Re-engineering Precision Therapeutics Through N-of-1 Trials: Personalized Trials for Stress Management Against Standard of Care
Phase: PHASE2
Conditions: Stress
Sponsor: Northwell Health

 
 
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Personalized Trials for Stress Management Against Standard of Care  
NCT05408832 
Version Date: 9/14/2022 
 
 

 
 
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RESEARCH PROTOCOL 
 
 
Protocol Title: 
Personalized Trials for Stress Management Against Standard of 
Care 
Principal Investigator: 
Karina W. Davidson, PhD, MASc 
Primary Contact Name: 
Challace Pahlevan-Ibrekic 
Primary Contact Phone: 
646-766-7169 
Primary Contact E-mail: 
cpahlevanibr@northwell.edu 
Date Revised: 
9/14/22 
IRB Number: 
21-0968-MRB 
 
 
Guidelines for Preparing a Research Protocol 
 
Instructions: 
 
• You do not need to complete this document if you are submitting an Application for 
Exemption or Application for a Chart Review.   
• Do not use this template if: 
o  Your study involves an FDA regulated product.  In this case, use the Clinical 
Trial Protocol Template. 
o Your study has a protocol from a sponsor or cooperative group.  In this case, use 
the Protocol Plus.   
o Your study is a registry or repository for data and/or samples,  In this case, use 
Protocol Template – Registry Studies.  .   
• If a section of this protocol is not applicable, please indicate such. 
• Do not delete any of the text contained within this document. 
• Please make sure to keep an electronic copy of this document.  You will need to use it, if 
you make modifications in the future.   
• Start by entering study information into the table above, according to these rules: 
o Protocol Title:  Include the full protocol title as listed on the application. 
o Investigator:  include the principal investigator’s name as listed on the application 
form 
o Date Revised:  Indicate the date at which the protocol was last revised 
o IRB Number:  Indicate the assigned IRB number, when known.  At initial 
submission, this row will be left blank.   
• Once the table information in entered, proceed to page 2 and complete the rest of the 
form. 
 
 
 

 
 
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 Continue to next page to begin entering information about this study  
 
 
1.  PREVIOUS STUDY HISTORY 
 
Has this study ever been reviewed and rejected/disapproved by another IRB prior to 
submission to this IRB? 
 
 No  
 Yes −  if yes, please explain:  
 
 
2. BRIEF SUMMARY OF RESEARCH 
• The summary should be written in language intelligible to a moderately educated, 
non-scientific layperson.  
• It should contain a clear statement of the rationale and hypothesis of your study, a 
concise description of the methodology, with an emphasis on what will happen to the 
subjects, and a discussion of the results.  
• This section should be ½ page 
 
 
The purpose of this study is to determine if an N-of-1 study design, or what we are 
terming “Personalized Trials” can improve health outcomes over standard practice 
for common stress management techniques. This study is an expansion on lessons 
learned from three feasibility pilots (19-0672, 20-0230, and 20-0835) of methods to 
remotely implement Personalized Trials.  
 
This study uses three different stress management interventions to improve 
individual self-report of perceived stress: guided mindfulness meditation, guided 
yoga, and guided brisk walking. Arm 1 (n=53) and Arm 2 (n=53) of the trial will 
deliver the interventions using a Personalized Trial format. Participants in Arm 3 of 
the trial (N=106) will be offered the same number of interventions, but will not be 
required to follow the established N-of-1 Personalized Trials framework. 
Participants in all arms of the study will be asked to respond to surveys daily and to 
wear a Fitbit device. Interventions will be delivered by virtual link to an online 
video or audio recorded by an experienced Zeel wellness provider. Zeel is the 
company that we have asked to provide the interventions for this research.  It is a 
commercial company that provides in-home or in-office services (such as 
stretching or yoga).  The company has been contracted to create these videos of the 
services they provide for our use in the research.  At the end of their Personalized 
Trial, participants in Arms 1 and 2 will receive a summarized report of their 
observed Fitbit and survey data and will be asked to select which stress 
management intervention they would like to continue with (after 12 weeks of 
intervention tracking and data collection). Participants in Arm 3 will also receive a 
report with summarized Fitbit and survey data and be asked to select which stress 
management technique they would like to continue with in the same timeframe 

 
 
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(after 12 weeks of intervention tracking and data collection). Both arms will 
receive 2 additional weeks of the stress management intervention of their choosing, 
while continuing to answer daily assessments and wear a Fitbit device. At the end 
of the study, all participants will be sent a satisfaction survey. Participants will be 
asked to participate in a qualitative interview to discuss their experiences until a 
random sample of 10% from each arm is achieved. 
   
With the popularity and accessibility of new technologies, and with the ability to 
process large data sets in a short period of time, we believe Personalized Trials are 
feasible to scale to clinical practice. Data collected to support our hypothesis 
include changes in Perceived Stress Scale two-weeks post intervention selection, 
adherence to Personalized Trial protocol components, adherence to interventions 
pre- and post-treatment decision, agreement between the Personalized Trial report 
and participant treatment selection, and satisfaction based on qualitative interviews 
and surveys.  
 
 
3. INTRODUCTION/BACKGROUND MATERIAL/PRELIMINARY STUDIES AND 
SIGNIFICANCE 
• Describe and provide the results of previous work by yourself or others, including 
animal studies, laboratory studies, pilot studies, pre-clinical and/or clinical studies 
involving the compound or device to be studied.  
• Include information as to why you are conducting the study and how the study differs 
from what has been previously researched, including what the knowledge gaps are. 
• Describe the importance of the knowledge expected to result 
 
This project represents the RCT project under the umbrella of the NIH-funded 
grant “Re-engineering precision therapeutics through N-of-1 trials” (Northwell IRB 
19-0572-MRB) which is funded to test use cases appropriate for N-of-1 
methodology and evaluate them for acceptability and scalability. 
 
The overarching objective of our parent grant is to develop, test, and implement an 
innovative technology platform for conducting N-of-1 trials that transforms 
precision therapeutics. Right now, clinicians are engaging in clinical encounters in 
which they are trying to determine the best therapy for individual patients. These 
encounters are likely to be unsuccessful. Clinicians rely on the best available 
evidence (e.g., results from parallel group, phase III randomized clinical trials; 
RCTs) for recommending therapies to a patient. Yet, conventional, between-group 
RCTs only provide estimates of the effect of therapies on the hypothetical 
‘average’ patient in those trials. Individual patients, however, often respond 
differently than the hypothetical average patient in the phase III RCTs, and thus, 
heterogeneity of therapy response plagues clinical decisions made for an individual 
patient every day.   
 
The most scientifically rigorous — and potentially transformative — method for 
determining optimal therapy for a patient is a single-patient (N-of-1) trial. N-of-1 

 
 
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trials are multiple crossover trials, usually randomized, and often masked, 
conducted within a single patient, with data collected objectively, continuously, 
and in the real-world, for a sufficient time period to determine whether the therapy, 
compared to a placebo or other active therapy, is optimal for a particular patient. 
They also yield information on off-target actions, such as side-effects or unintended 
consequences, so that a more complex picture can emerge about the overall 
benefits and harms of the therapy for that one individual patient. Clinicians and 
patients do not routinely engage in this type of scientific endeavor because they 
lack the tools.   
 
In many ways, Personalized or N-of-1 Trials are the foundational design for a 
truly patient-centered approach by serving as a clinical decision tool for 
patients. Historically, in introducing evidence-based medicine, Guyatt and others 
have described Personalized Trials as the pinnacle of the evidence-based design 
pyramid1.  Clinicians can use these techniques to monitor and make treatment 
decisions in chronically ill patients2, of whom 25% experience adverse treatment 
effects3. Personalized Trials are specifically designed to help patients and their 
clinicians make healthcare decisions that are informed by high-integrity, evidence-
based information uniquely relevant to the outcomes and values important to them4. 
In a series of demonstration trials, Personalized Trials led to valuable changes in 
treatment, cessation of treatment, or confirmation of the original treatment5-8. For 
example, of 71 N-of-1 trials for patients with any chronic pain, 46 patients (65%) 
decided to change their pain medication due to trial results9. However, Personalized 
Trials are conducted infrequently in clinical practice10-12. In post-mortem 
assessments as to why Personalized Trials had yet to become commonly employed, 
proponents concluded that they were insufficiently appealing to patients or 
clinicians to justify the cost and effort needed to design and implement them10,11. 
Specifically, Personalized Trial design specifications had mostly been driven by 
clinicians or researchers13,14, with little input from patients.  
 
Rationale for Selecting Stress Management as a Personalized Trial 
Participant report of perceived stress meets all of our criteria for selection as a use 
case as outlined in our umbrella grant: it has high public health burden, high 
heterogeneity of therapy response, multiple, evidenced-based treatments and is 
high priority for a Personalized Trial approach as determined by previously 
interviewed clinicians and patients. A recent survey of 3,617 adults found that on a 
scale of 1 to 10, Americans reported their average stress level as 4.9, while also 
reporting that a healthy stress level is on average 3.815. Prior studies examining the 
effects of mindfulness meditation, yoga, and physical activity for stress reduction 
found all three intervention types were associated with significant reductions in 
self-reported measures of stress and/or physiological measures of stress16-19. 
However, stress reduction interventions often have high levels of heterogeneity in 
treatment effects, indicating that not every intervention will provide uniform 
benefits for all patients. Very little information exists on determining which 
treatment will be most effective for stress reduction in an individual patient. As 

 
 
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personalized medicine approaches to treat depression, it is reasonable to utilize the 
same methods for stress treatment20. 
 
This instance will adapt our N-of-1 trial platform to comparing three stress 
interventions to standard of care.  
 
 
4. OBJECTIVE(S)/SPECIFIC AIMS AND HYPOTHESES 
• A concise statement of the goal(s) of the current study.  
• The rationale for and specific objectives of the study.  
• The goals and the hypothesis to be tested should be stated. 
 
We believe the incorporation of N-of-1 methodology through Personalized Trials 
will offer improved health outcomes over current standard clinical practice.  
 
Thus, the goals of this study are to:  
1. Conduct an RCT (N=212) of a Personalized Trial against standard practice that 
is delivered remotely to participants in the United States. 
2. Analyze how changes in participant’s perceived stress may differ from baseline 
after receiving the opportunity to test out three evidence-based stress management 
techniques in a Personalized Trial or standard practice format.  
3. Analyze how a participant’s personal wellness strategy may be impacted by the 
customized data report they receive in a Personalized Trial. 
4. Incorporate lessons learned from previous pilots of Personalized Trials, 
including minimum viable product specifications for a technology platform to 
deliver Personalized Trials, and assess additional requirements to deliver a 
randomized controlled trial.  
5. Elicit participant attitudes and opinions toward using Personalized Trials to help 
inform their personal wellness strategy. 
 
To determine whether this “precision therapeutics” paradigm-shifting approach 
creates added value for the learning healthcare system, and to confirm engineering 
these innovations into one platform and system to empirically determine the 
precise therapy for each patient is feasible, we will pool results across all projects 
using the N1Thrive platform.   
 
 
5.  RESOURCES AVAILABLE TO CONDUCT THE HUMAN RESEARCH 
• Explain the feasibility of meeting recruitment goals of this project and demonstrate a 
potential for recruiting the required number of suitable subjects within the agreed 
recruitment period 
o How many potential subjects do you have access to? 
• Describe your process to ensure that all persons assisting with the trial are 
adequately informed about the protocol and their trial related duties and functions 
 

 
 
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The study team is experienced with recruiting within the Northwell employee, 
graduate student and patient networks, and has recently conducted a study of over 
900 enrolled participants. The size of these expansive networks provides adequate 
opportunity for the enrollment of the projected sample size for this research and 
also ensures that adequate diversity in subject population may be achieved. 
 
All individuals on the study team will be required to attend mandatory biweekly 
meetings with the PI and project manager to discuss the study protocol, timelines, 
and issues as they come up in real-time. Additionally, all consenting coordinators 
will be trained in the operating procedures of this study by the study clinical 
research supervisor. 
 
 
 
6.  RECRUITMENT METHODS 
• Describe the source of potential subjects 
• Describe the methods that will be used to identify potential subjects 
• Describe any materials that will be used to recruit subjects.  A copy of any 
advertisements (flyers, radio scripts, etc.) should be submitted along with the 
protocol.  
• If monetary compensation is to be offered, this should be indicated in the protocol 
 
Potential participants will primarily be individuals who are current or past 
participants in research managed or conducted by the Center for Personalized 
Health.  Current or past participants will be contacted via email notification to 
invite them to participate.   
 
Study staff are experienced with utilizing the Northwell system’s vast electronic 
communication tools including weekly newsletters, E-blasts and social media 
(Northwell Facebook Group) forums. We will access similar electronic 
communications that serve Hofstra University programs. Additionally, a 
recruitment flyer will be posted on the Personalized Trials web page.  
 
However, since the proposed study will take place virtually, potential participants 
are not required to reside within travelling distance of Northwell Health.   
Therefore, the exclusion criteria do not preclude those living outside of New York 
state from passing screening, but only individuals who reside in states for which the 
Office of Legal Affairs has provided approval will be cleared for participation if 
eligible.  Individuals who do not live in a cleared state will have their enrollment 
workflow paused and may be removed from the waitlist if their state is cleared in 
the future. 
 
.  Potential participants will also be recruited via  
- 
Paid and unpaid social media advertisements targeted to individuals who 
meet study eligibility demographics and identify as having stress 

 
 
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- 
Online research listings, such as the Feinstein Institutes for Medical 
Research clinical trials listing (https://www.northwell.edu/clinical-trials) 
and ClinicalTrials.gov (https://www.clinicaltrials.gov/),  
- 
Flyers, shared at urgent care/walk-in and physician clinics, within and 
outside of the Northwell Health network. 
- 
Short promotional videos shared online or in clinic waiting rooms. 
- 
Recruitment posts within online wellness groups, such as those that discuss 
stress 
 
Interested participants will pre-screen using an electronic survey to determine 
potential eligibility. If the pre-screen and longer screen surveys deem the potential 
participant as possibly eligible, they will be allowed to continue with the consent 
process. 
 
 
7.  ELIGIBILITY CRITERIA 
• Describe the characteristics of the subject population, including their anticipated 
number, age, ranges, sex, ethnic background, and health status. Identify the criteria 
for inclusion or exclusion of any subpopulation.  
• Explain the rationale for the involvement of special classes of subjects, such as 
fetuses, pregnant women, children, prisoners or other institutionalized individuals, or 
others who are likely to be vulnerable.   You cannot include these populations in your 
research, unless you indicate such in the protocol 
• Similarly, detail exclusionary criteria: age limits, special populations (minors, 
pregnant women, decisionally impaired), use of concomitant medications, subjects 
with other diseases, severity of illness, etc. 
 
We aim to recruit a diverse pool of participants with varied ethnic and racial 
backgrounds. We estimate about 70% will be female and 30% will be male. 
 
Inclusion: 
- Age ≥ 18 years 
- English speaking 
- Self-report of perceived stress raw score of 20 or higher using the Perceived Stress 
Scale (PSS) 
- Owns and can regularly access a smartphone capable of receiving text messages and 
accessing the internet 
- Can regularly wear a Fitbit device 
- Lives in the United States  
 
Exclusion: 
- Women who are pregnant 
- Does not speak English 
- Does not own or cannot regularly access a smartphone capable of receiving text 
messages 
- Cannot regularly wear a Fitbit device 

 
 
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- Deemed unable to complete the study protocol as a result of cognitive impairment, 
severe medical or mental illness, or active or prior substance abuse 
- Planned surgeries 6 months from study start date 
- Individuals who have been previously told by a doctor to not engage in brisk 
walking 30 minutes, three times per week 
- Individuals who have been previously told by a doctor to not engage in yoga 
- Does not own or cannot regularly access a smartphone capable of receiving text messages 
-  
- Lives outside the United States 
 
 
 
 
 
8.  NUMBER OF SUBJECTS 
• Indicate the total number of subjects to be accrued locally.  If applicable, distinguish 
between the number of subjects who are expected to be pre-screened, enrolled 
(consent obtained), randomized and complete the research procedures. 
• If your study includes different cohorts, include the total number of subjects in each 
cohort. 
• If this is multisite study, include total number of subjects across all sites.   
 
For this research, we will enroll up to 1000 individuals with the goal of randomizing 
212 individuals total in study arms 1, 2, and 3 (53 in Arm 1, 53 in Arm 2 & 106 in Arm 
3). 
 
 
9. STUDY TIMELINES 
• Describe the duration of an individuals participation in the study 
• Describe the duration anticipated to enroll all study subjects 
• The estimated date of study completion 
 
The study will take place over the course of 18 weeks. The first 2 weeks will be a 
run-in period, where no stress management interventions are given, but data are 
collected, including daily surveys and Fitbit-derived sleep and activity data. Those 
who are deemed eligible will be randomized to receive 12-weeks of a Personalized 
Trial or standard care experience, where they will have the opportunity to test 3 
different stress management techniques while continuing to answer daily 
assessments and wearing their Fitbit device. At the end of the 12 weeks, 
participants will continue to answer daily surveys and wear their Fitbit device for 2 
weeks with no provided intervention while the study team creates a report 
containing the individual’s observed data. This report will be sent to each 
participant in all arms, and participants will have the opportunity to select one 
stress management technique to continue with for 2 additional weeks. After 
selection, participants will receive six additional sessions of their chosen treatment 
and will be observed for engagement in these additional wellness sessions. 
Participants will also be asked to complete daily survey assessments and Fitbit 

 
 
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wear for these two additional weeks. At the end of the 18-week study, a final 
survey will be sent assessing satisfaction with the study. A random sample of 10% 
of participants from each arm will be asked to participate in a qualitative interview 
to discuss their experiences. 
 
Potential participants will have the opportunity to choose from within a provided 
list of start dates during their enrollment process. Enrollment will be ongoing until 
up to 53 participants have been randomized into Arm 1, 53 participants have been 
randomized into Arm 2, and 106 participants have been randomized into Arm 3 of 
the study. We estimate that the final participant will be randomized by January 31, 
2023, and data collection will cease by May 31, 2023.  
 
 
10.  ENDPOINTS 
• Describe the primary and secondary study endpoints 
• Describe any primary or secondary safety endpoints  
 
The primary endpoint of this study is change in average daily perceived stress, 
assessed using ecological momentary assessment (EMA), two-weeks post 
treatment selection compared to baseline assessment.  
 
Secondary endpoints include: 
-Change in perceived stress, assessed using the Perceived Stress Scale, two-weeks 
post treatment selection compared to baseline assessment. 
-Agreement between the Personalized Trial report and participant treatment 
selection 
-Adherence to interventions pre- and post-treatment decision 
-Usability of personalized trials based on the System Usability Scale 
-Satisfaction based on qualitative interviews and surveys  
-Changes in daily EMA between stress management interventions 
-Changes in perceived stress, assessed using the Perceived Stress Scale, between 
stress management interventions 
 
 
11.  RESEARCH PROCEDURES 
• Include a detailed description of all procedures to be performed on the research 
subject and the schedule for each procedure. 
• Include any screening procedures for eligibility and/or baseline diagnostic tests 
• Include procedures being performed to monitor subjects for safety or minimize risks 
• Include information about drug washout periods 
• If drugs or biologics are being administered provide information on dosing and route 
of administration 
• Clearly indicate which procedures are only being conducted for research purposes. 
• If any specimens will be used for this research, explain whether they are being 
collected specifically for research purposes.   
• Describe any source records that will be used to collect data about subjects 

 
 
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• Indicate the data to be collected, including long term follow-up 
 
Potential participants who self-identify as having stress management concerns via 
virtual recruitment methods will be directed to an information screen with details 
about the study. Those who are interested in participating in this study will be 
directed to an initial pre-screening survey that collects contact information and 
their date of birth. If eligible according to prescreen, interested participants will 
then provide written (electronic) authorization prior to completion of the full 
screening survey.  The screening survey includes identifying symptoms via the 
validated Perceived Stress Scale (PSS), as well as other questions pertaining to 
inclusion and exclusion criteria. If eligible, those interested in participating will be 
given the opportunity to provide written (electronic) consent.  Once effective 
informed consent has been obtained, participants will receive an onboarding 
questionnaire to collect additional information needed to proceed to the baseline 
period. 
 
A Consenting Coordinator will confirm the start date of each participant’s baseline 
period and direct the participant to view short informational videos of what to 
expect during the study run-in period.  Participants who do not report having their 
own Fitbit device that is acceptable for this study will be provided a new device 
before their start date to ensure equitable subject enrollment.  Acceptable devices at 
this time are the Fitbit Sense, Fitbit Versa 3, Fitbit Charge 5, Fitbit Charge 4, Fitbit 
Luxe, and Fitbit Inspire 2, though new device models released by Fitbit in the 
future will be considered. These devices were specifically selected because they all 
accurately collect the data (ex: sleep stage data, heart rate, etc.) needed to analyze 
observed Fitbit data for participant's personalized reports.  It has been our 
experience that participants have repeatedly requested to use their own Fitbit 
device during participation in our research (either a device they have personally 
purchased outside of the context of the research, or one they have been provisioned 
through prior research participation). We do not intend to deny participation to 
individuals who request to use their own device, and likewise do not intend to deny 
participation to individuals who report they do not have a Fitbit device that can be 
used in this research. All participants (those who request to use their own device 
and those who are provisioned a device) will be instructed on how to sign into the 
Fitbit app with a coded study ID. All baseline periods will begin on a Monday.  
 
The baseline period will take place over the course of 2-weeks. Potential 
participants will not receive any stress interventions during the baseline period and 
will be instructed to continue managing their stress as they normally would. At 
three randomized times each day during waking hours identified by the potential 
participant during their onboarding survey, baseline participants will receive a text 
message asking them to rate their pain, fatigue, concentration, confidence, mood, 
and stress levels at that exact moment. At participant’s preferred evening time 
identified by the potential participant during their onboarding survey, baseline 
participants will receive a text message survey asking them to report if they did 
anything to relieve their stress that day, and report any experienced side effects 

 
 
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they attribute to that activity. At the end of each week on Sunday evenings, 
participants will receive a slightly longer survey that includes the modified PSS-10. 
 
During the baseline period, potential participants will be asked to wear their Fitbit 
all day and night, even while they are sleeping. Baseline participants will be 
instructed to sync their Fitbit device by opening the Fitbit app on their phone at 
least every two days, and to charge their Fitbit device as needed.  
Ten days into the baseline period, a Consenting Coordinator will review individual 
adherence to Fitbit wear and to survey responses. Adherence to Fitbit wear will be 
defined as recorded activity of greater than or equal to 12 hours a day and recorded 
sleeping activity. Survey adherence will be defined as submission of a given 
survey, including EMAs. Baseline participants that do not achieve at least 80% 
adherence of Fitbit wear and survey submission during the first 10 days of the 
baseline period will be given until day 14 of the trial to obtain 80% adherence. 
Those who still do not meet 80% adherence by day 14 will be withdrawn from the 
study. Those that maintain at least 80% adherence during the baseline period will 
be randomized to one of three study arms. Participants who are randomized will 
receive confirmation including their protocol timeline (for Arms 1 and 2, the 
timeline will outline their intervention sequence, or randomization). Participants 
will also receive additional video instruction and information on how to view 
upcoming mindfulness meditation videos, yoga videos, or brisk walking audio 
tracks. Enrollment will continue until up to 53 participants have been randomized 
into Arm 1, up to 53 participants have been randomized into Arm 2, and up to106 
participants have been randomized into Arm 3. 
 
In Arm 1 (n=53), participants will receive a Personalized Trial of the 3 stress 
management interventions in an ABCCBA treatment order, where A=mindfulness 
meditation, B=yoga, and C=brisk walking. Participants in this arm will be 
prompted to complete 30-minute stress management sessions during applicable 
treatment weeks. Participants will be limited to three views of study-provided stress 
management content each week.  
 
In Arm 2 (n=53), participants will receive a Personalized Trial of the 3 stress 
management interventions in a CBAABC treatment order, where A=mindfulness 
meditation, B=yoga, and C=brisk walking. Participants in this arm will be 
prompted to complete 30-minute stress management sessions during applicable 
treatment weeks. Participants will be limited to three views of the study-provided 
stress management content each week. 
 
In Arm 3 (n=106), participants will receive Standard Care of the 3 stress 
management techniques (mindfulness meditation, yoga, and brisk walking). 
Participants will receive access to the same number of views of the mindfulness 
meditation, yoga, and brisk walking content given to participants randomized in 
Arm 1 and Arm 2, however they will not be prompted to complete any session 
according to a randomization sequence. Participants will be limited to 36 total 
views of study-provided stress management content. 

 
 
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During all intervention weeks (12 weeks total) all participants will be asked to 
continue wearing their Fitbit device each day and night. They will continue to 
receive 3 randomized text messages each day with questions about their pain, 
fatigue, concentration, confidence, mood, and stress at that current moment, as well 
as an evening text asking them to report if they did anything to relieve their stress 
that day, and report any experienced side effects they attribute to that activity. At 
the end of each week on Sunday evenings, participants will receive a slightly 
longer survey that includes the PSS-10. A study phone number will be available as 
part of each survey to contact the study team.  
 
After 12 weeks of participants receiving the opportunity to complete mindfulness 
meditation, yoga, and brisk walking content for stress management, participants 
will continue to answer the same daily and weekly surveys they received during the 
intervention periodand wear their Fitbit device for 2 weeks, but participants will 
not receive any additional stress management content during that time to allow for 
a personalized report of their observed data to be generated. 
 
Once an individualized report has been generated, participants in all study arms 
will receive a copy of their observed data. Participants in Arm 1 and Arm 2 will 
receive a Personalized Trial report with insight into their tracked outcomes during 
each treatment order in the study. Participants in Arm 3 of the study will receive a 
Standard Care report with summarized data collected. Each participant, regardless 
of study arm, will be asked to select one stress management technique that they 
would like to continue with. Based on their selection, participants will receive 
another 6 sessions of stress management content (e.g. if yoga is selected, 
participants will receive 6 additional views of the yoga content). Participants will 
be observed for  2 weeks, and will have access to the additional stress management 
content monitored by the study team.  
 
Figure 1:  Study Design; For Arm #1 and Arm #2 A=mindfulness meditation, B=yoga, and C=brisk 
walking.   
 

 
 
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During the observational follow-up period, participants will be asked to continue 
wearing their Fitbit device each day and night. They will continue to receive the 
daily and weekly surveys they received during the intervention period. A study 
phone number will be available as part of each survey to contact the study team.  
 
At the end of the 2-week observational follow-up period, participants will be given 
a PSS post-assessment and satisfaction survey, which will be delivered by secure 
messaging, phone or video conference) as per participant preference. 
 
Participation in the study will end upon completion of the post-PSS assessment and 
the satisfaction survey. Alternatively, a participant may choose to withdraw from 
the study, or be withdrawn from the study by the research team. Upon completion 
of data monitoring, participants will be given instructions on how to un-link their 
Fitbit from the study account. Treatment adherence tracking will be suspended, as 
will daily text messages and survey prompts.  
 
A random sample of 10% of participants from each arm will be asked to participate 
in a qualitative interview to discuss their experiences. Selected participants will be 
sent a link to share their availability for a session with a consenting coordinator(s) 
held via video conference. On the rare chance that a participant cannot meet via 
video conference, we will hold the interview via phone call. The interview will last 
approximately 60 minutes. All interviews will be audio-recorded and transcribed 
via Microsoft Teams (or equivalent program) to ensure full capture of information 
provided during the discussion. Participants will be informed that the session will 
be recorded prior to initiating the interview. If the participant declines to be 
recorded, they may still participate in the interview and the study team will take 
notes of the conversation. Audio and transcription files will be stored securely on 
the PHI-approved SharePoint server. 
 
  
Participants may receive additional text messages to those outlined above with 
important reminders about their protocol (e.g. transition to a new treatment period). 
We will send a maximum of 7 text messages per day during the study, unless there 
are issues with participant’s data (battery/sync, etc.). 
 
In the event of an unanticipated circumstance that temporarily prevents a 
participant from completing study activities (illness, injury, death in the family, 
etc.), the participant will have the option of pausing their study to resume once their 
circumstance has been positively resolved. 
 
 
 
12.  STATISTICAL ANALYSIS 
• Describe how your data will be used to test the hypotheses.  

 
 
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• State clearly what variables will be tested and what statistical tests will be used. 
• Include sample size calculations.  
• If this is a pilot study, state which variables will be examined for hypothesis 
generation in later studies.  
 
Primary Hypothesis:  Participants assigned to Arm 1 and Arm 2 (the personalized 
trial arms) will demonstrate a greater reduction in the average momentary stress 
from baseline (run-in) to two weeks after treatment selection, when compared to 
Arm 3 (the standard of care arm). 
 
Figure 2:  Hypothesized change in average momentary stress; For Arm #1 and Arm #2 
A=mindfulness meditation, B=yoga, and C=brisk walking.   
 
The primary outcome for the current study is change in average momentary stress 
from baseline (run-in) to two weeks after treatment selection. To test the 
corresponding hypothesis using two-sample t-test comparing personalized trials 
arms (n = 84) and the standard care arm (n = 84) with 80% power and 5% 
significance (two-sided). The effect size is 0.307  
 
While the sample size is determined in accordance with the Primary Hypothesis, 
the power for detecting a difference in average momentary stress is 80%. The effect 
sizes are obtained from the findings of a pilot study (Protocol # 19-0672). To 
achieve a total 168 participants with complete data, under an assumed 20% 
attrition, we anticipate randomizing up to 212 participants total (n=106 in the 
personalized trial arms and n=106 in a standard care arm). 
 
All other hypotheses and outcome measures will be secondary to this study, 
including: 
• Change in mean within-subject difference in weekly Perceived Stress, 
using modified 10-item Perceived Stress Scale (PSS-10) between baseline 
(run-in) to two weeks after treatment selection. 

 
 
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• The proportion of participants in the personalized trial arm who select the 
treatment during follow-up recommended by their Personalized Trial 
report. 
• Mean scores on the System Usability Scale (SUS), a validated 10-item 
questionnaire21-22.  
• Mean participant satisfaction with Personalized Trials components 
supplemental to the SUS. 
• Mean Within-Subject Difference in Ecological Momentary Assessment 
Three-Times-Daily of Pain During 3 Treatment Periods from Mean 
Baseline, using the Numeric Pain Rating Scale adapted from McCaffery, 
Beebe et al. 198923 
• Mean Within-Subject Difference in Ecological Momentary Assessment 
Three-Times-Daily of Fatigue During 3 Treatment Periods from Mean 
Baseline 
• Mean Within-Subject Difference in Ecological Momentary Assessment 
Three-Times-Daily of Concentration During 3 Treatment Periods from 
Mean Baseline 
• Mean Within-Subject Difference in Ecological Momentary Assessment 
Three-Times-Daily of Confidence During 3 Treatment Periods from Mean 
Baseline 
• Mean Within-Subject Difference in Ecological Momentary Assessment 
Three-Times-Daily of Mood During 3 Treatment Periods from Mean 
Baseline 
• Mean Within-Subject Difference in Ecological Momentary Assessment 
Three-Times-Daily of Stress During 3 Treatment Periods from Mean 
Baseline, 
• Mean Within-Subject Difference in Device-Recorded Daily Steps from 
Mean Baseline, using participant Fitbit data 
• Mean Within-Subject Difference in Device-Recorded Nightly Sleep from 
Mean Baseline, using participant Fitbit data 
• Change in mean within-subject difference in weekly Perceived Stress, 
using modified 10-item Perceived Stress Scale (PSS-10) between 3 
Treatment Periods 
• Mean participant survey adherence rate, defined as completion of each 
assigned survey  
• Mean participant Fitbit adherence rate, defined as recorded heart rate data 
for ≥ 12 hours each day 
• Mean participant Fitbit sleep rate, defined as recorded sleep and wake 
cycles   
• Mean participant personalized trial intervention adherence rate, defined as 
a unique video views of the appropriate recorded intervention during 
assigned interventions 
• Mean participant standard care intervention adherence rate, defined as a 
unique video views of the available recorded interventions 

 
 
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• Mean participant selection adherence rate, defined as unique video views 
of the selected intervention video during the follow-up period 
• Descriptive content analysis of audio-recorded and transcribed qualitative 
interview data 
 
As participants will not be receiving stress management interventions every day, 
we do not assume that meditation mindfulness, yoga, and walking will have long-
lasting effects; therefore no washout period has been considered between each 
stress management intervention. 
 
Quantitative Intelligence (expert group of quantitative scientists, data scientists, 
clinical informatics specialists and staff) will provide services such as 
randomization, data analytics, cleaning, etc.  These individuals are not considered 
study personnel.  
 
Randomization will be done in blocks of 8 with arms A (personalized arm n=53), B 
(personalized arm n=53), and C (usual care n=106) with randomization ratio of 
1:1:2. The last block of patients will occur in a block of 4. The order in which an 
individual becomes eligible for one of these randomizations will determine the 
placement given (i.e. the first person eligible will be randomized to the treatment 
order given to participant 1, and continue sequentially). Eligibility is obtained by a 
participant maintaining at least 80% adherence of survey response and Fitbit wear 
≥ 12 hours a day during the baseline run-in period. A member of Quantitative 
Intelligence will alert the research coordinator of the assigned randomization once 
a participant becomes eligible during the baseline run-in period. 
 
 
13. SPECIMEN BANKING 
• If specimens will be banked for future research, describe where the specimens will be 
stored, how long they will be stored, how they will be accessed and who will have 
access to the specimens 
• List the information that will be stored with each specimen, including how specimens 
are labeled/coded 
• Describe the procedures to release the specimens, including:  the process to request 
release, approvals required for release, who can obtain the specimens, and the 
information to be provided with the specimens. 
 
N/A 
 
 
14.  DATA MANAGEMENT AND CONFIDENTIALITY 
• Describe the data and specimens to be sent out or received.  As applicable, describe: 
o What information will be included in that data or associated with the 
specimens? 
o Where and how data and specimens will be stored? 

 
 
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o How long the data will be stored? 
o Who will have access to the data? 
o Who is responsible for receipt or transmission of data and specimens? 
• Describe the steps that will be taken to secure the data during storage, use and 
transmission. 
 
Fitbit 
This study will use personally-owned (or provided if necessary) non-NFC, Fitbit 
devices to remotely monitor participant activity and sleep. All enrolled participants 
will be provided with a study account that has been created by the research team 
with no identifying information and participants will be instructed on how to exit 
their personal account to access the study account. The email address of the study 
account contains a unique identifier (e.g. northwellstudy25). Data collected will 
include daily steps, heart rate, floors climbed, activity, intensity, sleep duration, 
estimated minutes in sleep stages, and battery charge status, last sync date. A file 
linking the Fitbit identifier to the study participant will be housed in a Northwell-
approved drive to store PHI and be accessible only by members of the study team 
listed in the IRB application. Data collected from Fitbit wear will remain stored in 
a Northwell-approved drive indefinitely.  
 
Fitabase  
This study will use Fitabase to retrieve Fitbit data from participants. Fitabase is a 
secure, online portal. The Fitbit study account provided to the participants will 
be linked to an identification number in the Fitabase system (e.g. FLT01). No 
information that could be used to identify a participant will be stored on Fitabase. 
Only the research team will have access to data that will be able to connect 
a research participant to their Fitabase ID. Data collected will include last sync 
date, battery charge status, daily steps, heart rate, floors climbed, activity intensity, 
sleep duration, and estimated minutes in sleep stages. Fitabase will stop tracking 
participant data at the trial end date selected by the research coordinator. As an 
added measure, participants will be instructed to remove the Fitbit study account 
from their device.  
 
Interview Data 
Qualitative data collected from interviews with research participants will be 
collected and stored via REDCap, a Northwell-approved system for collecting and 
storing research data, including PHI. 
 
Video Adherence Data 
Zeel is a commercial company that provides in-home or in-office services (such as 
stretching or yoga).  The company has been contracted to create these videos of the 
services they provide for our use in the research.   No individual level data, nor any 
research data will be shared with Zeel.  Recorded video and audio stress 
management content will be stored on a commercial website, Vimeo. No 
information that could be used to identify a participant will be stored on Vimeo. 
Participants will be provided with a link and password to access their stress 

 
 
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management content, and will not be asked to provide any personal identifying 
information.  Data collected will include views, unique viewers, video finishes, 
video impressions, percentage/minutes of videos watched, views by device type, 
views by source URL, views by region, and date video was viewed. See 
confirmation from Vimeo that IP address or other identifying information is not 
collected.   
 
Survey Data 
Survey data will be collected by 4Peacocks/N1Thrive, a company that was formed 
specifically for the development of technology to support N-of-1 methodology. 
Additional study data will be collected and stored using the Northwell REDCap 
system. Coded data using unique generic participant IDs will be shared with 
4Peacocks in order to assist with analyzing the individual reports and to pool 
results across all projects using the N1Thrive platform.  Coded reports will be 
given back to the study team, who will identify the document before sending 
individualized reports to the participant via encrypted message or email.  Pooled 
results will be used to assess gaps in phenotypic understanding to empirically 
determine if modeling precise therapy is feasible.   
 
The study team takes data confidentiality very seriously.  Data collected for this 
research will be maintained  on a HIPAA-compliant Northwell-approved SQL 
database.  All members of the research team with access to identifiable and coded 
data will be trained and included on the IRB submission for approval. Regular 
meetings will take place with the PI and other members of the study team to ensure 
protocol adherence and data accuracy. Data collected for this study will be 
maintained in its original and unaltered source data state in a Northwell-approved 
SQL database on a Northwell-approved drive to store PHI indefinitely. Data collected 
under this research may be used for future research in coded format without 
additional consent as per the consent form participants sign and with appropriate 
IRB approval as required. Any additional data that must be shared will be done so 
according to the consent form participants signed.  Only research staff listed within 
this IRB submission will have access to identifiable information. Anonymized data 
may be stored indefinitely for reference following the conclusion of the study.  The 
participant will be made aware of all data collected in the consenting process.    
 
This research is funded by the NIH, thus a Certificate of Confidentiality has been 
issued for this research. Certificates of Confidentiality (CoCs) protect the privacy 
of research subjects by prohibiting disclosure of identifiable, sensitive research 
information to anyone not connected to the research except when the subject 
consents or in a few other specific situations.   
 
A limited data set (ie. dates such as dates associated with research procedures, date 
of birth, city, state, five digit or more zip code; and ages in years, months or days or 
hour) may be provided to IHSS faculty for cohort analyses and/or for future 
research.  These individuals will be unable to readily ascertain the identity of the 
subjects to whom the coded information pertain because they have entered into an 
agreement with the Principal Investigator prohibiting the release of the key to those 

 
 
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individuals under any circumstances, or unless they are added as research personnel 
to this protocol. These individuals are not considered integral nor engaged in the 
research and thus are not listed as study personnel.   
 
 
 
 
15.  DATA AND SAFETY MONITORING PLAN 
 
A specific data and safety monitoring plan is only required for greater than minimal risk 
research.  For guidance on creating this plan, please see the Guidance Document on the 
HRPP website. 
 
Part I – this part should be completed for all studies that require a DSMP.   
Part II – This part should be completed when your study needs a Data and 
Safety Monitoring Board or Committee (DSMB/C) as part of your Data and 
Safety Monitoring Plan.   
 
Part I:  Elements of the Data and Safety Monitoring Plan 
•  Indicate who will perform the data and safety monitoring for this study.   
• Justify your choice of monitor, in terms of assessed risk to the research subject’s 
health and well being.  In studies where the monitor is independent of the study staff, 
indicate the individual’s credentials, relationship to the PI, and rationale for selection 
• List the specific items that will be monitored for safety (e.g. adverse events, protocol 
compliance, etc) 
• Indicate the frequency at which accumulated safety and data information (items listed 
in # above) will be reviewed by the monitor (s) or the DSMB/C.   
• Where applicable, describe rules which will guide interruption or alteration of the 
study design.   
• Where applicable, indicate dose selection procedures that will be used to minimize 
toxicity. 
• Should a temporary or permanent suspension of your study occur, in addition to the 
IRB, indicate to whom will you report the occurrence.   
 
 
 
 
Part II:  Data and Safety Monitoring Board or Committee 
 
 
•  When appropriate, attach a description of the DSMB.   
• Provide the number of members and area of professional expertise.   
• Provide confirmation that the members of the board are all independent of the study. 
 
Attached please find the Charter document for the Personalized Trials Pilots 
DSMB. Personnel, roles, and areas of expertise are listed. As per the charter, the 
DSMB will meet at least once a year to review the research. All voting members of 
the DSMB are independent of the study.  
 

 
 
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16. WITHDRAWAL OF SUBJECTS 
• Describe anticipated circumstances under which subjects will be withdrawn from the 
research without their consent 
• Describe procedures for orderly termination 
• Describe procedures that will be followed when subjects withdraw from the research, 
including partial withdrawal from procedures with continued data collection.   
 
Circumstances under which participants may be withdrawn from the research 
without their consent include failure to follow study protocol, self-reported adverse 
side effects to two or more treatments, it is not in the participant’s best interest to 
continue on this study, and the study has stopped. We will not withdraw a 
participant based on non-adherence to wearing their Fitbit, completing their 
interventions, or completing daily surveys, as this absence of data is useful for 
feasibility purposes. Because of this, lack of adherence to Fitbit wear, completing 
interventions, or completion of daily surveys are not considered protocol 
deviations.  
 
Potential participants will be notified of the possibility of being removed from the 
study before treatment randomization due to adherence issues in the informed 
consent document. Participants who fail to maintain minimum adherence during 
baseline will be notified by the research team after 14 days of baseline 
participation.  Participants who fail to maintain protocol adherence during the 
intervention period will be contacted by a member of the study team with a 
reminder of the study protocol.   
Should a participant choose to withdraw from research, they will be instructed 
email or securely message the study team to withdraw. Participants will be 
contacted by a member of the research team confirming their study withdrawal, and 
to answer any questions they may have. The participant will stop receiving 
notification and survey prompts, and will be sent instructions to un-link their Fitbit 
device. Data collection will stop the business day the  email is received. All data up 
until the receipt date of the letter will be included in the research study.  
 
Partial withdrawal with continued data collection will be permitted on a case by 
case basis if a participant experiences an adverse event to one of the intervention 
options and chooses to stop receiving that intervention. Participant data will 
continue to be collected and monitored, while removing the self-reported adverse 
intervention option from their randomized protocol (i.e. skip the intervention days 
and continue with usual care). This will allow the participant to still evaluate their 
individual response to the self-reported non-aggravating treatment option.   
 
 
17. RISKS TO SUBJECTS 
• Describe any potential risks and discomforts to the subject (physical, psychological, 
social, legal, or other) and assess their likelihood and seriousness and whether side 

 
 
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effects are reversible. Where appropriate, describe alternative treatments and 
procedures that might be advantageous to the subjects.  
• Include risks to others , like sexual partners (if appropriate) 
• Discuss why the risks to subjects are reasonable in relation to the anticipated benefits 
and in relation to the importance of the knowledge that may reasonably be expected 
to results 
• Describe the procedures for protecting against or minimizing any potential risks, 
including risks to confidentiality, and assess their likely effectiveness.   
 
This study poses no greater than minimal risk to subjects. Monitoring for adverse 
side-effects will be performed during the N-of-1 trial. 
 
Intervention Adverse Events 
Mindfulness meditation, yoga and brisk walking have been shown to be safe and 
effective stress management options for many people. Some people, however, may 
experience mild physical side effects from yoga and/or brisk walking. The most 
common side effect is feeling sore 1-2 days after treatment. This should be a minor 
discomfort and temporary. Mindfulness meditation may include experiences that 
are pleasant, unpleasant, or neutral. It can lead to states of ease, joy, relaxation, 
peace and a sense of wellbeing. Unpleasant experiences such as agitation, physical 
discomfort, sleepiness, sadness and anger are also common. Such experiences are 
usually temporary. 
 
If participants experience discomfort during their treatment sessions, they will be 
instructed to immediately stop the activity and contact a research coordinator. 
 
Surveys 
Survey questions may make a participant feel uncomfortable. Should a participant 
report emotional distress in responding to survey questions, the research 
coordinators will refer to our Principal Investigator (a licensed clinical 
psychologist), who will recommend follow-up. 
 
Fitbit 
There is no additional risk with using a Fitbit activity monitor for research as 
compared to using the device as a consumer, including mild skin irritation (i.e. 
contact dermatitis) which occurs among a small proportion of users. Participants 
will be instructed via the consent form on methods to reduce irritation (e.g. keep 
the band clean and dry) and that they can remove the band for a short period of 
time. 
 
Loss of Confidentiality or Privacy 
 
All subjects will be informed that their responses are confidential and that they may 
refuse to participate in the project or withdraw at any time without explanation, 
and that such action will not affect their future interactions with their health care 
providers, employment, educational studies, or the research study. The risk of loss 

 
 
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of confidentiality will be minimized by securely storing data including PHI in a 
Northwell-approved database and minimizing the use of PHI. To ensure 
confidentiality, all data containing personal identifiers, and used to track contact 
with patients, will be kept in a secure, password-protected, encrypted Northwell-
approved database. No paper documents with personal identifiers will be kept. The 
PI will be responsible for ensuring that the confidentiality of the data is maintained 
at all times. All data will be obtained specifically for research purposes.  
  
 
 
 
 
 
18. RESEARCH RELATED HARM/INJURY 
• Describe the availability of medical or psychological resources that subjects might 
need as a result of anticipated problems that may be known to be associated with the 
research. 
• If the research is greater than minimal risk, explain any medical treatments that are 
available if research-related injury occurs, who will provide it, what will be provided, 
and who will pay for it.   
 
Research-related injuries are not expected for this no greater than minimal risk 
project.  
 
Participants who are experiencing anxiety or side effects related to study 
participation may withdraw from the study without negative consequences. 
Participants have access to study coordinators via email, secure messaging, and 
cellular phone should they be concerned about their symptoms, and will be referred 
to their primary care provider should they express continued concern. 
 
 
19. POTENTIAL BENEFIT TO SUBJECTS 
 
• Explain what benefits might be derived from participation in the study, noting in 
particular the benefit over standard treatment (e.g. a once-a-day administration 
instead of four times a day, an oral formulation over an IV administration).  
• Also state if there are no known benefits to subjects, but detail the value of knowledge 
to be gained 
 
Participants may or may not receive any direct benefit from participation in this 
research.  Sometimes yoga and brisk walking increase a participant’s chance of 
being healthier, and mindfulness meditation can sometimes result in pleasant 
experiences.  Although participants may not experience any personal, physical 
benefit from participation, there is a chance that participation in this study may help 
them better understand their individual response to different stress interventions so 
that they can learn how to manage stress.  

 
 
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This may result in their being more satisfied with their stress management regimen 
and in achieving reduced feelings of stress. Through pooling N-of-1 trial data, a 
greater understanding of the effectiveness of mindfulness meditation, yoga, and 
brisk walking will arise. Additionally, the information collected from participant 
involvement will inform the development of future Personalized Trials to help 
other research participants and eventually patients discover which treatment 
options are best for them as an individual. 
 
 
20. PROVISIONS TO PROTECT PRIVACY INTERESTS OF SUBJECTS 
 
• Describe the methods used to identify potential research subjects, obtain consent and 
gather information about subjects to ensure that their privacy is not invaded.  
• In addition consider privacy protections that may be needed due to communications 
with subjects (such as phone messages or mail).   
 
Recruitment links will lead to a study web page with more information about study 
requirements, eligibility, and who to contact for more information.  Interested 
individuals will then sign authorization to undergo brief screening to assess if they 
are eligible for participation, after which they will sign consent via a HIPAA 
compliant Northwell Health approved electronic platform.  Individuals may call the 
research team at any time to ask questions prior to signing consent. Should this 
occur, research personnel will ensure that the individual is in a private location for 
open conversation to protect the privacy interests of the individual.  All study-
related communications will be delivered via a secure, NWH email or via the NWH 
approved e-platform. 
 
 
 
21.  COSTS TO SUBJECTS 
 
• Describe any foreseeable costs that subjects may incur through participation in the 
research 
• Indicate whether research procedures will be billed to insurance or paid for by the 
research study.   
 
This research study is funded by the National Institutes for Health (NIH). All study 
related equipment, services, and devices will be provided to participants at no cost. 
Participant insurance will not be billed. 
 
This study uses text messaging to deliver notifications, reminders, and study 
questionnaires. Standard message and data rates from the participant’s wireless 
carrier may apply to the study participant. Study participants will not be 
compensated for any costs related to data usage or sending or receiving text 
messages by the study or by members of the study team. 
 

 
 
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22. PAYMENT TO SUBJECTS  
 
• Describe the amount of payment to subjects, in what form payment will be received 
and the timing of the payments.   
 
All participants who are randomized into the study will be eligible for a weekly 
lottery of $100. If the participant selected has maintained at least 80% adherence to 
survey responses and Fitbit wear for that week, they will be given a $100 Clincard. 
If the selected participant has not maintained at least 80% adherence, they will be 
advised to try again the following week. Although not likely, a participant can 
potentially be selected for the weekly lottery up to 12 times totaling $1200. 
Separate secure messaging notifications will be sent each week (see attached study 
related document).  
 
Participants who are invited to participate in a qualitative interview with a 
consenting coordinator(s) and who complete this qualitative interview will be given 
a $25 Clincard. 
 
For participants who do not report having their own Fitbit device that is acceptable 
for this study, or if a participant’s personal Fitbit device malfunctions or breaks, the 
study will replace the participant’s device at no charge. Participants will be allowed 
to keep devices provisioned at the end of the research, should they wish.   
 
 
23.  CONSENT PROCESS 
 
If obtaining consent for this study, describe: 
• Who will be obtaining consent 
• Where consent will be obtained 
• Any waiting period available between informing the prospective participant and 
obtaining consent 
• Steps that will be taken to assure the participants’ understanding 
• Any tools that will be utilized during the consent process 
•   Information about how the consent will be documented in writing.  If using a  
standard consent form, indicate such.   
• Procedures for maintaining informed consent.   
 
 
Each subject will receive written explanations of the purposes, procedures, and 
risks of this study in language appropriate for the individual’s level of 
understanding. All questions will be answered via email or phone, and if all 
inclusion criteria are met, and the subject volunteers to participate, digital written 
informed consent will be obtained.    
   

 
 
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Written, electronic consent (e-consent) will be obtained via REDCap, a web-
based platform capable of recording electronic signature. The e-consent 
document will contain all of the elements of informed consent required 
by applicable federal regulation for the protection of human subjects and 
elements of authorization required by the HIPAA Privacy Rule, and will begin 
with a concise and focused presentation of the key information that is most 
likely to assist participants in understanding the reasons why he/she might or 
might not want to participate in the research.   
  
Because consent will be obtained remotely, the electronic platform will be 
designed such that the consent form is easy to navigate. We will also employ 
interactive electronic-based technology such as instructional videos and a 
comprehensive knowledge check at the end of the consent process.  Potential 
participants may view informational videos or opt in or out of having a 30-
minute phone call/video conference to go over study details with a consenting 
coordinator to address any questions they may have. After the phone call/video 
conference takes place, the consenting coordinator will send the potential 
participant an email or text with a link to read and electronically sign the 
consent form.  If the participant opts out of having the call, they will be sent a 
link to read and electronically sign the consent form. Included in the link sent to 
participants who opted in and out of the call will be a short, animated video that 
explains key aspects of the protocol and consent process. 
  
The system will also incorporate electronic strategies to encourage participants 
to access all of the consent material before documenting his/her consent.   
Participants may contact a member of the research team at any time with 
questions about the research prior to signing consent.    
  
Included in these materials will be contact information to reach a consenting 
coordinator to answer any additional questions they have before signing the 
consent form. Both the research phone and email inbox will be monitored daily 
by consenting coordinators.  Potential participants will need to correctly answer 
4 questions about the protocol to demonstrate their understanding of the 
consent form.   Research coordinators will review names and signatures of all 
completed consent forms. Participants that do not provide effective consent 
(e.g. a slash, line or dot) will be contacted by a consenting research coordinator 
to confirm their identity and eligibility for the study.  PDF copies of signed 
consent forms will be made available to all participants.  A copy of all signed 
forms will be stored in a HIPAA-secured, Northwell approved storage drive 
with protected access to only the PI and research personnel listed on the study 
protocol.   
   
 
 
 
 

 
 
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In the state of NY, any participants under the age of 18 are considered children.  If your 
study involves children, additional information should be provided to describe: 
• How parental permission will be obtained 
• From how many parents will parental permission be obtained 
• Whether permission will be obtained from individuals other than parents, and if 
so, who will be allowed to provide permission.  The process used to determine 
these individual’s authority to consent for the child should be provided 
• Whether or not assent will be obtained from the child 
• How will assent be documented 
• Whether child subjects may be expected to attain legal age to consent to the 
procedures for research prior to the completion of their participation in the 
research.  If so, describe the process that will be used to obtain their legal 
consent to continue participation in the study.  Indicate what will occur if consent 
is not obtained from the now-adult subjects.   
 
N/A 
 
 
If the study involves cognitively impaired adults, additional information should be 
provided to describe: 
• The process to determine whether an individual is capable of consent 
• Indicate who will make this assessment 
• The plan should indicate that documentation of the determination  and 
assessment will be placed in the medical record, when applicable, in addition to 
the research record. 
• If permission of a legally authorized representative will be obtained, 
o  list the individuals from who permission will be obtained in order of priority 
o Describe the process for assent of subjects; indicate whether assent will be 
required of all, some or none of the subjects.  If some, which subjects will be 
required to assent and which will not. 
o If assent will not be obtained from some or all subjects, provide an 
explanation as to why not 
o Describe whether assent will be documented and the process to document 
assent 
o Indicate if the subject could regain capacity and at what point you would 
obtain their consent for continued participation in the study 
 
N/A 
 
 
If the study will enroll non-English speaking subjects: 
• Indicate what language(s) other than English are understood by prospective 
subjects or representatives 
• Indicate whether or not consent forms will be translated into a language other 
than English 

 
 
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• Describe the process to ensure that the oral and written information provided 
to those subjects will be in that language 
• If non-English speaking subjects will be excluded, provide a justification for 
doing so 
 
Our goal for this research is to test virtual research delivery capabilities for 
the digital health technology used for this specific use case.   We are 
focused on soliciting feedback from participants on the ease of platform 
use, if the research delivery was satisfactory, if the participant report was 
deemed useful, etc.  In the future, it will be especially important to obtain 
this feedback from individuals who are non-English speaking, and the 
intention once we document minimum use requirements, acceptability, and 
proof of greater effectiveness over traditional research methods through this 
RCT, is to seek funding so that we can work with N1Thrive to build virtual 
delivery capabilities that are fit-for-purpose in research involving 
individuals who are non-native English speakers. Having a platform capable 
of accurately displaying research requirements and study related material is 
especially important for speakers whose language involves characters that 
may not be easily displayed electronically or may introduce formatting 
errors.  We aim to be transparent that further research is needed to assess 
feasibility in the same delivery with non-English speaking individuals. 
Presently we hope to collect enough information to justify that this 
methodology offers greater benefit than standard RCT delivery to make the 
case that more significant financial investment should be made to have the 
platform scaled to larger clinical trials designed to assess safety and/or 
efficacy of the given interventions.  Injustice has no place in research with 
human subjects and undermines public trust in science, thus we are 
committed to enrolling a racially and ethnically diverse population in this 
protocol and for all research conducted by the Institute for Health System 
Science. Towards that commitment, we anticipate that many participants 
interested in this current research project will represent racial and ethnic 
minority groups, and we intend to advertise the research without restriction.   
Race and ethnicity (not just English proficiency) are strongly correlated 
with access to care, environmental exposures, income, employment, and 
other social determinants of health, which, by definition, affect health 
outcomes.  We will collect information on all of these factors to help inform 
virtual research delivery and do not believe that focusing on native English 
speaking participants in this pilot study - those that may be from ethnically 
and racially diverse populations -  will confirm pre-existing bias or will 
later negatively impact equitable access, participant comprehensibility or 
research design applicability to the diverse populations that may be solicited 
for participation in future clinical trials run under an N-of-1 design.    
 
 
24.  WAIVER OR ALTERATION OF THE CONSENT PROCESS       
 N/A          
 

 
 
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Complete this section if you are seeking an alteration or complete waiver of the consent   
process. 
• Describe the possible risks of harm to the subjects involved in this study and 
explain why the study involves no more than minimal risk to the subject:   
• Explain why the waiver/ alteration will not adversely affect the rights and welfare 
of subjects 
• Explain why it is impracticable to conduct this research if informed consent is 
required   
• Explain why it is not possible to conduct this research without using the 
information or biospecimens in an identifiable form 
• If appropriate, explain how the subjects will be provided with additional pertinent 
information after participation.   If not appropriate to do so, explain why.  
 
Since the consent process will be remote and self-directed, it is not 
practicable or feasible for the investigator to sign the consent form 
in REDCap  As such, we request a waiver of the investigator’s signature for 
this research which is no greater than minimal risk.  Individuals are 
encouraged to reach out to the study team via email and/or a direct phone line 
if they have any questions and prior to signing the consent form.   
 
 
Complete this section if you are obtaining informed consent but you are requesting a 
waiver of the documentation of consent (i.e., verbal consent will be obtained). To 
proceed with a waiver based on these criteria, each subject must be asked whether they 
wish to have documentation linking them to this study.  Only complete subsection 1 OR 
subsection 2.  
 
  SUBSECTION 1 
 
• Explain how the only record linking the subject to the research would be the 
consent document. 
• Explain how the principal risk of this study would be the potential harm resulting 
from a breach in the confidentiality 
• Indicate whether or not subjects will be provided with a written statement 
regarding the research. 
 
 
 
SUBSECTION 2 
•  Describe the possible risks of harm to the subjects involved in this study and 
explain why the study involves no more than minimal risk.   
• Confirm that the research only involves procedure for which consent is not 
normally required outside the research context.  
• Indicate whether or not subjects will be provided with a written statement 
regarding the research. 
 
 

 
 
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. 
 
25. WAIVER OF HIPAA AUTHORIZATION  
 
 
 
 N/A       
 
Complete this section if you seek to obtain a full waiver of HIPAA authorization to use 
and/or disclose protected health information.  
• Describe the risks to privacy involved in this study and explain why the study 
involves no more than minimal risk to privacy:   
• Describe your plan to protect identifiers from improper use or disclosure and to 
destroy them at the earliest time. 
•  Indicate why it is not possible to seek subjects’ authorization for use or 
disclosure of PHI. 
• Indicate why it is not possible to conduct this research without use or disclosure 
of the PHI.   
• Indicate if PHI will be disclosed outside NSLIJ Health System, and if so, to whom.   
Note:  PHI disclosed outside NSLIJ Health System, without HIPAA authorization 
needs to be tracked. Please see guidance at www.nslij.com/irb for information 
about tracking disclosures. 
 
 
 
Complete this section if you seek to obtain a partial waiver of the patient’s 
authorization for screening/recruitment purposes (i.e., the researcher does not have 
access to patient records as s/he is not part of the covered entity) 
Note: Information collected through a partial waiver for recruitment cannot be shared 
or disclosed to any other person or entity. 
• Describe how data will be collected and used:  
• Indicate why you need the PHI (e.g.PHI is required to determine eligibility, 
identifiers are necessary to contact the individual to discuss participation, other) 
• Indicate why the research cannot practicably be conducted without the partial 
waiver (e.g. no access to medical records or contact information of the targeted 
population, no treating clinician to assist in recruitment of the study population, 
other) 
 
 
 
26.  VULNERABLE POPULATIONS: 
 
Indicate whether you will include any of these vulnerable populations. If indicated, 
submit the appropriate appendix to the IRB for review: 
 
  Children or viable neonate 
  Cognitively impaired 
  Pregnant Women, Fetuses or neonates of uncertain viability or nonviable  

 
 
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  Prisoners 
  NSLIJ Employees, residents, fellows, etc 
  poor/uninsured 
  Students 
  Minorities 
  Elderly 
  Healthy Controls 
 
If any of these populations are included in the study, describe additional safeguards that 
will be used to protect their rights and welfare. 
 
This study is not targeting employees or students. However, all employees of the health 
system, as well as graduates and students of Hofstra University are eligible to 
participate in the study. Northwell Health has the most diverse employee workforce in 
the state of New York and it services a vast number of individuals from racial and 
ethnic minority groups. Hofstra University also has a significant number of students 
who identify as racial/ethnic minorities. As such, we expect a diverse subject 
population.  
 
Individuals with a supervisory relationship over an employee will not enroll any 
individual who reports to them in this study. Employee participation or non-
participation in this study will have no bearing on an individual’s position at Northwell 
Health.  
 
Similarly, professors or supervisory staff will not enroll individuals who report to or 
work or study under them. Student-participation or non-participation will have 
no bearing on an individual’s position at Hofstra University or Northwell Health.   
We do not intend to prevent study personnel or other employees of the Institute of 
Health System Science who express an interest in the research from participating. 
However, no supervisory personnel will be able to enroll participants who report to 
them in this research. We are not intentionally targeting minorities, but expect minorities 
to be part of those eligible for participation. 
 
We exclude women who are pregnant given yoga is a wellness strategy used in this 
research (yoga video that is pre-recorded for general use, excluding pregnant women, 
i.e. the poses cannot be modified for pregnant women). If this personalized trial 
research strategy is proven successful, additional research using video intervention 
specifically designed for pregnant women (i.e. prenatal yoga) will be evaluated. 
 
In addition, our goal for this research is to test virtual research delivery capabilities for 
the digital health technology used for this specific use case.   We are focused on 
soliciting feedback from participants on the ease of platform use, if the research 
delivery was satisfactory, if the participant report was deemed useful, etc.  In the 
future, it will be especially important to obtain this feedback from individuals who are 
non-English speaking, and the intention once we document minimum use 
requirements, acceptability, and proof of greater effectiveness over traditional research 

 
 
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methods through this RCT, is to seek funding so that we can work with N1Thrive to 
build virtual delivery capabilities that are fit-for-purpose in research involving 
individuals who are non-native English speakers. Having a platform capable of 
accurately displaying research requirements and study related material is especially 
important for speakers whose language involves characters that may not be easily 
displayed electronically or may introduce formatting errors.  We aim to be transparent 
that further research is needed to assess feasibility in the same delivery with non-
English speaking individuals. Presently we hope to collect enough information to 
justify that this methodology offers greater benefit than standard RCT delivery to make 
the case that more significant financial investment should be made to have the platform 
scaled to larger clinical trials designed to assess safety and/or efficacy of the given 
interventions.  Injustice has no place in research with human subjects and undermines 
public trust in science, thus we are committed to enrolling a racially and ethnically 
diverse population in this protocol and for all research conducted by the Institute for 
Health System Science. Towards that commitment, we anticipate that many 
participants interested in this current research project will represent racial and ethnic 
minority groups, and we intend to advertise the research without restriction.    Race and 
ethnicity (not just English proficiency) are strongly correlated with access to care, 
environmental exposures, income, employment, and other social determinants of 
health, which, by definition, affect health outcomes.  We will collect information on all 
of these factors to help inform virtual research delivery and do not believe that 
focusing on native English speaking participants in this pilot study - those that may be 
from ethnically and racially diverse populations -  will confirm pre-existing bias or will 
later negatively impact equitable access, participant comprehensibility or 
research design applicability to the diverse populations that may be solicited for 
participation in future clinical trials run under an N-of-1 design.   
 
 
27.  MULTI-SITE HUMAN RESEARCH (COORDINATING CENTER) 
 
If this is a multi-site study where you are the lead investigator, describe the management 
of information (e.g. results, new information, unanticipated problems involving risks to 
subjects or others, or protocol modifications) among sites to protect subjects. 
N/A 
 
 
 
28.  REFERENCES/BIBIOGRAPHY 
 
Provide a reasonable list of references directly related to the study. Any diagrams for 
new medical devices or brief reprints from journals might also prove useful. 
 
1. Guyatt, G.,Haynes, B., Jaeschke, R.,Cook, D.,Greenhalgh,T., 
Mead,M., Green, L.,Naylor, C.,Wilson,M., McAlister, F., & 
Richardson, W. (2002). Introduction: The philosophy of evidence-
based medicine. In G. Guyatt, & D. Rennie (Eds.), Users’ Guides to 

 
 
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the Medical Literature : A Manual for Evidence-based Clinical 
Practice (pp. 3–11). Chicago, IL: American Medical Association. 
2. Ridenour TA, Pineo TZ, Maldonado-Molina MM, Hassmiller-Lich K. 
Toward idiographic research in prevention science: Demonstration of 
three techniques for rigorous small sample research. Prevention Science. 
2013;14:267-78.  
3. Gandhi TK. Adverse drug events in ambulatory care. New England 
Journal of Medicine. 2003;348(16):1556-64.   
4. Duan N, Kravitz RL, Schmid CH. Single-patient (n-of-1) trials: a 
pragmatic clinical decision methodology for patient-centered 
comparative effectiveness research. J Clin Epidemiol. 2013;66(8 
Suppl):S21-8. 
5. Guyatt G, Jaeschke R, McGinn T. N-of-1 Randomized Controlled 
Trials: Study Design. In: Guyatt G, Rennie D, Meade MO, Cook DJ, 
eds. Users' Guides to the Medical Literature. 2nd ed. New York; 
London: McGraw Hill Medical 2008:179-92.  
6. Guyatt G, Keller J, Jaeschke R, Rosenbloom D, Adachi J, Newhouse M. 
The n-of-1 randomized controlled trial: clinical usefulness, our three-
year experience. Annals of Internal Medicine. 1990;112:293 - 9.  
7. Larson EB. N-of-1 trials: a new future? J Gen Intern Med. 
2010;25(9):891-2.  
8. Joy TR, Monjed A, Zou GY, Hegele RA, McDonald CG, Mahon JL. N-
of-1 (Single-Patient) Trials for Statin-Related Myalgia. Annals of 
Internal Medicine. 2014;160(5):301-10.  
9. Nikles CJ, Yelland M, Glasziou PP, Del Mar C. Do individualized 
medication effectiveness tests (n-of-1 trials) change clinical decisions 
about which drugs to use for osteoarthritis and chronic pain? Am J Ther. 
2005;12(1):92-7. 
10. Kravitz RL, Duan N, Niedzinski EJ, Hay MC, Subramanian SK, 
Weisner TS. What ever happened to N-of-1 trials? Insiders' perspectives 
and a look to the future. Milbank Q. 2008;86(4):533-55.  
11. Guyatt G. N of 1 randomized trials: a commentary. J Clin Epidemiol. 
2016;76:4-5.  
12. Gabler NB, Duan N, Vohra S, Kravitz RL. N-of-1 trials in the medical 
literature: a systematic review. Medical Care. 2011;49(8):761-8.  
13. Recommended principles and practices for the provision of humanistic 
psychosocial services: Alternative to mandated practice and treatment 
guidelines. Humanistic Psychologist. 2004;32(1):3-75.  
14. Gabler NB, Duan N, Vohra S, Kravitz RL. N-of-1 trials in the medical 
literature: a systematic review. Med Care. 2011;49(8):761-8.  
15. American Psychological Association (2019). Stress in America: Stress 
and Current Events. Stress in America™ Survey. 
16. Goyal, Madhav, et al. "Mindfulness meditation programs for 
psychological stress and well-being: a systematic review and meta-
analysis." JAMA internal medicine 174.3 (2014): 357-368. 

 
 
Version Date: 09.14.22 
 
Page 34 of 34 
17. Pascoe, Michaela C., David R. Thompson, and Chantal F. Ski. "Yoga, 
mindfulness meditation-based stress reduction and stress-related 
physiological measures: A meta-analysis." Psychoneuroendocrinology 
86 (2017): 152-168. 
18. Strehli, Ildiko, et al. "Mind–Body Physical Activity Interventions and 
Stress-Related Physiological Markers in Educational Settings: A 
Systematic Review and Meta-Analysis." International journal of 
environmental research and public health 18.1 (2021): 224. 
19. Khoury, Bassam, et al. "Mindfulness meditation-based stress reduction 
for healthy individuals: A meta-analysis." Journal of psychosomatic 
research 78.6 (2015): 519-528. 
20. Simon, Gregory E., and Roy H. Perlis. "Personalized medicine for 
depression: can we match patients with treatments?." American Journal 
of Psychiatry 167.12 (2010): 1445-1455. 
21. Bangor, A., Kortum, P.T. and Miller, J.T., 2008. “An empirical 
evaluation of the system usability scale”. Intl. Journal of Human–
Computer Interaction, 24(6), pp.574-594. 
22. Brooke, J. 1996. “SUS: A “quick and dirty” usability scale”. In 
Usability evaluation in industry, Edited by: Jordan, P. W., Thomas, B. 
A. Weerdmeester and McClelland, I. L. 
23. McCaffery, M. and Beebe, A., 1989. The numeric pain rating scale 
instructions. Pain: Clinic Manual for Nursing Practice.