Initial Testing of a Mobile App Pain Coping Intervention for Outpatient Oncology Settings
Phase: NA
Conditions: Colorectal Cancer
Sponsor: Duke University

Official Title: Initial Testing of a Mobile App Pain Coping Intervention for Outpatient 
Oncology Settings (PainPac) 
NCT: NCT05686122 
Document Date: 6/3/2024 

Research Summary
State your primary study objectives
Aim 1: Test whether PainPac is feasible (primary aim and outcome), low burden, engaging, and 
acceptable (secondary outcomes for primary aim). 
Hypothesis: PainPac will have high feasibility (accrual [N=60]), attrition [<25%], adherence [>75%]), as 
well as low patient burden (physical, emotional, financial), high engagement (PainPac log in and coping 
skills practice >3 times/week), and high acceptability (>80% satisfaction) that is at least comparable to 
PCST-Video.
State your secondary study objectives
Aim 2: Examine the impact of PainPac on pain severity, pain interference, pain self-efficacy, emotional 
distress, and quality of life (secondary outcomes for secondary aim). 
Hypothesis: PainPac will demonstrate improvements in pain-related outcomes (e.g., self-efficacy, 
emotional distress) and quality of life for patients that are at least equivalent to the improvements 
experienced by PCST-Video participants.
Aim 3: Gather quantitative and qualitative post-treatment data on patients’ preferences, confidence in 
using technology, barriers, and facilitators regarding PainPac to update and optimize PainPac for a future 
large randomized clinical effectiveness trial. 
Hypothesis: This data will lead to optimization of PainPac to improve pain-related outcomes in cancer 
patients.
Please select your research summary form:
Standard Research Summary Template
This is the regular (generic) research summary template which is required  for all regular applications (unless 
your protocol fits under the other research summary templates in this category).  Use of these instructions is 
helpful for ensuring that the research summary contains all necessary elements.
Standard Research Summary
Purpose of the Study
Objectives & hypotheses to be tested
Aim 1: Test whether PainPac is feasible (primary aim and outcome), low burden, engaging, and 
acceptable (secondary outcomes for primary aim). 
Hypothesis: PainPac will have high feasibility (accrual [N=60]), attrition [<25%], adherence [>75%]), as 
well as low patient burden (physical, emotional, financial), high engagement (PainPac log in and coping 
skills practice >3 times/week), and high acceptability (>80% satisfaction) that is at least comparable to 
PCST-Video.

Aim 2: Examine the impact of PainPac on pain severity, pain interference, pain self-efficacy, emotional 
distress, and quality of life (secondary outcomes for secondary aim). 
Hypothesis: PainPac will demonstrate improvements in pain-related outcomes (e.g., self-efficacy, 
emotional distress) and quality of life for patients that are at least equivalent to the improvements 
experienced by PCST-Video participants.
Aim 3: Gather quantitative and qualitative post-treatment data on patients’ preferences, confidence in 
using technology, barriers, and facilitators regarding PainPac to update and optimize PainPac for a future 
large randomized clinical effectiveness trial. 
Hypothesis: This data will lead to optimization of PainPac to improve pain-related outcomes in cancer 
patients.
This work has the potential to create a paradigm shift for behavioral pain intervention practice. This 
project will be one of the first to demonstrate that a theory-based standalone mobile app (PainPac) with 
wide implementation potential is feasible and beneficial to cancer patients. PainPac may drastically 
increase the availability of behavioral pain interventions. PainPac may be particularly likely to benefit 
patients in low-resourced areas with no or limited access to trained behavioral pain specialists and patients 
unable to engage in interventions during business hours. If PainPac is feasible and shows promise for 
benefits, this work will result in a larger RCT (R01) optimizing and testing the effectiveness of PainPac.
Background & Significance
Should support the scientific aims of the research
SIGNIFICANCE. Pain is one of the most common, interfering and distressing symptoms for patients with 
cancer.
 Pain has been identified as a significant problem that does not improve with time in cancer 
1,2
patients.  A meta-analysis of studies (N=52) reported that more than half of patients with cancer report 
3
pain, with over 1/3 of patients reporting moderate to severe pain.  Studies have routinely found that 
4
cancer patients report high levels of pain that are distressing and persistent across the cancer spectrum.4-6
Research has shown cancer patients with pain are more likely to experience psychological distress, 
physical disability, physical symptoms, lower quality of life, and increased financial difficulty than patients 
without pain.3,5-9
Decades of work have shown behavioral pain interventions are efficacious for cancer-related pain.
 
10-12
Teaching patients cognitive and behavioral strategies (i.e., relaxation, activity pacing, cognitive 
restructuring) for managing psychosocial factors related to pain can lead to decreased pain severity, 
increased pain coping self-efficacy, and decreased psychological distress.
These interventions are 
13 
traditionally delivered in person at a medical center by a trained masters or doctoral level behavioral pain 
specialists over 8-12 weekly sessions, all of which presents system, provider, and patient access barriers 
(e.g., availability, time, cost, burden). Our group and others have shown brief behavioral pain 
interventions (3-6 sessions) reduce pain and improve aspects of quality of life.
We have developed and tested numerous cognitive behavioral pain coping skills training protocols that 
enhance the abilities of patients with chronic disease to manage their pain, leading to improvements in 
pain and other important pain-related outcomes.
 Our group has extended this research by 
14,17-25
designing and testing pain coping skills protocols that use mobile health (mHealth) technology for cancer 
patients with pain.
 These protocols focus on decreasing patient burden and increasing patient 
26-28
accessibility and engagement by creating shorter protocols (4-6 sessions), using hybrid in person and 
videoconferencing methods, and using mHealth strategies (e.g., websites, smartphones, text messaging, 
real-time data collection with personalized feedback) to reduce intervention barriers (e.g., in person 
sessions).
 These mHealth pain coping skills interventions have shown high patient acceptability, 
24,27-29
feasibility, and efficacy.
 We published a large trial (N=178) showing a 4 session behavioral cancer 
24,27-30
pain intervention delivered with home-based videoconferencing is just as efficacious as a protocol 
delivered in person at the medical center.28 Importantly, the videoconferencing protocol showed 
significantly greater feasibility (i.e., attrition [16% vs. 30%], adherence) than the in person protocol.
Use of mHealth strategies and videoconference delivered behavioral pain interventions can improve patient 
access and decrease patient burden. However, videoconference delivered protocols retain some access 
barriers for many patients due to the therapist-led delivery model and resources required (e.g., expert 
pain therapist, scheduled appointments). Much more is needed to improve access for the greater than 22 
million cancer survivors expected over the next 10 years.
 Developing additional behavioral 
31,32
approaches to cancer pain management is critical. A standalone behavioral cancer pain mobile application 
that uses efficacious cognitive and behavioral pain management strategies is likely to dramatically increase 
access to such interventions. A standalone app would eliminate the need for a therapist, be available to 
the patient at all times, and be easily accessible on a smartphone or tablet. Mobile apps also offer 
increased options for real-time personalization (e.g., messaging based on daily pain assessment) which 
can increase engagement and improve overall 
outcomes.
We have developed a mobile application – PainPac – that has been used only as an adjunct to in person 
and videoconferencing interventions. PainPac is a comprehensive mobile app program that provides 
patients four coping skills modules of efficacious cognitive-behavioral theory (CBT) based pain 

management strategies (i.e., relaxation, activity pacing, cognitive restructuring). PainPac is a 
downloadable app available through iOS or Android. PainPac has been designed using information from 
three decades of research applying cognitive- behavioral pain management strategies to patients with 
chronic diseases including cancer.
 It uses Social Cognitive Theory
 to promote behaviors to improve 
33-37
38
self-efficacy for pain management and, in turn, improve pain and pain-related quality of life indices.
 
39
PainPac’s therapeutic elements are modeled after efficacious cognitive- behavioral interventions designed 
and tested by our group of behavioral pain experts (PI: Kelleher, Co-I: Somers, Mentor: Francis Keefe, 
PhD). Further, Drs. Kelleher and Somers completed a qualitative project with 33 national stakeholder 
interviews (e.g., policy makers, organization leaders, providers) that generated data to inform PainPac 
(see Preliminary Data); this is expected to improve our ability to generalize PainPac to settings outside of 
Duke.
 Importantly, PainPac’s content is extended to patients in their daily life through interactive 
40
components like text messaging to improve skills engagement. Daily assessment of pain and skills practice 
will inform personalized messaging to further promote engagement. Finally, an engagement tool based on 
a reward system will be used for skills use engagement. We are currently using it as an adjunct to a 
videoconferencing intervention in two NIH funded trials (1R21CA235083, R01CA237892); we have not 
tested it as a standalone intervention.
PainPac is innovative as it is designed to be implemented through automated, electronic submission to 
patients via text, email, and/or MyChart when a patient reports pain at 
4/10 at a clinical oncology 
>
appointment. PainPac has been carefully designed by our expert team of behavioral pain clinical scientists, 
a healthcare and research mobile app firm, and our institutional technology teams (see letter of support 
from Matthew Roman, Chief Digital Strategy Officer at Duke). PainPac is expected to be beneficial to 
patients as a standalone intervention for the following reasons. PainPac has been designed to exploit three 
factors that, according to Social Cognitive Theory,
 strongly influence self-efficacy for pain control. First, 
38
PainPac enhances patients’ mastery of pain coping skills by allowing them to access the intervention, 
practice skills, and receive encouragement on their own time, in their own environment, when they need 
it. Patients learn skills in short sessions (8 min) and receive daily prompts to apply the skills based on their 
symptom report (e.g., pain of 6/10 prompts a message to practice relaxation) – in this way patients are 
also getting what they need, not a static protocol. With traditional models, skill mastery can be difficult as 
patients are taught at the medical center and asked to go home and remember to practice, with 
assessment only at their next appointment and little personalization. Second, PainPac provides vicarious 
learning (i.e., modeling) experiences for each coping skill. Skills modeling takes place through videos and 
patient stories. Patients can access content any time via their smartphone; to increase salience of 
vicarious learning, the content has been targeted to cancer patients with pain. Third, patients will receive 
encouragement or corrective feedback personalized to their skills practice and symptom report (e.g., your 
pain is higher than normal, try practicing a skill that has worked for you in the past). These prompts are 
intended to provide feedback for patients that is psychoeducational and lends to a better mastery of self-
management of pain.
A technology-based mobile application like we are proposing has the potential to drastically advance 
cancer patient behavioral pain management access. There is a time sensitive and critical need to optimize 
the impact of modern technology-based behavioral pain interventions to reach the growing number of 
cancer patients in the US. PainPac has been used only as an adjunct to our in person and 
videoconferencing interventions and the next step in this line of work is to test PainPac as a standalone 
intervention. This work could create a paradigm shift for behavioral pain intervention practice. If PainPac is 
feasible and acceptable to patients and shows promise for benefits, PainPac has the potential to drastically 
increase the availability of behavioral cancer pain interventions and lead to improved pain management for 
a greater number of cancer patients with pain.
Design & Procedures
Describe the study, providing details regarding the study intervention (drug, device, physical 
procedures, manipulation of the subject or the subject’s environment, etc.). Discuss justifications for 
placebo control, discontinuation or delay of standard therapies, and washout periods if applicable. 
Identify procedures, tests and interventions performed exclusively for research purposes or more 
frequently than standard of care. Include alternative therapies, concurrent therapies discontinued per 
protocol, risk benefit ratio, and use of tissue/specimens. Discuss monitoring during washout periods if 
applicable. Include brief description of follow-up, if any.
Research Plan and Design. We will use a pilot RCT to examine PainPac feasibility (primary aim and 
outcome), patient burden, engagement, acceptability, and initial pain-related outcomes, compared to a 
therapist led videoconference delivered behavioral pain intervention (PCST-Video) in colorectal cancer 
patients with pain (N=60). We will use quantitative and qualitative data to optimize PainPac. Participants 
will complete assessments at pre-treatment (A1), post-treatment (A2; 4 weeks post-A1), and 1 month 
follow-up (A3; 1 month post-A2) (months 5-22). Assessment contents can be found in the attached 
document, Data Dictionary, and will be distributed to both study groups. These assessments contain items 
that will be used to assess Aim 2 for both study groups. The pain management strategies are relevant and 
efficacious across cancer types. Due to the pilot nature of this work, we will enroll an opportunity sample 
of colorectal cancer patients. Dr. Kelleher (PI) has tested behavioral symptom management protocols in 
colorectal cancer patients and has an established relationship with Dr. Uronis (Co-I) and the GI cancer 
clinic teams, all of which allows for an efficient start up. Further, colorectal cancer is associated with 
significant pain, impacts men and women, and spans a large age range, making it a good population for 
this early work. The preliminary work for PainPac has been in cancer patients including breast, prostate, 
lung, and stem cell transplant patients. If PainPac is feasible and shows promise, this project will lead to 
effectiveness testing in diverse cancer patients.

Participants and Recruitment. Participants will include (N=60) colorectal cancer patients at the Duke 
Cancer Institute (DCI) that report pain 
4 at a clinical oncology appointment. Standard care is to record a 
>
0=no pain to 10=worst imaginable score at every clinic appointment and pain 
4 represents clinically 
>
significant pain and allows for pre- to post clinically significant change.
 Patients’ pain will be re-
46,47
assessed at enrollment to confirm eligibility. Other eligibility criteria: 1) 
18 years and 2) stage I-IV 
>
colorectal cancer diagnosis <2 years. Exclusion criteria: 1) cognitive impairment, 2) brain metastases, 3) 
severe psychiatric condition (e.g., psychosis) that would contraindicate safe participation, or 4) 
participation in behavioral pain management in the past 6 months.
Recruitment (months 4-18). Dr. Steven Patierno, Deputy Director of DCI, and Dr. Hope Uronis, oncologist 
and Co-I, will assist with recruitment. In 2021, there were 1,457 unique patients with colorectal cancer 
seen at DCI. This suggests more than adequate numbers to complete the proposed work. We will use our 
established screening procedures that use electronic medical records (EMR) to identify eligible patients and 
the same Duke IRB-approved, direct-to-patient recruitment method that has resulted in high rates of 
enrollment in our previous work. Under a HIPAA waiver, staff will use DEDUCE to query the Duke EMR and 
identify potential participants. After chart review to verify eligibility, staff will mail patients a study 
brochure and introductory letter. The letter includes a number to call if the patient is interested (or to opt 
out) and explains that a staff member will contact them soon. All patients who meet eligibility criteria will 
be contacted unless they opt out. If interested and eligible, patients will complete electronic consent. We 
have successfully recruited for many trials using this well-developed EMR-based system and remote, direct-
to-patient approach.
Randomization. Following consent and baseline assessment, patients will be randomized with equal 
allocation to: 1) a mobile app behavioral cancer pain intervention (PainPac) or 2) a therapist led 
videoconference delivered behavioral cancer pain intervention (PCST-Video). For patients randomized to 
PainPac, eligibility will result in electronic push of study information to the patient through MyChart, email, 
and/or text, and research staff will confirm app download. All participants will continue to receive standard 
care from their medical team. No participant will be asked to change pain management strategies. Data 
from 2021 suggests the majority of Americans (85%) own a smartphone,
 and similar statistics are 
48
reported in cancer patients.49,50 Participants who do not have a smartphone will be loaned one with a 
data plan to access the PainPac app or PCST-Video sessions. Participants will receive instructions for 
PainPac or PCST-Video technology, handouts with FAQs and troubleshooting strategies, and contact 
information for the study team and tech support. Therapists and staff will check in with participants 
regarding technology usability and tech assistance will be available within 24 hours.
PainPac. PainPac is a patient-focused intervention developed using cognitive-behavioral theory and 
empirically supported strategies to enhance patients’ ability to manage their pain. Dr. Francis Keefe 
(mentor to Drs. Kelleher and Somers) first developed and tested Pain Coping Skills Training (PCST) 
intervention protocols for patients with arthritis;
 he has conducted many trials demonstrating the 
45,51
efficacy of these protocols. Drs. Kelleher and Somers have applied their experiences working with Dr. 
Keefe to work with cancer patients with pain, and have developed and tested PCST interventions for 
cancer patients and focused on making them more accessible.
 PainPac is a logical extension of this 
24,26
work and expected to be an efficacious and innovative option for a highly scalable, implementable, and 
efficacious behavioral pain management intervention for patients with cancer. PainPac is a mobile app 
available to patients on a smartphone or tablet. PainPac uses Social Cognitive Theory to promote behaviors 
to improve pain, self-efficacy for pain management, and pain-related quality of life indices. It also uses 
real-time data to personalize the intervention and messaging to participants. PainPac contains 4 modules, 
each including a skill that has shown efficacy for reducing pain in patients with cancer. The 4 skills 
modules are: 1) progressive muscle relaxation (PMR), 2) imagery relaxation, 3) activity rest cycling and 
pleasant activity planning, and 4) cognitive restructuring. Patients are prompted to complete one module 
each week for 4 weeks; each module requires patients to attend to content for 8 minutes and includes 
text, video, and audio presentation of skill rationale and expected outcomes, skill modeling and tips for 
daily use, and a patient story about skill use. The first 3 minutes include a rationale for the pain coping 
skill and expected outcomes of skill mastery and use delivered through audio with text on screen. The next 
3 minutes include video with skill modeling and tips for use/practice. The final 2 minutes include a patient 
story about their experiences (challenges/benefits) with the skill. Each module has complementary content 
designed to lead to skills practice and mastery. For example, the PMR module has PMR audio clips for full 
(15min), medium (5min), and short (2min) practice. Importantly, the app also has interactive components 
to improve coping skills engagement. App messaging includes: 4/week coping messages encouraging 
practice; daily assessment of pain and skills use that informs personalized messaging to further promote 
engagement; reminders for skills practice / module completion. PainPac includes an engagement tool with 
rewards based on completion of modules, assessments, and skills practice. Pattern Health (Durham, NC) 
specializes in patient-centered apps for medical research with expertise in patient engagement. Pattern 
Health has a portfolio of funded work with NIH researchers and an established relationship with the study 
team and Duke, and will be contracted for this study.
Videoconference Delivered Pain Coping Skills Training (PCST-Video). Participants randomized to 
PCST- Video will receive 4 behavioral cancer pain intervention sessions delivered by videoconferencing by 

a pain therapist in the medical center to the patient in their natural environment (e.g., home). Sessions 
will be scheduled weekly for 45-60 min and mimic in person sessions. In rare circumstances when the 
participant is not able to connect via videoconferencing, the PCST-Video sessions can be delivered via 
phone. This is a backup option that will rarely if ever be used due to extenuating circumstances. PCST-
Video session content is based on Pain Coping Skills Training (PCST) designed by Dr. Francis Keefe 
(mentor to Drs. Kelleher and Somers) and matches the PainPac skills modules described above. PCST-
Video participants will complete assessments at the same intervals as PainPac participants. Interventionist 
Training (months 2-4). PCST-Video will be delivered by a masters or doctoral level psychologist with 
experience delivering behavioral pain interventions. Drs. Kelleher and Somers will provide training and 
therapists will be certified (>90% ratings of competence and protocol adherence
) to deliver the 
52
intervention. Therapists will follow a manualized protocol; treatment strategies will be taught through 
didactic instruction, audio-/video-recorded illustration from model cases, and role-play of common 
scenarios. Sessions will be recorded and reviewed in supervision by Dr. Kelleher. Procedures to Ensure 
Consistency of Treatment. 1) The therapist will follow a manual; 2) Weekly supervision will occur; 3) 
Session recordings will be reviewed and feedback provided; and 4) Ratings of treatment adherence and 
competence will be conducted. Treatment Adherence and Therapist Competence.
 Ratings of protocol 
52
adherence will be made by Drs. Kelleher and Somers. Protocol adherence criteria will be developed for 
each session with satisfactory adherence ≥90% on the rating scale. Ratings of therapists’ competence52 
will be used to evaluate 20% of PCST-Video sessions.52
Selection of Subjects
List inclusion/exclusion criteria and how subjects will be identified.
Participants and Recruitment. Participants will include (N=60) colorectal cancer patients at the Duke 
Cancer Institute (DCI) that report pain 
4 at a clinical oncology appointment. Standard care is to record a 
>
0=no pain to 10=worst imaginable score at every clinic appointment and pain 
4 represents clinically 
>
significant pain and allows for pre- to post clinically significant change. Patients’ pain will be re-assessed at 
enrollment to confirm eligibility. Other eligibility criteria: 1) 
18 years and 2) stage I-IV colorectal cancer 
>
diagnosis <2 years. Exclusion criteria: 1) cognitive impairment, 2) brain metastases, 3) severe psychiatric 
condition (e.g., psychosis) that would contraindicate safe participation, or 4) participation in behavioral 
pain management in the past 6 months. 
Recruitment (months 4-18). Dr. Steven Patierno, Deputy Director of DCI, and Dr. Hope Uronis, oncologist 
and Co-I, will assist with recruitment. In 2021, there were 1,457 unique patients with colorectal cancer 
seen at DCI. This suggests more than adequate numbers to complete the proposed work. We will use our 
established screening procedures that use electronic medical records (EMR) to identify eligible patients and 
the same Duke IRB-approved, direct-to-patient recruitment method that has resulted in high rates of 
enrollment in our previous work. Under a HIPAA waiver, staff will use DEDUCE to query the Duke EMR and 
identify potential participants. After chart review to verify eligibility, staff will mail patients a study 
brochure and introductory letter. The letter includes a number to call if the patient is interested (or to opt 
out) and explains that a staff member will contact them soon. All patients who meet eligibility criteria will 
be contacted unless they opt out. If interested and eligible, patients will complete electronic consent. We 
have successfully recruited for many trials using this well-developed EMR-based system and remote, direct-
to-patient approach.
Subject Recruitment and Compensation
Describe recruitment procedures, including who will introduce the study to potential subjects. Describe 
how you will ensure that subject selection is equitable and all relevant demographic groups have access 
to study participation (per 45 CFR 46.111(a) (3)). Include information about approximately how many 
DUHS subjects will be recruited. If subjects are to be compensated, provide specific prorated amounts 
to be provided for expenses such as travel and/or lost wages, and/or for inducement to participate.
We will use a pilot RCT to examine PainPac feasibility (primary aim), patient burden, engagement, 
acceptability, and initial pain-related outcomes, compared to a therapist led videoconference delivered 
behavioral pain intervention (PCST-Video), in patients with colorectal cancer and pain. This study will be 
conducted at the Duke Cancer Institute (DCI) and involve 60 colorectal cancer patients with pain. Dr. 
Steven Patierno, Deputy Director of the Duke Cancer Institute, and Dr. Hope Uronis, GI oncologist 
physician champion and Co-Investigator, will work closely with Dr. Kelleher and the study team to assist 

with recruitment. Drs. Patierno and Uronis are committed to this work; Dr. Kelleher has a history of 
support from both Drs. Patierno and Uronis, and has worked closely with Dr. Uronis on past trials and 
successfully recruited cancer patients with pain. All recruitment procedures comply with HIPAA guidelines 
and will receive approval from the Duke University Health System (DUHS) institutional review board (IRB). 
During our most active phase of recruitment, we will recruit approximately 12-18 patients per quarter (4-6 
.
patients/month) over the course of 15 months (N=60) of this two-year R21 project
Patient participants will be recruited through our well-developed recruitment system that uses linked 
electronic medical records at Duke University Medical Center (DUMC) to identify patients who meet study 
criteria. We will use the same Duke IRB-approved, direct-to-patient recruitment method that has resulted 
in high rates of enrollment in our group’s previous work, including PainPac preliminary work and trials with 
patients with colorectal cancer. Under a HIPAA waiver, study staff will use DEDUCE to query the Duke 
electronic medical records (EMR) and identify potential participants. After a careful chart review to verify 
initial eligibility (e.g., 
18 years, colorectal cancer diagnosis, stage I-IV, in the last 2 years), study staff 
>
will mail potential participants a study brochure and introductory letter signed by the PI. The letter will 
state that the patient may be eligible to participate in a research study evaluating a mobile app behavioral 
cancer pain intervention for patients with cancer and pain. The letter includes a number to call if the 
patient is interested in learning more about the study (or would like to opt out) and explains that a study 
staff member will contact them about the study. Patients will then be called by highly trained study staff to 
assess interest. All patients who meet eligibility criteria will be contacted 
. Consistent 
unless they opt out
with Duke’s direct-to-patient recruitment guidelines, we will only attempt to contact patients a maximum 
of three times if we are unable to reach them. If a patient is interested when contact is made with a study 
team member, they will be provided with information about the study, its purposes, requirements, and 
time commitment. Interested patients will complete a scripted telephone screening (e.g., BPI pain 
severity) compliant with DUHS IRB policies to confirm full eligibility. Those who do not pass the telephone 
screening but ask for resources will be provided with a list of free resources available through the Duke 
Cancer Patient Support Program (e.g., financial support, individual and couple counseling). Eligible patients 
who wish to enroll in the study will complete an electronic consent form; a member of the study team will 
provide private consent and answer any questions that the potential participant may have. Those who do 
not have access to the internet for completing the electronic consent form will be mailed a paper copy. 
This remote, direct-to-patient recruitment approach has allowed us to efficiently reach more patients while 
reducing numerous obstacles encountered with methods that require physician time and clinic resources. 
We have successfully recruited for many trials using this well-developed recruitment system.
Participants will complete assessments at pre-treatment (A1), post-treatment (A2; 4 weeks post-A1), and 
1 month follow-up (A3; 1 month post-A2) (months 5-22). Participants will receive $30 for each 
assessment (totaling up to $90 for all 3).
Consent Process
Complete the consent section in the iRIS Submission Form.
Subject’s Capacity to Give Legally Effective Consent
If subjects who do not have the capacity to give legally effective consent are included, describe how 
diminished capacity will be assessed. Will a periodic reassessment occur? If so, when? Will the subject 
be consented if the decisional capacity improves?
If patient is cognitively impaired, they will be excluded from the study per study protocol.
Study Interventions
If not already presented in #4 above, describe study-related treatment or use of an investigational 
drug or biologic (with dosages), or device, or use of another form of intervention (i.e., either physical 
procedures or manipulation of the subject or the subject’s environment) for research purposes.

Study interventions presented in #4 above.
Risk/Benefit Assessment
Include a thorough description of how risks and discomforts will be minimized (per 45 CFR 46.111(a) (1 
and 2)). Consider physical, psychological, legal, economic and social risks as applicable. If vulnerable 
populations are to be included (such as children, pregnant individuals, imprisoned persons or 
cognitively impaired adults), what special precautions will be used to minimize risks to these subjects? 
Also identify what available alternatives the person has if he/she chooses not to participate in the 
study. Describe the possible benefits to the subject. What is the importance of the knowledge expected 
to result from the research?
Potential Risks
In the proposed study, the potential risks to participants are minimal and rare. The potential risks are 
associated with (1) confidentiality related to the use of smartphones and a mobile app, and self-report 
data, and (2) potential emotional upset due to questioning about thoughts, feelings, and personal/family 
history of cancer when completing intervention sessions and assessments. First, breach of confidentiality is 
a possible risk. This will be clearly stated in the consent form. All efforts will be made to maintain 
confidentiality. Participants’ data and research records will be carefully stored (See protections against 
risk). Second, participants will be asked about their thoughts and feelings about their cancer, pain, and 
symptoms; thus, it is possible they may experience distress. The psychological risk associated with 
answering questions is expected to be minimal. Although some participants may find certain questions or 
topics to be upsetting, heightened awareness of existing psychosocial and practical needs may be the first 
step in resolving these concerns. The recruitment letter will clearly acknowledge the voluntary nature of 
participation and patients will have the ability to decline further contact from study personnel at any time 
(i.e., to opt out). Participants will be fully informed about the study during the informed consent process 
and instructed to decline to answer any question or to discuss any issues they find troubling. If a 
participant reports significant distress during study participation, the study team will consult with Drs. 
Kelleher and Somers (licensed clinical psychologists). If the participant requires additional treatment, we 
will initiate the appropriate referral. Out team has extensive experience conducting psychosocial 
intervention trials with patients with cancer and have not encountered significant psychological distress 
caused by study participation. Moreover, patients with cancer often report benefits from participating in 
psychosocial research. Thus, the risk of psychological distress is minimal and these safeguards should be 
adequate. 
Adequacy of Protection Against Risks
a. Informed consent and assent. Recruitment will take place through the Duke Cancer Institute (DCI),
an NCI-designated Comprehensive Cancer Center. Recruitment procedures will receive Institutional Review
Board (IRB) approval and comply with HIPAA regulations. This study will follow the same recruitment
procedures used in previous RCTs conducted by our team with cancer patients, including colorectal cancer
patients, and including multiple federally-funded projects conducted by the Duke Pain Prevention and
Treatment Research Program. In March of 2019, Duke implemented a revised Recruitment and
Engagement Policy that allows Duke researchers to utilize “direct-to-patient” or “cold contacting” methods.
Rather than requiring physician approval before approaching potential participants, Duke researchers can
use IRB-approved methods of direct contact. The Duke Notice of Privacy Practices informs all patients that
Duke is an “opt-out” institution. That is, patients’ medical records may be reviewed for research purposes,
and patients may be contacted about research unless they “opt-out” of such contacts. This policy change
was largely driven by respect for patients’ autonomy (i.e., empowering patients to choose whether to
participate in research), need for increased patient awareness of research opportunities, and research
demonstrating “op-out” methods result in stronger recruitment rates and more representative study
samples.
Under a HIPAA waiver, potentially eligible patients will be identified by study staff using the Duke 
Enterprise Data Unified Content Explorer (DEDUCE) to query the Duke Electronic Medical Record (EMR) on 
a weekly basis. After a careful chart review to verify initial eligibility (e.g., age 
 18 years, English 
>
speaking, stage I-IV colorectal cancer diagnosis, pain score of 4 or greater at a Duke clinical oncology 
appointment), study staff will mail potential participants a study brochure and introductory letter signed by 
the Principal Investigator. The letter explains that the patient may be eligible to participate in a research 
study evaluating a mobile app behavioral cancer pain intervention for patients with cancer and pain. The 
letter includes a number to call if the patient is interested in learning more about the study (or would like 
to opt out) and explains that a study staff member will contact them in around five days to discuss the 
study. Patients will then be called by highly trained study staff to assess interest. All patients who meet 
eligibility criteria will be contacted 
. Consistent with Duke’s direct-to-patient 
unless they opt out

recruitment guidelines, we will only attempt to contact patients a maximum of three times if we are unable 
to reach them. If a patient is interested when contact is made with a study team member, they will be 
provided with information about the study, its purposes, requirements, and time commitment. Interested 
patients will complete a scripted telephone screening (e.g., symptom ratings) compliant with DUHS IRB 
policies to confirm full eligibility. Those who do not pass the telephone screening but ask for resources will 
be provided with a list of free resources available through the Duke Cancer Patient Support Program (e.g., 
financial support, individual and couple counseling). Eligible patients who wish to enroll in the study will 
complete electronic consent using REDCap. Those who do not have access to the internet for completing 
the electronic consent form will be mailed a paper copy. A member of the study team will provide private 
consent and answer any questions that the potential participant may have. This remote, direct-to-patient 
recruitment approach has allowed us to efficiently reach more patients while reducing numerous obstacles 
encountered with methods that require physician time and clinic resources. We have successfully recruited 
for many trials using this well-developed recruitment system.
b. Protections against risk. Risks associated with the proposed study are low and not expected, but
nonetheless will be carefully monitored. The study investigators, including Drs. Kelleher (PI) and Somers
(Co-I), both licensed clinical psychologists, and Dr. Uronis (Co-I), medical oncologist, and the study team
will take all precautions possible to avoid and minimize potential risks. The consent form will address all
possible risks. Should any of these occur, appropriate emergency care will be provided. The proposed
significance of study findings outweighs this risk. Here we detail all procedures for protecting against or
minimizing potential risks.
Confidentiality. Breach of confidentiality will be a potential risk noted in the consent documents and 
verbally discussed with the patients during recruitment. Protection of confidentiality is a central priority. All 
efforts will be made for confidentiality to be maintained by using study ID numbers to identify participants’ 
research records and by having a limited number of individuals who have access to identifying information. 
As noted, participants’ data and research records will be protected using subject identification numbers. A 
document linking participant names to subject identification numbers will be stored separately from data 
and research records in a password-protected database. All paper research records (e.g., paper consent 
documents) will be kept in a locked file cabinet in a locked office. Electronic data files (e.g., audio 
recordings of sessions) will be stored on an Office of Information Technology (OIT) secured DUMC network 
drive. This drive will be backed up and secured by the OIT department on a daily basis. Only approved 
study staff will have access to the research records. There is some risk of loss of confidentiality inherent to 
the use of videoconferencing to conduct the PCST-Video intervention sessions. To protect patient privacy, 
we will use Zoom videoconferencing, which has standard internationally-recognized and accepted 
encryption algorithms. Zoom meetings will have end-to-end encryption (E2EE). In a meeting with E2EE 
enabled, no one except each participant—not even Zoom’s servers—has access to the encryption keys 
being used to encrypt the meeting. No recording will be conducted within Zoom. Audio-recording of 
intervention sessions will be conducted using Voice Recorder on the study teams’ encrypted Duke-issued 
and maintained laptops. Audio-recordings will be saved to the DUMC server and deleted from the laptop. 
All audio-recordings will be deleted at the end of the study. All study staff will be required to complete 
Duke University Health System Institutional Review Board’s online training course (i.e., Protecting 
Research Subjects) as well as human research subjects’ protection training and certification through the 
Collaborative Institutional Training Initiative (CITI) program, both of which address confidentiality. The 
anticipated significance of the study results and likely benefits to participants outweigh the minimal risks.
Two password protected databases will be used for this study to ensure confidentiality. First, a tracking 
database will be used for recruitment and follow-up. This data will house information related to tracking 
the participants in the study, such as phone numbers and addresses. Identifying information will be kept 
separate from research records. No medically sensitive or outcome data will be stored in this database. 
This database will also track nonparticipants (i.e., those who have declined participation) only to the barest 
minimum to ensure that they are not contacted again about participation. At the end of the study, all 
identifiable data of non-participants such as their names will be deleted. Tracking data on participants will 
be retained for the usual required period. Second, all study data will be stored in a separate password 
protected REDCap database without any personal identifiers. Data in this database will be derived from 
patients’ direct input into the electronic patient reported outcomes system which is an online survey 
system; data entered into this system is stored on a secure server housed behind the DUMC firewall. Only 
a unique study identification number will link the electronic data to the study data file. Patient data that 
goes into the mobile behavioral pain application (PainPac) will only be identified with a number and the 
app is designed so that data, like self-report data, is stored on a secure server housed behind the DUMC 
firewall. The tracking data and study data will be stored in a file on a secure DUMC psychiatry server which 
can only be accessed by necessary members of the research team. Access to the Duke network requires a 
password protected, 128-bit encrypted virtual private network connection provided by Cisco systems. 
The PI has completed Duke University Health System Institutional Review Board’s online training course: 
Protecting Research Subjects, as well as human research subjects’ protection training and certification 
through the Collaborative Institutional Training Initiative (CITI) program, both of which address 
confidentiality. All other individuals involved in this study will be required to complete these courses and 
ongoing training. The risks associated with the proposed study are low. The PI and investigative team have 
conducted research in the proposed area and have not encountered medical emergencies or significant 

psychological distress caused by study procedures. In fact, participation in the proposed study procedures 
and intervention is associated with few negative side effects and potentially multiple benefits to physical 
health, mood, and quality of life. The proposed significance of study findings outweighs the limited risk. 
Smartphone Security Measures. Smartphones used for this study will be configured for minimal use 
necessary for the purpose of the study and will not be used for personal use by staff or study participants. 
Specifically, the following steps will be taken: 1) Study staff will keep the operating system on the most 
current version. 2) We will enable encryption on the device and verify that data protection is enabled, set 
“require passcode” to immediately, and enable erase data to “automatically erase the device” after 10 
failed passcode attempts. 3) We will set Auto-Lock. 4) Study staff will use Restrictions to restrict any 
unnecessary access including changing account settings. 5) We will reset smartphones between use for 
different participants. 6) At end of device life, we will send the device to Duke Procurement Surplus & 
Salvage for secure destruction. Study participants will have the option to use a Duke Health study 
smartphone or their personal smartphone. The study mobile application will be made available to 
participants regardless of whether they use a study smartphone or their personal smartphone.
Mobile App Data Storage and Security. Pattern Health (Durham, NC) is a digital health company 
specializing in patient-centered web and mobile products for clinical and medical research and health data 
tracking and analysis, with expertise working with wireless devices and improving patient engagement. 
Pattern Health has an established relationship with the PI and study team, as well as other researchers at 
Duke, the Duke Medicine Information Security Office (ISO), Duke Health Technology Services (DHTS), and 
the Duke Digital Strategy Office. Pattern Health is contracted for the implementation of a mobile app for 
use in the current study, which is similar to the mobile app developed and tested 
 in Dr. 
adjunctively
Kelleher’s prior work. App data is stored in a MySQL database. This is a standard security feature, which 
allows the database to be kept separate from the web server to protect access to the database. In 
addition, the hard drive of the database machine will be encrypted, which will provide security in case the 
hard drive is physically compromised. Duke ISO, DHTS, and the Duke Digital Strategy Office will review 
and approve Pattern Health's documents outlining their data collection process, and data storage and 
security for the proposed study; these Duke entities previously approved Pattern Health’s data collection, 
storage and security for Dr. Kelleher’s ACS RSG and previous NIH R21 projects, and these procedures will 
be the same for the proposed R21 project.
Emotional Upset. The risk of emotional upset associated with intervention sessions and assessments is 
rare, and all interactions with study participants will be under the direction of PI Dr. Kelleher, a licensed 
clinical psychologist. To address risks related to the possibility of psychological distress, participants will 
have the option of withdrawing from the study without loss of benefit. Interventionists and study staff in 
this trial will have experience working with distressed patients with chronic disease. They will be trained, 
specifically in the context of this trial, to monitor participants’ psychological status and for any signs that 
participants are experiencing high levels of physical or emotional distress that need to be addressed 
outside the context of this trial. Interventionists will be trained to report any concerns immediately and 
directly to the PI. If this is determined to be the case, the PI will work directly with the participant to move 
forward in a way that is in the best interest of the patient. No participant will be kept in the trial if they are 
experiencing increased or extreme distress. As noted previously, intervention sessions will be audio-
recorded and reviewed by Drs. Kelleher and Somers to ensure the delivery of effective and ethical 
treatment. Further, the study Clinical Research Coordinators (CRC) will monitor daily all assessments with 
particular attention paid to the suicidal ideation item on the Brief Symptom Inventory. The CRC will 
immediately report all elevated responses on this item to the study PI. Dr. Kelleher (PI) will also be 
contacted when 
 emotional distress is identified in a participant. The study assessments have been well 
any
validated for use with patients with cancer. Moreover, these assessments were specifically chosen for their 
. Participants will be reminded that they can omit responses to 
brevity in order to reduce patient burden
any questions that they do not feel comfortable answering. Again, all research personnel who have direct 
contact with patients will be trained to observe and immediately report any adverse events to Dr. Kelleher. 
Dr. Kelleher will report any adverse events to the institutional review board at Duke University and to NIH, 
and will consult Drs. Somers (licensed clinical psychologist and senior level faculty Co-I), and Uronis 
(experienced physician) to collaboratively develop a course of action, which may involve facilitating 
referrals for additional treatment. These referrals may be made to various members of the Duke Cancer 
Patient Support Program, including psychiatrists, psychologists, and medical family therapists, as 
appropriate. Participants will be provided with emergency contact numbers as well as access to numerous 
support services offered through the DCI. Dr. Kelleher works directly with Cancer Patient Support and Care 
at Duke Cancer Institute as a practicing licensed clinical psychologist and as a supervisor to psychology 
trainees (i.e., advanced graduate students, clinical psychology pre-doctoral interns) and Dr. Somers (Co-I) 
directs the clinical psychology training program within the Duke Cancer Patient Support Program at the 
Duke Cancer Center. Both Drs. Kelleher and Somers are integrated into the psychosocial clinical care 
program at the Cancer Center and have experience referring cancer patients who are distressed to 
appropriate psychosocial or psychiatric care within this large team of mental health professionals. Dr. 
Kelleher will use these same resources when making referrals for distressed participants in this study. The 
PI and entire investigative team have conducted research in the proposed area and have not encountered 
significant psychological distress caused by study procedures. In fact, participation in the proposed study 
procedures and intervention is associated with few negative side effects and potentially multiple benefits to 
physical health, mood, and quality of life. The proposed significance of study findings outweighs the limited 

risk. Finally, it is important to note that all participants will continue to receive usual care from their 
medical team. Consistent with numerous behavioral pain intervention protocols in our group, no 
participant will be asked to change or decline any strategies for pain management based on their 
.
participation in the study
Potential Benefits of the Proposed Research to Research Participants and Others
There are numerous potential benefits of the proposed research. Colorectal cancer patients with persistent 
pain may learn ways to enhance their pain coping and may experience significant decreases in pain and 
disability; the proposed intervention may lead to improvement in participants’ pain and pain-related 
outcomes. There are currently no evidence-based standalone mobile app behavioral cancer pain 
interventions for patients with cancer and pain. This study has the potential to be of great benefit to this 
heavily burdened patient population. We also anticipate the results from this study will spur more research 
into mobile health-based behavioral symptom self-management interventions for patients with cancer and 
pain.
Costs to the Subject
Describe and justify any costs that the subject will incur as a result of participation; ordinarily, subjects 
should not be expected to pay for research without receiving direct benefit.
No cost to the subject.
Data Analysis & Statistical Considerations
Describe endpoints and power calculations. Provide a detailed description of how study data will be 
analyzed, including statistical methods used, and how ineligible subjects will be handled and which 
subjects will be included for analysis. Include planned sample size justification. Provide estimated time 
to target accrual and accrual rate. Describe interim analysis including plans to stop accrual during 
monitoring. Phase I studies, include dose escalation schema and criteria for dose escalation with 
definition of MTD and DLT.
Statistical Design and Analyses. A pilot trial (N=60) will be used to compare PainPac (n=30) to PCST-
Video (n=30) on measures of feasibility (primary aim), burden, acceptability, engagement, and initial pain-
related outcomes. Sample size was informed by pilot trial guidelines for RCTs of behavioral interventions,63,
 and past similar studies,
 that suggest 30 participants per condition is sufficient for determining 
64
26,65-67
feasibility and acceptability, and feasibility of a future definitive trial. We anticipate no more than 25% 
attrition by 1 month post- baseline, based on previous psychosocial studies with cancer patients.
 
65,68-70
Both groups of 30 participants are needed because we aim to demonstrate two types of feasibility: 
feasibility of the PainPac app, which only requires the 30 PainPac participants, and feasibility of the 
subsequent larger RCT (i.e., recruitment, assessments), which requires all 60 PainPac and PCST-Video 
participants. We are recruiting both sexes and all genders, and we expect a nearly equal sample size 
between sexes. To account for sex as biological variable, we will describe all outcomes disaggregated by 
sex. We will examine intervention effects and use this data to optimize PainPac. 
 Feasibility (accrual, 
Aim 1.
attrition, adherence), burden, acceptability, and engagement will be assessed post-treatment and 
descriptive statistics will be produced for PainPac and PCST-Video. Overall trial feasibility benchmarks 
include reaching target accrual (N=60) within 15 months and <25% attrition by 1 month post- baseline. 
Descriptive statistics will be used to report non-eligibility and refusal. Data of non-completers will be 
compared to completers. 75% completed will serve as our feasibility benchmark. If >25% of consented 
patients drop out, PainPac will not be considered feasible. We do not expect attrition to be greater in the 
PainPac condition compared to PCST-Video. PainPac feasibility benchmarks include protocol adherence 
indicated by calculating the degree to which participants are willing/able to complete study assessments 
(pre, post, follow- up) and the 4 PainPac skills modules or 4 PCST-Video sessions. 75% completed will 
serve as our benchmark. If >25% of consented patients do not complete the intervention (modules
/sessions and assessments), PainPac will not be considered feasible. We expect adherence in the PainPac 
condition will be at least comparable to PCST-Video. Patient Burden will be measured as a continuous 
variable by assessing physical, emotional, and financial burden of engaging in the study intervention. We 
expect burden will not be greater in PainPac compared to PCST-Video. Patient Engagement will be 
assessed by electronic app data (e.g., PainPac weekly log-ins) and patient self-report defined as the 

number of times per week they practice the coping skills. 
3 times/week will serve as the benchmark; if 
>
participants log into PainPac and/or practice the coping skills <3 times/week, PainPac will not be 
considered engaging. We expect engagement in PainPac will be at least comparable to PCST-Video. 
Acceptability will be indicated by 80% of patients reporting satisfaction with PainPac and PCST-Video (M=3.
2/4) on the CSQ. 
 Between-group differences at follow-up will be characterized using Cohen’s d and 
Aim 2.
95% confidence intervals. Consistent with recommendations for small pilot RCTs of behavioral 
interventions,
 we propose a conservative approach that focuses on describing effect size estimates 
63,64
and their variability instead of testing for significant group differences. As this is a small trial intended to 
provide signals the intervention is promising and data for a larger trial, all pre- to post-intervention and 1 
month variables will be characterized using graphs/plots and descriptive statistics (e.g., mean, standard 
deviations, range). We will examine the pattern of findings to determine the best analytic plan for the 
subsequent trial. Pain may vary based on pain medications and disease stage/treatment; we will describe 
these variables and include them, when appropriate, as covariates in future larger trials. The subsequent 
trial will be fully powered to test two active conditions. Given our proposed sample size (N=60), an a priori 
power calculation using G-Power suggests we will have >80% power to detect medium-sized effects of 
d=0.74 (α=0.05, two-tailed). However, as noted above, our analytic plan focuses on describing between-
group differences rather than testing for significant effects. 
 We will use methods from applied 
Aim 3.
thematic analysis
 to analyze interview data. First, we will create a codebook a priori that corresponds to 
71
major content areas from the interview guide. The codebook will include a coding matrix with categories, 
codes, and definitions. The analysts (Dr. Erkanli and a study member) will segment interview transcripts 
into major content areas using Nvivo and then use an inductive and iterative approach to identify data-
driven codes. As new codes emerge, they will be applied to previously coded sections until all relevant 
information is captured. All codes will be grouped into themes and subthemes. The analysts will meet to 
discuss coding and resolve discrepancies in interpretation, and maintain an audit trail of coding and 
analytic decisions. The study team will review the qualitative findings and develop action steps for 
modifying the protocol. All data will be used to optimize PainPac for a large randomized clinical 
effectiveness trial. We will optimize areas related to patient preferences, barriers, beliefs, and cultural 
tailoring to increase usability and engagement and meet user needs.
Data & Safety Monitoring
Summarize safety concerns, and describe the methods to monitor research subjects and their data to 
ensure their safety, including who will monitor the data, and the frequency of such monitoring. If a 
data monitoring committee will be used, describe its operation, including stopping rules and frequency 
of review, and if it is independent of the sponsor (per 45 CFR 46.111(a) (6)).
This research study carries minimal risk. All patients in the study will continue their usual care during the 
course of this trial, thus their doctors will provide monitoring of the patients’ overall medical status. All 
research personnel who have direct contact with patients will be trained to observe and report any adverse 
event to the principal investigator (PI). The PI will report any adverse events to the institutional review 
board (IRB) at Duke University and to NIH. An adverse event is defined as any untoward medical 
occurrence during the clinical investigation that has a causal relationship to the study protocol. A serious 
adverse event is defined as any event which results in death, is immediately life threatening, results in 
persistent or significant disability/incapacity, patient hospitalization, or is serious for any other reason 
representing significant hazard. We will also appoint one data safety officer who is a physician (MD) and 
not associated with this study. The appointed MD officer will have experience with clinical research and 
trials with oncology populations and have a thorough understanding of adverse events. The appointed data 
safety officer will also have technology expertise and will have an annual responsibility to evaluate our 
current methods of assessment and intervention and identify any problems.
All adverse events will be reported to Duke’s IRB and the data safety officer in real-time. All data will be 
stored on a secure server with multiple backups created regularly. All interactions with study participants 
will be under the direction of a licensed clinical psychologist (PI: Dr. Kelleher). Dr. Kelleher is supported by 
a strong and experienced team of investigators, including Dr. Somers, a senior investigator and licensed 
clinical psychologist. Study investigators and staff for this trial will be taught to monitor for any signs that 
participants are experiencing high levels of physical or emotional distress that need to be addressed 
outside the context of this trial. If this is determined to be the case, the PI will work directly with the 
participant to move forward in a way that is in the best interest of the patient. No participant will be kept 
in the trial if they are experiencing increased or extreme distress. Dr. Kelleher works directly with Cancer 
Patient Support and Care at Duke Cancer Institute as a practicing licensed clinical psychologist and as a 
supervisor to psychology trainees (i.e., advanced graduate students, clinical psychology doctoral interns); 
she is integrated into the psychosocial care program at the Cancer Center and has experience referring 
cancer patients who are distressed to appropriate psychosocial or psychiatric care within this large team of 
mental health professionals. She will use the same resources when making referrals for distress 
participants in this study.

Potential Risks. Risks associated with the proposed study are minimal and rare. Psychological risks 
include anxiety or distress due to questioning about thoughts, feelings, and personal/family history of 
cancer. There is the possibility of a breach of confidentiality due to the use of mailing of information. The 
consent form will address this possibility. All efforts will be made for confidentiality to be maintained by 
using case numbers to identify participants’ research records and by having a limited number of individuals 
with access to identifying information. Identifying information will be kept separate from research records. 
All research records will be kept in a locked file cabinet and password protected computer files. Only the PI 
and other trained staff will have access to the research records. To ensure that there are no changes in 
potential risk during the course of the study and that confidentiality is maintained the PI and sponsors will 
implement a Data and Safety Monitoring Plan.
The primary risks of this study are those associated with confidentiality. There is some risk attendant to 
confidentiality of self-report data. Two password-protected databases will be used for this study to ensure 
confidentiality. First, a tracking database will be used for recruitment and follow-up. This data will house 
information related to tracking the participants in the study, such as MRN, name, phone numbers and 
addresses. No medically sensitive or outcome data will be stored in this database. This database will also 
track non-participants (i.e., those who have declined participation) only to the barest minimum to ensure 
that they are not contacted again about participation. At the end of the study, all identifiable data of non- 
participants such as their names will be deleted. Tracking data on participants will be retained for the usual 
required period. Second, all study data will be stored in a separate password protected database without 
any personal identifiers. Data in this database will be derived from patients’ direct input into the electronic 
patient reported outcomes system (e.g., REDCap), which is an online survey system; data entered into 
this system is stored on a secure server housed behind the Duke University Medical Center (DUMC) 
firewall. Only a unique study identification number will link the electronic data to the study data file. The 
tracking data and study data will be stored in a file on a secure DUMC psychiatry server which can only be 
accessed by necessary members of the research team. Access to the Duke network requires a password 
protected, 128-bit encrypted virtual private network connection provided by Cisco systems.
Mobile App Data Storage and Security. Pattern Health (Durham, NC) is a digital health company 
specializing in patient centered web and mobile products for clinical and medical research and health data 
tracking and analysis, with expertise working with wireless devices and improving patient engagement. 
Pattern Health has an established relationship with researchers at Duke and is contracted for the 
development of a mobile app for use in the current study. Pattern Health will have access to PHI. Study 
personnel will input participant information including name, phone number, email, birth date, language 
preference, time zone, and gender to create a profile for the participant. Participants will enter their full 
name, date of birth and e-mail address to access the corresponding profile. MAG and ISO have reviewed 
and approved Pattern Health's documents outlining this data collection process, and data storage and 
security. The RDSP and corresponding exception requests for this will go through full approval. A contract 
will be executed between Pattern Health and Duke. Patients may enter assessment data via the study 
mobile app or on their own online or by phone with a study team member. Assessment data entered via 
the mobile app will be temporarily stored on the cloud-based app platform (Pattern Health) and imported 
to REDCap via an assigned study ID number. Assessment data will be transported from the cloud-based 
app into REDCap for storage. Pattern Health uses a MySQL database. This is a standard security feature, 
which allows the database to be kept separate from the web server to protect access to the database. In 
addition, the hard drive of the data base machine will be encrypted, which will provide security in case the 
hard drive is physically compromised. 
Data Safety Management Reporting
Monitoring of data and safety procedures will ensure that the protocol is conducted in accordance with 
Good Clinical Practice (GCP), that data are of high quality and integrity, and that the facilities and staffing 
are adequate for continued participation in the study.
Data Safety and Monitoring Plan. This trial carries minimal risk. All patients in the trial will continue 
their usual care during the course of the trial, thus their doctors will provide monitoring of the patients’ 
overall medical status. All research personnel who have direct contact with patients will be trained to 
observe and report any adverse event to the PI (Dr. Kelleher). The PI will report any adverse events to the 
institutional review board at Duke University and to the NIH. An adverse event is defined as any untoward 
medical occurrence during the clinical investigation that has a causal relationship to the study protocol. A 
serious adverse event is defined as any event which results in death, is immediately life threatening, 
results in persistent or significant disability/incapacity, patient hospitalization, or is serious for any other 
reason representing significant hazard. We will appoint one data safety officer who is a MD and not 
associated with this study. The appointed MD officer will have experience with clinical research and trials 
and have a thorough understanding of adverse events. The appointed data safety officer will also have an 
annual responsibility to evaluate our current system of assessment and intervention and identify any 
problems. All adverse events will be reported to Duke’s IRB and the data safety officer in real-time. All 
data will be stored on a secure server with multiple backups created regularly.
Protection Against Risk. All interactions with study participants will be under the direction of a Licensed 
Clinical Psychologist (Dr. Kelleher [PI]). Interventionists in this trial will have experience with distressed 

patients with chronic disease. They will be trained, specifically in the context of this trial, to monitor for 
any signs that participants are experiencing high levels of physical or emotional distress that need to be 
addressed outside the context of this trial. If this is determined to be the case, the PI will work directly 
with the participant to move forward in a way that is in the best interest of the patient. No participant will 
be kept in the trial if they are experiencing increased or extreme distress. Interventionists in this trial will 
be carefully trained to monitor participants’ psychologist status and report to the PI. Dr. Kelleher (PI) will 
be contacted when emotional distress is identified in a participant. Dr. Kelleher works directly with the 
Cancer Patient Support Program at the Duke Cancer Institute as a practicing licensed clinical psychologist 
and as a supervisor to psychology trainees (i.e., advanced graduate students, clinical psychology interns); 
she is integrated into the psychosocial care program at the cancer center and has experience referring 
cancer patients who are distressed to appropriate psychosocial or psychiatric care within this large team of 
mental health professionals. She will use the same resources when making referrals for distress 
participants in this study.
There is the possibility of a breach of confidentiality. The consent form will address this possibility. All 
efforts will be made for confidentiality to be maintained by using case numbers to identify participants’ 
research records and by having a limited number of individuals who have access to identifying information. 
Identifying information will be kept separate from research records. All research records will be kept in a 
locked file cabinet and password protected computer files. Only the PI and other trained research staff will 
have access to the research records. The PI has completed Duke University Health System Institutional 
Review Board’s online training course: Protecting Research Subjects, which addresses confidentiality. All 
other individuals involved in this study will be required to complete this course and ongoing training.
The Data and Safety Management (DSM) Report: In addition to the above monitoring of data safety, 
there will also be a DSM Report generated quarterly by the CRC and data manager and presented to the 
PI. A full DSM report will be provided to the Data and Safety Monitoring officers annually or more 
frequently as needed. DSM Reports will contain the following:
Study Overview with a review of study protocol, purpose of the study, primary outcomes, a 
description of key study personnel involved, and study timeline.
Recruitment Data with total number of patients approached and 
screened, total participants enrolled, and data on reasons for inclusion/exclusion of 
potential participants.
Sociodemographic Data from study participants with reference to expected age, racial, ethnic, 
sex, gender, and economic profiles.
Participant Retention including a description of reasons for participant attrition.
Quality Assurance including a report on data integrity processes, data transfer, encryption, any 
issues with paper and electronic data.
Regulatory Issues including a report on IRB changes and protocol changes and the reasons for 
these changes.
Adverse Events including a report on which events were study-related and which were not, how 
these AEs were managed and reported. Given that this is a behavioral virtual reality technology-
based intervention focused on coping with pain, no medical emergencies are expected. However, if 
they arise, we will immediately contact the patient’s oncologist. Dr. Tamara Somers (Co-I) directs 
the clinical psychology training program within the Duke Cancer Patient Support Program at the 
Duke Cancer Center. For psychosocial distress, the PI will contact Dr. Somers immediately to 
discuss the most appropriate course of action. If additional treatment is indicated, the PI and Dr. 
Somers will facilitate appropriate referrals. The PI and study team (Drs. Kelleher and Somers [Co-
Is]) have conducted research in the proposed area and have not encountered significant 
psychological distress caused by study procedures.
Serious Adverse Events including a detailed report on the individual(s) for whom this occurred, 
timing of the event, relationship to study procedures, timing and completion of reporting, and 
actions of Duke IRB, and the NIH as necessary. For the purpose of this behavioral trial, a SAE is 
defined as an even that, as a direct result of the study, causes serious harm to the subject (e.g., 
study involvement caused death or serious injury). We do not anticipate any SAEs. 
Privacy, Data Storage & Confidentiality
Complete the Privacy and Confidentiality section of the iRIS submission form.