Assessing the Feasibility of a Patient-centered Activity Regimen in Patients With Advanced Stage Lung Cancer
Phase: NA
Conditions: Lung Neoplasm Malignant
Sponsor: Yale University

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HRP-503B – BIOMEDICAL RESEARCH PROTOCOL 
(2016-1)
Protocol Title: Assessing the feasibility of a patient-centered activity regimen in patients with lung cancer. 
Version Date: 24 October 2017
Principal Investigator: Brett Bade
Instructor in Medicine
Section of Pulmonary, Critical Care, and Sleep Medicine
(If applicable) Clinicaltrials.gov Registration #: NCT03352245
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INSTRUCTIONS
This template is intended to help investigators prepare a protocol that includes all of the necessary information 
needed by the IRB to determine whether a study meets approval criteria. Read the following instructions 
before proceeding:
1.
Use this protocol template for a PI initiated study that includes direct interactions with research 
subjects. Additional templates for other types of research protocols are available in the system Library.
2.
If a section or question does not apply to your research study, type “Not Applicable” underneath.
3.
Once completed, upload your protocol in the “Basic Information” screen in IRES IRB system.
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SECTION I: RESEARCH PLAN
1.
Statement of Purpose: State the scientific aim(s) of the study, or the hypotheses to be tested.
The first phase of this study was performed at the Medical University of South Carolina (MUSC) and 
established the feasibility of monitoring physical activity in patients with advanced stage lung cancer via a FitBit® 
(San Francisco, CA) accelerometer for one week.1 Though feasibility was established with monitoring for 1 
week, when the monitoring period was extended to 4 weeks, both data collection and adherence fell 
significantly.
In this Phase 2 of the project, we will evaluate the feasibility of implementing a low-intensity, patient- 
centered activity regimen (PCAR) that prioritizes education and communication over a 12-week period in 
advanced stage lung cancer patients. Our primary outcomes will include number of patients increasing their 
overall step count over the study period and adherence to step count recommendations. Secondary outcomes 
will include quality of life (QoL), dyspnea, and depression scores before and after the intervention as well as a 
patient feedback questionnaire (to guide further interventions). There will also be a blood draw before and after 
the intervention to analyze biomarkers related to lung cancer. Our goals are to increase overall step count and 
obtain adherence of >50%.
2.
Probable Duration of Project: State the expected duration of the project, including all follow-up and data 
analysis activities.
We estimate the project’s duration at 16 months. At MUSC, n=15 subjects were enrolled between August 
2016 and May 2017 (10 months). Using the same rate of enrollment, with 2 sites we estimate enrolling 3 
patients/month. We estimate ~13 months to enroll the remaining 40 subjects. We have added an additional 3 
months to ensure all data is collected and to perform data analysis.
3.
Background: Describe the background information that led to the plan for this project. Provide references to 
support the expectation of obtaining useful scientific data.
Background:
Despite increasing treatment options, lung cancer remains second in cancer frequency and first in 
cancer mortality.2 It is also one of the most burdensome cancers, with patients having more symptoms, lower 
activity, and worsened QoL than their healthy counterparts.3 As might be expected, patients’ symptoms and 
activity levels worsen with time and treatment.4 The pattern of symptom progression is consistent with the 
concept of the “dyspnea spiral” in patients with chronic lung disease, wherein dyspnea develops, activity is 
avoided, functional capacity is lost, and dyspnea worsens. A recent review showed that physical activity studies 
in lung cancer patients are limited but overall suggest benefit.3 In addition, despite a heavier symptom burden,5 
patients with advanced stage disease are less frequently studied. Survey data reveals that stage III and IV lung 
cancer patients prefer to receive activity guidance from their oncologist,6 and a recent retrospective study of 
lung cancer survivors showed that approximately 80% of patients requesting exercise recommendations would 
prefer walking.7 Unfortunately, physical activity recommendations by clinicians are infrequent.6
Though likely beneficial, activity studies in lung cancer patients show low adherence in both early and 
advanced disease,8,9 and prior studies have accepted exercise adherence of 50-70%.10,11 Interestingly, clinicians 
treating chronic obstructive pulmonary disease (COPD) are using pedometers to predict exacerbations,12 predict 
clinical outcomes,13 and assess changes in QoL.14,15 Accelerometer use in patients with lung cancer is
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infrequently studied, practical, has the advantage of objectively monitoring low-impact physical activity, and has 
the potential to improve adherence to physical activity recommendations. In summary, lung cancer patients are 
interested in exercise though research and clinical application are infrequent. If a clinically practical regimen 
that improves activity adherence can be identified, clinical benefit in lung cancer is likely. Step counting with 
digital monitoring and tailored messaging may achieve this goal.
Significance:
Since lung cancer patients with advanced stage disease have higher symptom burden and more activity 
impairment, this population may obtain more benefit from increased physical activity than patients with early 
stage disease. However, little data is available regarding physical activity or the clinical utility of using 
accelerometers with an exercise prescription in patients with advanced stage lung cancer. Success of this study 
would establish a real-world, implementable, low-impact activity regimen that improves QoL in lung cancer 
patients.
Preliminary Studies:
Our phase I study collected data for 7 days in 30 patients.1 Most patients were interested in 
participating in the physical activity study and strongly positive Spearman Rank correlation between step count 
and overall QoL (ρ=0.46), physical functioning (ρ=0.61), and emotional functioning (ρ=0.40) as well negative 
correlation between step count and depression (ρ =-0.40), dyspnea (ρ=-0.54), and pain (ρ=-0.37) were noted. 
Patients with higher step counts had higher QoL scores and lower symptom and depression scores (see Figures 
1, 2, and 3).
Without changing our design, we collected 4 weeks of step count data in 29 patients using an escalating 
regimen (see activity regimen below). Communication with subjects during the 4-week period was inconsistent. 
In this cohort, 21% (6/29) of patients did not use the device. Of those who used the device 61% (14/23) 
increased their weekly step count at some point during the 4 week period, though weekly prescriptions were 
followed in <50% of cases (unpublished). Patient participation during this 4-week period may have been too low 
to have a therapeutic benefit. To improve patient participation and adherence to activity prescriptions, we will
(1) provide an educational session at enrollment, (2) increase subject communication via tailored electronic 
messaging, and (3) utilize a wrist-bound device (FitBit Flex 2) rather than one clipping to clothing (FitBit Zip).
4.
Research Plan: Summarize the study design and research procedures using non-technical language that can 
be readily understood by someone outside the discipline. Be sure to distinguish between standard of care vs. 
research procedures when applicable, and include any flowcharts of visits specifying their individual times and 
lengths. Describe the setting in which the research will take place.
Study Design
Randomized trial enrolling n=40 patients (Usual care: n=20; Intervention group: n=20).
Randomization: Participants will be randomized into one of 2 study arms using a random permuted block design 
of varying block size in a 1:1 ratio (n=20 to intervention, 20 to usual care).  Since the study utilizes text 
messaging as an intervention, blinding will not be possible.
Definitions
Intervention Group will receive the interventions mentioned above, including an educational session at 
enrollment, tailored electronic messaging with walking goals, and a wrist-bound accelerometer.
Usual care group will receive standard of care management from their Oncologist.
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Exercise Adherence will be defined as (the number of weeks a subject follows the activity prescription)/(the 
number of “usable” weeks). As per the literature, a week is considered “usable” if 5/7 days of step counts are 
available, and days with <200 steps/day are considered not usable. Thus, not all weeks will have enough data to 
provide an appropriate average daily step count nor a prescription. Our goal is to obtain >50% exercise 
adherence.
Inclusion/Exclusion Criteria 
Inclusion criteria:

Pathologic evidence of any stage non-small cell stage lung cancer (NSCLC)

Approval of the treating clinician

Adult patients (age >21 years) willing to wear a FitBit® device (FitBit, Inc., San Francisco, CA)

Access to a smartphone, agree to receive twice/daily text messages for 12 weeks (including any costs), and 
willingness to download the FitBit application to their smartphone.

Low activity level as judged by a brief physical activity questionnaire (i.e., <150 minutes/week of moderate- 
intensity exercise, <75 minutes/week of vigorous aerobic exercise, or an equivalent combination).
Exclusion criteria:

Memory impairment (as judged by the treating clinician)

Communication impairment (as judged by the treating clinician)

Treating clinician’s request not to alter physical activity

Physical inability to safely walk (as judged by the treating clinician)
The FitBit® Flex 2 device is a convenient accelerometer that is worn on the wrist and wirelessly 
synchronizes with smartphones. FitBit® devices have been validated in COPD patients,16 and the accuracy is 
similar to other wearable pedometers.17
Patients with lung cancer are eligible regardless of the timing of therapy. That is, patients who are 
diagnosed but before treatment, currently receiving treatment, survivors, or long-term survivors are eligible. 
Since this study focuses on adherence to an intervention, fallout patients will not be replaced.
Recruitment and Informed Consent
Subjects will be identified from medical record review and recruited in person at the Smilow Cancer 
Hospital Thoracic Oncology clinic. Study staff will inform the treating clinician of potential participation in the 
study. If the treating clinician agrees to participation in the study, patients will be approached while they are 
waiting for their standard of care visit or immediately after the visit. Study staff will explain that participation is 
voluntary and that the participant may choose to end their study participation at any time. A study handout will 
be provided if the patient is interested. After 2 days, study staff will contact the patient by phone to inquire 
about participation. If interested, a visit to consent the patient and collect blood samples will be arranged.
Documents provided to the patient during enrollment will include an informational handout, an educational 
pamphlet, HIPAA authorization, and the consent form. Patients will be instructed that refusal to participate will 
in no way affect their medical care.
If the patient agrees to participate, meets inclusion criteria, and signs the consent and HIPAA 
documents, study staff will explain the study’s purpose, potential risks/benefits, and components of the study. 
If the patient volunteers to participate, the written consent and HIPAA documents will be reviewed and signed. 
Written consent forms will be collected and stored in a locked cabinet in a locked office in the Anlyan Center at 
Yale University.
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Demographics
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We anticipate that certain populations will be more or less likely to participate in physical activity 
regimens. However, other studies have shown that predictors for exercise are incompletely understood.18 We 
will collect from medical records age, general demographics (e.g., race, height, weight, marital status, etc), 
cancer histology, disease stage, lung cancer treatment history, medical comorbidities (i.e., COPD, depression, 
and anxiety), treatment of medical comorbidities, smoking status, and performance status. This information 
may help in predicting who is more likely to participate in/benefit from increasing physical activity.
Surveys
Once consenting to participation, subjects will complete 4 voluntary, self-administered, validated
surveys the same day after signing consent and at the end of their 12 week study duration : (1) Patient Health 
Questionnaire (PHQ-9), (2) Quality of Life Questionnaire (QLQ-C30, Version 3), (3) Modified Medical Research 
Council (MMRC) Dyspnea Scale, (4) the Physical Activity Questionnaire (PAQ). Study staff will explain the 
purpose of each survey, and subjects will complete the surveys in a private exam room. Study staff will be 
available to assist in survey completion, if needed.
Randomization will be performed via an envelope system. Prior to beginning the study, 40 envelopes 
indicating Intervention or Usual care group will be created and sealed using the randomization schema 
described above. After consenting to the study, the envelope corresponding to the patient’s enrollment number 
will be opened.
At the end of the intervention, the PHQ-9, QLQ-C30, MMRC, and PAQ will be re-administered. In 
addition, a 10-item Feedback Survey in order to guide future studies. Participants may fill out the follow-up 
surveys at their regularly-scheduled appointments, via questionnaires mailed to the patient with a self- 
addressed envelope to return, or by phone with research staff. Study staff will try to obtain the final 
questionnaires within 4 weeks of the last day of activity collection, and in-person questionnaire completion will 
be attempted before mail-in questionnaires or telephone completion. Whether in person or over the phone, 
study staff will help the subjects remove the study account from the FitBit application and offer to assist in 
setting up their personal account. Those subjects in the usual care group will be provided a FitBit Flex 2 at the 
end of the study, and study staff will offer to help set up the device.
A total of 55 patients will be enrolled between Yale University, and the Medical University of South 
Carolina (MUSC). Those who agree to participate will be given a unique patient Study ID which will be used to 
identify completed surveys. De-identified survey data will be entered into the REDCap™ study database.
This study will be performed at both MUSC and Yale University, and de-identified data from both 
institutions will be stored on REDCap servers maintained by each institution. At the end of the study, data will be 
pooled for analysis. Since dates of treatment will be collected for the study, a shared data use agreement between 
Yale University and MUSC is in place.
Biomarkers
Fasting blood (> 12 hours) will be collected at baseline and at 12 weeks. Two 10-ml red-top tubes will be 
collected for serum, one 10-ml lavender-top tube will be collected for EDTA plasma, and two 4.5-ml light blue- top 
tubes will be collected for citrate plasma (total volume 39 mL of blood at each visit). Technicians will centrifuge 
the EDTA samples at 2,000 rpm for 15 minutes at 4°C within 1 hour of collection. Plasma and buffy coat will be 
separated, and, along with the serum, will be transferred into cryovials and labeled with freezer-proof labels with 
participant ID #s and date. All specimens will be stored temporarily at -20°C after aliquotting prior to delivery to 
the YCCI freezer (within 2 hours), and then stored at -80 degrees C until analysis. Each subject’s baseline and 
follow-up samples will be assayed in the same batch, and an equal number of intervention and control samples 
also will be included in each batch. Appropriate blinded quality control samples (low and high levels) will be used
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to monitor the reliability of each assay. Insulin will be measured in serum using an enzyme-linked immunosorbent
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assay (ELISA) kit (Millipore Sigma, Burlington, MA; EZHI-14K). The other testing will be measured in the serum 
using kits from Life Technologies Inc, Carlsbad, CA: Leptin (KAC2281), soluble PD-1 (BMS2214), soluble PD-L1 
(BMW2212), and CRP (KHA0031).
Subjects will be invited to allow blood samples (specimens) to be stored for future use regarding biomarker testing 
associated with lung cancer. Genetic testing will not be performed in this study. The storage and future testing of the 
blood samples is described in the consent, and subjects will have the option to decline future use of the sample as well as 
being contacted for future studies. If the subject declines future use of the samples, the specimen will be destroyed after 
this study is completed. If the subject changes their mind, samples will not be destroyed but the code connecting your 
identifiers to the samples will be deleted so your samples will then be anonymous.
Educational Session
Study staff will provide a brief educational session guided by an informational pamphlet addressing 
physical activity in lung cancer. Study staff will also discuss use of the FitBit device, the smartphone application, 
and methods by which subjects will be contacted (i.e., text messaging, e-mail, or telephone). Any subject 
questions will be answered.
Activity Monitoring and messaging
We will provide the subject with a FitBit Flex®, and ask him/her to wear it every day for 12 weeks, and 
request that it is charged it every 3-4 days (or when the battery is low). We will download the 
FitBit® application to the subject’s smartphone and set up a generic email account and sign-in to 
the FitBit
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application using that account. We will show the subject how to use the FitBit® and how to use the phone 
application. The subject will be given contact information for study personnel in case he/she has any 
questions or problems.
Step counts are recorded in and collected from the FitBit website. Since an e-mail address is required 
for a FitBit account, a unique Yale e-mail address will be created (i.e., xlungc.#@yale.edu). This e-mail address 
will be used to activate the FitBit account but will not include patient information.
Patients will be asked to wear the FitBit Flex device every day and night for 12 weeks excepting when 
the device needs to be charged and when the device may get wet (e.g., bathing or swimming).
The first 7 days of step count monitoring will be used to establish an average daily step count. After 7 
days, participants will be instructed to increase their daily step count by 400 steps/day from their average daily 
step count and will maintain this daily goal for one week. For example, if a patient has an average baseline of 
8000 steps per day for the first 7 days, their goal will be to increase their step count to 8400 steps/day for the 
next 7 days (2nd week). This cycle will be continued weekly for a total of 12 weeks. If the patient reaches an 
average of >10,000 steps/day, instructions will be to maintain their current activity level.
The subjects’ progress and step count goals will be relayed via twice/daily via smartphone text 
messaging. The text message application is secure, password-protected, and HIPAA-compliant. Text messages 
have been developed and will be the same for each patient (excepting replacement messages that will be sent 
when step counts are not collected, see below). Messages will include the subject’s name, their most recent 
step count, their current step count goal, a motivational statement, reminders to wear and charge the device, 
and gain-framed messages. Gain-framed messages emphasize the benefits of a certain behavior19 and have 
been shown to increase activity in older men,20 healthy women,21 and overweight patients.22 An example text 
for Mr. John Doe: “John, last week was great! Your average was 5000 steps. Today, we'd like you to walk 5400 
steps. Good luck!”
Three separate messages may replace the regularly-scheduled message if step counts are declining or 
not collected:

If step counts are declining, the following text message may be used once, “Mr. Doe, your step 
counts are lower. Daily walking will improve your energy level! Call us with problems.”

If a step count is not collected for 1 day, the following text message will be used once, “John, 
your step counts are low. Please wear and sync the FitBit. Walking improves fatigue. Call with 
questions.”

If a week is “unusable” per study definitions, the following text message will be used once, 
“John, we missed steps for 3 days last week; too few to average. Please wear the FitBit every 
day; try for (average+400)!
If no step counts are recorded for 2 or more days, the study team will call the patient to evaluate for 
difficulty with the FitBit device. If difficulty with the device is discovered, a member of the study team will 
arrange to meet the patient at a regularly-scheduled clinic visit.
Due to patient feedback during the initial part of the study, if a patient has “0” steps recorded, the line 
referencing how many steps were taken will be deleted from the text message. Specifically, we will not send 
text messages saying, “John, you walked 0 steps today.”
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At the end of the 12-week period, usual care participants will be provided a FitBit device. Study staff 
will offer to help remove the study account from intervention group participants and assist in setting up 
personal accounts in both the intervention and usual care groups. De-identified activity data from will be 
added to the REDCap™ study database. Recorded step counts will be rounded to the nearest whole number.
Sleep Monitoring
Because recent studies have shown that poor sleep quality is common in patients with lung cancer,23 
and poor sleep quality is associated with lower QoL,24 total sleep time and the number of awakenings will be 
collected. Collection of nightly sleep time and number of awakenings will not influence the specific aims of this 
study but may guide future studies. Sleep data will also be recorded in the REDCap™ study database. Recorded 
values will be rounded to the nearest whole number.
5.
Genetic Testing
N/A ☒
a.
Describe
i.
The types of future research to be conducted using the materials, specifying if immortalization of cell lines, 
whole exome sequencing, genome wide association studies, or animal studies are planned
ii. The plan for the collection of materials or the conditions under which material will be received
iii. the types of information about the donor/individual contributors that will be entered into adatabase
iv. the methods to uphold confidentiality
b.
What are the conditions or procedures for sharing of materials and/or distributing for future research 
projects
c.
Is widespread sharing of materials planned?
d.
When and under what conditions will materials be stripped of all identifiers?
e.
Can donor-subjects withdraw their materials at any time, and/or withdraw the identifiers that connect 
them to their materials?
i. How will requests to withdraw materials be handled (e.g., material no longer identified: that is anonymized) 
or material destroyed)?
f.
Describe the provisions for protection of participant privacy 
Describe the methods for the security of storage and sharing of materials
6.
Subject Population: Provide a detailed description of the types of human subjects who will be recruited into 
this study.
This study will recruit adult patients with any stage non-small cell lung cancer who are prior to treatment, 
receiving active treatment, or have completed active treatment. Patients must be willing to wear a wrist-bound 
accelerometer, have access to a smartphone, and willing to download the FitBit application to their smartphone. 
Patients with impairments in memory, communication, or ambulation will not be enrolled.
As the patient’s treating clinician is in the best position to judge their appropriateness for low impact 
physical activity, the treating oncologist will be involved in the decision to include the patient in the study.
7. Subject classification: Check off all classifications of subjects that will be specifically recruited for enrollment in 
the research project. Will subjects who may require additional safeguards or other considerations be enrolled 
in the study? If so, identify the population of subjects requiring special safeguards and provide a justification 
for their involvement.
☐Children
☐ Healthy
☐Fetal material, placenta, or dead fetus
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☐Non-English Speaking
☐ Prisoners
☐Economically disadvantaged persons
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☐Decisionally Impaired
☐ Employees
☐Pregnant women and/or fetuses
☐Yale Students
☐ Females of childbearing potential
NOTE: Is this research proposal designed to enroll children who are wards of the state as potential subjects?
Yes ☐ No ☒
8. Inclusion/Exclusion Criteria: What are the criteria used to determine subject inclusion or exclusion?
Inclusion criteria:

Pathologic evidence of non-small cell stage lung cancer (NSCLC)

Approval of the treating clinician

Adult patients (age >21 years) willing to wear a FitBit® device (FitBit, Inc., San Francisco, CA)

Access to a smartphone, agree to receive twice/daily text messages for 12 weeks (including any costs), and 
willingness to download the FitBit application to their smartphone.
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
Low activity level as judged by a brief physical activity questionnaire (i.e., <150 minutes/week of moderate - 
intensity exercise, <75 minutes/week of vigorous aerobic exercise, or an equivalentcombination).
Exclusion criteria:
• Memory impairment (as judged by the treating clinician)
• Communication impairment (as judged by the treating clinician)
• Treating clinician’s request not to alter physical activity
• Physical inability to safely walk (as judged by the treating clinician)
9. How will eligibility be determined, and by whom? Write here
Eligibility (i.e., meeting inclusion criteria and not having exclusion criteria) will be determined by the 
study staff during medical record review. The treating oncologist will confirm the patient’s appropriateness for 
the study. If inclusion criteria are met (and no exclusion criteria are identified), then the physical activity 
questionnaire will be used to confirm eligibility.
10. Risks: Describe the reasonably foreseeable risks, including risks to subject privacy, discomforts, or 
inconveniences associated with subjects participating in the research.
Potential Risks
There are no major associated risks or harms with the collected surveys. Survey content may be 
minimally associated with psychological discomfort if the participant interprets the question as invasive.
In multiple published studies and reviews, low-impact physical activity interventions are considered safe 
in patients with lung cancer.3 In a recent review of patients with advanced cancer (multiple cancer types), 6 
minor musculoskeletal adverse events were reported.25 Estimated patient risk with the proposed intervention 
is, therefore, low. Since this study prioritizes implementing standard-of-care techniques, we have not pursued 
safety monitoring. Put another way, since walking is not restricted in patients outside the research arena, no 
increased risk is suspected.
Drawing blood has a minor risk of bleeding, bruising, infection, phlebitis, inflammation, discomfort, or 
blood clot at the site of the injection. Pressure will be applied to where the blood was drawn afterwards to stop 
the bleeding. The subject may also feel dizzy or faint during or after the blood draw. We will suggest that they 
lie down and will provide them with fluid and snacks.
Loss of confidentiality is also a risk in this study. Techniques to protect data will include (1) storage of 
consents/questionnaires in a locked office and locked cabinet, (2) storage of labeled blood samples in a YNHH 
facility, (3) storage of electronic data within a protected network, and (4) use of a password-protected 
database with de-identified data.
11. Minimizing Risks: Describe the manner in which the above-mentioned risks will be minimized.
Risk of psychological discomfort
The subjects will be informed that if (s)he agrees to participate (s)he may choose to end the survey at 
any time, thereby minimizing any minimal psychological discomfort that may be experienced. The subjects will 
be reassured that their refusal to participate will in no way affect their medical care. If a subject indicated (s)he 
had feelings of being “better off dead” in the PHQ-9, he/she will be assessed by a member of the research team 
to be sure the subject understood the question and answered it accurately. If the subject is actually suicidal,
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they will be referred for urgent psychiatry evaluation, per standard of care.
Risk of blood draw
We will apply pressure to the site of the injection to make sure that we stop the bleeding. There will also be gauze 
over the wound that will clot the site. If they are feeling dizzy or faint we will lay them down until they feel better.
There will also be snacks and drinks at the HRU.
Risk to confidentiality
Consent and HIPAA forms will be stored in a locked cabinet in a locked office in the Anlyan Center at 
Yale University. Subjects will be assigned a unique subject ID. An electronic spreadsheet will be stored on the 
Yale network and keep track of screened patients, enrolled patients, their assigned subject ID, cell phone
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number, cell phone carriers, and dates of interaction with the study team. Questionnaire data will be collected 
on forms identifiable only by Study ID number to protect the subject’s confidentiality. The completed paper 
copies of the surveys and consents will be stored in a locked cabinet in a locked office in the Anlyan Center at 
Yale University. De-identified survey and activity data will be entered into a secure REDCap™ database created 
for this study; the de-identified data will be exported at study’s end for analysis.
Since this study will be performed at both MUSC and Yale University, de-identified data from both 
institutions will be stored on a REDCap server maintained by MUSC. A shared data use agreement between Yale 
University and MUSC is in place.
Screening for adverse events will be accomplished by asking subjects to contact the study team by 
phone or email if they fall, are admitted to the hospital, or develop a musculoskeletal injury. In addition, at the 
end of the study period the study team will ask patients about adverse events during the study and perform a 
chart review to evaluate for falls, hospitalizations, or musculoskeletal injuries.
If an adverse event is identified, study staff will gather data about the injury (i.e., date of injury, type of 
injury, if injury was related to walking) and document the information in the REDCap database. Study staff will 
also contact the treating Oncologist to ensure he/she is aware of the injury and is in agreement with ongoing 
activity escalation. If no activity escalation is recommended, future texts will not recommend increased walking 
distances until recommended by the clinician.
12. Data and Safety Monitoring Plan: Include an appropriate Data and Safety Monitoring Plan (DSMP) based on 
the investigator’s risk assessment stated below. (Note: the HIC will make the final determination of the risk to 
subjects.)
a.
What is the investigator’s assessment of the overall risk level for subjects participating in this 
study?
i.
Minimal
b.
If children are involved, what is the investigator’s assessment of the overall risk level for the 
children participating in this study?
i.
Not applicable
c.
Include an appropriate Data and Safety Monitoring Plan. Examples of DSMPs are
available here http://your.yale.edu/policies-procedures/forms/420-fr-01-data-and-safety- 
monitoring-plans-templates for
i.
Minimal risk
d. For multi-site studies for which the Yale PI serves as the lead investigator:
i.
How will adverse events and unanticipated problems involving risks to subjects or others be 
reported, reviewed and managed?
Screening for adverse events will be accomplished by asking subjects to contact the study team by 
phone or email if they fall, are admitted to the hospital, develop a musculoskeletal injury, or have concerns 
about their physical activity. In addition, the study team will perform a chart review at the end of 12 weeks to 
evaluate for falls, hospitalizations, or musculoskeletal injuries. If an adverse event is identified, details will be 
collected and documented by the study team via the Adverse Event Documentation form. Study staff will gather 
data about the injury or event (i.e., date of injury, type of injury, if injury was related to walking). study staff will 
contact the treating Oncologist to ensure he/she is aware of the event and is in agreement with ongoing activity 
escalation. If no activity escalation is recommended, future texts will not recommend increased walking 
distances until recommended by the clinician. The treating Oncologist and site PI will determine if the adverse
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event was related, possibly related, or unrelated to the study. All serious adverse events (SAE; e.g., death, 
shortness of breath, chest pain, falls, or hospitalizations) will be reported to the Institutional Review Board in 
addition to being discussed with the treating oncologist. Outside participating institutions will immediately 
report SAEs to the Yale Lead Investigator. Adverse events that are unexpected, related or possibly related, but 
not serious will also be reported to the IRB to ensure the process is safe.
ii.
What provisions are in place for management of interim results?
An interim analysis evaluating study acceptability to patients and comparing patient participation to our 
prior work (using weekly phone calls) has been performed. No further analysis is planned until the study is 
completed.
iii.
What will the multi-site process be for protocol modifications?
If protocol modifications are necessary, both Yale University and MUSC investigators will agree to the 
protocol modifications, and IRB approvals will be obtained at both sites.
13. Statistical Considerations: Describe the statistical analyses that support the study design.
Data Analysis
This portion of the study is to focus on feasibility of increasing physical activity via an exercise regimen 
and adherence with study recommendations. As a feasibility study, we will aim to enroll n=55 subjects. Simple 
descriptive statistics (e.g. percentages, confidence intervals, means, medians, etc.) will be utilized where 
necessary and calculated using SAS v9.3. Exploratory analyses will involve measuring associations (i.e. Spearman 
rank correlations) between activity measurements and changes in survey domain scores.
Primary study endpoints will include the following: (1) overall number and percentage of patients 
increasing their average daily step counts over 84 days and (2) adherence with study recommendations. 
Adherence will be defined as (the number of weeks a patient achieved the recommended walking goal)/(the 
number of recommendations made). Other endpoints will include biomarkers in blood (C-reactive protein, 
leptin, insulin, PD-1, and PD-L1), survey-specific domain scores (e.g. QLQ-C30 physical functioning, bodily pain, 
etc.), changes in those domain scores after the 84-day period, and analysis of feedback questionnaires (using 
simple statistics).
Within this phase, statistical analyses will involve the use of Spearman correlations to assess the extent 
to which changes in step counts over time are associated with changes in health related QoL domain scores.
Since step counts will be measured daily, we will also construct generalized linear mixed models (GLMMs) to 
assess these relationships. The GLMMs will allow us to account for the fact that step counts will likely be 
correlated within individuals over time. If sleep time and number of awakenings can be collected, Spearman 
correlations will also be calculated for step counts and survey-specific domain scores.
Sample size justification
We will calculate the proportion of patients who are willing to wear and utilize the Fitbit® Flex™ 
pedometer. Based on prior studies in healthy patients, we anticipate that consent to participation and 
compliance with the device can reach 70-80%.26 Our adherence will surely be lower due to enrolling patients 
with lung cancer. With n=50 subjects participating in activity monitoring and survey collection, estimates of 
adherence and survey domain scores will be sufficiently precise. For example, should 40 of the 50 subjects be 
fully compliant, the 95% confidence interval for that compliance rate will range from 66% to 90%, providing
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evidence that this intervention is feasible in this patient population. Confidence intervals on mean estimates of
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SECTION II: RESEARCH INVOLVING DRUGS, BIOLOGICS, RADIOTRACERS, PLACEBOS AND DEVICES
SECTION III: RECRUITMENT/CONSENT AND ASSENT PROCEDURES
the survey domains would span approximately ±0.3 standard deviation units. With n=50 subjects included in the 
follow-up assessments of association, we will also be able to detect correlations as small as r=0.4 with 80% 
power, assuming 2-sided hypothesis testing and an alpha level of 0.05.
If this section (or one of its parts, A or B) is not applicable, check off N/A and delete the rest of the section.
A. RADIOTRACERS
B. DRUGS/BIOLOGICS
4.
Use of Placebo:
☐Not applicable to this research project
If use of a placebo is planned, provide a justification which addresses the following:
Not applicable.
5.
Continuation of Drug Therapy After Study Closure ☒Not applicable to this project
B. DEVICES
1. Targeted Enrollment: Give the number of subjects:
a.
Targeted for enrollment at Yale for this protocol:
A) 40 subjects
b.
If this is a multi-site study, give the total number of subjects targeted across all sites:
A) 40 subjects
2.
Indicate recruitment methods below. Attach copies of any recruitment materials that will be used.
☐Flyers
☐ Internet/web postings
☐ Radio
☐Posters
☐ Mass email solicitation
☐ Telephone
☐Letter
☐ Departmental/Center website
☐ Television
☒ Medical record review*
☐ Departmental/Center research boards
☐ Newspaper
☐Departmental/Center newsletters
☐YCCI Recruitment database
☐Other:
☐Web-based clinical trialregistries
☐Social Media(Twitter/Facebook):
☐Clinicaltrails.gov
* Requests for medical records should be made through JDAT as described at
http://medicine.yale.edu/ycci/oncore/availableservices/datarequests/datarequests.aspx
3. Recruitment Procedures:
☒N/A
☒N/A
☒N/A
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a. Describe how potential subjects will be identified.
Subjects will be identified by medical record review at the scheduled appointment in the Thoracic 
Oncology Clinic at Smilow Cancer Hospital. To confirm appropriateness, the treating Oncologist will be informed 
prior to study inclusion.
b. Describe how potential subjects are contacted.
Subjects will be approached at their standard of care Oncology clinic visit. There will also be a follow-up phone 
call after approaching them at the clinic visit to determine their interest in the study.
c. Who is recruiting potential subjects?
Subjects will be recruited via the primary investigator or study staff.
4. Assessment of Current Health Provider Relationship for HIPAA Consideration:
Does the Investigator or any member of the research team have a direct existing clinical relationship with any 
potential subject?
☐Yes, all subjects
☒Yes, some of the subjects
☐No
If yes, describe the nature of this relationship.
There are no clinical current relationships. Since Dr. Bade works in the Thoracic Oncology clinic, it is 
possible that would see enrolled subjects or those eligible for enrollment in his clinic. If Dr. Bade sees patients in 
both a clinical and research capacity, the roles will be clearly distinguished during the clinic visit.
5. Request for waiver of HIPAA authorization: (When requesting a waiver of HIPAA Authorization for either the 
entire study, or for recruitment purposes only. Note: if you are collecting PHI as part of a phone or email 
screen, you must request a HIPAA waiver for recruitment purposes.)
Choose one:
☐For entire study
☒ For recruitment/screening purposes only
☐For inclusion of non-English speaking subject if short form is being used and there is no translated HIPAA 
research authorization form available on the University’s HIPAA website at hipaa.yale.edu.
i.
Describe why it would be impracticable to obtain the subject’s authorization for use/disclosure of this 
data:
HIPAA authorization will be obtained during enrollment in the study. Authorization for medical record 
review to determine if the subjects meets inclusion criteria is not practicable since many patients will not meet 
enrollment criteria.
ii.
If requesting a waiver of signed authorization, describe why it would be impracticable to obtain the 
subject’s signed authorization for use/disclosure of this data: Write here
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The investigator assures that the protected health information for which a Waiver of Authorization has been 
requested will not be reused or disclosed to any person or entity other than those listed in this application, 
except as required by law, for authorized oversight of this research study, or as specifically approved for use 
in another study by an IRB.
Researchers are reminded that unauthorized disclosures of PHI to individuals outside of the Yale HIPAA-Covered 
entity must be accounted for in the “accounting for disclosures log”, by subject name, purpose, date, recipients, 
and a description of information provided. Logs are to be forwarded to the Deputy HIPAA Privacy Officer.
6.
Process of Consent/Assent: Describe the setting and conditions under which consent/assent will be obtained, 
including parental permission or surrogate permission and the steps taken to ensure subjects’ independent 
decision-making.
Subjects will be recruited in person at the Smilow Cancer Hospital Thoracic Oncology clinic. Study 
investigators and study staff will inform the treating clinician of potential participation in the study, and patients 
will be approached while they are waiting for their standard of care visit or immediately after the visit. Study 
staff will explain the following: goals of the study, groups in the study (i.e., intervention group and usual care 
group), length of the study, anticipated risk/benefits of study involvement, measures taken to minimize risk, and 
requirements for participating in the study (i.e., need for a smartphone, willingness to download a FitBit 
application to the smartphone, willingness to wear an accelerometer for 12 weeks, and willingness to receive 2 
text messages/day for 12 weeks). The patient will be given the opportunity to ask questions.  Study staff will 
also explain that participation is voluntary, and any participant may choose to stop participating in the study at 
any time. Study staff will also explain that participation (or non-participation) in the study will not influence 
their clinical care. Documents provided to the patient will include an informational handout, an educational 
pamphlet, HIPAA authorization, and the consent form. If patients volunteer to participate, copies of the study 
consent and HIPAA form will be provided.
7.
Evaluation of Subject(s) Capacity to Provide Informed Consent/Assent: Indicate how the personnel obtaining 
consent will assess the potential subject’s ability and capacity to consent to the research being proposed.
A subject’s appropriateness for study participation and capacity to provide informed consent will be 
assessed in 2 ways. First, study staff will screen patients via medical record review for exclusions. Patients with 
impairments in cognition or memory will not be included. Second, the treating oncologist will be approached to 
confirm the patient’s appropriateness for the study. If the study staff member who is recruiting the patient is 
concerned about patient appropriateness for the study or understanding of the study/consent process, study 
staff will notify to the treating oncologist and Primary Investigator to discuss their concerns. Ultimately, the 
primary investigator and treating oncologist must agree to the patient’s inclusion in the study. If either the 
oncologist or Primary Investigator have concerns regarding the patient’s capacity or appropriateness for the 
study, the patient will not be enrolled.
8.
Non-English Speaking Subjects: Explain provisions in place to ensure comprehension for research involving 
non-English speaking subjects. If enrollment of these subjects is anticipated, translated copies of all consent 
materials must be submitted for approval prior to use.
Since communication between the study team and the patient is crucial and translated materials are not 
currently available, non-English speaking patients will not be enrolled in this study.
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Note* If more than 2 study participants are enrolled using a short form translated into the same language, then 
the full consent form should be translated into that language for use the next time a subject speaking that 
language is to be enrolled.
Several translated short form templates are available on the HRPP website (yale.edu/hrpp) and translated HIPAA 
Research Authorization Forms are available on the HIPAA website (hipaa.yale.edu). If the translation of the short 
form is not available on our website, then the translated short form needs to be submitted to the IRB office for 
approval via modification prior to enrolling the subject. Please review the guidance and presentation on use of 
the short form available on the HRPP website.
If using a short form without a translated HIPAA Research Authorization Form, please request a HIPAA 
waiver in the section above.
For a waiver of signed consent, address the following:
Would the signed consent form be the only record linking the subject and the research? YES ☐ NO ☐
Does a breach of confidentiality constitute the principal risk to subjects? YES ☐ NO☐
OR
Does the research pose greater than minimal risk? YES ☐ NO☐
Does the research include any activities that would require signed consent in a non-research context? YES ☐ 
NO ☐
As a limited alternative to the above requirement, will you use the short form* for consenting process if you 
unexpectedly encounter a non-English speaking individual interested in study participation and the translation of 
the long form is not possible prior to intended enrollment? YES ☐ NO ☒
9.
Consent Waiver: In certain circumstances, the HIC may grant a waiver of signed consent, or a full waiver 
of consent, depending on the study. If you will request either a waiver of consent, or a waiver of signed consent 
for this study, complete the appropriate section below.
☐☒Not Requesting any consent  waivers
☐Requesting a waiver of signed   consent:
☐Recruitment/Screening only (if for recruitment, the questions in the box below will apply to 
recruitment activities only)
☐Entire Study (Note that an information sheet may be required.)
☒☐ Requesting a waiver of consent:
☒☐ Recruitment/Screening only (if for recruitment, the questions in the box below will apply to 
recruitment activities only)
☐Entire Study
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SECTION IV: PROTECTION OF RESEARCH SUBJECTS
For a full waiver of consent, please address all of the following:

Does the research pose greater than minimal risk to subjects?
☐Yes If you answered yes, stop. A waiver cannot be granted.
☒☐ No

Will the waiver adversely affect subjects’ rights and welfare? YES ☐ NO☒☐
Why would the research be impracticable to conduct without the waiver? Consent waiver for medical 
record review to determine if the subjects meets inclusion criteria since many patients will not meet 
enrollment criteria.

Where appropriate, how will pertinent information be returned to, or shared with subjects at a later date?
na
Confidentiality & Security of Data:
1.
What protected health information (medical information along with the HIPAA identifiers) about subjects will 
be collected and used for the research?
The four sources of data for this study are:
1)
The medical record to determine demographic data, cancer histology and stage, cancer treatment 
history, medical comorbidities, drug treatment for medical comorbidities.
2)
Survey instruments (as described above)
3)
Biomarkers analyzed in blood (C-reactive protein, leptin, insulin, PD-1, and PD-L1)
4)
Step count and sleep data downloaded from the Fitbit® device
The study database will contain date of birth, date of enrollment, demographic information, cancer 
treatment details, past medical history, and medication regimen (including psychoactive medication use). In the 
database, subjects will be identified by Subject Number. An electronic document linking the enrolled patient 
name and medical record number to the subject number will be maintained at each institution’s office.
2.
How will the research data be collected, recorded and stored?
Data from the medical record will be collected and directly stored in the REDCap database. Survey 
instruments will be collected on paper forms (identifiable only by Study ID) during the clinic visit and recorded in 
the REDCap database for future analysis. The paper copies will be stored in a locked office in the Anlyan Center. 
All activity and sleep data will be acquired from the FitBit website and stored directly in the REDCap database.
Blood will be stored in the YCCI freezer on 300 George Street in New Haven.
3.
How will the digital data be stored? ☐CD ☐DVD ☐Flash Drive ☐Portable Hard Drive ☒Secured Server
☐Laptop Computer ☒Desktop Computer ☐Other
4.
What methods and procedures will be used to safeguard the confidentiality and security of the identifiable
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study data and the storage media indicated above during and after the subject’s participation in the study?
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All portable devices must contain encryption software, per University Policy 5100. If there is a technical reason a 
device cannot be encrypted please submit an exception request to the Information Security, Policy and Compliance 
Office by clicking on url http://its.yale.edu/egrc or email it.compliance@yale.edu
SECTION V: POTENTIAL
As above, data from the medical record will be collected and directly stored in the REDCap database. 
Survey instruments will be collected on paper forms (identifiable only by Study ID) during the clinic visit and 
recorded in the REDCap database for future analysis. The paper copies will be stored in a locked office in the 
Anlyan Center. All activity and sleep data will be acquired from the FitBit website and stored directly in the 
REDCap database. Lists of screened and enrolled subjects will be kept in password-protected Excel files that are 
stored on a limited access Yale drive (\\med1.med.yale.edu\home\721774c\Bade, Brett).
All paper documents will be maintained in a locked cabinet in a locked office in the Anlyan center. All 
documents excepting the consent and HIPAA forms will be identified by the patient’s Study ID number.
Similarly, subjects will be identified in the REDCap database by their subject number rather than their name or medical 
record. The text messages will identify the patients by first only, and no information about the patient’s diagnosis, status, or 
treatment will be sent via the text messages. Text messages will reference the benefits of physical activity in chronic lung 
disease and lung cancer. At the end of the study, limited access databases at Yale and MUSC will be combined for data 
analysis. Since cancer treatment dates will be included, a data use agreement is in place between the institutions. No direct 
patient identifiers will be shared between Yale and MUSC.
5.
What will be done with the data when the research is completed? Are there plans to destroy the identifiable 
data? If yes, describe how, by whom and when identifiers will be destroyed. If no, describe how the data and/or 
identifiers will be secured.
When the study is completed, patient documents will be maintained for 3 years in a locked office. After 3 
years, documents from the study may be shredded on university campus by the site primary investigator. The 
shredded documents will be disposed of by the university team. Information on the de-identified database will be 
maintained in anticipation of future studies.
6.
If appropriate, has a Certificate of Confidentiality been obtained? Write here
Potential Benefits: Identify any benefits that may be reasonably expected to result from the research, either to 
the subject(s) or to society at large. (Payment of subjects is not considered a benefit in this context of the risk 
benefit assessment.)
Potential benefits for the individual include potential improvements in QoL, increased physical activity, 
better mood, and improved symptom control. These benefits are potential and should not be a reason for 
patient participation. Participants in both the intervention and usual care groups will receive FitBit Flex 2 
devices at the end of the study.
The potential benefit to society is the ability for a low-impact activity regimen to reduce inactivity in 
patients.
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SECTION VI: RESEARCH ALTERNATIVES AND ECONOMIC CONSIDERATIONS
1.
Alternatives: What other alternatives are available to the study subjects outside of the research?
Subject alternatives include not participating in the research study or asking their clinician about feasible 
and safe methods to increase physical activity levels at home (outside study participation).
2.
Payments for Participation (Economic Considerations): Describe any payments that will be made to subjects, 
the amount and schedule of payments, and the conditions for receiving thiscompensation.
No payments will be provided to subjects. Participants in both the intervention and usual care groups will receive 
FitBit Flex 2 devices at the end of the study.
3.
Costs for Participation (Economic Considerations): Clearly describe the subject’s costs associated with 
participation in the research, and the interventions or procedures of the study that will be provided at no cost 
to subjects.
The FitBit devices will be provided at no cost, and the participant will be able to keep the FitBit 
upon completion of the study. The FitBit smartphone application is free.
4.
In Case of Injury: This section is required for any research involving more than minimal risk, and for minimal 
risk research that presents the potential for physical harm (e.g., research involving blood draws).
a.
Will medical treatment be available if research-related injury occurs? Write here
b.
Where and from whom may treatment be obtained? Write here
c.
Are there any limits to the treatment being provided? Write here
d.
Who will pay for this treatment? Write here
e.
How will the medical treatment be accessed by subjects? Write here
If the subject is injured while on study, he/she should seek treatment and contact the study doctor 
as soon as possible.
Yale School of Medicine does not provide funds for the treatment of research-related injury. If the 
subject is injured as a result of participation in this study, treatment will be provided. The subject 
or the subject’s insurance carrier will be expected to pay the costs of this treatment. No additional 
financial compensation for injury or lost wages is available.
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A billable service is defined as any service rendered to a study subject that, if he/she was not on a study, would 
normally generate a bill from either Yale-New Haven Hospital or Yale Medical Group to the patient or the patient’s 
insurer. The service may or may not be performed by the research staff on your study, but may be provided by 
professionals within either Yale-New Haven Hospital or Yale Medical Group (examples include x-rays, MRIs, CT 
scans, specimens sent to central labs, or specimens sent to pathology). Notes: 1. There is no distinction made 
whether the service is paid for by the subject or their insurance (Standard of Care) or by the study’s funding 
mechanism (Research Sponsored). 2. This generally includes new services or orders placed in EPIC for research 
subjects.
If answered, “yes”, this study will need to be set up in OnCore, Yale’s clinical research management system, for 
Epic to appropriately route research related charges. Please contact oncore.support@yale.edu
If you answered “no” to question 4a, or "yes" to question 4b or c, please contact the YNHH Department of 
Physician Services (688-2615) for prior approval before commencing with your research protocol.
IMPORTANT
Will this study have a billable service? Yes ☒
No☐
Are there any procedures involved in this protocol that will be performed at YNHH or one of its affiliated entities?
Yes ☒ No ☐
If Yes, please answer questions a through c and note instructions below.
a. Does your YNHH privilege delineation currently include the specific procedure that you will perform? Yes ☐ No
☐
b. Will you be using any new equipment or equipment that you have not used in the past for this procedure? Yes
☐No ☐
c. Will a novel approach using existing equipment be applied? Yes ☐ No ☐
IMPORTANT REMINDER ABOUT RESEARCH AT YNHH
Please note that if this protocol includes Yale-New Haven Hospital patients, including patients at the HRU, the 
Principal Investigator and any co-investigators who are physicians or mid-level practitioners (includes PAs, APRNs, 
psychologists and speech pathologists) who may have direct patient contact with patients on YNHH premises 
must have medical staff appointment and appropriate clinical privileges at YNHH. If you are uncertain whether 
the study personnel meet the criteria, please telephone the Physician Services Department at 203-688-2615. By 
submitting this protocol as a PI, you attest that you and any co-investigator who may have patient contact has a 
medical staff appointment and appropriate clinical privileges at YNHH.
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Bade BC, Brooks MC, Nietert SB, et al. Assessing the Correlation Between Physical Activity 
and Quality of Life in Advanced Lung Cancer. Integr Cancer Ther. 2016:1534735416684016.
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Cancer Facts and Figures 2015. 2015:1-10. Accessed 8/21/2015.
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Bade BC, Thomas DD, Scott JB, Silvestri GA. Increasing physical activity and exercise in lung 
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Granger CL, McDonald CF, Irving L, et al. Low physical activity levels and functional decline in 
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accelerometers for internet-based self-monitoring of physical activity in patients with chronic 
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wearable devices for tracking physical activity data. JAMA. 2015;313(6):625-626.
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Courneya KS, Segal RJ, Gelmon K, et al. Predictors of adherence to different types and doses of 
supervised exercise during breast cancer chemotherapy. Int J Behav Nutr Phys Act.2014;11:85.
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life in patients with lung cancer. Cancer Nurs. 2015;38(1):60-70.
25.
Heywood R, McCarthy AL, Skinner TL. Safety and feasibility of exercise interventions in 
patients with advanced cancer: a systematic review. Support Care Cancer. 2017.
26.
Zoellner J, Powers A, Avis-Williams A, Ndirangu M, Strickland E, Yadrick K. Compliance and 
acceptability of maintaining a 6-month pedometer diary in a rural, African American 
community-based walking intervention. J Phys Act Health. 2009;6(4):475-482.
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Figure 1: Average Daily Step Count vs Physical Functioning
Average Daily Step Count
2000
4000
6000
8000
10000
12000
14000
0
120
100
80
60
40
20
0
Physical Functioning vs Activity
QLQ-
30
Physic 
al 
Functi 
oning 
Score
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APPROVED BY THE YALE UNIVERSITY IRB 3/6/2020
Page 31 of 24
Figure 2: Average Daily Step Count vs Dyspnea score
Average Daily Step Count
14000
12000
10000
8000
6000
4000
2000
0
3.5
3
2.5
2
1.5
1
0.5
0
Dyspnea vs Activity
M
M 
R 
C 
D
y 
s 
p 
n 
e 
a
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APPROVED BY THE YALE UNIVERSITY IRB 3/6/2020
Page 32 of 24
Figure 3: Average Daily Step Count vs Depression scores
Average Daily Step Count
10000
12000
14000
8000
4000
6000
2000
0
25
20
15
10
5
0
Depression vs Activity
P
H 
Q
- 
9
D
e 
p 
r 
e 
s
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