SIMPRO Research Center: Integration and Implementation of PROs for Symptom Management in Oncology Practice
Phase: NA
Conditions: Other Cancer, Gastrointestinal Cancer, Thoracic Cancer, Gynecologic Cancer
Sponsor: Dana-Farber Cancer Institute

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
1 
 
 
 
 
PROTOCOL TITLE: 
SIMPRO Research Center: Integration and Implementation of PROs for Symptom Management 
in Oncology Practice. 
 
Sponsor and Coordinating Center:  
Dana-Farber/Harvard Cancer Center (DF/HCC)  
Department of Medical Oncology 
Coordinating Center PI and Technology PI: Michael Hassett 
Dana-Farber Cancer Institute 
Boston, MA 02215 
Email Address: Michael_Hassett@dfci.harvard.edu  
Telephone Number: 617-632-4587 
 
CO-STUDY CHAIRS: 
 
Deborah Schrag MD, MPH 
Chair, Department of Medicine  
Memorial Sloan Kettering Cancer Center  
New York City, NY 10065 
 
Raymond Osarogiagbon MD 
Director, Thoracic Oncology Research Group 
Baptist Memorial Hospital 
Covington, Tennessee 38019 
 
 
Sandra Wong MD 
Chair, Department of Surgery 
Dartmouth College 
Lebanon, NH 03756 
 
 
VERSION NUMBER: 
Version 9 
 
DATE: 
Version date: August 4, 2023 
 
FUNDING: 
National Cancer Institute, UM1CA233080. 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
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ACRONYMS USED THROUGHOUT PROTOCOL: 
eSyM  
Electronic symptom management system 
ePRO 
Electronic patient-reported outcomes 
EHR 
Electronic health record 
eSyM+ 
Assigned to use eSyM  
eSyM- 
Assigned not to use eSyM  
Gyn 
Gynecologic  
GI 
Gastrointestinal 
SOP 
Standard operating procedure 
FTP 
File transfer protocol 
SASS 
Research questionnaire  
SIV 
Site initiation visit 
CTMS 
Clinical trial management system 
DF/HCC Dana-Farber/Harvard Cancer Center 
ODQ 
DF/HCC Office of Data Quality 
QI 
Quality Improvement  
NHSR 
Not Human Subjects Research  

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
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Table of Contents 
Contents 
1.0 
Schema ................................................................................................................................. 4 
2.0 
Background .......................................................................................................................... 5 
3.0 
Objectives ............................................................................................................................ 8 
3.1 
Hypothesis............................................................................................................................ 8 
4.0 
Inclusion and Exclusion Criteria or Activity Population ..................................................... 9 
5.0 
Protocol Activities ............................................................................................................... 9 
6.0 
Study-Wide Number of Subjects ....................................................................................... 31 
7.0 
Study-Wide Recruitment Methods .................................................................................... 32 
8.0 
Multi-Site Research ........................................................................................................... 32 
9.0 
Study Timelines ................................................................................................................. 32 
10.0 Study Endpoints and Statistical Analyses .......................................................................... 32 
11.0 Procedures Involved........................................................................................................... 36 
12.0 Data Management and Confidentiality .............................................................................. 36 
13.0 Provisions to Monitor the Data to Ensure the Safety of Subjects ...................................... 46 
14.0 Future Use of Data ............................................................................................................. 46 
15.0 Withdrawal of Subjects ...................................................................................................... 47 
16.0 Risks to Subjects ................................................................................................................ 47 
17.0 Potential Benefits to Subjects ............................................................................................ 48 
18.0 Vulnerable Populations ...................................................................................................... 48 
19.0 Sharing of Results with Subjects ....................................................................................... 48 
20.0 Setting ................................................................................................................................ 48 
21.0 Resources Available........................................................................................................... 48 
22.0 Provisions to Protect the Privacy Interests of Subjects ...................................................... 49 
23.0 Compensation for Research-Related Injury ....................................................................... 49 
24.0 Economic Burden to Subjects ............................................................................................ 49 
25.0 Consent Process ................................................................................................................. 49 
26.0 Appendices ......................................................................................................................... 50 
 
 
 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
4 
 
1.0 
Schema 
 
 
 
Activity 1 (Waiver of consent): Obtain stakeholder feedback to 
inform eSyM finalization and implementation from: 
• patient advisory councils  
• health system leaders  
• clinicians, clinic support staff/administration, and 
IT/Informatics staff  
Activity 2 (NHSR): Build and deploy eSyM and finalize 
training materials based on findings from stakeholder 
engagement 
Activity 3: Pilot Test eSyM  
• Activity 3a (NHSR/QI): eSyM usage  
• Activity 3b (Waiver of documentation of consent): 
User acceptability testing  
• Activity 3c (Waiver of consent): Medical record 
abstraction 
Activity 4: Pragmatic stepped-wedge cluster randomized study  
• Activity 4a (NHSR/QI): eSyM usage  
• Activity 4b (Waiver of documentation of consent): 
SASS questionnaire  
• Activity 4c (Waiver of consent): Medical record 
abstraction 
• Activity 4d (Written Consent): Patient qualitative 
interviews 
Constant 
refinement of 
eSyM  
based on 
findings from 
each activity 
Evaluation of the 
Implementation 
will occur 
throughout the 
entire 
implementation 
process, not just 
at the end 
Activity 5 (Exempt): Integration of eSyM Data - Develop 
algorithms to estimate the risk of experiencing an outcome 
among cancer patients  

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
5 
 
2.0 
Background 
 
Deficits in management of common symptoms cause substantial morbidity for cancer 
patients. In the United States, nearly 1.74 million people will be diagnosed with cancer in 2018.1  
While there will be approximately 600,000 cancer deaths, better treatment has contributed to 
lower mortality rates. However, the morbidity toll of cancer treatment remains immense.1-5 Poor 
symptom control decreases quality of life, increases the need for emergency care,6-8 and even 
deters some patients from receiving effective therapy.9,10 For patients with cancer receiving 
chemotherapy, adverse symptoms add to distress. For surgical patients, poorly managed 
symptoms delay recovery and interfere with timely receipt of adjuvant treatments11-13 and the 
return to usual activity levels. Patients are reluctant to “complain” or perceive that symptoms are 
unavoidable.14 The raging US opioid epidemic has further complicated pain management for 
cancer patients.15 
 
Because the health care delivery system is structured to be reactive and not proactive, there 
are missed opportunities to optimize symptom control. The current cancer care delivery 
system is not well-equipped to anticipate, monitor and prevent adverse symptoms before they 
escalate.16 Typically, patients initiate outreach to address a problem which clinicians try to solve 
during office visits. Between these face-to-face encounters, communication is scarce and almost 
entirely patient initiated. For patients with chronic illness like cancer, this model is maladaptive. 
Many choose to endure their symptoms, hesitate to adjust medications, or are reluctant to 
mention adverse symptoms for fear of compromising the ability to receive treatment. Moreover, 
effective symptom control typically requires careful titration of combinations of pain, nausea, 
and bowel medications to achieve optimal equilibrium. Although many patients and their 
caregivers gain proficiency over time, others struggle to cope, particularly at treatment initiation 
or care transitions. Surgeons, medical oncologists, and oncology nurses have experience with 
symptom management, but they are often preoccupied by treatment decisions about cancer 
therapy during visits.17 In some settings, palliative care physicians, rehabilitation specialists, and 
social workers partner with oncologists to support patients, or there are resources to teach self-
management skills. However, in many centers, these resources are constrained or unavailable.   
  
Growth in Internet access and proliferation of smartphones has created an opportunity to 
re-engineer cancer care delivery. Eighty-eight percent of adults in the US had web access and 
77% had a smartphone in 2016. Although adoption is lower in the elderly and the poor, use is 
rising, and many use the internet to manage their health.20,21 Mobile phones in general, and web 
access more generally, extend capacity for patient-clinician communication to optimize symptom 
management beyond the confines of 
a face-to-face encounter.22 Patient 
engagement has been called the 
“blockbuster” drug23,24 of the 21st 
century based on the recognition that 
motivated and activated patients 
have improved well-being and 
consistently achieve better health 
 
Smartphone18 
Web access19 
Population 
2010 
2016 
2010 
2016 
All adults 
33% 
77% 
76% 
88% 
Age 65+ 
17% 
54% 
43% 
64% 
Rural 
26% 
67% 
69% 
81% 
<$30,000 income 
24% 
64% 
61% 
79% 
Black 
29% 
72% 
68% 
85% 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
6 
 
outcomes.25,26 Strong theoretical foundations from social cognitive theories of self-efficacy27,28 
and the chronic care model29 support the importance of patient engagement30-34 as a strategy to 
minimize the morbidity of cancer treatment.  
 
Electronic symptom tracking and feedback is a promising strategy to improve symptom 
control. Electronic patient reported outcome (ePRO) monitoring of cancer symptoms has been 
shown to decrease symptom burden,35 improve quality of life, reduce acute care36 and even 
extend survival.37 There is evidence to support two primary mechanisms of action. First, 
systematic reporting may activate patients to be more knowledgeable and effective at self-
management.38 This aligns with self-efficacy theory. Second, systematic reporting can trigger 
between-visit clinician actions that improve symptom control. This enhanced communication, 
facilitated by technology, could make health care more responsive to patient needs.39,40  
 
Critical knowledge gaps will prevent successful implementation of ePRO systems in 
oncology practice. The NCI has invested in the development of measurement tools to facilitate 
symptom reporting such as the PRO-CTCAE (Patient-Reported Outcomes version of the 
Common Terminology Criteria for Adverse Events), a patient-reported outcome measurement 
system to capture symptomatic adverse events in cancer patients.41-43 This item-bank enables 
symptom reporting and tracking using a consistent set of validated metrics for both clinical trials 
and routine care. The PRO-CTCAE, access to web-technology and the rapid proliferation of 
EHRs have created a context that is ripe for scaling a more proactive approach to cancer care 
delivery such as ePRO tracking. However, 4 critical knowledge gaps remain that will prevent 
successful implementation of ePROs to improve symptom management. They are: 
 
1. The ePRO effectiveness evidence base is limited to major cancer centers. Evidence 
supporting the efficacy of ePRO symptom management stems largely from clinical trials and 
effectiveness studies conducted in large well-resourced cancer centers.44,45 It is unknown 
whether the benefits found in these studies are generalizable to cancer care in rural, small and 
community-based settings, and evidence for their effectiveness and the adaptations necessary 
to make ePROs successful in these contexts is needed. 
 
2. ePRO systems are not fully integrated with EHRs. While ePROs have demonstrated 
effectiveness without being fully embedded into the EHR,46,47 integration would dramatically 
improve secure patient and clinician access to symptom reports and clinical utility of ePRO 
systems. Without integration, patients and clinicians must access separate systems to view 
symptom reports and cannot easily take actions such as ordering a medication or 
coordinating care with another relevant provider.48 Full integration of ePRO systems into the 
EHR would facilitate secure two-way exchange of information and the ability to track 
symptoms, convey appropriately tailored educational materials, provide information about 
expected symptom profiles, send alerts, take actions, and coordinate care. 
 
3. ePRO systems have not leveraged demonstrably effective symptom coaching strategies. 
Early ePRO research focused on feasibility, metric development and overcoming 
technological and regulatory obstacles. The efferent limb of the ePRO feedback loop has 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
7 
 
received considerably less attention.49,50 First, there has been limited work developing the 
information content that these systems deliver to help patients cope.48,51 Where evidence-
based symptom management tools exist, they are not fully leveraged.52 Similarly, giving 
patients feedback about the extent to which their symptom profiles are typical or deviate 
from what is expected can provide reassurance or alert them to escalate treatment or seek 
help.  
 
4. Insufficient attention to implementation strategies will compromise the impact of 
ePROs. There are myriad examples of effective health care interventions that do not realize 
their potential for impact because of insufficient attention to implementation.53-55 ePRO 
systems require a shift in the traditional orientation of clinicians which typically confines 
symptom assessment to clinical encounters. There is inadequate knowledge about the 
implementation strategies that are facilitators of successful ePRO systems. How much 
training do patients require to engage in self-reporting? How much reinforcement is 
necessary? What level of training do clinic support staff, nurses, and clinicians require? What 
is the optimal design of dashboards to facilitate review of and acting on ePRO symptom 
reports? Established implementation science frameworks exist but have not been applied to 
ePRO systems. 
 
A multi-disciplinary team of investigators from 6 health systems have formed the Symptom 
Management IMplementation of Patient Reported Outcomes in Oncology (SIMPRO) Research 
Center. SIMPRO will use functioning ePRO prototypes to create and refine the electronic 
symptom management system eSyM. eSyM is the name of the platform the team will refine, 
integrate, implement, and evaluate. eSyM addresses each of the 4 evidence gaps noted above by: 
1. Implementing eSyM in cancer centers in small, rural, or community-based systems. 
2. Integrating eSyM into the EHR of the predominant vendor used nationwide. 
3. Leveraging evidence-based tools, patient engagement, and population management. 
4. Executing this work using the Consolidated Framework for Implementation Research 
(CFIR, see figure below)56 across all phases to maximize the chances that eSyM and 
similar systems achieve their intended goals and decrease the morbidity of cancer 
treatment at a population level. 
 
 
Using CFIR as a guide, we will utilize the plan-engage-execute-evaluate cycles across all aims. 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
8 
 
3.0 
Objectives 
 
Overall Research Goals are: (1) to create and refine eSyM, a reporting and management 
system that integrates ePROs with the EHR; (2) to evaluate the impact of eSyM on 
patient outcomes, treatment delivery, and healthcare system utilization using a pragmatic 
cluster randomized study design; and (3) to undertake a systematic, deliberative approach 
to implementation to allow for the identification of barriers and facilitators that contribute 
to the adoption and sustainability of eSyM in routine oncology care. 
 
Aim 1: Adapt existing ePRO symptom management systems and integrate them into the 
EHR and routine clinical workflow at six health systems. Specifically:  
Aim 1a. Obtain patient, clinician, staff, and leadership input on ePRO form and 
function 
Aim 1b. Refine the content and algorithms for self-management, alerts, and feedback   
Aim 1c. Develop ePRO training materials for patients, clinicians, and staff  
Aim 1d. Pilot an ePRO symptom manager at test and study sites and prepare an 
implementation strategy 
 
Aim 2: Determine the effectiveness of an EHR-integrated ePRO symptom management 
system on health outcomes. Specifically: 
Aim 2a. Healthcare utilization, measured by the need for emergency and acute care 
Aim 2b. Impact on cancer care delivery, specifically chemotherapy treatment duration 
and delays  
Aim 2c. Patients’ outcomes, indicated by levels of self-efficacy and symptom burden  
Aim 2d. Patients’ satisfaction with their cancer care 
 
Aim 3: Evaluate the facilitators and barriers to implementation of an EHR-integrated 
ePRO symptom management system from the patient, clinician, and organizational 
perspectives. Specifically: 
Aim 3a. Patient adoption (including program feedback and experiences via qualitative 
interviews), clinician utilization, and their perspectives on appropriateness and 
acceptability 
Aim 3b. The sustainability of ePRO symptom management within a health system 
Aim 3c. Penetration and scalability of ePROs for symptom management  
Aim 3d. Extent of adaptation of ePRO systems over the course of the implementation 
process 
 
 
3.1 
Hypothesis 
 
Detailed hypotheses per aim can be found in the stats section of the protocol.  Overall, 
investigators hypothesize that eSyM will enable patients to be more effective stewards of their 
own care and enable their clinicians to anticipate problems and intervene to manage symptoms 
before they escalate. 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
9 
 
 
4.0 
Inclusion and Exclusion Criteria or Activity Population 
 
The eligibility criteria/activity population vary for each activity.  See section 5.0 for details. 
 
 
5.0 
Protocol Activities 
 
There are 5 protocol activities, each detailed in section 5.0. 
• Activity 1: Obtain stakeholder feedback from patient advisory councils, health system 
leaders, clinicians, clinic support staff/administration, and IT/Informatics  
• Activity 2: Build and deploy eSyM and finalize training materials based on findings from 
stakeholder engagement 
• Activity 3: Pilot test eSyM  
o Activity 3a: eSyM usage 
o Activity 3b: User acceptability testing 
o Activity 3c: Medical record abstraction  
• Activity 4: Pragmatic stepped-wedge cluster randomized trial 
o Activity 4a: eSyM usage 
o Activity 4b: SASS questionnaire 
o Activity 4c: Medical record abstraction 
o Activity 4d: Patient qualitative interviews  
• Activity 5: Integration of eSyM data to develop algorithms to estimate the risk of 
experiencing an outcome, including, but not limited to, ED usage and hospitalization 
among cancer patients  
 
 
 
 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
10 
 
Activity 1: Obtain stakeholder feedback from stakeholders, including (but not required) 
patient advisory councils, health system leaders, clinicians, clinic support 
staff/administration, and IT/Informatics  
 
Brief description of activity: Before eSyM go-live, study team members from each site will 
solicit input via emailed survey, remote meetings and/or in-person meeting on the use of ePROs 
in oncology from stakeholders to obtain input regarding adaptation, anticipated challenges, and 
implementation (questions will be selected from the CFIR, AIM/IAM, NOMAD and CSAT 
Question Banks – see Appendix A G, J, and Y) and follow-up probes. The study team may adapt 
or create de novo questions as needed.   
 
At least 30 days after eSyM go-live and on an ongoing basis, we will evaluate the 
implementation process at each of the sites with a focus on adoption, appropriateness, 
acceptability, sustainability, penetration, and scalability. We will do this using a combination of 
methods including evaluating medical record (and/or local cancer registry) reviews (see activities 
3c and 4c), eSyM usage reports (see activities 3a and 4a), SASS questionnaire responses (see 
activity 4b), and feedback from emailed surveys and/or discussions with health system 
leadership, clinicians, clinic support staff, and informatics/IT staff (activity 1). Stakeholder 
questions will be selected from the CFIR, AIM/IAM, NOMAD and CSAT Question Banks – see 
Appendix A G, J, and Y) and follow-up probes. The study team may adapt or create de novo 
questions as needed.   
 
Human Subjects Research Category (NHSR, exempt, expedited, full review): Exempt 
because the stakeholders at each site are acting in their normal business capacity and this is a 
negligible risk activity. 
 
Informed Consent: Waiver of informed consent. Because eSyM will be implemented at each 
site for use in routine clinical care and because this is a quality improvement (QI) activity, it is 
necessary to consult each site’s stakeholders during ePRO design and implementation.  This 
activity is negligible risk. 
 
Activity 1 Population: 
• Age ≥ 18 years 
• The potential stakeholders are patient advisory council members, health system leaders, 
clinicians, clinic support staff/administration, and IT/Informatics staff.  
 
Number of subjects (per site and overall):  
• Approximately 5-25 patient advisory council participants per site (30-150 patient 
advisory council participants overall) 
• Approximately 4-10 health system leaders per site (24-60 health system leaders overall) 
• Approximately 60 clinicians, clinic support staff/administration, and IT/Informatics staff 
per site.  (360 clinicians, clinic support staff/administration, and IT/Informatics staff 
overall) 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
11 
 
• We anticipate sending emailed surveys and/or presenting 2 separate times at 
approximately 6 meetings per site (a thoracic surgery, thoracic medical oncology, 
gynecological surgery, gynecological medical oncology, GI surgery, and GI medical 
oncology meeting).  If 10 people participate from each setting, then we will collect data 
from approximately 120 people per site which totals 720 participants study-wide.   
 
**Total number of stakeholder participants through surveys and meetings can be larger 
or smaller depending on availability. 
 
When, where, and how potential subjects will be recruited: The study PI at each site or 
his/her designee will send email surveys and/or meet with stakeholders individually, will get on 
upcoming meeting agendas, and/or will convene ad hoc meeting(s).   
 
Materials that will be used to recruit subjects: See sample email in Appendix K and/or L.  
Each site may modify to meet their needs. 
 
Duration of subject’s participation in the study: If done via emailed survey (REDCap): The 
emailed survey will take approximately 15 minutes to complete.  If interviewed in-person or 
remotely: Approximately 1 hour, the length of a meeting. 
 
Duration anticipated to enroll all study subjects: We anticipate that it will take approximately 
three months prior to the go-live at each site to complete all initial stakeholder engagement. 
Implementation evaluation will occur throughout the five-year project period with a designated 
1-year post-implementation survey/interview conducted at all sites.  
 
Study design: Discussion guides and/or question slide decks will be used to facilitate 
stakeholder engagement.  
 
Description of all research procedures being performed: The study PI (or designee) at each 
site will obtain feedback from the stakeholders at their site; feedback will be collected via 
emailed survey, and a meeting to be held one-on-one, in group settings, or remotely via writing, 
discussion, or handheld polling devices. All sites will be responsible for maintaining a list of 
stakeholders who will be invited to provide feedback. 
 
The eSyM stakeholder interview guide (see appendix Y) may include selected items from CFIR, 
AIM, NOMAD, and CSAT (see appendices A, G, J, and Y). The eSyM questionnaire may 
include selected items from CFIR, AIM, NOMAD, and CSAT and will be sent stakeholders to be 
completed in REDCap. The study team may adapt or create de novo questions as needed.  
 
In person and/or remote follow-up meetings will be conducted in group or one-on-one settings. 
Before any meetings may be conducted, all discussion facilitators must be trained by the Overall 
PI Deb Schrag or her designee on how to conduct the discussion; facilitators will be taught how 
to ask questions in a non-leading manner, how to respond to answers in a non-biased fashion, 
and how to ask appropriate follow up probe questions as/if needed. All discussion facilitators 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
12 
 
will utilize the interview guide developed by the study team and probe as needed.  A member of 
the team will take notes of all discussions and all discussions will be audio-recorded when 
possible. Clicker questions may also be used to collect feedback from stakeholders during larger 
group meetings. Feedback will also be ascertained through email and one-on-one discussions; 
written notes will be categorized and summarized for study analysis purposes.  
 
All feedback collected will be submitted via REDCap or emailed to the coordinating center 
(Dana-Farber) for synthesis, summarization, and transcription as needed. Feedback may be 
collected in an identifiable fashion.  For example, the CIO’s comments may be attributed to “the 
CIO.” 
 
Monitor subjects for safety or minimize risks: Not applicable. 
 
What data will be collected and how: Feedback and demographic information will be collected 
from stakeholders at each site regarding stakeholder views on adaptation, anticipated challenges, 
and implementation of ePRO (electronic patient reported outcomes).  
 
Long-term follow-up: Stakeholders will be consulted and kept informed throughout the study 
period. 
 
 
 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
13 
 
Activity 2: Build and deploy eSyM and finalize training materials 
 
Brief description of activity: Using all of the feedback collected during pervious activities, the 
study team will finalize the content and build the eSyM system. 
 
Human Subjects Research Category (NHSR, exempt, expedited, full review): Not Human 
Subjects Research. 
 
Informed Consent: Not applicable. 
 
Tasks that will be completed by the study team: 
• Finalize eSyM’s specifications:  
o prompt patients to report symptoms at user-defined intervals 
o track symptom profiles over time in via graphs 
o trigger delivery of symptom coaching in response to symptoms 
o alert patients to contact their clinicians in response to severe symptom reports  
o alert clinician about patients with severe symptoms 
o enable creation of dashboards that facilitate symptom burden monitoring of user-
defined patient cohorts  
o use MyChart/Epic to securely access patient data 
o allow a proxy to report on behalf of a patient  
o eSyM will be integrated in the EHR and patient portal so that clinicians can 
expediently review and respond to ePROs with access to complete health records 
including medications, labs and visit notes with minimal disruption to workflow 
and with reliable record keeping 
• Finalize the algorithms that control what eSyM does in response to user inputs. 
• Finalize eSyM’s patient-facing content. 
• Finalize eSyM’s clinician-facing content. 
• Obtain necessary permissions or licensing agreements.  
• The informatic team will finalize the eSyM build based on the specs provided by the 
study team. 
• Each site may customize where allowed (example, where permissible, sites may brand 
their instance of eSyM with their own logos). 
• Finalize eSyM training materials (see appendices AA through KK):  
o Patient-facing training materials (when and how to use eSyM). 
o Clinician-facing training materials (when and how to use eSyM). 
o Clinical staff-facing training materials (how to teach a patient to use eSyM). 
• Depending on initial data and eSyM adoption rates, the study team (or a designee) may 
text, call, portal message and/or email patients to remind them to use eSyM. 
 
 
 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
14 
 
Here is a sample of what the specifications for the build will look like: 
 
Example of the Component Tools that Support eSyM for Diarrhea.  
MODIFIED PRO-CTCAE SURVEY QUESTION 
In the last 24 hours, how OFTEN did you have LOOSE OR WATERY STOOLS (DIARRHEA)? 
 
0: Never  
1: Rarely 
2: Occasionally 
3: Frequently 
4: Almost constantly 
DEPLOYMENT RULES & ADAPTATIONS 
 
MEDICAL ONOCLOGY 
SURGERY 
Starting point 
1 day after chemo start 
1 day after discharge 
Frequency 
2/week x 24 weeks  
3/week x 2 weeks then 2/week x 2 weeks then 
1/week x 4-8 weeks 
SYMPTOM CLASSIFICATION (threshold for action – will depend on the symptom) 
ACTION 
FREQUENCY RESPONSE 
No intervention IF: 
= 0  
Symptom management advice IF: 
= 1 or 2 or 3 
Alert clinical team via InBasket IF: 
= 4 
SYMPTOM EDUCATION FOR PATIENTS (selected examples) 
Eat small meals that are easy to digest. Eat 5 or 6 small meals each day instead of 3 big meals. Choose foods that will help 
with diarrhea, such as applesauce, bananas, crackers, cream of wheat, eggs, toast, oatmeal, peanut butter, boiled potatoes, and 
rice. 
Drink more each day. Drinking more won’t stop the diarrhea, but it will help replace fluids you are losing to prevent 
dehydration. Most people who have diarrhea need 8 to 12 cups a day. Clear broth, water, tea, oral rehydration/electrolyte 
drinks (e.g., Pedialyte®), juice, and soda are good choices. 
Take medications your team may have prescribed such as Imodium or Lomotil. 
Avoid these foods: Some foods can make diarrhea worse. Don’t have dairy, such as milk, cheese, and sour cream. Try 
“lactose-free” products instead. Don’t eat spicy, greasy, or fried foods. 
Call your cancer team if: You feel lightheaded, dizzy, or faint. These are symptoms of dehydration. You develop a fever of 
100.5 F or higher. Your stool looks black or bloody. You are experiencing diarrhea that wakes you up from sleep at night. 
SYMPTOM MANAGEMENT SUPPORT FOR CLINICIANS (selected examples) 
Alert the clinician whenever a severe symptom is reported via InBasket. 
Add the patient to a color-coded report of patients reporting symptoms in the last 7 days. 
Symptom responses visible in patient EHR (e.g., snapshot report).   
 
For a full list of symptoms, see the PRO-CTCAE bank (Appendices H & I); we will prioritize the 
symptoms below. PRO-CTCAE items may be modified, as needed (e.g., symptom lookback 
period): 
 
eSyM Questionnaire Items 
 
Required 
Optional 
All Patients: Medical Oncology and 
Surgery 
Anxiety 
Constipation 
Fatigue 
Pain  
Poor Appetite  
Nausea 
Shortness of Breath 
Trouble Drinking Fluids 
Vomiting 
Bleeding  
Coughing  
Difficulty Concentrating 
Difficulty Sleeping 
Difficulty Swallowing 
Dizziness 
Feeling Discouraged 
Feeling Sad 
Fever 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
15 
 
Overall Wellbeing  
Physical Function 
Hand-Foot Syndrome  
Headache 
Heart Palpitations 
Heartburn 
Itching 
Mouth/Throat Sores 
Swelling  
Wheezing 
Medical Oncology 
Diarrhea  
Numbness and Tingling  
Rash 
Painful Urination  
Surgery 
Painful Urination 
Wound Discharge 
Wound Redness 
Diarrhea 
Numbness and Tingling  
Rash  
 
Here is a sample of what a patient-facing eSyM screen might look like: 
 
 
Here is a summary of the eSyM functionalities that will be designed and built: 
 
The main patient-facing tools will include the following (accessed via computer or app): 
1. Alerts → Reminders about when to complete PRO reporting  
2. Symptom Reporting → Surveys that will allow patients to report outcomes for modified 
PRO-CTCAE items  
3. Visualizations → Display previously reported PROs 
4. Education → Evidence-based symptom management tools (see appendix T) 
 
The main clinician/staff-facing tools will include (accessed via computer or app): 
1. Messaging → Message notifying when critical PROs have been reported 
2. Visualizations → Display previously reported PROs for a given patient, highlighting 
critical symptoms 
3. Reports → Display patients who are enrolled in the program, view results of multiple 
patients, and identify patients who did not report PROs on schedule 
 
Activity 3: Pilot test eSyM  
 
Brief description of activity: eSyM will be UAT/pilot tested at up to 6 sites.  The primary 
purpose of UAT/pilot testing is for the research team to observe patients, clinicians, and staff 
interacting with the new system, identify challenges, and iteratively refine the system, training 
materials, or clinic workflow prior to the launch of the full-scale pragmatic stepped-wedge 
cluster randomized trial. 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
16 
 
 
SIV (Site Initiation Visit): The SIV, protocol, and eSyM training is critically important to the 
success of the pilot study.  All involved staff (on the research team and clinical teams) will be 
required to complete training using the materials and methods developed via Activity 2.  
Training activities include: 
• Training clinicians and clinic staff at each site on new clinic workflow SOPs. 
• Training clinicians and clinic staff on how to get a patient set up with eSyM. 
• Training each user audience (clinicians and patients) how to use their eSyM interface. 
• Training informatics/IT staff at each site how to support and maintain eSyM. 
** See appendices AA through LL for study resources. Please note – training materials and 
project resources will be routinely updated and branded to meet site needs.  
 
Activity 3 Population: 
• Age ≥ 18 years 
• Priority population will be patients who meet one of the following: 
o Suspected thoracic cancer AND is inpatient following thoracic surgery. 
o Suspected gastrointestinal cancer AND is inpatient following gastrointestinal 
surgery. 
o Suspected gynecologic cancer AND is inpatient following gynecologic surgery. 
o Diagnosis of thoracic cancer AND scheduled to start a new treatment plan for 
thoracic cancer. 
o Diagnosis of gastrointestinal cancer AND scheduled to start a new treatment plan 
for gastrointestinal cancer. 
o Diagnosis of gynecologic cancer AND scheduled to start a new treatment plan for 
gynecologic cancer. 
• Total population allowed to use eSyM: 
o Any patient at any participating site.  
**Please note – Patients undergoing thoracic, gynecologic, or gastrointestinal surgery 
may not be diagnosed with cancer. These patients are still eligible for eSyM usage, 
questionnaire completion, and medical record abstraction.  
 
Activity 3 population will be operationalized as follows:  
• To determine if a patient has a diagnosis of one of the above cancer types, use ICD-10 
diagnosis codes: 15.0-16.99 (esophago-gastric) C17.0-C21.9 (small int. colorectal) 
C22.0-24.9 (hepatobiliary) C23-C25.9 (pancreas), C34-34.9: lung, C53.0-53.9 (cervix) 
C54-54.9 (uterine) and/or C56-57.9 (ovarian).  When it comes time to execute, this list 
may be modified. CPT and procedure codes and EPIC’s OPTIME operating room 
scheduling module will be used to determine if a patient is scheduled for a priority 
surgery. 
 
Mode of Participation: Patients will have a choice of their preferred mode of eSyM 
participation and switching can be accommodated. Patients with a smart phone will be offered 
that approach first. Alternatives include participation in eSyM via any web-enabled device 
(laptop/tablet/desktop). Patients may designate a caregiver willing to elicit their symptoms and 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
17 
 
report responses on their behalf (proxy reporting). This flexibility facilitates the intervention’s 
reach to frail patients who may be those most likely to benefit. As needed, patients will also be 
offered eSyM training through in-person, phone, and/or virtual visits. 
 
Number of subjects (per site and overall): For Activity 3, user acceptability testing (UAT) will 
be done with up to 390 patients from up to 6 participating sites. At the lead site (Dana-Farber), 
we anticipate conducting UAT with 90 participants distributed as follows: 15 patients from each 
cancer/type modality combination (15 thoracic surgical, 15 gynecologic surgical, 15 GI surgical, 
15 thoracic medical oncology, 15 gynecologic medical oncology, and 15 GI medical oncology). 
We anticipate that at each of the 5 remaining participating sites, each site will conduct UAT with 
up to 60 participants distributed as follows: 10 patients from each cancer/type modality 
combination (10 thoracic surgical, 10 gynecologic surgical, 10 GI surgical, 10 thoracic medical 
oncology, 10 gynecologic medical oncology, and 10 GI medical oncology).  Protocol does not 
mandate equal distribution of participants among participating sites.  If a site is running behind 
or facing lower than anticipated accrual to the activity, then the other sites may enroll additional 
participants to make up the difference until the study wide UAT goal has been reached. The 
numbers referenced above are meant to serve as an estimate and sites may suspend or continue 
UAT as needed. 
 
Materials that will be used to recruit subjects: None. 
 
Duration anticipated to enroll all study subjects: We anticipate that it will take three months 
prior to eSyM launch at each site to enroll all UAT/pilot participants, but the actual duration may 
vary.  
 
Monitor subjects for safety or minimize risks: The risk to participants is minimal with the 
primary risk being loss of confidentiality/privacy. To monitor the risk of loss of 
confidentiality/privacy, the informatics/IT team will routinely monitor eSyM and investigate 
inquiries from study teams. Furthermore, patients who report severe symptoms will be prompted 
to call their clinic immediately, and clinicians will receive in-basket notifications in the Epic 
EHR of the severe symptom report. 
 
 
 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
18 
 
Activity 3a: eSyM Usage 
 
Human Subjects Research Category (NHSR, exempt, expedited, full review): NHSR/QI 
Because eSyM will be implemented at each site for use in routine clinical care and because this 
is a quality improvement (QI) activity, this is not human subjects research.  
 
Informed Consent: Waiver of consent. When a patient becomes eligible for eSyM, he/she/they 
will receive an automated welcome message, which includes an electronic disclaimer that 
contains important information about the purpose of eSyM, how/when it should be used, and 
what it does and does not communicate to their care team (see Appendices N & Q).   
 
Methods that will be used to identify potential subjects: Access to eSyM will be automated.  
EPIC will automatically deliver the invitation to use eSyM to all patients defined above (See 
Section: “Activity 3 population will be operationalized as follows”).   
 
Duration of subject’s participation in the study: Per protocol, eSyM usage continues for up to 
60-180 days from their trigger event (i.e., new chemotherapy treatment plan and/or surgery), but 
extended use of eSyM is at the discretion of the site and each patient participant. 
 
What data will be collected and how:  
• Participant responses to the symptom reporting questions within eSyM will be collected. 
• Clinician responses to symptom reports will be collected. 
• Data on eSyM usage by all user types will be collected. 
 
Long-term follow-up: We will follow patients for 1-year after the trigger event (i.e., new 
chemotherapy treatment plan and/or surgery) for outcomes data captured via medical record 
abstraction. 
 
 
 
 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
19 
 
Activity 3b: User Acceptability Testing (UAT)  
 
Informed Consent: Waiver of documentation of consent. Before observing the patient using 
eSyM, the patient will be provided with a letter (see appendix O) with the elements of informed 
consent, as well as the option not to be observed. They will be notified that participation is 
completely voluntary and can be stopped at any time for any reason. This activity is minimal 
risk.  
 
Methods that will be used to identify potential subjects: Under a HIPAA waiver, study staff 
will look in the scheduling views of the electronic medical record and scheduling systems to 
identify potential participants.  Study staff may also query Epic, administrative/operations/billing 
databases, order entry databases, and/or cancer registry databases to identify potential 
participants.  Study staff may also accept potential patient referrals from site clinicians.  
Purposive sampling based on data from the electronic medical record (e.g., demographics, cancer 
stage, number of recent hospitalizations, number of prescription drugs) will be used to ensure 
that perspectives of diverse patients are included.  Ideally, sites will use the developed eSyM 
reporting workbench reports in Epic to automatically pull a patient list for UAT.  
 
When, where, and how potential subjects will be recruited: The clinical/study staff will 
approach the patient to see if they would be interested in participating in UAT.  If a patient is 
interested in participating, the site will present the participant with a study letter and then begin 
observations. Patients may be approached in-person, via phone, via email or through a virtual 
visit. 
 
Description of procedures being performed for UAT: Surgical patients will be set up to use 
eSyM at the time of surgical discharge (or at the site’s discretion).  Medical oncology patients 
will be set up to use eSyM at the time of their first chemotherapy dose visit (or at the site’s 
discretion). The study staff will observe the patient accessing eSyM, the patient being trained on 
how to use eSyM, the patient using eSyM to do their first symptom reporting session.   
 
Duration of subject’s participation in the study: Per protocol, UAT observation will last 
approximately 30 minutes or less.  
 
What data will be collected and how: The study staff will write down their observations as 
well as staff/patient feedback (see appendix P).  
 
Study design: User acceptability testing.   
 
Long-term follow-up: None. UAT is a one-time 30-minute session. 
 
Activity 3c: Medical record abstraction  
 
Informed Consent: Waiver of consent to conduct medical record (and/or local cancer registry) 
reviews/Epic queries on all patients in the UAT/pilot to ascertain demographics and outcomes.  

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
20 
 
 
Methods that will be used to identify potential subjects: Automated and/or manual medical 
record (and/or local cancer registry) review will be done on all UAT/pilot patients. 
 
When, where, and how potential subjects will be recruited: All participants in the UAT/pilot 
will undergo medical record (and/or local cancer registry) reviews.  The medical record (and/or 
local cancer registry) reviews will be accomplished using both automated data extraction and 
manual data abstraction. 
 
What data will be collected and how:  
• Study-related health information and outcomes will be collected via medical record 
(and/or local cancer registry) review (automated and manual).  
• Data will be submitted to the coordinating site (Dana-Farber) via REDCap or SFTP.  
 
Study design: Medical record abstraction (both manual and automated).   
 
Long-term follow-up: The patients’ medical record may be reviewed for outcomes for up to 1-
year after the trigger event (i.e., new chemotherapy treatment plan and/or surgery).  
 
 
 
 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
21 
 
Activity 4: Pragmatic stepped-wedge cluster randomized trial 
 
Brief description of activity: A multisite, pragmatic stepped-wedge cluster randomized trial 
will be conducted in order to determine the effectiveness of eSyM on health outcomes including: 
healthcare utilization, measured by the need for emergency and acute care; impact on cancer care 
delivery, specifically chemotherapy treatment duration and delays; patients’ outcomes, indicated 
by levels of self-efficacy and symptom burden; and patients’ satisfaction with their cancer care.   
 
The trial involves patients in five ways:  
1) Patients assigned to eSyM (eSyM+) will report their symptoms via the eSyM 
questionnaires delivered through MyChart. Patients are strongly encouraged to report 
their symptoms at home/between clinic visits with eSyM. Study teams and clinicians may 
elect to ask eSyM-eligible patients to complete eSyM questionnaires in the clinic via a 
table, computer, and/or mobile device if patients have difficulties reporting or decline to 
report at home. Site study teams should consult the central study team before they initiate 
this workflow. 
 
2) A subset of eSyM+ patients will be asked to complete a research questionnaire called the 
“SASS Questionnaire (eSyM+ or eSyM+ Non-Responder version)” asking about their 
Self-efficacy, Attainment of information needs, Symptom burden, and Satisfaction with 
care (see PROMIS, CAHPS, IAM/AIM question banks – Appendices C through G).  The 
eSyM+ version is for patients who were assigned to eSyM and completed at least one 
eSyM questionnaire. The eSyM+ Non-Responder version is for patients who were 
assigned to eSyM but never completed an eSyM questionnaire. The questionnaires will 
stop being administered once a minimum of 1,980 total surveys have been received in 
accordance with the following breakdown: 
SASS Questionnaire accrual numbers 
 
Surgery 
Medical Oncology 
Totals  
 
eSyM+ 
Version 
eSyM- 
Version 
eSyM+ 
Non-
Responder 
Version 
eSyM+ 
Version 
eSyM- 
Version 
eSyM+ 
Non- 
Responder 
Version 
 
Site 1 
75 
75 
15 
75 
75 
15 
330 
Site 2 
75 
75 
15 
75 
75 
15 
330 
Site 3 
75 
75 
15 
75 
75 
15 
330 
Site 4 
75 
75 
15 
75 
75 
15 
330 
Site 5 
75 
75 
15 
75 
75 
15 
330 
Site 6 
75 
75 
15 
75 
75 
15 
330 
Totals  
450 
450 
90 
450 
450 
90 
1,980 
 
3) Select patients NOT assigned to eSyM (control group, eSyM-) will also be asked to 
complete the “SASS Questionnaire (eSyM- version)” (see Appendices U-X). Both Drug 
Therapy and Surgical Recover Experience eSyM- versions will not ask questions 
evaluating eSyM as the cohort will not be exposed to eSyM at the time of the survey. The 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
22 
 
questionnaire will stop being administered once a minimum of 1,980 total surveys have 
been received in accordance with the above breakdown. ** Total number of SASS 
participants through surveys can be larger or smaller depending on availability.  
 
4) A small subset of eSyM- and eSyM+ patients will be invited to take part in follow-up 
qualitative interviews. See table below for recommended recruitment accrual. The 
interviews will be conducted following a developed interview guide (Appendix RR). 
Patients may or may not have previously completed SASS or eSyM questionnaires. 
Interviews will continue until thematic saturation is reached, or until 100 interviews are 
completed, whichever is first.  
 
Patient Qualitative Interviews 
Site 
Recommended Minimum Patient  
Interview Accrual 
Site 1 
4 
Site 2 
4 
Site 3 
4 
Site 4 
4 
Site 5 
4 
Site 6 
4 
Total 
24 
Total accrual can be larger or smaller depending on patient availability and interest. No more 
than 100 interviews will be conducted study-wide. Protocol does not mandate equal distribution 
of participants among sites.  
 
5) Regardless of whether a patient is assigned to eSyM+, eSyM-, or eSyM+ Non-
Responder, and regardless of whether a patient completes the SASS Questionnaire or not, 
we are requesting a waiver of consent and HIPAA waiver to conduct medical record 
(and/or local cancer registry) reviews/Epic data queries on all patients in the denominator 
(for the definition of “denominator”, please see the section “how to operationalize the 
denominator” below) to ascertain demographics and outcomes.  Because eSyM has QI 
implications and is part of routine clinical care, we must be able to compare responders 
with non-responders and eSyM+ with eSyM- and the combinations thereof to inform 
implementation beyond this initiative. 
 
 
 
 
 
 
 
 
 
 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
23 
 
Informed Consent:    
 
Activity 4a: eSyM Usage (eSyM+): NHSR/QI.  
Because eSyM will be implemented at each site for use in routine clinical care and because this 
is a quality improvement (QI) activity, using eSyM is not human subjects research, and therefore 
does not require consent. When a patient becomes eligible for eSyM, he/she/they will receive an 
automated welcome message with a disclaimer that contains important information about the 
purpose of eSyM, how/when it should be used, and what it does and does not communicate to 
their care team (see Appendices N & Q).   
 
Activity 4b: SASS QUESTIONNAIRE PARTICIPANTS (eSyM+ , eSyM-, and eSyM+ 
Non-Responder): Waiver of documentation of consent.   
Eligible patients will receive a study letter in-person, by email, and/or by postal mail asking them 
to consider participating in a questionnaire that asks about their self-efficacy, attainment of 
information needs, symptom burden, and satisfaction with care (see Appendix Z).  This 
invitation will include the elements of informed consent (see Appendix R). The study letter will 
notify participants that the questionnaire is completely voluntary and can be stopped at any time 
for any reason. The letter will be sent from the health system where the patient receives care and 
signed by the site PI. For example, a patient at Dartmouth will receive a letter/email inviting 
participation from Dartmouth signed by Dr. Sandra Wong and a patient from West Virginia 
University will receive a letter/email inviting participation from Dr. Hannah Hazard. The letter 
includes a statement that survey completion has no influence or impact on a patient’s medical 
care. This activity is minimal risk.  
 
Activity 4c: MEDICAL RECORD REVIEW: Waiver of consent.  
Waiver of consent to conduct medical record (and/or local cancer registry) reviews/Epic queries 
on all patients in the “denominator” to ascertain demographics and outcomes regardless of 
whether a patient is assigned to eSyM+ or eSyM- and regardless of whether a patient completes 
the questionnaire or not.  Because eSyM has QI implications and is part of routine clinical care, 
we must be able to compare responders with non-responders and eSyM+ with eSyM- and the 
combinations thereof to inform implementation beyond this trial. The medical record review 
meets all the conditions to obtain a waiver of consent (i.e., not FDA-regulated, involves no more 
than minimal risk, waiver will not adversely affect the rights and welfare of the subjects, and 
activity could not be practicably carried out without a waiver). 
 
Activity 4d: PATIENT QUALITATIVE INTERVIEWS: Written informed consent. 
Eligible patients will receive a study letter in-person, by email, by Epic MyChart portal message, 
and/or by postal mail inviting them to participate in a qualitative interview that asks about their 
experiences with and feedback about the eSyM program and/or their care experience.  This 
invitation will include a written consent form (see Appendices QQ & SS), which will be signed 
by the participant. Informed consent can be obtained through wet ink (returned in-person or via 
snail mail) or e-consent through REDCap. The provided study letter and consent form will notify 
participants that the interview is completely voluntary and can be stopped at any time for any 
reason. The consent form will also request patient approval for their contact information (name, 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
24 
 
email, address, and phone number) to be shared with the coordinating center (Dana-Farber 
Cancer Institute) for the purposes of conducting the interviews. All patient qualitative interviews 
will be conducted by the study team at the coordinating center, who will reach out to the patient 
once the signed consent form is received. The study letter and consent form will be sent from the 
health system where the patient receives care and signed by the site PI. For example, a patient at 
Dartmouth will receive a letter/email inviting participation from Dartmouth signed by Dr. Sandra 
Wong and a patient from West Virginia University will receive a letter/email inviting 
participation from Dr. Hannah Hazard-Jenkins. The letter includes a statement that survey 
completion has no influence or impact on a patient’s medical care. This activity is minimal risk. 
 
Methods that will be used to identify potential subjects: The denominator will be identified 
algorithmically; eSyM/MyChart/REDCap will be programmed so that the correct patients will 
automatically receive an invitation to use eSyM. When manual support is needed, under a 
HIPAA waiver, study staff will run reports in Epic, administrative/operations/billing databases, 
order entry databases, and/or cancer registry databases.  
 
Under a HIPAA waiver, study staff will run reports in Epic as part of the eSyM registry and/or to 
identify patients meeting eSyM registry criteria to identify medical and surgical patients for 
eSyM+, eSyM-, eSyM+ Non-Responder SASS questionnaires, and patient qualitative interviews. 
Select eSyM- patients will be identified and surveyed before eSyM’s launch at their site but after 
the registry has been created, ensuring that they have never been exposed to the program but 
would have been eligible to use it. Patients eligible to complete the eSyM- questionnaire will be 
identified using the patient registry and/or a site-developed Epic report to identify patients who 
had a qualifying surgery or new chemo start within the last 6 months. Patients eligible to 
complete the eSyM+ and eSyM+ Non-Responder questionnaires will be identified using the 
registry after eSyM has been launched at their site and 30-60 days after their surgery or new 
chemotherapy. The eSyM+ SASS questionnaire will be distributed to patients who were assigned 
to eSyM and completed at least one eSyM questionnaire. The eSyM+ Non- Responder SASS 
questionnaire will be distributed to patients who were assigned to the eSyM program but never 
completed an eSyM questionnaire. Sites may begin distributing eSyM+ and eSyM+ Non- 
Responder questionnaires as soon as they are able to do so after go-live and will continue until a 
minimum of 75 eSyM+ surveys and a minimum of 15 eSyM+ Non-Responder surveys have been 
collected for the medical oncology and surgery versions. Patients eligible to participate in the 
qualitative interviews will be identified using Epic reports and invitations will be sent to patients 
meeting eSyM program eligibility. Patients may or may not have previously completed SASS or 
eSyM questionnaires. Interviews will be conducted until thematic saturation is reached, or until 
100 interviews have been completed, whichever is reached first.  
 
In addition, under a HIPAA waiver, email and postal addresses will be obtained for all eSyM+, 
eSyM-, eSyM+ Non-Responder and qualitative interview patients. Email and postal addresses 
will be utilized to share the SASS questionnaire invitation through REDCap and/or mailing (see 
Appendix Z) and to send the interview invitations and consent forms via email and/or mailing 
(see Appendix SS and QQ).  
 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
25 
 
Activity 4 Population:  
• Age ≥ 18 years 
• Priority population will be patients who meet one of the following: 
o Suspected thoracic cancer AND is undergoing thoracic surgery. 
o Suspected gastrointestinal cancer AND is undergoing gastrointestinal surgery. 
o Suspected gynecologic cancer AND is undergoing gynecologic surgery. 
o Diagnosis of thoracic cancer AND scheduled to start a new treatment plan for 
thoracic cancer. 
o Diagnosis of gastrointestinal cancer AND scheduled to start a new treatment plan 
for gastrointestinal cancer. 
o Diagnosis of gynecologic cancer AND scheduled to start a new treatment plan for 
gynecologic cancer. 
• Total population allowed to use eSyM: 
o Any patient at any participating site.  
**Please note – Patients undergoing thoracic, gynecologic, or gastrointestinal surgery 
may not be diagnosed with cancer. These patients are still eligible for eSyM usage, 
questionnaire completion, and medical record abstraction.  
 
Defining and operationalizing the denominator: 
• To determine if a patient has a diagnosis of one of the priority cancer types, use ICD-10 
diagnosis codes: 15.0-16.99 (esophago-gastric) C17.0-C21.9 (small int. colorectal) 
C22.0-24.9 (hepatobiliary) C23-C25.9 (pancreas), C34-34.9: lung, C53.0-53.9 (cervix) 
C54-54.9 (uterine) and/or C56-57.9 (ovarian).  When it comes time to execute, this list 
may be modified.  CPT and procedure codes as well as EPIC operating room scheduling 
lists will be used to determine if a patient is scheduled for a priority surgery. 
• Participants assigned to eSyM+ may be trained to use eSyM by their local clinic/study 
staff.  Surgical patients may be trained to use eSyM at the time of surgical discharge (or 
at the site’s discretion patients may receive training in how to use eSyM at a preoperative 
visit).  Med Onc patients may be trained to use eSyM at the time of their first 
chemotherapy dose visit or at the time of a pre-treatment visit for chemotherapy teaching 
(at the site’s discretion). Epic reports may also be used to identify eligible patients who 
are assigned or will be assigned to eSyM so that training of the eligible patients can be 
done by study research staff via telephone or email before or after beginning treatment or 
having surgery.  
• Participants in the eSyM- cohort will meet priority population criteria and be seen at a 
participating site between 1/1/2018 and the site’s eSyM go-live date. Participants in the 
eSyM+ cohort will meet priority population criteria and be seen at a participating site 
after their eSyM go-live date through March 31, 2024.  
 
Mode of Participation: Patients will have a choice of their preferred mode of eSyM 
participation and switching can be accommodated. Patients with a smart phone will be offered 
that approach first, however all patients will be notified that access to eSyM is available as long 
as they can access the secure patient portal (MyChart). eSyM can be accessed securely through 
the MyChart portal on any web-enabled device. Alternatives to smart phone reporting include 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
26 
 
participation in eSyM via any web-enabled device (laptop/tablet/desktop). Patients may 
designate a caregiver willing to elicit their symptoms and report responses on their behalf (proxy 
reporting). This flexibility facilitates the intervention’s reach to frail patients who may be those 
most likely to benefit. The influence of mode of participation and reliance on self- versus proxy-
reporting will be analyzed in multivariable models. 
 
The denominator is defined above. Automated and/or manual medical record (and/or local 
cancer registry) review will be done on all patients in the denominator. 
Number of subjects (per site and overall): For Activity 4, there will be a minimum of 6,048 
eSyM+ patient users. Prespecified eSyM- accrual numbers can be found in Appendix TT (SAP). 
eSyM users and control patients can be from any of the 6 participating sites.  We anticipate that 
each of the 6 hospitals in the stepped wedge trial will have a minimum of 900 patients. Protocol 
does not mandate equal distribution of participants among participating sites.  The entire 
statistical analysis section is predicated on a minimum N=6048. Because the goal is broad-based 
systems-level implementation, we anticipate having much a higher N which will enable us to 
examine effectiveness in subgroups of interest. 
 
When, where, and how potential subjects will be recruited: Once the population definition 
has been programmed into eSyM/ MyChart, the system will automatically deliver the invitation 
to use eSyM to the patients in the eSyM+ group (see randomization schedule figure below under 
the title “stepped wedge rollout”). eSyM- patients will be identified using Epic query reports. 
Study staff will deliver the invitation to participate in the SASS Questionnaire to all patients in 
the denominator (eSyM+, eSyM-, and eSyM+ Non- Responder) using the registry before and 
after eSyM launch until at least 1,980 have participated. Because different patients are reachable 
by different methods, patients may be contacted through email, postal mail, by phone, or in clinic 
inviting them to use eSyM and/or participate in the SASS Questionnaire. 
 
There are six versions of the SASS Questionnaire: surgical experience eSyM+, eSyM-, and 
eSyM+ Non-Responder and drug therapy eSyM+, eSyM-, and eSyM+ Non-Responder. All 
versions contain validated PRO items (including PROMIS and CAHPs) and validated computer 
and internet use items from PEW. The eSyM+ versions contain additional items to evaluate 
usability and satisfaction with eSyM. The eSyM+ Non-Responder versions include additional 
questions to evaluate why eligible eSyM patients did not respond to the eSyM questionnaires. 
The SASS Questionnaire may be administered through REDCap, by phone, email, postal mail, 
or in clinic. Multiple methods of collection are allowed in order to minimize barriers to 
participation. As needed, patients will also be offered eSyM training through in-person, phone, 
and/or virtual visits. 
 
The patient qualitative interviews will follow the interview guide in Appendix RR. The interview 
will ask questions regarding patients’ overall experience with the program, suggested 
improvements they would make to the eSyM symptom questionnaire or the overall program, and 
any potential or real barriers to accessing or using the program. The interviews may take place 
by phone, via Zoom/video conference, or in-person. Multiple methods of collection are allowed 
to minimize barriers to participation. 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
27 
 
 
Materials that will be used to recruit subjects: See Appendices M and N for the message that 
will be sent to patients inviting them to participate in the questionnaire and/or eSyM, 
respectively. As a reminder, participating in the SASS questionnaire or eSyM survey will not 
influence a patient’s medical care in any manner. The purpose of these questionnaires is to help 
care teams learn about the best way to help patients cope with symptoms between visits (for 
medical oncology) and after surgery (for surgical patients).  
 
See Appendices SS and QQ for the message and consent form that will be sent to patients 
inviting them to participate in the qualitative interview. Participating in the qualitative interview 
will not influence a patient’s medical are in any manner. The purpose of these interviews is to 
gather direct patient feedback for study research staff about eSyM to inform future optimizations 
to the program.  
 
Duration of subject’s participation in the study:  
1) Per protocol, eSyM usage continues for up to 60-180 days but can continue indefinitely at 
the site’s discretion.   
2) The SASS Questionnaire is a one-time, 20-minute survey administered 30-180 days after 
surgery or first dose of chemotherapy.   
3) The patient qualitative interview(s) will last approximately 30 (but no more than 120) 
minutes; they will be administered any time after eSyM assignment at a time that is 
convenient for the subject.  
4) All eSyM- control and eSyM+ intervention patients will be followed for outcomes for up 
to 1-year after the trigger event (i.e., new chemotherapy treatment plan and/or surgery). 
 
Duration anticipated to enroll all study subjects: We anticipate that it will take five years to 
complete this activity. 
 
Study design: Hybrid effectiveness-implementation stepped-wedge cluster randomized trial.  
 
Description of all research procedures being performed: 
a) Epic, administrative/operations/billing databases, order entry databases, and/or cancer 
registry databases may be queried to identify denominator patients under a HIPPA 
waiver. 
b) Patients assigned to eSyM+ will be set up to use eSyM by their local clinic/study staff.  
Surgical patients will be set up to use eSyM at the time of surgical discharge (or at the 
site’s discretion).  Medical oncology patients will be set up to use eSyM at the time of 
their first chemotherapy dose visit (or at the site’s discretion). 
c) Select eligible participants will receive a message inviting them to participate in the 
SASS questionnaire 30-days after surgery or first chemo dose (Appendix Z). 
d) Participants who participate in the SASS questionnaire and indicate that they wish to 
receive a gift card will receive $15 gift card. Gift cards will be mailed or emailed 
according to patient preference. Please note, emailed gift cards will come directly from 
Amazon.com or sent by a study research staff member. 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
28 
 
e) Participants who participate in the qualitative interviews and indicate that they wish to 
receive a gift card will receive a $15 gift card. Gift cards will be mailed or emailed 
according to patient preference. Please note, emailed gift cards will come directly from 
Amazon.com or sent by a study research staff member. 
f) All denominator patients (eSyM- control and eSyM+ intervention) will undergo medical 
record (and/or local cancer registry) reviews.  The medical record (and/or local cancer 
registry) reviews will be accomplished using both automated data extraction and manual 
data abstraction under a HIPAA waiver.  
 
Monitor subjects for safety or minimize risks: The risk to participants is minimal with the 
primary risk being loss of confidentiality/privacy. To monitor the risk of loss of 
confidentiality/privacy, the informatics team will routinely monitor eSyM reports and data 
extracts and investigate inquiries from study teams. Furthermore, patients who report severe 
symptoms will be prompted to call their care team immediately, and clinicians will receive in-
basket notifications in the Epic EHR of the severe symptom report. All interview participants 
from outside of Dana-Farber Cancer Institute will provide written consent to have their 
information shared with the Dana-Farber research staff members who will contact them to 
conduct the interviews. 
 
What data will be collected and how:  
• Participant responses to the symptom reporting questions within eSyM will be collected. 
• Patient and clinician eSyM usage reports will be collected. 
• Patient-reported self-efficacy, attainment of information needs, symptom burden, and 
satisfaction with care will be collected via the SASS Questionnaire. 
• Patient feedback on the eSyM program and experiences with care team and symptom 
management via qualitative interviews.  
• Study-related health information and outcomes will be collected via medical record 
(and/or local cancer registry) review (automated and manual).  
• Hospital/clinic characteristics will be collected. 
• All data collected for this study will be submitted to the coordinating center (Dana-Farber 
Cancer Institute).  
 
Long-term follow-up: The patient’s medical record may be reviewed for outcomes for up to 1-
year after the trigger event (i.e., new chemotherapy treatment plan and/or surgery). 
 
Activity 5: Integration of eSyM data to develop algorithms to estimate outcomes, including 
the risk of ED usage and hospitalization, among patients with suspected or confirmed 
cancer 
 
Brief description of activity: Patients receiving treatment for metastatic cancer have high 
symptom burdens and high rates of adverse events, including emergency department (ED) use 
and hospital admissions, which can impact patients’ quality of life.57,58 Some of these adverse 
events may be preventable if providers can match patients with appropriate outpatient services. 
However, to achieve this goal, we must improve our ability to prospectively identify the patients 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
29 
 
at increased risk for near-term adverse events and most likely to benefit from intensification of 
outpatient care.  
 
Several studies have used EHR data to predict risk of death in cancer patients.59,60 However, 
efforts to date have several limitations. They rely on computationally-intensive methods that are 
difficult to implement in routine clinical practice. Little work has been done to develop models 
that predict adverse events which are actionable in the near-term. Existing risk-prediction models 
are susceptible to racial biases; little research has evaluated whether these models’ calibrations 
may have racial biases.61 And few efforts have incorporated newer data sources, such as ePROs, 
into risk prediction models. ePROs, which are now frequently collected in routine clinical care, 
may improve predictions.62  
 
We aim to develop methods to predict which patients are at the highest risk for undesirable 
outcomes, including hospitalization and ED use. These predictions will lay the foundation for 
future work to develop targeted interventions to intensify outpatient care and reduce preventable 
adverse events. Specifically, we will use SIMPRO data (including demographics, conditions, 
medications, encounters, ePROS, etc.) to develop predictive models that are built suing machine 
learning clinical risk prediction techniques. Through these efforts, we seek to address a number 
of important questions, including how ePRO data affect model performance; how clinical risk 
scores perform relative machine learning algorithms; and whether there are differences in model 
performance among different patient subgroups (to determine whether predictive model 
calibrations based on EHR data may be intrinsically biased). 
 
Using data from six health systems will allow us to evaluate algorithms to predict adverse events 
in diverse clinical settings 
 
Specific Aims: 
1. Develop algorithms to estimate the risk of adverse events, including ED usage and 
hospitalization, among patients with suspected or confirmed cancer who are treated in 
community settings.  
2. Assess whether inclusion of ePROs improves algorithm performance and how predictions 
from clinical risk scores compare to predictions from computationally intensive machine 
learning approaches 
3. Assess model performance among historically under-represented populations, including 
Black patients, and assess for evidence of racial bias in model calibration.  
 
Human Subjects Research Category (NHSR, exempt, expedited, full review): Exempt  
 
Informed Consent: Waiver of consent (retrospective data review).   
 
Activity 5 Population: All patient-level data collected in Activity 4 will be utilized. To date, the 
SIMPRO consortium has collected more than 50,000 survey responses and EHR data for more 
than 13,000 medical oncology and surgical oncology patients across these systems. These data 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
30 
 
present an opportunity to develop and test algorithms to predict adverse events in patients 
receiving care for a suspected or confirmed cancer.  
 
Number of subjects (per site and overall): All patient-level data collected in Activity 4 will be 
utilized. 
 
When, where, and how potential subjects will be recruited: Not applicable. Only previously 
collected patient-level data will be utilized.  
 
Materials that will be used to recruit subjects: Not applicable. Only previously collected 
patient-level data will be utilized. 
 
Duration of subject’s participation in the study: Not applicable.  
 
Duration anticipated to enroll all study subjects: Not applicable.  
 
Study design: Retrospective data analysis project.  
 
Description of all research procedures being performed: We will use data previously 
collected for the SIMPRO project to develop and evaluate the performance of predictive models 
for adverse events among patients with suspected or confirmed malignancy. The only new 
procedures will include novel analyses of existing data. 
 
Monitor subjects for safety or minimize risks: Not applicable, only deidentified datasets will 
be utilized for predictive modeling work.  
 
What data will be collected and how: Not applicable, previously collected data will be utilized.  
 
Long-term follow-up: Not applicable. 
 
 
 
 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
31 
 
6.0 
Study-Wide Number of Subjects 
 
 
Activity 1 – Stakeholder Engagement 
 
Activity 2 
Activity 3- 
Patient 
Engagement 
Activity 4 - Patient 
Engagement 
Activity 5 – 
Predictive 
Modeling 
Algorithms  
 
Patient 
Advisory 
Council 
Health 
system 
leaders 
Clinicians 
and staff 
Follow-
up 
Build 
eSyM 
UAT/Pilot study 
Pragmatic stepped-
wedge cluster 
randomized trial 
Integration of 
eSyM data 
 
Exempt, waiver of consent 
 
NHSR 
3a) NHSR 
3b) Waiver of 
documentation 
of consent 
3c) Waiver of 
consent  
4a) NHSR 
4b) Waiver of 
documentation of 
consent 
4c) Waiver of 
consent 
4d) Written consent  
Exempt, 
waiver of 
consent  
Study-
Wide 
Accrual 
30-150a 
24-60a 
360a 
720a 
n/a 
390 
6,048 (minimum)d 
[1,980 of whom will 
complete the SASS 
Questionnaire and 48 
patient interviews] 
n/a 
Accrual 
per site 
5-25a,c 
4-10a,c 
60a,c 
120a,c 
n/a 
90c at Dana-
Farber, and 
60c at each of the 
other 
participating 
sites. 
1,008c (minimum)d 
at each of the six 
participating sites 
[330 of whom will 
complete the SASS 
Questionnaire and 8 
taking part in patient 
interviews] 
n/a 
 
GRAND TOTAL MAXIMUM ACCRUAL ACROSS ALL STUDY ACTIVITIES PER SITE = 5,000 
GRAND TOTAL MAXIMUM ACCRUAL ACROSS ALL STUDY ACTIVITIES STUDY-WIDE = 30,000 
a Number can be larger or smaller depending on meeting attendance and availability of staff. 
b Interviews/surveys will continue until thematic saturation is reached. 
c Protocol does not mandate equal distribution of participants among participating sites. 
dThe entire statistical analysis section is predicated on minimum N = 6048. Because the goal is 
broad-based systems-level implementation, we anticipate having much higher N which will 
enable us to examine effectiveness in subgroups of interest. 
 
 
 
 
 
 
 
 
 
 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
32 
 
7.0 
Study-Wide Recruitment Methods 
Each activity utilizes slightly different recruitment methods.  See section 5.0 for details. 
 
8.0 
Multi-Site Research 
This is a multi-site study.  The lead site and coordinating center for this protocol is Dana-
Farber Cancer Institute. The regulatory sponsors are Dr. Deborah Schrag MD MPH (Co-
Grant PI and Study Chair) and Dr. Michael Hassett MD MPH (Co-Grant PI and 
Coordinating Center Site PI). All participating sites are required to adhere to the Data 
Safety and Monitoring Plan (DSMP) for this study (see Appendix S). 
 
9.0 
Study Timelines 
The duration of an individual subject’s participation in the study and the duration 
anticipated to enroll all study subjects varies by activity.  See section 5.0 for details. 
The estimated date for the investigators to complete primary analyses is September 30, 
2023. Secondary analyses are estimated to be completed by August 31, 2024. The 
estimated date of study completion is December 31, 2024. Dates are subject to change.  
10.0 
Study Endpoints and Statistical Analyses 
The detailed protocol statistical analysis plan (SAP) can be found in Appendix TT.  
 
Analysis of activity 1 (stakeholder engagement):  
Quantitative interviews will be scored using their established scoring metrics: 
• The NOMAD instrument is a 23-item survey that measures implementation processes 
from the perspective of professionals directly involved in the work of implementing 
complex interventions in healthcare. [Appendix J] 
• The AIM (Acceptability of Intervention Measure), IAM (Intervention Appropriateness 
Measure), and FIM (Feasibility of Intervention Measure) instruments are four-item 
measures of implementation outcomes that are often considered “leading indicators” of 
implementation success. [Appendix G]  
• The CSAT (Clinical Sustainability Assessment Tool) instrument is a 49-item survey with 
7 domains used be evaluators and researchers to determine the extent to which a practice 
is being implemented effectively. (Appendix Y) 
• The ORCA (Organizational Readiness to Change Assessment) instrument is a 74-item 
survey with three domains, each item has been mapped to a CFIR construct, and will be 
scored according to Helfrich et al.'s (2009). [Appendix B] 
• The OCM (Organizational Change Manager) instrument is a 60-item survey with 15 
domains, each item has been mapped to a CFIR construct, and will be scored according 
to Gustafson et al.’s (2003). [Appendix B2] 
 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
33 
 
Qualitative interviews (audio recordings and notes) will be evalutated for common themes. 
Results from the qualitative and quantitiative interviews and surveys will be used to inform 
eSyM, its content, its rollout, and the training materials. 
 
Analysis of Activity 3 (UAT/Pilot study): 
Study staff will observe patient/proxy, clinician and clinical support staff action steps and 
interactions with the system.  Observations will be recorded and used to refine eSyM, its rollout, 
and the training materials. 
 
Any patient data collected will be analyzed as per the analysis plan for the stepped-wedge cluster 
randomized trial described below. 
 
Analysis of Activity 4 (stepped-wedge trial): 
 
Additional details can be found in Appendix TT. Please reference Appendix TT for the most 
updated SAP.   
 
Study Design:  Type II Hybrid Effectiveness-Implementation Stepped Wedge Cluster 
Randomized Trial.  The research team will partner with software developers at Epic to adapt 
working ePRO symptom management systems, one in surgical and one in medical oncology, and 
fully integrate them into the EHR at 6 health systems. After pilot testing, we will conduct a 
pragmatic stepped wedge cluster randomized trial to measure the effectiveness of the ePRO 
system on outcomes that matter to patients and clinicians. Throughout, we will evaluate the 
implementation process to optimize sustainability and generate actionable knowledge that 
facilitates scaling to other settings. The proposed study is a hybrid effectiveness-implementation 
type I trial according to the Curran schema.131 The study meets PRECIS-2 criteria for pragmatic 
trials based on scores of 4 or higher in each domain.132 Reports will adhere to the revised Criteria 
for Reporting the Development and Evaluation of Complex Interventions in healthcare 
(CReDECI2),133 the CONSORT PRO134 and cluster randomized extensions,135  and the stepped 
wedge reporting guidelines proposed by Grayling.136 
 
The PICOTS FRAMEWORK.63   
Populations 
1) Adult patients with GI, GYN, or Thoracic cancer having a new treatment plan  
2) Adult patients with suspected GI, GYN, or thoracic cancer having a priority surgery  
 
**Patients were seen at the participating sites between January 1, 2018 and March 31, 
2024. Dates are subject to change.** 
Intervention 
eSyM: A multi-component ePRO Symptom Management system based on PRO-CTCAE 
with: 
1. Patient-facing components:  
• 
Prompts for between-clinic visit symptom reporting and the ability to view profiles 
over time 
• 
Evidenced-based education for self-management in response to symptom reports 
• 
Alerts to contact the clinical team in response to severe or escalating symptoms 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
34 
 
2. Clinician-facing components:  
• 
View patient profiles in EHR flowsheet, accessible between or during visits, easily 
added to notes 
• 
Receive alerts for severe symptoms in the EHR, same as for abnormal lab tests  
• 
Dashboard functionality to track symptoms for groups of patients    
Control 
No eSyM symptom reporting 
Outcomes 
Emergency department visits culminating in discharge, hospitalizations, symptom burden, 
care satisfaction 
Timing 
4-year study of surgical and medical oncology patients each followed for up to 1 year after 
the trigger event (i.e. new chemotherapy treatment plan and/or surgery) 
Setting 
Six health care systems, all small cancer centers. All use an Epic EHR. 
Design 
A hybrid Type II effectiveness-implementation pragmatic cluster randomized trial, with 
stepped wedge rollout (6 steps), patient as the unit of analysis and closed (cross-sectional) 
cohort design 
 
Randomization:  
 
We will conduct a stepped wedge cluster randomized trial to determine whether ePROs are 
clinically effective. This stepped wedge design has 6 steps, and we randomize 6 sites (Table) to 
the steps.  
 
Table: Six participating sites and region 
Site 
Region 
WVU 
Southern 
Baptist 
Dartmouth 
Northern 
Maine 
DFCI/BWH/MGH 
Urban 
Lifespan 
 
To ensure that two sites with the same attribution will not be assigned to the same rollout step 
group (early MO/late surgery or late MO/early surgery), we employ a stratified randomization by 
region. As a result, each of the two groups has a site from each of the three regions (Northern, 
Southern, and Metropolitan). The stepped wedge design includes seven time-periods, including a 
run-in period (Figure). .  
 
Figure: Study design 
Group 
Step 
Run-in 
Period 1 
Period 2 
Period 3 
Period 4 
Period 5 
Period 6 
Early MO 
/late surgery group 
Step 1 
 
MO 
MO 
MO 
MO 
MO 
MO 
 
Surgery 
Step 2 
 
MO 
MO 
MO 
MO 
MO 
 
Surgery 
Surgery 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
35 
 
Step 3 
 
MO 
MO 
MO 
MO 
 
Surgery 
Surgery 
Surgery 
Late MO 
/early surgery 
group 
Step 4 
 
MO 
MO 
MO 
 
Surgery 
Surgery 
Surgery 
Surgery 
Step 5 
 
MO 
MO 
 
Surgery 
Surgery 
Surgery 
Surgery 
Surgery 
Step 6 
 
MO 
 
Surgery 
Surgery 
Surgery 
Surgery 
Surgery 
Surgery 
MO: Medical oncology  
Surgery: Surgical patients  
 
The sites were randomized on 11/6/18 as follows: 
 
Group 
Step 
Run-in 
Period 1 
Period 2 
Period 3 
Period 4 
Period 5 
Period 6 
Early MO 
/late surgery group 
Baptist 
 
MO 
MO 
MO 
MO 
MO 
MO 
 
Surgery 
Maine 
 
MO 
MO 
MO 
MO 
MO 
 
Surgery 
Surgery 
Dana-
Farber/BWH 
 
MO 
MO 
MO 
MO 
 
Surgery 
Surgery 
Surgery 
Late MO 
/early surgery 
group 
Lifespan  
 
MO 
MO 
MO 
 
Surgery 
Surgery 
Surgery 
Surgery 
Dartmouth 
 
MO 
MO 
 
Surgery 
Surgery 
Surgery 
Surgery 
Surgery 
WVU 
 
MO 
 
Surgery 
Surgery 
Surgery 
Surgery 
Surgery 
Surgery 
 
 
Analysis of Activity 4d (Patient qualitative interviews): 
Qualitative interviews (audio recordings and notes) will be evalutated for common themes using 
NVIVO. Results from the qualitative interviews will be used to inform eSyM enhancements, 
program content, program rollout, and implementation strategies. 
 
Analysis of Activity 5: 
 
We will extract structured data from the six health systems participating in SIMPRO. These data 
include ePROs, demographics, diagnoses, treatment plans, medications, and inpatient and 
outpatient encounters. We will develop risk prediction models for adverse events, especially 
including, but not limited to hospitalizations and emergency department visits. Planned 
hospitalizations will be identified and excluded based on A) admissions within 24 hours of the 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
36 
 
triggering surgery among surgical patients; and B) admissions associated with curative-intent 
surgeries among medical oncology patients with early-stage cancers. For models incorporating 
ePROs as predictors, the analytic cohort will include patients who completed at least one survey. 
For models excluding ePROs as predictors, the analytic cohort will include all patients in the 
database.  
 
Data from at least one health system will be removed from the dataset to serve as an external test 
set. Among the remaining health systems, the population will be split at the patient level with 
70% randomly assigned to a training cohort, 15% assigned a validation cohort and 15% assigned 
to an internal test set. To account for differences in clinical practice and demographics across 
health systems, randomization will be stratified by system. The same cohorts will be used to train 
and test all algorithms.  
 
To determine the optimal machine learning model, we will evaluate multiple types of 
architectures, including logistic regression, random forests, gradient boosted machines, extreme 
gradient boosting, neural networks, and ensemble models. Hyperparameters will be tuned using 
the validation cohort and models iteratively trained until a final candidate model is identified. 
This model will then be evaluated on the held-out internal test set and the external test cohort, 
after which no further model training will be performed. These steps will be performed 
separately for the ePRO-responding cohort and the total cohort. 
 
To develop clinical risk scores, we will select approximately 20 independent variables that can 
be easily abstracted from a patient’s medical chart, such as diagnosis, treatment, comorbid 
conditions, recent hospitalizations, and demographics. Within the training cohort, we plan to use 
logistic regression with L1 regularization to select variables for inclusion and define the 
prediction model. The amount of regularization will be tuned using the validation cohort and 
models will be iteratively trained until a final candidate model is identified. Like above, these 
steps will be completed separately for the ePRO-responding and total cohorts. The area under the 
receiver operator characteristic curve (AUC-ROC) will be used to compare the performance (i.e., 
predictive ability) of different models.  
 
11.0 
Procedures Involved 
The study design, study procedures and safety monitoring vary by activity.  See section 
5.0 for details. 
12.0 
Data Management and Confidentiality 
 
DF/HCC uses a clinical trial management system (CTMS) called OnCore, which is managed by 
the Office of Data Quality (ODQ). 
• Activity 1 is research exempt from IRB review and involves engaging stakeholders.  
This will be achieved via emailed surveys or in group settings using discussion and 
handheld polling devices.  We will collect basic demographic information.  We will 
collect age group, gender, race, and ethnicity.  We will NOT collect each 
participant’s initials and date of birth.  We will enter summary/batch accrual 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
37 
 
information into Dana-Farber’s CTMS OnCore for Activity 1. Individual 
registration is not feasible as OnCore mandates DOB. 
• Activity 2 is NHSR; registration in OnCore is not applicable. 
• Activities 3 and 4 will be largely automated.  Epic will be programmed to identify 
and/or push eSyM out to applicable patient recipients. This is an implementation/QI 
study, not a traditional research study, so the consent/registration/intervention 
paradigm does not fit activities 3, 4a, 4b, and 4c. Activity 4d will include patient 
consent. Furthermore, activity 4 will accrue a minimum of 6048 participants.  For 
these reasons, manual registration of each participant into OnCore before exposure 
to eSyM and/or the SASS questionnaire is not possible.  Initials, date of birth, 
gender, race and ethnicity will be collected, and we will work with ODQ to provide 
ODQ with this data for all participants from all sites so that it can be imported into 
OnCore. 
• Activity 5 will involve a retrospective review of data collected in Activity 4. 
Registration in OnCore is not applicable. 
 
Data security: PHI data will be collected using multiple applications: REDCap, 
eSyM/MyChart, Epic. 
 
REDCap: For this study, data will be collected using the Partners instance of REDCap 
(redcap.partners.org). Consent for Activity 4D will also be collected using REDCap.  In 
collaboration with the Harvard Catalyst | The Harvard Clinical and Translational Science 
Center, REDCap (Research Electronic Data Capture) is a free, secure, HIPAA compliant 
web-based application hosted by Partners HealthCare Research Computing, Enterprise 
Research Infrastructure & Services (ERIS).  Vanderbilt University, with collaboration 
from a consortium of academic and non-profit institutional partners, develops this 
software application for electronic collection and management of research and clinical 
study data. Data collection is customized for each study or clinical trial by the research 
team with guidance from ERIS REDCap administrators.  REDCap is built around HIPAA 
guidelines and is 21 CFR Part 11 capable.   
 
eSyM (which will be built into Epic): Epic applications employ a variety of technical 
safeguards to protect the confidentiality, integrity, and availability of personal 
information including supporting Transport Layer Security (TLS)/Secure Sockets Layer 
(SSL) certificate technology and encryption. 
 
To maximize data security, both REDCap and eSyM/Epic employ: 
 
User Privileges. To ensure that users have access only to data and information that they 
are supposed to have within the application, user privileges are utilized within the 
software. Each user has their own account, and their user account will only have access to 
information that they themselves have created or to which administrators have granted 
them access. 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
38 
 
 
Password-protection & Authentication. Both systems are password protected and 
implement authentication to validate the identity of end-users that log in to the system. 
 
Auto-logout setting will automatically log a user out of the system if they have not had 
any activity (e.g., typing, moving the mouse) on their current web page for the set amount 
of time. This prevents someone else from accessing their account and their data if they 
leave a workstation without properly logging out or closing their browser window. 
 
Logging and Audit Trail. Both systems maintain built-in audit trails that log all user 
activity and all pages viewed by every user. 
 
 
Study specific procedure to maximize data security: 
 
Controlled access: The REDCap administrator at the coordinating site (Dana-Farber) will 
set up all user accounts so that each user only has access to their own site’s data. 
 
Use of unique study ID numbers: REDCap automatically assigns unique study ID 
numbers to each new case.   
 
Extensive training: All personnel involved in this study are required to complete and 
document completion of extensive protocol training.  Furthermore, all project 
investigators and staff are required to have valid certification of human subjects’ research 
training. 
 
Quality control: The staff at the coordinating center (Dana-Farber) will be responsible for 
monitoring the data for completion, accuracy, and compliance. 
 
SFA storage: All study files will be maintained on a MGB HIPPA-compliant SFA. 
Backup copies will also be saved on an encrypted external hard drive. The study PI and 
PM will oversee user privileges to each of these storage areas and perform regular user 
audits to ensure proper access is maintained to all study files.  
 
 
Data collection and submission processes: 
 
At each local site: Hard copies of applicable study documents (i.e., printed SASS questionnaires, 
qualitative interview consent forms, etc.) will be kept in local study files in locked cabinets.  
Local copies of study materials may be destroyed 5-years after the primary completion date or at 
the discretion of the local site PI and local site IRB. NOTE: Prior to conducting any patient 
qualitative interviews, the coordinating center will request that a copy of the signed patient ICF 
be transmitted to DFCI. See below for data transmission methods. As appropriate, electronic ICF 
may also be obtained using REDCap.  

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
39 
 
 
Data submission to the central coordinating site:  Local sites will transmit data to the central 
coordinating site using multiple methods: (1) study data will be submitted via REDCap; for this 
study, we will use the Partners Healthcare instance of REDCap available here: 
https://redcap.partners.org/redcap/.  Sites will log into REDCap, fill out CRFs and upload source 
documentation and other files, and submit.  (2) data downloads from eSyM/Epic will be 
transmitted to the central site using secure file transfer protocol (FTP).  We will use a secure FTP 
managed by the Epic EHR vendor or we will use Partner’s Healthcare secure FTP available here: 
https://transfer.partners.org/courier/web/1000@/wmLogin.html or the Partners automated 
Diplomat SFTP platform.  (3) When appropriate, sites may transmit data via email.  When 
appropriate, the email can be encrypted by typing “Send Secure” in the email subject line.  (4) 
Epic may share site-specific data reports with the coordinating center (5) Due to the size and 
complexity of this project, other methods may be used if they are preapproved by the Dana-
Farber PI and IT.  
 
Please note: All sites will transmit a limited data set to the coordinating center in accordance 
with the SIMPRO-developed Data Use Agreement, which has been agreed upon by all 
participating sites.  
 
 
 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
40 
 
Summary of data collection: 
 
Data Sources & Representative Data Elements 
Epic Data 
Patient 
survey 
Collection/ 
abstraction 
Derived data 
Patient 
interview 
Entered 
by the 
patient 
Entered 
by a 
clinician 
Recorded 
processes 
 
 
 
 
PROs, 
medical 
history 
Medical 
problems; 
chemo 
regimens 
Hospital 
admissions; 
proportion of 
surveys 
completed 
Quality of 
life; 
symptoms, 
self-efficacy 
Cancer stage; 
disease status 
 
Provider/hospital 
type & volume 
Number of 
urgent clinic 
visits for 
symptom 
management; 
Comorbidity 
Feedback 
on eSyM 
experiences 
(to be 
recorded 
and 
transcribed) 
 
Data Levels, Descriptions & Representative Data Elements 
Patient-
encounter 
Patient 
Population 
Healthcare system 
Patient features 
that could 
change/recur 
over time 
Patient features that 
do not change over 
time 
Feature of multiple 
patients 
Feature of a site or 
provider 
PROs 
Disease status 
Urgent clinic 
encounters 
ED encounters 
Hospitalizations 
Chemotherapy 
plans  
Health literacy 
Date of birth/age 
Race/ethnicity 
Cancer type 
Cancer diagnosis 
date 
Surgery type and 
date 
Proportion of 
patients reporting a 
serious (i.e., high 
grade) symptom 
Proportion of 
patients responding 
to a survey 
Urban/rural setting 
Medical/surgical 
provider 
High/low volume 
facility 
Teaching hospital 
status 
 
 
 
 
 
 
 
 
 
 
 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
41 
 
 
 
Data collection from EPIC: 
 
 
 
 
Summary of Data Sharing: 
 
Each Data Provider, including DFCI/BWH/MGH, will provide the following DATA SET to 
DFCI on a quarterly basis: 
 
Activity 1 (Stakeholder Feedback): Stakeholders include physicians, nurses, allied health care 
professionals, practice administrators, information technology support staff and administrators 
• Email addresses for stakeholder participants (for REDCap administration ONLY)  
• Basic demographic information from stakeholders (including # of years working for their 
organization, professional job category, gender, racial background, ethnicity, age group) 
collected via Clicker questions, REDCap, and/or email 
• Audio recordings from UM1 focus groups and/or individual qualitative interviews  
• Transcripts from UM1 focus groups and/or qualitative interviews  
o Meeting minutes from UM1 focus groups. Feedback may be collected in an 
identifiable fashion. For example, the CIO’s comments may be attributed to “the 
CIO.” 
• Clicker-question responses from UM1 focus groups (i.e., NOMAD, CFIR, AIM items 
etc.) 
• REDCap survey responses (i.e., NOMAD, CFIR, AIM Items, etc.) 
 
Activity 2 (Build & deploy eSyM)  
• NO data transfer required  
 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
42 
 
Activity 3a (eSyM App Usage) 
• Participant responses to the symptom reporting questions within eSyM (collected via 
Epic/MyChart) 
• Participant MyChart activity including login dates, mode of usage, and number of 
messages sent to the care team  
• Clinician responses to symptom reports (collected via Epic) including # of documented 
eSyM encounters and InBasket message responses  
• Data on eSyM usage by all user types (collected via Epic/MyChart) 
 
Activity 3b (eSyM User Acceptability Testing) 
• Notes and observations taken during user acceptability testing   
**No PHI will be collected during UAT 
 
Activity 3c (Medical Record Abstraction): This activity is necessary to understand how exposure 
to eSyM influences rates of acute care visits. 
• Patient identifier - study ID # which may be an encrypted MRN (collected via Epic and 
encrypted as needed by site study team). Study teams at each site will encrypt actual MRNs 
and provide a study ID#. Suggested algorithms and code will be provided but this must be 
done at each site. Each site must separately store the “master key” that links real MRN to 
study ID#. Actual MRNs will not be released to the DFCI or shared with the NCI. 
• Patient study site – identifying which hospital system and which clinic site a patient is seen at 
for those hospitals having more than one site. 
• Patient zip code of residence (collected via Epic) 
• Patient DOB – This may be encrypted.  The year of birth is required. However, sites can elect 
to encrypt birth date and month. For example, a site may encrypt through an algorithm that: 
a) adds 4 months and 11 days to all birth dates that are in even number calendar years and 
subtracts 3 months and 16 days from all birth dates that are in odd number years. Each site is 
responsible for developing and deploying its own encryption file and storing it locally in 
secure fashion.  
• Patient vital status  
• Patient demographic information, including sex, race, ethnicity, language, marital status, 
employment status, and education level  
• Patient eSyM inclusion information, including cancer diagnosis data and/or procedure data 
o Cancer diagnosis code (ICD-10 codes), date and description  
o Complete Epic problem list  
o Procedure code (CPT code), date, description, and goal 
o Cancer staging code  
o Treatment plan information, including start date, end date, intention  
o Medications list  
• Patient dates of service including surgery, chemo administration, follow-up appointments, 
etc. (collected via Epic)  
• Study-outcomes collected via Epic including: 
o Hospital readmission rates within 90 days for surgical patients 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
43 
 
▪ Information will include visit dates, discharge diagnosis codes 
o Hospital admission rates within 90 days of chemotherapy for medical oncology 
patients. 
▪ Information will include visit dates, discharge diagnosis codes 
o Emergency department visits (including those that culminate in admission versus 
those that culminate in discharge) for surgical and medical oncology patients 
▪ Information will include visit dates, discharge diagnosis codes 
o Dates of chemotherapy administration  
 
**Please note – Additional medical record data and outcomes will be collected via Epic as 
determined by the SIMPRO consortium. All requested items will still fall within the parameters 
of a limited data set** 
 
Activity 4a (eSyM App Usage) 
• Participant MyChart activity including login dates, mode of usage, and number of 
messages sent to the care team  
• Data on eSyM usage by all user types  
• Clinician responses to symptom reports (collected via Epic) including # of documented 
eSyM encounters and InBasket message responses  
 
Activity 4b (SASS Questionnaire) 
• Patient contact information (email address and/or postal address) to be inputted into 
Partners REDCap for survey administration ONLY. There is no other use of patient 
emails as part of this study.  
• Patient-reported self-efficacy, attainment of information needs, symptom burden, and 
satisfaction with care using validated metrics.  
 
Activity 4c (Medical Record Abstraction) 
• Patient identifier for all patients in the denominator cohort (eSyM users and non-users) - 
study ID # and/or encrypted MRN (collected via Epic and encrypted as needed by site study 
team) 
• Patient study site ID for all patients in the denominator cohort (eSyM users and non-users)   
• Patient zip code of residence (collected from Epic registration field) 
• Patient DOB for all patients in the denominator cohort (eSyM users and non-users) – DOB 
can have encrypted birth month and day as described above under activity 3c. 
• Patient vital status  
• Patient demographic information, including sex, race, ethnicity, language, marital status, 
employment status, and education level  
• Patient eSyM inclusion information, including cancer diagnosis data and/or procedure data 
o Cancer diagnosis code (ICD-10 codes), date and description  
o Complete Epic problem list  
o Procedure code (CPT code), date, description, and goal 
o Cancer staging code  

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
44 
 
o Treatment plan information, including start date, end date, intention  
o Medications list 
• Patient dates of service including surgery, chemo administration, follow-up appointments 
(collected via Epic) for all patients in the denominator cohort (eSyM users and non-users) 
Please see detail under Activity 3c. 
• Study-outcomes collected via Epic including: 
o Hospital readmission rates within 90 days for surgical patients 
▪ Information will include visit dates, discharge diagnosis codes 
o Hospital admission rates within 90 days of chemotherapy for medical oncology 
patients. 
▪ Information will include visit dates, discharge diagnosis codes 
o Emergency department visits (including those that culminate in admission versus 
those that culminate in discharge) for surgical and medical oncology patients 
▪ Information will include visit dates, discharge diagnosis codes 
o Dates of chemotherapy administration  
 
Activity 4d (Patient Interviews)** 
• Name, phone number, and email addresses for consented patient participants (for 
interview scheduling purposes)  
• Basic demographic and diagnosis information as well as eSyM history will be collected 
directly from patients 
• Audio recordings from qualitative interviews  
• Transcripts from qualitative interviews  
o Transcripts will be deidentified (e.g. names, treatment location, state, etc) 
 
**NOTE: As Activity 4d is a consented protocol activity, identifiable information will be shared 
with the coordinating center. During the consenting process, enrolling participants will be made 
aware and attest through their written consent that their contact information will be shared with 
the coordinating center and that interviews will be conducted directly by the coordinating center, 
not the local study team. Participants will have the option to opt out at any time. After consent 
and upon completion of the qualitative interviews, audio recordings will be transcribed and 
interview transcripts will be deidentified prior to analyses, publications, or future data sharing 
activities 
 
Please note – Additional medical record data and outcomes will be collected via Epic as 
determined by the SIMPRO consortium. All requested items will still fall within the parameters 
of a limited data set. 
 
Please note: All data stored at the Dana Farber Cancer Institute (SIMPRO Coordinating 
Center) is kept under double password protected servers that routinely have audits to examine 
access.  
Investigators at all SIMPRO Data Provider institutions will have access to the full compiled 
program limited data set (e.g., all data explicitly listed above as well as any other data 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
45 
 
collected and shared through this limited data set agreement). In addition, this complete 
data set will be shared with the designated study chair and team at Memorial Sloan 
Kettering Cancer Center.  
 
DFCI will provide the following limited dataset to the National Cancer Institute (IMS): 
• Stakeholder Data  
o Aggregate site participation #’s  
o Hospital and provider characteristics (as available) 
o Transcripts from UM1 focus groups and/or qualitative interviews  
▪ Meeting minutes from UM1 focus groups. Feedback may be collected in 
an identifiable fashion. For example, the CIO’s comments may be 
attributed to “the CIO.” 
o Stakeholder clicker-question responses from UM1 focus groups (i.e., NOMAD, 
CFIR, AIM items etc.) 
o Stakeholder REDCap survey responses (i.e., NOMAD, CFIR, AIM Items, etc.) 
• Patient Data 
o Study ID for SASS survey respondents  
o Responses for each survey respondent  
o Patient demographics 
▪ Patient zip code  
▪ Age (interval linked to anchor date)  
▪ Sex, race, ethnicity, language, marital status, employment status, state of 
residence and education level 
o Enrollment 
▪ Procedure type and category 
▪ Tx plan and type  
o Clinical encounters and appointments 
▪ Encrypted date of procedure 
▪ Interval between surgery and hospital discharge  
▪ Interval between hospital discharge and eSyM symptom reports  
▪ Interval between hospital discharge and ED visits  
▪ Interval between hospital discharge and rehospitalizations  
▪ Encrypted date of new chemo and treatment administrations  
▪ Interval between new chemo and eSyM reports 
▪ Interval between new chemo and ED visits 
▪ Interval between new chemo and rehospitalizations  
▪ Hospital readmission and ED rates within 30 and 90 days of 
chemo/surgery 
o Cancer diagnoses  
o Comorbid condition diagnoses 
o Procedures performed during encounters 
▪ Laboratory data with encrypted date fields (i.e., intervals based on anchor 
date)   
o Cancer-directed medication administrations and/or orders 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
46 
 
▪ Medication list with encrypted date fields (i.e., intervals based on anchor 
date) 
o Symptom-directed medication administrations and/or orders 
o Vital signs data (body mass index (BMI) measurements only) 
 
**Please note – Additional medical record data and outcomes will be collected via Epic as 
determined by the SIMPRO consortium and may be shared with the NCI. All requested items will 
still fall within the parameters of a limited data set** 
 
Please note: 
• Deidentified, patient level data will be compiled from the SIMPRO consortium (Dana-
Farber Cancer Institute, Maine Health, Dartmouth-Hitchcock Memorial Hospital, 
Baptist Memorial Health Care Corporation, Lifespan Cancer Institute/Rhode Island 
Hospital, West Virginia University Hospitals, Inc.) 
• The PI and project manager of each of the 6 SIMPRO sites will review all data to be 
shared with the NCI. 
 
13.0 
Provisions to Monitor the Data to Ensure the Safety of Subjects 
 
Please see the Data Safety and Monitoring Plan (Appendix S). 
 
14.0 
Future Use of Data 
 
This study does not involve any specimen collection/banking of any kind. 
Personal health information will be collected as part of this study. 
 
All data collected during this study will be stored and used for future research.  Any personal 
identifiers will be removed so that the information cannot be linked back to a patient. Details on 
data use cases can be found below:  
 
1) Local site investigators utilizing SIMPRO data collected at their home institution 
(one site) – Investigators should receive local site PI approval to obtain and analyze 
internal site data. IRB approval should be obtained locally as needed.  
2) SIMPRO investigators utilizing SIMPRO data – All analyses are covered through this 
protocol. No additional approvals are needed.  
3) Investigators at SIMPRO sites utilizing SIMPRO data outside of the scope of the 
original grant - Investigators, including those from collaborating institutions, can request 
the data collected from this study for new research.  Requests must be sent to the 
Coordinating Center Site PI (Michael Hassett MD, MPH). All data requests and analysis 
plans must be approved by the coordinating center sIRB (WIRB) and local site IRBs, as 
required, through this protocol or stand-alone protocols.  
4) NCI and IMPACT collaborators utilizing SIMPRO data - Per the SIMPRO-
developed data use agreement, a limited data set will be shared with the National 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
47 
 
Institutes of Health (National Cancer Institute) and IMPACT consortium member sites in 
accordance with funding requirements. Publications and presentations resulting from 
analyses using SIMPRO data will include appropriate credits and authorship as agreed to 
with SIMPRO investigators.  
5) External collaborators utilizing SIMPRO data – Data may also be shared with outside 
non-profit academic investigators as well as with for-profit pharmaceutical investigators 
or commercial entities with whom Dana-Farber collaborates.  Requests must be sent to 
the Coordinating Center Site PI (Michael Hassett MD, MPH). All data requests and 
analysis plans must be approved by the coordinating center and appropriate IRB 
approvals and data transfer agreements will be obtained.  
 
The study letters inform the participant that data collected for this study may be used in the 
future.  Participants will not be asked to provide additional informed consent for the use of de-
identified information in future research.  
 
There is no scheduled date on which the information and data that is being used or shared 
for this research will be destroyed, because research is an ongoing process. The eventual 
goal is to make deidentified SIMPRO data publicly available through collaborations with 
the NCI. 
 
 
15.0 
Withdrawal of Subjects 
 
Symptom reporting via eSyM per protocol will continue for 60-180-days; after this period, the 
local site may decide whether to continue having the patient report symptoms via eSyM or not.  
Observational follow-up will continue for 1-year.  If a patient submits a request in writing to be 
removed from eSyM, then their local site will deactivate their account.  Any data collected up to 
that point will be kept and included in analyses.  Patient status [denominator group, eSyM active 
in 60-90-day window, eSyM active beyond 60-90-day window, written request of withdrawal, 1-
year observational window, or post-1-year observational window] will be captured via eSyM and 
REDCap CRF. 
 
 
16.0 
Risks to Subjects 
 
There are risks to taking part in any research study.  The primary risk of this study is loss of 
privacy or confidentiality. The risk of loss of privacy or confidentiality by using eSyM or taking 
part in this study is minimal.  The study team has taken many steps to prevent any loss of privacy 
or confidentiality, including training of all clinic and research staff in best practices, rules, and 
regulations surrounding privacy and confidentiality, collecting research data using unique study 
ID numbers instead of names or other identifying information, and use of data collection systems 
that meet the NIH’s data security standards. 
 
 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
48 
 
17.0 
Potential Benefits to Subjects 
 
Using eSyM may or may not benefit participants.  We hope that by using eSyM, patients are able 
to better manage their symptoms and the increased flow of information between a patient and 
their care team improves their experiences.  We also hope the information learned from this 
research study will provide more information about how to best help patients, caregivers, and 
their care team work together during and between visits to achieve better symptom management 
in cancer patients. 
 
 
18.0 
Vulnerable Populations 
 
This protocol does not involve vulnerable populations of prisoners and children. 
Prisoners and children are excluded. 
Cognitively impaired adults may participate because the risk is negligible. This protocol 
only involves questionnaires, opinion surveys and symptom reporting via an internet 
enabled app (MyChart). Additionally, cognitive status is not reliably captured in the EHR 
and, as this project involves automated identification of patients, we will not be able to 
exclude patients prior to eSyM assignment based on cognitive status. 
Pregnant women may participate because the risk to the woman and her fetus is 
negligible. This protocol only involves questionnaires, opinion surveys and symptom 
reporting via an internet enabled app (MyChart). 
 
19.0 
Sharing of Results with Subjects 
 
Participants will be directed to clinicaltrials.gov for research study results. 
 
20.0 
Setting 
 
This is a multi-site study that will take place at 6 sites in the US. Dana-Farber will serve as the 
coordinating site. 
 
 
21.0 
Resources Available 
 
The feasibility of this study is based on estimates obtained from the 2016 analytic cases of the 
tumor registrar at each of the participating sites. Although there is some heterogeneity based on 
tumor type, there are more than adequate new cancer cases at each participating site to meet the 
study minimum accrual goals of 144 surgical and 144 medical oncology patients per year. The 
entire statistical analysis section is predicated on minimum accrual targets. Because the goal is 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
49 
 
broad-based systems-level implementation, we anticipate having much higher accrual which will 
enable us to examine effectiveness in subgroups of interest. Additional patient accrual adds 
relatively little to the cost of executing the study given that we propose a limited number of 
surveys and limited manual record review. Ascertaining potential subjects, their outcomes and 
relevant covariates can be done through Epic. The hard work is implementation and changing 
clinical workflow. Once successfully implemented, we project that the incremental work of 
engaging more patients in eSyM will be minimal. 
 
 
22.0 
Provisions to Protect the Privacy Interests of Subjects 
 
Please see sections 11 and 12 for details. 
 
 
23.0 
Compensation for Research-Related Injury 
 
There is no compensation in the event of research related injury. 
 
24.0 
Economic Burden to Subjects 
 
Costs that subjects may be responsible for because of participation in the research: 
Subjects participating in this study will be asked to complete online surveys and/or report 
their symptoms from home using an internet-enabled device.  Participants will have to 
use their own hardware (e.g., smartphone, tablet, computer) and their own Wi-Fi or Data 
Plan which may cost them money; subjects are responsible for these costs.  Devices 
and/or data plans will not be provided by the study. 
 
 Patients who participate in the SASS questionnaire and/or patient qualitative interviews 
will each be offered a $15.00 gift card as a thank you.  
 
 
25.0 
Consent Process 
 
Each activity utilizes different consent methods.  See section 5.0 for details. 
 
 
 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
50 
 
 
 
26.0 
Appendices 
**All appendices may be branded with site-specific logos as needed; wherever applicable, the 
Dana-Farber Cancer Institute logo may be removed and replaced with the applicable site logo. 
In addition, all materials will regularly be reviewed and updated as eSyM content is revised 
 
Question Banks: 
Appendix A: CFIR Qualitative Question Bank 
Appendix B: ORCA Quantitative Question Bank 
Appendix B2: OCM Quantitative Question Bank 
Appendix B3: eHIQ Quantitative Interview Question Bank 
Appendix C: CAHPS Question Bank for cancer surgery 
Appendix D: CAHPS Question Bank for cancer drugs 
Appendix E: CAHPS Question Bank supplemental questions  
Appendix F: PROMIS Question Bank 
Appendix G: AIM/IAM Question Bank  
Appendix H: PROCTCAE Question Bank – English 
Appendix I: 
PROCTCAE Question Bank – Spanish 
Appendix J:  NOMAD Question Bank  
 
Recruitment/Consent Materials: 
Appendix K: Stakeholder recruitment email 1 (informing development) 
Appendix L: Stakeholder recruitment email 2 (evaluating implementation) 
Appendix M: Patient Invitation to participate in research questionnaire 
Appendix N: Patient Invitation to use eSyM 
Appendix O: Model Study Letter for Activity 3b (UAT) (waiver of documentation of consent) 
Appendix P:  UAT Observation Guide 
Appendix Q:  eSyM Disclaimer (NHSR) 
Appendix R:  Model Study Letter for Activity 4b (SASS Questionnaire) (waiver of 
documentation of consent) 
Appendix S: DSMP 
 
Study References: 
Appendix T1: eSyM Medical Oncology Patient-Facing Tip Sheets 
Appendix T2: eSyM Surgical Patient-Facing Tip Sheets 
Appendix U1: Patient-Facing SASS Questionnaire – MO eSyM+ Version  
Appendix U2: Patient-Facing SASS Questionnaire – MO eSyM+ Non-Responder Version 
Appendix V: Patient-Facing SASS Questionnaire – MO eSyM- Version  
Appendix W1: Patient-Facing SASS Questionnaire – SO eSyM+ Version  
Appendix W2 : Patient-Facing SASS Questionnaire – SO eSyM+ Non-Responder Version 
Appendix X: Patient-Facing SASS Questionnaire – SO eSyM- Version  
Appendix Y: Stakeholder Interview Guide 
Appendix Z: Patient-Facing SASS Questionnaire Cover Letter  

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
51 
 
 
eSyM Training & Marketing Materials:  
Appendix AA: eSyM Clinician User Guide  
Appendix BB: Clinician-Facing eSyM Flyer 
Appendix CC: Clinician-Facing FAQs Page 
Appendix DD: Patient-Facing eSyM Flyer 
Appendix EE: Patient-Facing eSyM Pamphlet 
Appendix FF: Patient-Facing eSyM User Guide 
Appendix GG: Patient-Facing FAQs Page 
Appendix HH: Patient-Facing FAQs Page for eSyM Home Page 
Appendix II: Site Staff eSyM User Guide  
Appendix JJ: Patient eSyM Promo Video 
Appendix KK: Provider eSyM Promo Video   
Appendix LL: Project Website 
Appendix MM: Other Resources Medical Oncology 
Appendix NN: Other Resources Surgical 
Appendix OO: Patient-Facing eSyM Additional Questions (Activity Level & Overall Wellbeing) 
Appendix PP: Training Flipbooks (Patient & Staff-Facing) 
 
Additional Appendices: 
Appendix QQ: Model Informed Consent Form for Activity 4d  
Appendix RR: Qualitative Patient Interview Guide  
Appendix SS: Qualitative Patient Interview Intro Letter  
Appendix TT: Statistical Analysis Plan (SAP) 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
52 
 
 
 
 
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Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
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Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
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Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
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Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
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Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
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PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
58 
 
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PROTOCOL TITLE: SIMPRO Research Center: Integration and Implementation of PROs for Symptom 
Management in Oncology Practice  
Version 9, August 4, 2023 
sIRB: Western IRB Tracking No. 20182593; Study No. 1248093 
Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
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Management in Oncology Practice  
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Sponsor: DF/HCC Investigator Michael Hassett MD MPH Protocol No. 18-986R/18-734 
 
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