patients’ length of stay in hospice, with an equivalence margin 
of 6 days. 
 
2.2.2 To compare the effect of telehealth versus in-person PC on caregiver 
participation in PC visits. 
 
Hypothesis 1: Compared to caregivers receiving in-person PC, those 
receiving telehealth PC will participate in a higher percentage of visits 
with the PC clinician. 
 
2.2.3 To compare patient and caregiver satisfaction with telehealth versus in- 
person PC. 
 
Hypothesis: Patients and caregivers will be more satisfied with telehealth 
PC compared to in-person early integrated PC. 
 
2.3 
Exploratory Aims 
2.3.1 To compare coping strategies in patients assigned to telehealth versus in- 
person PC. 
2.3.2 To compare prognostic understanding in patients and caregivers assigned 
to telehealth. 
2.3.3 To compare the effect of telehealth versus in person PC on caregivers’ 

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outcomes, including QOL and mood. 
2.3.4 To compare the effect of telehealth versus in-person PC on patients’ 
mood. 
 
3.0 
Research Subject Selection 
We will recruit 1250 patients with advanced NSCLC and up to 1250 of their caregivers 
(2500 total) receiving their care at Massachusetts General Hospital and Palliative Care 
Research Cooperative (PCRC) designated institutions to participate in a multi-site 
comparative effectiveness trial of early integrated telehealth versus in-person PC in 
patients with advanced lung cancer. Patients without willing or available caregivers are 
still eligible to participate in the study. Patients will be randomized using blocked 
randomization and stratified by site. 
 
3.1 
Patient Eligibility Criteria 
Inclusion Criteria: 
The patient eligibility criteria will mirror those of our prior early PC studies in this 
patient population. 
1. 
Diagnosed with advanced NSCLC being treated with non-curative intent, and 
informed of advanced disease within the prior twelve weeks 
2. 
Eastern Cooperative Oncology Group (ECOG) Performance Status from 0 
(asymptomatic) to 3 (symptomatic and in bed >50% of the day) 
3. 
The ability to read and respond to questions in English or Spanish 
4. 
Receiving primary cancer care at one of the participating sites 
5. 
Age > 18 years 
Exclusion Criteria: 
Patients will be excluded if: 
1. 
They are already receiving outpatient PC or hospice services 
2. 
They have cognitive or psychiatric conditions as determined by the treating 
oncologist to prohibit study consent or participation 
 
3.2 
Caregiver Eligibility Criteria 
Inclusion Criteria: 
The caregiver eligibility criteria will mirror those of our prior early PC studies in this 
patient population. 
1. Relative or friend who is identified by the patient participant and lives with the 
patient or has contact with them at least twice per week. 
2. The ability to read and respond to questions in English or Spanish 
3. Age > 18 years 
 
Exclusion Criteria: 
1. They have cognitive or psychiatric conditions as determined by the treating 
oncologist to prohibit study consent or participation 
 
4.0 
Research Subject Entry 
4.1 
Patient Screening 
At all participating sites, the research team will screen all patients presenting to the 

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outpatient thoracic oncology clinic for study participation. By reviewing the electronic 
scheduling system and health record to determine cancer stage and treatment goals, the 
research team will identify all patients with advanced NSCLC who are not being treated 
with curative intent. This determination will be made based upon stage of disease and the 
designated treatment goal in the chemotherapy treatment plan or health record, as some 
patients with locally advanced disease cannot be treated for cure and some patients with 
metastatic disease are treated with curative intent. If the determination about treatment 
intent cannot be determined based upon the chemotherapy plan or documentation in the 
health record, the research team will confer with the oncology team about the goals of 
cancer treatment. We will institute the same patient screening procedures in all 
participating thoracic oncology clinics. 
 
We are requesting a HIPAA Waiver of Authorization to Review Preparatory to Research 
from the Institutional Review Board (IRB). This waiver is being requested to allow the 
research team to screen the thoracic oncology clinic schedules and identify potential 
study participants from a minimal chart review. In accordance with the DF/HCC policy, 
this Waiver: (1) is being sought solely to review Protected Health Information as 
necessary to prepare a research protocol; (2) will not include removing Protected Health 
Information from the Covered Entity by the researcher, and (3) the Protected Health 
Information for which we are requesting access is necessary for research purposes. 
 
4.2 
Participant Recruitment and Enrollment 
We will use the same recruitment and enrollment procedures used in our previous and 
ongoing trials.7,28 Prior to the study start, site investigators will meet with their respective 
thoracic oncology teams to review recruitment and enrollment procedures. Specifically, 
the research team will send an email (see appendix) to the oncology clinicians to notify 
them when their patients appear to be eligible for study participation. If an oncology 
clinician reports that the patient is being treated with curative intent or otherwise does not 
meet eligibility criteria, the research team will document the reason. 
 
4.3 
Informed Consent Process 
Either research team member or the oncology clinician can review the study details, offer 
study participation, and obtain informed consent in-person or verbally. Both the written 
and the verbal consent forms describe all study procedures, information about potential 
risks and benefits of participation, and information regarding who they can contact for 
further questions. The forms also state that participation is voluntary, that participants can 
refuse to answer any questions, that they can withdraw from the study at any time, and 
that study participation is in no way related to their medical care. Study participants who 
do not provide consent will be asked the reason why they prefer to not participate in the 
study. 
 
4.3.1 In-Person Informed Consent Process 
Willing participants will be presented with a detailed, HIPAA-compliant consent form 
and given the opportunity to sign written informed consent either with the research team 
member or their oncology clinician. 
 
Patients who speak Spanish will have all study procedures and information regarding 

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risks, benefits and study contacts explained to them verbally by a Spanish-speaking 
research team member or via the use of an interpreter as a first preference, or family 
member as a second preference. Spanish speaking participants may be given the 
institutional Spanish consent short form for signing, as well as a copy of the full English 
consent form for their own reference. The Spanish consent short form will be signed by 
the participant and by a witness. The witness will be either an interpreter, a Spanish- 
speaking research team member or a family member. Spanish speaking participants will 
be provided with Spanish-version baseline demographic and study questionnaires. 
 
4.3.2 Verbal Informed Consent Process 
We are requesting a Waiver of Written Documentation of Consent. This study meets the 
requirements for a waiver as it is a Minimal Risk study and all study procedures can be 
communicated verbally. This Waiver will allow research team member to recruit 
participants remotely to address barriers to study enrollment including infrequent in- 
person visits, lack of space in clinic, and patients’ time constraints. All patients who 
provide verbal consent will receive an unsigned copy of the written informed consent. 
 
The research team member or an oncology clinician may contact eligible, English 
speaking patients via telephone to obtain verbal consent using the HIPAA-compliant 
verbal consent form. Verbal consent procedures will not apply to Spanish speaking 
patients. If the patient does not answer the telephone, the clinician or research team 
member may leave a voicemail (see appendix). 
 
4.4 
Baseline Completion and Registration 
Patients will be asked to complete baseline demographic and study questionnaires in 
person, online, or over the telephone with a research team member on the day of consent. 
Patients will be registered for the study and randomized once the baseline demographic 
and study questionnaires are completed. If patients do not complete the baseline 
demographic and study questionnaires (either on paper in the clinic or at home, via email, 
or via telephone) within two weeks of signing informed consent or completing the verbal 
consent process, they will not be permitted to be enrolled on the study. 
 
The research team will collect data from each patient who enrolls about whether they 
have a person who would fit the criteria to be an enrolled caregiver, and this data will be 
recorded for all enrolled participants. As caregivers are often not present at every clinic 
appointment, they will be eligible to consent, either in person or via telephone, for the 
study on the day that the patient is registered for the study and for four weeks thereafter. 
Caregivers will be asked to complete the baseline demographic and study questionnaires 
on the day of consent. If caregivers do not complete the baseline demographic and study 
questionnaires (either on paper in the clinic or at home, via email, or via telephone) 
within two weeks of signing informed consent or completing the verbal consent process, 
they will not be permitted to be enrolled on the study. However, patients may remain on 
study even if their caregiver is not eligible or does not remain on study. The research 
team may share the one-page study information sheet (see appendix) with the patient or 
caregiver to learn about the study as they decide to participate. 
 
If the patient or caregiver requests additional information about palliative care, the 

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clinician or research team member may provide a brochure about palliative care, such as 
institutionally approved materials, the National Institute of Nursing Research brochure 
“Palliative Care: The Relief You Need When You Have a Serious Illness” or the Center 
to Advance Palliative Care brochure “Palliative Care: What You Should Know”. This 
additional information is meant to be a resource for potential study participants who are 
interested in learning more about palliative care. 
 
If either the patient requests that we do not approach or contact the caregiver to 
participate in the study or if the caregiver defers study participation, the research team 
will document the reason. The clinician or research team member will also review the 
study procedures and consent form with caregivers and obtain written informed consent 
or verbal consent. 
 
DF/HCC institutions will register eligible participants from all sites in the Clinical Trials 
Management System (CTMS) Oncore, as required by DF/HCC SOP REGIST-101. 
Registration must occur prior to the initiation of protocol-specific procedures or 
assessments. 
 
For registration of patients from DF/HCC institutions, the research team will complete 
the protocol-specific eligibility checklist using the eligibility assessment documented in 
the participant’s medical record and/or research chart. The research team will confirm 
that the participant meets all inclusion criteria as described in this protocol and the 
criteria on the eligibility checklist. 
Patients from other participating sites will be entered on the study centrally by the MGH 
research team. The research team from the participating institution will confirm 
eligibility criteria and fax or email the following documents to the research team at 
MGH: deidentified signed consent form/s or deidentified verbal consent form/s, copy of 
baseline assessment, and a completed eligibility checklist. The MGH research team will 
follow DF/HCC Standard Operating Procedure for Human Subject Research Titled 
Subject Protocol Registration (SOP #: REGIST-101) and register the participant on the 
protocol. Once the patient has been registered, a member of the MGH research team 
(independent from research team member who recruit, enroll and administer assessments 
to participants) will perform randomization procedures using on a computer-generated 
randomization schema, stratified by study site. The MGH research team will fax or e- 
mail the information about randomization to the research team at the participating site. 
The MGH research team may also call the research team at the participating site to 
verbally confirm registration and randomization. 
 
Study participants will not be compensated for their participation in the research study. 
 
5.0 
Study Design and Methods 
5.1 
Study Design 
We will conduct a randomized comparative effectiveness trial of early integrated 
telehealth versus in-person PC in patients with advanced lung cancer and their caregivers. 
 
5.2 
Selection of Instruments 

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We selected instruments based on our prior studies and the theoretical framework of our 
intervention, which seeks to improve patients’ QOL, illness understanding, use of 
adaptive coping strategies and ultimately communication and delivery of EOL care. The 
research team will administer study assessments at baseline and multiple follow-up time 
points from the date that the baseline surveys were completed (with a +/- two-week 
window) to accommodate patient schedules (see table of Self Report Measures). The 
selected self-report measures have strong psychometric properties and have been well 
validated in previous studies. All study measures are available in both English and 
Spanish, except the Self-Administered Comorbidity Questionnaire, Prognosis and 
Treatment Perceptions Questionnaire, Caregiver Oncology QOL Questionnaire, 
Satisfaction with Care Delivery Questionnaire, and After Death Assessment, which we 
translated (forward and backward) into Spanish with a native Spanish speaking clinician. 
 
Patient Measures: 
Demographic Questionnaire: Participants will self-report their gender, race/ethnicity, 
marital status, religion, education level, employment status, tobacco use, computer 
experience, travel time and transportation mode to the cancer center, and health insurance 
co-payment charge. 
 
Self-Administered Comorbidity Questionnaire (SCQ): Medical comorbidity will be 
assessed at baseline with the Self-Administered Comorbidity Questionnaire.39 Patients 
will report on the presence of twelve comorbidities such as heart disease, lung disease, 
diabetes and arthritis. They will also have the option of reporting up to three further 
unlisted comorbidities and will be assigned a comorbidity score ranging from 0-45. 
 
Functional Assessment of Cancer Therapy-Lung (FACT-L): The FACT-L is a 35-item 
QOL tool that assesses physical, social/family, emotional, and functional well-being, as 
well as lung cancer specific symptoms over the past 7 days.40 We have used this measure 
in three prior PC trials in patients with lung cancer, demonstrating that early involvement 
of PC improves FACT-L scores.7,11 
 
Hospital Anxiety and Depression Scale (HADS): The HADS is a 14-item questionnaire 
that contains two 7-item subscales assessing depression and anxiety symptoms during the 
past week. 41 
 
Patient Health Questionnaire-9 (PHQ-9): The PHQ-9 is a nine-item measure that 
evaluates symptoms of major depressive disorder according to the criteria of the 
Diagnostic and Statistical Manual of Mental Disorders, which can be scored 
continuously or categorically.42 
 
Brief Cope: The Brief Cope is a 28-item questionnaire that assesses methods of coping 
(e.g., active, acceptance, denial) using a 4-point Likert scale ranging from 1 “a lot” to 4 
“never.”43 The psychometric properties of the Brief Cope have been demonstrated in 
studies of patients with serious illness and cancer.43,44 For our prior study, to minimize 
questionnaire burden, we solicited feedback from our research and PC teams about the 
coping strategies most likely to be influenced by our early PC intervention. We chose to 
exclude items such as self-distraction, substance use, and venting. We will limit our 

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evaluation to eight coping strategies (16-items) deemed most relevant for the study (i.e., 
emotional support, positive reframing, active coping, acceptance, self-blame, denial, 
spiritual coping and behavioral disengagement). 
 
Support Service Utilization: At the 24-week primary endpoint, patients will be 
administered a single item assessing mental healthcare utilization since diagnosis. This 
item is designed to capture information which is routinely missing from the health record, 
as patients often either receive mental health services external to the hospital or access 
services which are not routinely documented in the electronic health record (EHR). 
 
Prognosis and Treatment Perceptions Questionnaire (PTPQ): The PTPQ is a tool that 
assesses patients’ (and their caregivers’) illness understanding, communication about 
prognosis and goals of care, as well as discussions and preferences regarding EOL care.45 
The PTPQ includes the item: “Have you discussed any particular wishes you have about 
the care you would want to receive if you were dying?” (Yes/No). This item has been 
previously used to assess EOL communication in patients with cancer.46 
 
The Satisfaction and Care Delivery Questionnaire: is a 13-item satisfaction questionnaire 
which assesses patients’ satisfaction with their PC visits. This questionnaire is adapted 
from the Visit-Specific Satisfaction Instrument (VSQ-9).47 Each response item is given a 
score of 0-4 and items are summed together to obtain a composite satisfaction score. This 
will be given starting at week 12. 
Caregiver Measures: 
Demographic Questionnaire: Caregivers will report their age, gender, race/ethnicity, 
marital status, religion, education level, relationship to the patient and travel time to the 
cancer center. 
 
Caregiver Oncology QOL Questionnaire (CARGOQOL): The CARGOQOL is a 29-item, 
well-validated instrument to measure caregiver QOL in multiple domains.48 
 
HADS: The HADS is a 14-item questionnaire that contains two 7-item subscales 
assessing depression and anxiety symptoms during the past week. 41 
 
PTPQ: The caregiver PTPQ is a tool that assesses caregivers’ perceptions of their loved 
ones’ illness and prognosis and their communication with their doctors about their 
prognosis and EOL care preferences.45 
 
The Satisfaction and Care Delivery Questionnaire (for caregivers): is a 12-item 
satisfaction questionnaire which assesses caregivers’ satisfaction with the PC visits. This 
questionnaire is adapted from the Visit-Specific Satisfaction Instrument (VSQ-9).47 Each 
response item is given a score of 0-4 and items are summed together to obtain a 
composite satisfaction score. This will be given starting at week 12. 

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After Death Assessment: We will ask family caregivers to rate care in the last week of 
life using a 10-point scale for (1) quality of patient’s death (ranging from “worse 
possible” to “best possible); (2) physical distress (ranging from “none” to “extremely 
distressed”); and (3) psychological distress (ranging from “none” to “extremely upset”).46 
 
5.3 
Description of Intervention 
5.3.1 Multi-site research team training 
To ensure vigorous recruitment and enrollment, all study lead PC investigators and 
research team members will participate in a one-day in-person training session in Boston. 
The MGH-based investigative team has conducted seven prior and ongoing PC trials in 
oncology. Thus, we have considerable experience training research teams to: (1) identify 
potentially eligible patients via chart review, (2) track potentially eligible patients until 
their cancer diagnosis is documented, (3) communicate with oncology clinicians about 
patient eligibility, (4) obtain written informed consent or verbal consent from patients and 
caregivers, (5) monitor patients and caregivers longitudinally to administer study 
questionnaires, (6) collect data from the health record, and (7) enter all study data into the 
study specific database. The MGH investigators developed a training program for the site 
investigators and research teams on how to collaborate with oncology clinicians to 
implement this trial successfully. 
 
We will draw on these experiences to conduct a one-day training session with the lead 
research team members (led by our MGH PC Research Project Manager Chardria 
Trotter) and site investigators (led by Drs. Temel, Jackson and Greer). The MGH 
TeleHealth Program will also participate in this one-day in-person session to educate the 
lead investigators on utilizing telehealth for virtual home visits and the research teams on 
training patients and clinicians to use the technology. 
 
Finally, we will facilitate quarterly teleconference calls with the site investigators and 
monthly calls with research team members to ensure vigorous recruitment and address 
any implementation challenges. Ms. Trotter will lead the teleconference calls with the 
research teams to address any difficulties with patient identification, recruitment, 
enrollment, and data collection. The MGH based study investigators will lead the 
teleconference calls with the site investigators to address any issues with study 
implementation as well as perform site visits as necessary to provide more direct 
assistance with study issues. The PCRC has extensive experience overseeing multi-site 
trials and will also support participating institutions through email communication, 
teleconference calls, and site visits throughout the study. To conduct this study with 
established research principles, site visits may be conducted during the study to evaluate 
study conduct. Sites will be monitored by the PCRC for patient enrollment, compliance 
with protocol procedures, completeness and accuracy of data entered, and the occurrence 
and reporting of any study related challenges. 
 
5.3.2 Telehealth Arm 
The research team will contact patients randomized to telehealth within three business 
days of enrollment to inquire if they have video capacity (camera and sufficient internet 
connection) for telehealth visits. Patients who do not have video capacity will be sent a 

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tablet with cellular service, which will be programmed for secure videoconferencing 
only. Upon request, patients may receive an instructional guide on how to operate the 
tablet device and currently approved telehealth software. The research team will contact 
patients (and caregivers who wish to participate in the telehealth visits from a separate 
location) to conduct a videoconference test call prior to the first telehealth PC visit. Any 
patients whose equipment is not sufficient for the videoconference platform will be sent 
the study iPad with cellular service. Caregivers at other locations from the patient 
wishing to join telehealth visits will be required to use their own video and cellular 
service. 
 
Video visits will be conducted using any HIPAA-compliant vendor that is licensed for 
clinical use and meets institutional informational security regulations. Sites will practice 
in accordance with their institutional policies for practicing medicine via telehealth across 
state lines. Sites will be encouraged, but not required to use the video visit platform 
supported by MGH. If sites chose to utilize a non-MGH supported video visit platform, 
they must obtain approval from the MGH study team. 
 
The first visit with the PC clinician will be conducted in person in the oncology clinic 
within four weeks of enrollment to enable the patient and clinician to establish rapport. 
All subsequent visits will take place in patients’ homes (or the setting of their choice) via 
telehealth at least every four weeks until death. Patients admitted to rehabilitation or 
skilled nursing facilities should continue to have contact with PC via telehealth at least 
every four weeks if possible. PC can continue to perform at least monthly telehealth 
visits with patients receiving hospice services, at their discretion. PC clinicians may see 
patients more frequently than every four weeks at their discretion. Patients scheduled to 
meet with PC clinicians who do not speak their native language will be seen in 
conjunction with an interpreter service used by the hospital or with a family member or 
friend who speaks the language. As PC and oncology clinicians will not be meeting 
patients in the same location, the PC clinician should make every effort to communicate 
with the oncology clinicians via email or telephone or in person after each patient 
encounter. 
 
If technical problems occur with the telehealth technology during a patient’s scheduled 
virtual visit, then the PC clinician should immediately switch to calling the patient and 
conducting the visit via telephone. The PC clinician should notify the research team to 
address the technical issue prior to the patient’s next scheduled telehealth appointment. 
 
Patients may be scheduled to meet with the PC clinician in the clinic if requested by the 
patient or a clinician. If a patient has an in-person visit with the PC clinician, they will 
still be scheduled for their telehealth visits every four weeks. 
 
If a patient defers telehealth visits but is still participating in the study, they should 
continue to have in-person or telephone contact with the PC clinician at least every four 
weeks. The patient should be encouraged to reinitiate telehealth visits by the PC clinician 
or research team when possible. 

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Participating sites are not required or prohibited from submitting claims for telehealth 
visits. Submitting claims for telehealth visits will be at the discretion of the participating 
institution and should comply with state and federal laws and regulations that govern the 
practice of medicine. However, sites that choose to submit claims must ensure that 
patients are not charged in excess of their insurance copayment. Participating sites are 
required to ascertain their state laws and regulations that govern the practice of medicine, 
as this is not the responsibility of the funding agency (PCORI) or lead study site (MGH). 
 
5.3.3 In-Person Arm 
Patients randomized to in-person PC will be scheduled for their first PC visit within four 
weeks of enrollment and then at least every four weeks thereafter until the patient is no 
longer coming into the clinic (i.e. due to enrollment in hospice) or death. PC visits will be 
scheduled on the same day as oncology visits unless the patient is agreeable to scheduling 
the PC visit on a different day. Joint visits with PC and oncology (with both clinicians 
seeing the patient together in one visit) are recommended but not required. PC clinicians 
may see patients more frequently than every four weeks at their discretion. If patients do 
not have a scheduled visit to the cancer center the PC clinician will contact them via 
telephone within four weeks of their prior appointment to conduct the visit. Patients 
admitted to rehabilitation or skilled nursing facilities who are still coming into the cancer 
clinic for oncology visits should continue to meet with PC at least every four weeks. 
Patients who are receiving hospice services but still coming into the cancer clinic for 
oncology visits should continue to meet with PC at least every four weeks. Patients 
scheduled to meet with PC clinicians who do not speak their native language will be seen 
in conjunction with an interpreter service used by the hospital or with a family member or 
friend who speaks the language. In-person PC visits will require a standard co-payment 
as per the patients’ insurance requirements, and PC will bill for the services. 
 
5.3.4 Both Study Arms 
PC clinicians will document all patient encounters (in-person, telehealth, or telephone) in 
the patient’s medical records. They will also complete an electronic survey after each 
clinical encounter to note the topics addressed during each study visit and whether any 
caregiver was present (see Data Collection). 
 
If participants on either arm miss their scheduled visit and it cannot be rescheduled within 
four weeks of their prior visit, the PC clinician will attempt to contact them via telephone 
within seven days from the missed visit to conduct a visit via telephone. The PC clinician 
will document the telephone calls in the health record. If the patient is unable to be 
reached by telephone, the PC clinician will document in the health record that the PC 
team has attempted to contact the patient, or they have left a voicemail asking for a return 
call if there are issues needing to be addressed. Patients surviving greater than 18 months 
will be permitted to decrease the frequency of PC visits as per the discretion of their PC 
and oncology teams. 
 
While the study protocol entails every four-week patient contact with a PC clinician, a 
variety of uncontrollable factors may impact intervention delivery. Patient factors 
include a change in their cancer treatment schedule, cancellation of cancer treatment, or 

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fatigue that prohibits participation in a visit. Clinician factors include clinic delays 
leading to missed patient appointments and insufficient staffing, especially due to 
meetings and vacations. We will document missed contact as a minor violation and 
institute a corrective action plan if more than 15% of all planned patient contact with PC 
does not take place per study protocol at a study site. 
 
If the standard practice of the participating PC service is to have the inpatient PC team 
follow patients who receive outpatient PC if they are admitted to a hospital, the inpatient 
PC team will follow this practice and see the patient during their hospitalization. 
If patients are admitted to the hospital and miss a scheduled PC visit, they will have four 
weeks from the date of discharge for their next in-person or telehealth visit. 
 
5.4 
Data Collection 
The research team will administer study assessments at baseline, and every 12 weeks 
(from the date patient baseline was completed) up to 48 weeks with a two-week window 
to accommodate patient schedules and will collect measures during regularly scheduled 
visits when possible. We have utilized similar data collection strategies in our prior trials. 
We will ask participants to provide their email address to allow us to send study 
assessments using a secure electronic system when patients do not have a scheduled, in- 
person appointment within the follow-up time points. Patients who opt out of using 
secure email may either receive paper copies of the survey by mail or complete the 
questionnaires verbally over the telephone. The assessment battery takes approximately 
15 minutes to complete. Patients who are receiving hospice services will not be asked to 
complete study assessments. Table 1 depicts the assessments, measurements, and time 
points for the data collection. 
 
We will contact caregivers approximately 3 months after the patient’s death to complete 
the After Death Assessment either via email, telephone, or paper. If they are unable or 
unwilling to complete the questionnaires, the research team will attempt to contact the 
caregiver again in one month. For caregivers who refuse participation at any time, we 
will document their refusal and make no further attempts at data collection. Caregivers 
who do not object to being contacted at a future time will receive monthly reminders via 
telephone, mail or email until six months after the patient’s death. 
 
Table 1. Self-report instruments and time-points for administration. 

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5.4.1 Data from Electronic Health Record: 
Clinical information regarding tumor type, date of diagnosis of incurable disease, 
previous diagnosis of early stage disease, tumor genotype, and ECOG Performance 
Status will be collected at baseline. 
 
Health care utilization data will be collected after death or at 18-months from the date the 
last patient enrolled on the study. We will collect data on: (1) outpatient (in-person and 
telehealth) and inpatient PC visits; (2) chemotherapy and radiation therapy 
administration; and (3) emergency department, hospital and intensive care unit 
admissions. EOL care measures will include referrals to and length of stay on hospice 
and location of death. 
 
5.4.2 Data on PC Visits and Resource Utilization: 
1. PC clinicians will enter data on the topics addressed during the study visit after each 
patient encounter, using a Research Electronic Data Capture (REDCap) survey. The 
domains included in the REDCap survey correspond to the those in the Early PC 
Treatment Guide to allow the PC clinician to document the content areas addressed 
during the visit, any referrals or medications prescribed, and whether a caregiver was 
present.50 The PC clinician will also document the type of visit (in-person, telehealth, or 
telephone) and the approximate duration of the visit. In our recent MGH trial, all PC 
clinicians completed REDCap entries after their clinical interactions with study patients 
for over 99% of their encounters. We will use the identical successful study procedures to 

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ensure documentation of all PC clinical interactions in this proposed trial. Prior to the 
study start, we will train the lead investigators from each site on the use of the REDCap 
survey and importance of entering these data. The site lead investigators will then train 
their participating PC clinicians on completing the REDCap survey during the study 
period. On the morning of each patient encounter, a research team member will send a 
secure email with the patient’s name and a link to the REDCap system. PC clinicians will 
receive an email after the visit to remind them to complete the data entry. If the PC 
clinician does not complete the REDCap entry, they will continue to receive periodic 
email reminders until the end of the 28-day window. We will not accept REDCap entries 
more than 28 days later than the appointment date. While we have trained study sites to 
complete these surveys after each patient encounter, it is not feasible for them to 
complete 100% of this documentation. As such, we will not consider missed REDCap 
surveys from the PC clinicians to be protocol violations. 
5.4.3 Data Storage: 
Patient data will be collected at each institution using REDCap. Each site will maintain 
their own separate list of participant names and study IDs. Participants will be identified 
on study forms and in the REDCap database by participant number only. To further 
prevent the loss of confidentiality, all electronic information stored on the main database 
within MGH is password protected, and is protected by anti-virus software. Only the 
research team will have access to the study data on shared file areas. We are requesting a 
partial HIPAA waiver of authorization to identify potential study participants. 
 
Data abstracted from the health record in Section 5.4.1will be maintained in REDCap, 
which is a free, secure, HIPAA-compliant web-based application hosted by the Partners 
HealthCare Research Computing, Enterprise Research Infrastructure & Services (ERIS) 
group. 
 
5.5 
Description of Study Processes 
 
5.5.1 Instrument Administration 
The research team will administer study assessments at baseline and multiple follow-up 
time points (see table of Self-Report Measures) with a +/- two-week window to 
accommodate patient schedules. The assessment battery takes approximately 15 minutes 
to complete. The baseline assessments and follow-up measures may be completed either 
in the clinic, online via REDCap email, on paper at home, or via telephone (see cover 
letters for mailed and emailed surveys in appendix). We will attempt to collect follow-up 
self-reported measures in person at scheduled visits to the outpatient clinic whenever 
possible. We will ask patients to provide their email address to allow us to email study 
measures using a secure electronic system when patients do not have a clinic appointment 
within the follow-up time points. For patients who opt out of using email, we will either 
send them paper copies of the survey or ask them to complete them verbally over the 
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Spanish speaking participants will have the option of completing follow-up assessments 
in -person as a first preference or otherwise via mail. Spanish version questionnaires will 
not be administered over the telephone (due to the fact that research assistants may not 
speak Spanish) nor via email as the REDCap assessments cannot be in multiple 
languages. 
 
Surveys that are completed on paper at home will be labeled only with a case number and 
no identifying information; we will also add a note reminding participants to please not 
add their name or identifying information to the survey. We will provide a pre-paid, 
stamped envelope for participants who want to return questionnaires by mail. 
 
5.5.2 PC Intervention Administration 
Drs. Greer and Jackson developed the Early PC Treatment Guide based upon our prior 
studies that details the elements of PC in the outpatient care setting.50-52 This guide does 
not determine the timing of addressing each of the content areas, as the relevance of the 
topics (e.g., symptom management and advance care planning) depends on the patient’s 
course of illness and experience with cancer. However, it does provide guidance for PC 
clinicians about addressing each content area, when appropriate in the patient’s course of 
illness. We also developed a series of training videos to illustrate the techniques included 
in the manual. Both the intervention guide and training videos are being used in our 
ongoing NCI Alliance for Clinical Trials multisite PC trial. For the proposed study, all 
participating PC clinicians will undergo training to ensure that the provision of services is 
consistent across study sites. We will utilize a “train-the-trainer” approach by having the 
study site lead PC clinicians participate in a one-day training session in Boston to educate 
them on the key components of the intervention, to standardize and troubleshoot the 
delivery of the intervention in each setting, and to prepare them to train their respective 
clinical staff to deliver the intervention. Prior to the study start, all participating PC 
clinicians will watch the PC and telehealth training videos, review the intervention guide, 
and read several required papers on the early PC model. 
 
The practice of early integrated PC includes six domains: (1) Developing and maintaining 
the therapeutic relationship with patients and caregivers; (2) Assessing and treating 
patient symptoms; (3) Providing support and reinforcement of coping with advanced 
cancer in patients and caregivers; (4) Assessing and enhancing prognostic awareness 
and illness understanding in patients and caregivers; (5) Assisting with treatment 
decision-making; and (6) Planning for EOL care. Although the content domains of early 
PC often occur across multiple sessions or several may occur within a single consultation, 
the Early PC Treatment Guide presents the information according to the types of PC 
interventions that occur most prominently during the following time frames: initial visits 
at the initiation of treatment; visits throughout the entire course of disease; visits at 
clinical turning points (e.g., changing to a new regimen of chemotherapy or after being 
discharged from the hospital); and visits upon the conclusion of ambulatory treatment 
and/or transition to hospice services. A summary of the treatment guide is included in 
Table 2 below: 

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Table 2. Summary of palliative care treatment 
 
Timing 
Domain 
Elements 
Key Points 
Initial 
Visits 
Therapeutic 
Relationship 
• Introducing PC 
•  Understanding the 
Patient and Caregiver 
Experience 
•  Building Trust with 
the Patient and 
Caregiver 
•  Develop a strong therapeutic relationship with patients 
and caregivers 
•  Learn about the values, life goals, and experiences of 
patients and their caregivers both prior to and after the 
cancer diagnosis 
•  Develop trust and credibility with patients and caregivers 
by providing reassurance and outlining parameters of 
communication 
All 
visits 
Patient 
Symptoms 
• Preparing for 
Symptoms 
• Assessing & Treating 
Symptoms 
•  Coordinating 
Symptom Management 
with Oncology 
•  Providing Referral for 
Symptom Management 
•  Clarify the symptoms the patient will likely experience 
and offer reassurance about the methods for reporting 
and treating symptoms 
• At every visit, elicit existing and new symptom concerns 
•  Maintain ongoing, effective communication with 
oncologists to define mutual collaboration and work 
within their preferred practice patterns 
•  Emphasize team approach to care by referring to 
specialty care, mental health, alternative medicine, and 
spiritual support as needed 
Coping with 
Advanced 
Cancer 
•  Reviewing & 
Validating Prior 
Coping Efforts 
•  Discussing & 
Advocating for 
Different Methods of 
Coping 
• Supporting Caregiver 
Coping 
•  Providing Referral for 
Additional Support 
•  Recognize that patients and caregivers bring their own 
expertise in coping to the current circumstance based on 
prior experiences 
•  Introduce strategies to help improve adjustment and 
meaning in life (e.g., behavioral, cognitive, and spiritual 
approaches; social support) 
•  Bolster caregiver coping by assessing burden, enhancing 
their communication with patients, and recommending 
additional support 
•  Involve other members of the team for patients and 
caregivers who may be experiencing severe distress (e.g., 
social work, psychology) 
Prognostic 
Awareness 
& Illness 
Understandi 
ng 
• Communicating with 
Oncology 
• Exploring Goals & 
Values 
•  Assessing & Informing 
Patient Expectation of 
Prognosis 
•  Conducting Separate 
Conversations with 
Caregivers 
•  Consult with the oncologist to ensure the care team is 
consistent with their understanding of the patient’s 
prognosis 
•  Assess patient’s hopes and expectations for treatment 
and future to clarify the patient’s level of prognostic 
awareness 
•  Recognize that illness understanding often vacillates 
between more & less realistic expectations and work to 
improve prognostic awareness 
•  Include both patients and caregivers in conversations 
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Treatment 
Decision- 
making 
•  Assessing Patient 
Values in Treatment 
Decision-Making 
•  Discussing Treatment 
Considerations 
• Supporting Treatment 
Decisions 
•  Elicit information from patients and caregivers regarding 
their decision-making style, quality versus quantity of 
life concerns, and life goals 
•  Provide support for patients and caregivers to understand 
the efficacy, and risks and benefits associated with 
cancer treatment 
•  Clarify any misunderstanding about treatment, support 
patient decision-making and freedom to change course 
Visits 
Near 
EOL 
EOL Care 
• Discussing EOL Care 
Options 
•  Supporting Caregivers 
in EOL Care 
Coordination & 
Bereavement 
•  Discuss/review selection of healthcare proxy, 
determination of resuscitation preferences, transition to 
hospice care, and location of death 
•  Determine available resources for EOL care and whether 
it is appropriate for patients to receive care in the home 
or other settings; and provide resources and counseling 
for bereavement for caregivers 
 
5.5.3 Ensuring Fidelity of Study Design, Training, and Intervention 
We will take several steps to ensure the fidelity of our study design, training, and 
intervention delivery. The table below depicts the steps we will take to ensure the fidelity 
of our study design and intervention training and delivery. 
Table 3. Summary of methods for treatment fidelity 
 
 
Types of 
Fidelity 
Procedures to Ensure Fidelity 
Fidelity Assessment 
Study Design 
• Intervention development based on a 
well-defined conceptual model and 
systematic review of literature 
• Standardization of intervention dose 
with clear feasibility data based on 
prior work 
• Minimization of cross 
contamination effects given both groups 
will receive PC 
• Utilize evidence-based PC intervention guide 
developed through multiple prior trials 
• Measure number of PC intervention visits 
and visit duration using electronic PC 
clinician encounter survey 
• Measure number of in-person PC visits in the 
telehealth group and telephone visits in the in-
person group 

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Training 
• Development of PC intervention guide 
and videos 
• Initial in-person training of lead site 
investigators on PC intervention and use 
of telehealth 
• Initial in-person training of site 
research team members on study 
procedures and use of telehealth 
• Onsite training at each participating site 
with all PC clinicians providing care to 
study patients 
• Quarterly conference calls (led by Drs. 
Temel & Jackson) with site investigators 
to address study issues 
• Monthly conference calls (led by 
Chardria Trotter) with the research 
team to address study procedures 
• Annual retraining seminar via video 
conferencing with lead site 
investigators 
• Complete review of PC intervention guide 
and training videos 
• Complete training of all site investigators in 
protocol administration, intervention 
delivery, and standardized material 
• Complete training of research team 
members on study procedures, protocol 
and use of technology 
• Assess pre- and post-knowledge that PC 
clinicians and research team members 
acquired during training 
• Send meeting minutes from 
conference calls to all lead site 
investigators 
• Send meeting minutes from conference 
calls to all site research team members 
• Assess pre- and post-knowledge that lead site 
investigators acquired during retraining 
Intervention 
Delivery by 
PC Clinicians 
• Utilization of PC intervention guide 
with standardized content areas 
• Completion of electronic survey after 
each study encounter to record the 
content and topics that the PC clinician 
addressed 
• Documentation of clinical encounters in 
site medical record 
• Conduct ongoing training of any new staff in 
standardized PC intervention guide and 
videos 
• Review PC electronic surveys quarterly to 
ensure adherence to content (by Dr. Greer). 
These findings will be discussed during 
quarterly meetings with lead site investigators 
• Review a random sample of PC visit notes 
quarterly to ensure adherence to content (by 
trained research team member) 

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5.5.4 Special Concerns 
The study investigators will meet on a weekly basis to discuss any issues or concerns 
with study procedures. If it is decided that the protocol needs to be amended or modified, 
the overall PI will make the necessary changes and submit an amendment to the DF/HCC 
IRB for approval. Once the amendment has been approved by the DF/HCC IRB, then the 
amendment will be submitted to the PCRC designated participating sites. 
 
5.6 
Adverse Reactions and their Management 
5.6.1 Reporting Adverse or Unanticipated Events 
Identification of adverse events may come through notification from the study 
participant, caregiver, clinician, or from review of the health record. In such 
circumstances, the PIs and investigative team will follow the following procedures: 
 
Serious Adverse Events: Given that this study is PC intervention, we do not anticipate 
any study-related events meeting the FDA definition of a SAE (i.e., any fatal event, 
immediately life-threatening event, permanently or substantially disabling event, event 
requiring or prolonging inpatient hospitalization, or any congenital anomaly). This study 
population is comprised of individuals diagnosed with advanced lung cancer who 
frequently experience disease worsening, high symptom burden, and hospitalizations 
from the underlying disease and/or side effects of treatment. Therefore, as advanced lung 
cancer is a chronic-type terminal illness, regular fluctuations in cancer-related symptoms, 
disease worsening, hospitalizations, emergency department visits, and deaths are to be 
expected throughout the study, and we will not consider or report such events as SAEs in 
this trial. 
 
Non-Serious Adverse Events: The IRB will be provided with unblinded summaries of 
study related non-serious adverse events by treatment group at the continuing reviews. 
These reports will include types of events, severity, and treatment phase. To date, we 
have had very few non-serious adverse events in our supportive care studies. Examples 
of potential non-serious adverse events are participants’ discomfort with the study 
assessments or with their assignment group. 
 
5.6.2 Anticipated Reactions 
As this is a behavioral study, there are no ingested medications, and no biomedical 
procedures. Thus, participants will not be at any risk for physical harm due to their study 
participation. 
 
Participants may find some of the questions asked in the questionnaire to be emotionally 
upsetting and may experience some fatigue from the length of the assessment battery. 
5.6.3 Reaction Management 
A detailed consent form will be signed by each participant following the explanations by 
the research team member or clinician. The consent form will include all study 
procedures, information about potential risks and benefits of participation, and 
information regarding whom the participant can contact for further questions. It also will 
state that participation is voluntary, that participants can refuse to answer any question, 
that they can withdraw from the study at any time, and that study participation is in no 

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way related to their medical care. All research team members will complete the required 
human subjects training before working on any human subject aspects of the study. 
 
Should a participant exhibit or express distress, they will be reassured by the research 
team that they need not answer any questions they find upsetting. They will also be 
reminded that study participation is voluntary. If participants remain distressed, both the 
site PI and the primary oncology clinician will be notified. Should several participants 
express distress over an individual item, the research team will review the questionnaire 
and contact the IRB to consider removing it from the study. 
 
If a participant reports severe distress or suicidal ideation during the study conduct, the 
research team member has a formal obligation to inform the site PI and/or patient’s PC or 
oncology team. These clinicians will determine the need to involve psychiatry and take 
further action as deemed necessary. The research team will review sensitive items 
regarding suicidal ideation within 120 hours (5 business days) of receipt of completed 
surveys and will report any suicidal ideation to the site PI and/or patients PC or oncology 
team. 
6.0 
Ethical and Legal Issues 
6.1 
Confidentiality 
Patient data will be collected at each participating institution using REDCap. Each site 
will maintain their own separate list of patient names and study ID’s, which will be saved 
in password protected files. Participants will be identified on study forms by case number 
only to protect confidentiality. Identifiers such as name will only be used during the 
initial data retrieval process and can be destroyed once all data records have been 
obtained and data analysis has been completed as discussed previously. At the 
completion of the study, de-identified data files will be shared between the PCRC and 
MGH using a secure data transfer. 
 
Participants’ responses to survey questions will remain confidential unless there is active 
suicidal ideation confirmed by the research team. Under these circumstances, as clearly 
stated in the patient consent form, participants will be informed that the research team has 
a formal obligation to inform the site PI and/or a member of the patient’s PC or oncology 
team. These clinicians will then determine the need to involve psychiatry and/or take 
further action as deemed necessary. 
 
7.0 
Statistical Analysis 
7.1 
Primary Endpoint 
To determine whether telehealth PC is equivalent to in-person PC for improving 
patients’ QOL. 
7.2 
Secondary Endpoints 
7.2.1 To determine whether telehealth PC is equivalent to in-person PC with 
respect to patient-clinician communication about EOL preferences. 
7.2.2 To determine whether telehealth PC is equivalent to in-person PC with 
respect to length of stay in hospice. 
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participation in PC visits. 
7.2.4 To assess the superiority of telehealth versus in-person PC on patient 
satisfaction. 
7.2.5 To assess the superiority of telehealth versus in-person PC on caregiver 
satisfaction.  
 
7.3 
Exploratory Endpoints 
7.3.1 To compare coping strategies in patients assigned to telehealth versus in- 
person PC. 
7.3.2 To compare prognostic understanding in patients and caregivers assigned 
to telehealth. 
7.3.3 To compare the effect of telehealth versus in person PC on caregivers’ 
outcomes, including QOL and mood. 
7.3.4 To compare the effect of telehealth versus in-person PC on patients’ 
mood. 
7.4 
Sample Size and Power Calculation 
The primary endpoint of the study is to establish that telehealth PC is equivalent to in- 
person PC in patient-reported QOL at week-24, as measured by the FACT-L. Although 
the primary endpoints in our previous studies assessed the change in FACT-L from 
baseline to week-12, we chose to focus on QOL at 24 weeks as the life-expectancy of 
patients with advanced lung cancer has increased over the last few years. In our most 
recent randomized trial of early integrated PC versus standard oncology care, we 
observed a 7.5 (SD = 17.0) point difference in the FACT-L at week-24 favoring the early 
integrated PC group. Thus, we chose a conservative equivalence margin of 4 points, 
which is slightly more than 50% of the previously observed advantage with early 
integrated PC compared to oncology care alone. As a 6-point difference in FACT-L score 
is considered the lowest range of a clinically meaningful difference, our equivalence 
margin would not reach the threshold of clinically meaningful difference in QOL between 
telehealth PC and in-person PC.53 With 469 patients per group, we would have 95% 
power to establish the equivalence of telehealth PC compared to in-person PC on the 
FACT-L, with a two-sided alpha of 0.05, and an equivalence margin of 4 points. In our 
recent trial, we observed 25% missing data at 24 weeks. Therefore, we increased our 
sample size to 625 per group (total sample size = 1250 patients) to ensure we have 
adequate power to assess the equivalence of telehealth PC compared to in-person PC. 
Importantly, we chose to be conservative in estimating the sample size of this trial given 
the proposed testing of equivalence of telehealth PC to in- person PC on secondary 
outcomes as well as the planned subgroup analyses. 
The proposed study will also have adequate power to assess for equivalence of telehealth 
PC compared to in-person PC in EOL communication and hospice length-of-stay. With a 
sample size of 1250, we will have 89% power, with a two-sided alpha of 0.05, to assess 
the equivalence of telehealth to in-person PC on patient-reported EOL communication 
with an equivalence margin of 8%, assuming the rate of EOL communication in the in- 
person PC group is 30% (based on our recent trial). With this sample size, we will also 
have 94% power to establish the equivalence of telehealth PC compared to in-person PC 
in hospice length-of-stay, with a two-sided alpha of 0.05, and an equivalence margin of 6 

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days (SD = 30.0). Given that this is an equivalence trial, we were conservative with the 
power estimations by using the highest observed standard deviation for all outcomes from 
our prior studies. 
 
7.5 
Analysis Plan 
Aim 1: To determine whether telehealth PC is equivalent to in-person PC for improving 
patients’ QOL 
We will begin with descriptive and graphical summaries of the endpoints to evaluate 
whether normality assumption is reasonable or if transformation is necessary. As the goal 
of the proposed study is to establish that patient-reported QOL with telehealth PC is 
equivalent to in-person PC, statistical testing for equivalence of the primary outcome will 
be two-sided with an alpha level of 0.05. We will use analysis of covariance (ANCOVA) 
models controlling for baseline values, and demographic and clinical factors (as 
necessary for any imbalances in baseline variables) to assess the effect of telehealth PC 
compared to in- person PC on QOL at 24 weeks. We will also use linear mixed models of 
the longitudinal data, allowing us to account for dependency among means over time and 
to control for demographic and clinical factors (as necessary for any imbalances in 
baseline variables) when examining change between groups in QOL across multiple time 
points (i.e., baseline, week-12, week-24, week-36, and week-48). Lastly, we will test 
Heterogeneity of Treatment Effect (HTE) based on age, gender, race, computer 
experience, and enrollment of caregivers using interaction terms in the linear mixed 
models (see HTE analysis plan). 
 
We will use ANCOVA models controlling for baseline values, and demographic and 
clinical factors as necessary to assess the effect of telehealth PC compared to in-person 
PC on patient mood (HADS, PHQ-9), and coping strategies (Brief Cope subscales) at 24 
weeks. We will then utilize linear mixed models of the longitudinal data as described 
above to examine change in depression and coping between groups across multiple time 
points. Lastly, we will also compare illness understanding as measured by the PTPQ 
between the two groups through week-24, analyzing items using linear or logistic 
regression as appropriate and adjusting for demographic and clinical factors as 
necessary. The patient’s final post-baseline PTPQ assessment within 24 weeks will be 
used. 
 
Aim 2: To determine whether telehealth PC is equivalent to in-person PC with respect to 
patient-clinician communication about EOL care preferences and length of stay in 
hospice 
We will examine patient-report of discussing EOL care preference with their clinicians 
using the following item: “Have you and your doctors discussed any particular wishes 
you have about the care you would want to receive if you were dying?” (Yes/No). 
Although patients will complete this measure repeatedly during the study, we will use 
the final assessment for this analysis. We will assess differences between study groups in 
the rate of patients reporting “Yes” to this item using a Fisher’s exact test with a two-
sided alpha of 0.05 (equivalence margin=8%). We will then use a logistic regression 
model adjusting for any demographic and clinical factors that are imbalanced to assess 
differences in this dichotomous outcome between the two groups. 
 

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Additionally, we will assess the equivalence of hospice length-of-stay between telehealth 
PC and in-person PC with an equivalence margin of 6 days. We will use linear regression 
models adjusting for demographic and clinical factors as necessary to compare hospice 
length-of-stay between telehealth PC and in-person PC. Although hospice length-of-stay 
is not normally distributed, based on a sample size of 1250, the means would have a 
normal distribution (central limit theorem). Nonetheless, we will also perform poisson 
regression or Wilcoxon rank sum test to compare our results to those obtained with linear 
regression. 
 
Aim 3: To compare the effect of telehealth versus in-person PC on caregiver participation 
in PC visits and outcomes 
We hypothesize that caregivers receiving telehealth PC will participate in a higher 
proportion of their loved ones’ PC visits during the study and that the participating 
caregiver will report better QOL at 24 weeks compared to those randomized to in-person 
PC (superiority aim). We will compare rates of caregivers’ participation in PC visits 
between the two groups using mixed logistic models in to account for correlation 
between multiple PC visits for each caregiver (controlling for any imbalances in 
demographic and clinical factors). In addition, we will compare caregiver QOL 
(CARGOQOL) at week-24 between the study groups using ANCOVA adjusting for 
baseline values and any imbalances in clinical and demographic factors. We will also use 
linear mixed models of the longitudinal data to account for dependency among means 
over time and to control for demographic and clinical factors (as necessary for any 
baseline imbalances) when examining change between groups in QOL across multiple 
time points (i.e., baseline, week-12, week-24, week-36, and week-48). 
 
We will compare caregiver mood on the HADS at week-24 between groups using 
ANCOVA models as described previously. We will then evaluate linear mixed models of 
the longitudinal data as described above to examine change in caregiver depression and 
anxiety symptoms between groups across multiple time points. To compare caregiver 
illness understanding (as measured by the PTPQ) within 24 weeks between groups, we 
will analyze items using linear or logistic regression analyses as appropriate to adjust for 
clinical and demographic variables. The caregiver’s final post-baseline PTPQ assessment 
within 24 weeks will be used. Lastly, we will compare caregivers’ perception of quality 
of care at the EOL (per the After Death Assessment) between the two groups using 
ANCOVA as described previously. 
 
Specific Aim 4: To compare patient and caregiver satisfaction with telehealth PC versus 
in-person PC 
We will measure patient and caregiver satisfaction with the intervention using The 
Satisfaction and Care Delivery Questionnaire. Although patients and caregivers will 
complete this measure repeatedly during the study, we will use the final assessment for 
this analysis. We will compare scores between the telehealth PC and the in-person PC 
using ANCOVA adjusting for study site and any imbalances between the two groups. 
 
Tests for Heterogeneity. We will analyze Heterogeneity of Treatment Effect (HTE) by 
testing for interaction effects between the intervention group and the following variables: 
patient age (>65, ≤65), gender (male vs. female), race/ethnicity (White vs. Black; White 

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vs. Asian; Non-Hispanic White vs. Hispanic/Latino), computer experience (yes vs. no), 
and enrollment of caregiver (yes vs. no). The interaction terms will be tested in the linear 
mixed effects models examining patient QOL, depression, hospice length-of-stay as well 
as in a logistic regression model examining EOL communication. Observing an 
interaction effect (P < 0.15), 54 we will conduct separate subgroup analyses to assess for 
HTE of the telehealth intervention compared to in-person PC. Since this trial is testing 
the modality of delivery of PC (telehealth vs. in-person), all HTE analyses are considered 
exploratory and hypothesis-generating. 
 
Prior studies have found that age, gender, and race can moderate the impact of PC in 
patients with cancer.55,56 However, it remains unclear whether these factors would 
contribute to HTE of the telehealth intervention versus in-person PC. While studies 
utilizing mobile and computer technology have not shown that computer experience 
moderates the effect of interventions with adequate training,57,58 we will specifically 
assess HTE based on computer experience to ensure generalizability of our findings. 
Lastly, since the use of telehealth may facilitate the presence of a caregiver during the 
appointments, we will also examine whether the enrollment of a caregiver contributes to 
the HTE of the telehealth PC compared to in-person PC. 
 
Multiple testing: For all significance tests of secondary outcomes, we will use the false 
discovery rate (FDR) control method to address the issue of multiple tests. We selected 
an FDR of 0.15, which denotes the acceptable percentage of results that potentially 
represent false positives. Analyses of exploratory outcomes will not be adjusted for 
multiple comparisons, and presented results will emphasize estimates and confidence 
intervals.   
 
7.3.1 Stratification Factors and Intervention Allocation Plan for Randomized Studies. 
Patients will be randomized between study groups using block randomization with 
stratification by study site. 
 
7.3.2 Stratification Factors and Their Impact on Design 
Stratification factors do not impact the design of the study but will be considered during 
the data analysis to compare baseline statistics and outcomes based on initial eligibility 
criteria to participate in the study. 
 
7.3.3 Early Stopping Rules 
Not applicable. Participants will be included in the study as long as they continue to seek 
care at the participating study site. Death or discontinuation of clinic visits are the only 
reasons for participants to not be included in the full intervention. 
 
7.3.4 Definition of and Allowance in Design for Unevaluable/Ineligible Participants. 
No unevaluable and/or ineligible participants will be included in this study. 
7.6 
Handling of Missing Data 
As in our prior PC trials, we will utilize rigorous methodology in reporting reasons for 
dropout and missing data during the study period. Specifically, we will report the 
following reasons for missing data: 1) patient death, 2) inability to complete the study 

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due to illness (too ill, hospitalized, hospice), 3) transfer of care, 4) withdrawal of consent, 
and 5) unable to contact for follow up. During the quarterly meetings with the lead site 
investigators, led by Drs. Temel and Jackson, the investigative team will review missing 
data rates for all participating sites to address any discrepancies in missing data compared 
to prior studies and to ensure rigorous retention and follow-up procedures. 
 
The analyses will initially focus on the study completers to compare telehealth PC with 
in-person PC in patients who completed the protocol as intended without imposing 
assumptions about missing data. We will also use the intention-to-treat (ITT) principle 
with all randomized subjects, conducting sensitivity analyses to explore how various 
assumptions about missing data and differences between completers and non-completers 
affect the estimated outcomes. If data appear to be missing at random, we will employ 
multiple imputation methods. However, if we find that participants do not complete the 
study because of disease worsening, suggesting that data are not missing at random, we 
will employ terminal decline joint modeling approach, under the direction of the study 
statistician. The advantage of the terminal decline approach is that it models the trend in 
participant-reported outcomes backward from the time of the patient’s death rather than 
prospectively from the time of enrollment. Thus, this approach controls for the known 
relationship between patient and caregiver QOL deterioration as the patient’s death 
approaches. Notably, the terminal decline approach also accounts for missing outcome 
data. It utilizes a mixed-effects model for the longitudinal outcomes to provide valid and 
efficient estimates for missing outcome data. We will analyze the terminal decline and 
survival distributions with semiparametric models applied to both groups. Based on the 
fitted models, we will compare participant-reported outcomes at specified times before 
death (one, three, and six months prior to the patient’s death). All models will adjust for 
baseline criterion scores, and any potential imbalances between the two groups. The 
terminal decline joint modeling approach has been utilized in multiple prior PC studies 
given its ability to account for deterioration in outcomes closer to death.59 
 
8.0 
Disseminating the Study Results 
Expanding the application of telemedicine to the care of patients with chronic illness and 
establishing the effectiveness of a novel delivery model to increase access to PC for 
diverse patients in community settings are two questions of significant importance to 
patients and caregivers, PC clinicians, as well as health care institutions, insurers and 
organizations. Thus, our dissemination and implementation plan will address these key 
stakeholders. First, we will work closely with the MGH Public Affairs office to 
disseminate study findings to patients and caregivers through news outlets, such as 
newspapers (e.g., USA Today), social media (e.g., Twitter and Facebook), and news 
shows (e.g., NPR). We will also work with our lead site investigator and health care 
organization stakeholders to work with their respective media and public affairs offices 
to disseminate study findings throughout the country. Second, we will disseminate study 
results to the oncology and PC community through manuscripts in high-profile peer 
review publications, national meetings (such as ASCO and the American Association of 
Hospital and Palliative Medicine), and advocacy organizations (such as the Center to 
Advance PC [CAPC)]). Our study co-investigator and stakeholder, Dr. Lee Schwamm, 
has published key manuscripts about implementing telehealth technology, including 
“Telehealth: seven strategies to successfully implement disruptive technology and 

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transform health care” in Health Affairs.32 Thus, as a third strategy to disseminate and 
implement study findings, we will collaborate with Dr. Schwamm to publish the study 
findings in journals, such as Health Affairs, which influence policy makers and leaders 
of health care institutions. We will also present study findings throughout Partners 
HealthCare and strongly encourage our site lead investigators to present the results at 
their institutions. Our stakeholder engagement plan includes members from five key 
health care insurers, and so as a fourth strategy, we will engage our MGH and Partners 
HealthCare colleagues and stakeholders to assist us in meeting with these insurers to 
develop a plan to implement telemedicine PC (specifically developing reimbursement 
models). Fifth, we have engaged multiple key health care organizations and advocates, 
including ASCO, ACS, and CAPC to help us disseminate study findings through their 
organizations and to advocate for health care policy changes to increase the number of 
trained PC clinicians and reimbursement for telemedicine. Sixth, we will publish and 
present our methodology for training staff, clinicians, patients and caregivers on the use 
of the telemedicine video platform to enable the dissemination of this care model. 
 
We will disseminate all study results to patients and caregivers who participated in this 
study through both email (which we collect as part of our study procedures) and direct 
mailings. We will also engage our study patient and caregiver stakeholders, which 
includes two individuals at each of the participating sites to communicate study results to 
local hospital and advocacy organizations, including their cancer clinics’ patient and 
advisory councils. 

34 
 
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