A Randomized Trial Of The SYNC APP
Phase: NA
Conditions: Breast Cancer, Prostate Cancer, Hematologic Malignancy, Survivorship, Fatigue
Sponsor: University of Michigan Rogel Cancer Center

A RANDOMIZED TRIAL OF THE SYNC APP 
 
Protocol Number: UMCC 2020.157 
National Clinical Trial (NCT) Identifier: NCT04827446 
 
Principal Investigator:   
Sung Won Choi, MD, MS 
1500 E. Medical Center Dr, D4118 MPB 
Ann Arbor, MI 48109-5718 
Phone: 734-615-5707 
Fax: 734-615-0464 
Email: sungchoi@med.umich.edu 
 
Co-Investigators: 
 
Muneesh Tewari PhD, N. Lynn Henry MD PhD, Joshi Alumkal  
MD, Daniel Forger PhD, John Maciejewski MD PhD 
 
Biostatistician:  
 
Walter Dempsey PhD 
 
 
 
 
Phone: 734-936-0039  
 
 
 
Email: wdem@umich.edu 
 
Single Center:  
 
University of Michigan 
Version:  
 
 
April 4, 2022 
 

2 
Table of Contents 
 
 
 
PROTOCOL SYNOPSIS 
3 
STUDY SCHEMA: SCHEDULE OF EVENTS 
6 
TIME AND EVENTS TABLE 
7 
INTERVENTION ARM VS CONTROL ARM 
8 
1. 
BACKGROUND AND SIGNIFICANCE 
9 
2. 
STUDY DESIGN 
13 
3. 
STUDY ENDPOINTS 
17 
4. 
PATIENT ENROLLMENT AND EVALUATION 
18 
5. 
STATISTICAL CONSIDERATIONS 
20 
APPENDIX A: DESCRIPTION OF DEVICES 
23 
Fitbit Charge 3 
30 
Apple Watch 
36 
APPENDIX B: SYNC COMPONENTS 
51 
APPENDIX C: USER-REPORTED OUTCOME MEASURES 
62 
APPENDIX D: REFERENCES 
60 
 
 

3 
PROTOCOL SYNOPSIS 
 
A RANDOMIZED TRIAL OF THE SYNC APP 
 
 
Principal Investigator: 
Sung Won Choi 
 
Study Design: 
This is a study to assess whether individually tailored lighting and 
behavioral interventions delivered through an app are able to reduce 
symptoms of fatigue and improve quality of life across three populations of 
cancer patients. We will recruit 138 patients (69 control, 69 interventional) 
across three cancer populations: breast cancer and prostate cancer, and 
patients who have undergone hematopoietic stem cell transplant (HSCT). 
Participants will be randomized 1:1 to either the interventional SYNC app 
or to a control app.  
 
 
Primary Objective: The primary objective is to test the statistical significance or difference 
between the intervention arm and the control arm in the measured outcome 
of fatigue, as quantified by daily fatigue surveys and weekly PROMIS Short 
Form v. 1.0 Fatigue 4a surveys. 
 
Secondary Objective: 
The secondary objective will be to assess user sleep disturbances, 
anxiety, depression, physical function, and global health via a suite of 
PROMIS questionnaires.   
 
Exploratory Objectives: 
Exploratory objectives will be to assess: i) physical activity through 
physiological data capture using the wearable sensor; ii) health care 
utilization (i.e., total count of hospital days, ED visits, readmissions, and 
ambulatory care clinic visits), and iii) sleep aid usage, as measured by self-
report.  
 
Eligibility Criteria:  All patients will be outpatient, though most will still be undergoing long-term 
treatment: breast cancer patients often receive endocrine therapy; prostate 
cancer patients often receive androgen deprivation therapy; and HSCT 
patients will be recovering their immune system from the high-dose 
chemotherapy that was administered in preparation for their transplant. We 
will exclude patients actively receiving chemotherapy at the time of 
enrollment to avoid potential confounding factors. However, post-transplant 
maintenance chemotherapy will be allowed. We will also exclude night shift 
workers, where night shift work is defined as working a significant number 
of hours (i.e. more than half) between the hours of 11PM and 6AM on a 
regular basis. Participants will be required to be able to read and write 
English, be at least 18 years old, and report their baseline fatigue level as 

4 
moderate (4 or higher on a 10-point scale). Patients must own an iPhone 
6s or later (with iOS 14 or later, or willing to update to iOS 14+) and be able 
to complete surveys on it, or they must agree to utilize a loaner iPhone 
provided by the study team to use during the study and return at the end of 
the study. 
 
Treatment Description: 
All participants will be given access to an app into which they enter 
their research ID number. The research ID number will determine which 
version of the app is loaded on their phone. Participants will also be given 
a wearable device and a pair of glasses. Interventional group participants 
will be given a pair of blue light-blocking glasses. Participants in the control 
group will be given a pair of glasses that does not block visible light. All 
participants will wear the wearable device day and night over the course of 
the 12-week trial. Participants in the interventional group will use a version 
of the app that gives them personalized lighting recommendations (e.g. 
"Seek bright light") and a time interval over which the recommendation 
applies (e.g. "8:30 - 9:45 am").  
Control arm:  
Control group participants will use a version of the app that makes 
recommendations to use the glasses; however, the time intervals 
recommended will be chosen to occur in the period of time when any 
change in lighting is expected to have no effect on the circadian clock (e.g. 
around noon, for many people already entrained to a diurnal schedule). 
Participants will be informed that they should only wear the glasses if it is 
reasonable for them to do so.  
Accrual Objective: We will enroll 138 cancer patients, with half in the intervention arm and half 
in the control arm. Our primary endpoint is the PROMIS 4-item Fatigue 
Short Form.  The age- and sex-adjusted norm for the Fatigue scale is 50 
points, with a standard deviation of 10 points. These statistics have been 
shown to be largely generalizable to the cancer patient population (mean: 
52, standard deviation 7.6). Our study will have power of 0.80, assuming a 
two-sided Type I error rate of 0.05, to detect an effect size of half the 
standard deviation between the intervention and control arms if 64 cancer 
patients are enrolled in each of the control and intervention groups. A mean 
difference of one-half a standard deviation is clinically meaningful and is 
considered a medium effect size for clinical trials. During the primary 
analysis, we will adjust for the fact that there are three cancer populations 
in our data and will look for a well-defined effect that is marginal within each 
population. We will accrue a total of 69 patients in each arm to account for 
attrition of data, assuming a 7% dropout rate from the trial.  
 
Accrual Period: 
The estimated accrual period is 1.5 years 
 

5 
Study Duration: 
Data will be collected from participants for 12 weeks. Passive collection of 
wearable data through the app will continue for up to one year for each 
participant who opts-in to continue using the app, and medical records may 
be accessed for up to five years after the conclusion of the 12-week 
collection period. 
 
 
 

6 
STUDY SCHEMA: SCHEDULE OF EVENTS 
 
 
 
Diagram outlining the survey data collected over the trial. Note: “Control actions” here refers 
to following “dummy” lighting recommendations that are minimally expected to affect the 
circadian clock. 

7 
 
TIME AND EVENTS TABLE 
 
 
Patient Events Timeline 
Every day after starting 
the trial: 
Every week, starting on 
the first day of the trial:  
On the first day and last 
day of the trial:  
At any point in time:  
Single question daily 
fatigue survey 
PROMIS Fatigue survey, 
“How is your experience 
with the app?” 
questionnaire, sleep aid 
usage survey  
PROMIS Sleep, Anxiety, 
Depression, Physical 
Function, Global Health 
App experience free 
response  
 
 
 
 

8 
Intervention Arm vs Control Arm 
 
 
 
Intervention Arm 
 
Wearable sensor:  
Patient is given a wearable 
device to wear for 12 weeks. 
 
Blue-blocking glasses:  
Patient is given blue-blocking 
glasses to wear at instructed 
times. 
 
Full SYNC app:  
Patient downloads the SYNC 
app and is given light 
interventions designed to 
have a targeted, personalized 
effect on the circadian clock. 
Control Arm 
 
Wearable sensor:  
Patient is given a wearable 
device to wear for 12 weeks. 
 
Clear glasses:  
Patient is given glasses that 
block no visible light.  
 
“Dummy” SYNC app:  
Patient downloads the SYNC 
app and is given light 
interventions designed to 
have minimal impact on the 
circadian clock. 

9 
 
1. 
BACKGROUND AND SIGNIFICANCE 
1.1. 
Circadian rhythms are chronically disrupted in cancer patients, leading to worsened 
symptoms and outcomes. A growing body of evidence links circadian rhythms to human 
health and disease. These rhythms, which repeat approximately once a day and are kept 
in sync with the local environment by the timing of light exposure, face constant disruption 
in the modern era of artificial lighting and smartphones (Wittmann et al. 2006; Roenneberg 
et al. 2012; Parsons et al. 2015). Sleep, the behavior most famously under circadian 
control, is not the only process affected: these rhythms feature prominently in nearly every 
major function in the body, from immune response to metabolism (Eckel-Mahan and 
Sassone-Corsi 2013; McClung 2013; Paganelli et al. 2018). Yet despite increased 
awareness of their importance for human health, circadian rhythms are rarely targeted in 
clinical interventions.  
1.2. 
Light as a treatment for circadian disruption. Light therapy, in which people 
intentionally expose themselves to bright light and/or avoid light at specific times of day, 
holds promise for reducing circadian rhythm disruption to improve symptoms such as 
fatigue. However, all intervention studies carried out so far have been one-size-fits-all, 
with a single light intervention of fixed timing and without real-time personalization to 
match an individual patient's day-to-day variation in circadian rhythm. Even with these 
limitations, breast cancer patients exposed to 30 minutes of bright light in the morning 
experience reduced desynchrony (Neikrug et al. 2012), mitigated fatigue (Ancoli-Israel et 
al. 2012), and protection from a significant decline in quality of life (QOL) (Jeste et al. 
2013). Other studies have found blocking evening light led to improved sleep in healthy 
populations, though no comparable studies have been carried out in cancer patients (van 
der Lely et al. 2015, Burkhart and Phelps 2009). 
1.3. 
Tracking circadian rhythms has historically been challenging in real-world 
conditions. There is great promise for lighting interventions as therapy, yet several 
hurdles stand in the way. The first is awareness. Many patients are unaware of the effects 
of light on their bodies and how these effects change over the course of the day. In 
addition, daily exposure to morning light requires habit-formation, which can be 
burdensome. Importantly, the timing of light interventions in previous work has never been 
tailored to match the individual’s circadian rhythm, instead opting for catch-all instructions; 
e.g., “on awakening” or “in the morning.” This is despite the fact that sleep and circadian 
rhythms are distinct processes, particularly in people experiencing irregular sleep and light 
exposure.  
1.4. 
Mathematical models and wrist-worn wearables can be used to predict circadian 
time. The gold standard for estimating circadian time is the costly and time-consuming 
dim light melatonin onset (DLMO) test. This salivary assessment, which takes hours to 
collect and costs hundreds of dollars, has made personalizing circadian recommendations 
impractical in the past. Recent work by our group and others has suggested that circadian 
rhythms can be tracked by coupling mathematical models to wearable devices that 
measure activity, light and/or heart rate (Stone et al. 2019; Woelders et al. 2017; Huang 
et al., In revisions; Bowman et al., in preparation). Building on these methods, it is now 
possible to deliver light interventions tailored to the individual user, making them both more 
habit-building and more effective.   
1.5. 
Prior work: Embedding circadian algorithms in mobile apps. In our previous work, 
our team developed a prototype mobile application, SYNC, which tracked the circadian 

10 
clock indirectly using wrist-worn wearable sensor data (i.e., minute-by-minute 
activity/steps and heart rate) as input. The SYNC app makes behavioral recommendations 
to correct circadian misalignment in patients. The general types of recommendations are: 
1) When to seek and avoid light; 2) When to seek and avoid caffeine; 3) Ideal window for 
sleep. These recommendations are given with associated time periods and tailored to 
match the user’s ability and desire to control their light exposure (e.g. the ability to wear 
blue-blocking glasses, or be exposed to very bright light) and home time zone. For 
example, the app will only recommend that the user avoid light by wearing blue-blocking 
glasses if they have marked that they are willing to use blue-blockers in the Settings page, 
and will only recommend caffeine timing if the person is a caffeine user.  
 
1.6. 
Preliminary data suggests strong potential for wearables. To assess the viability of 
cancer participants using a wrist-worn wearable and lighting hardware, participants were 
given a version of the app that passively collected data from an Apple Watch device 
without making active recommendations, a smart-bulb that could be controlled by the app 
(to change color to dim red) and red-tinted, blue-blocking glasses, but no specific 
instructions on how to use these beyond a simple educational primer on how light affects 
sleep. Overall, users in our Phase I usability trial found the wrist-worn wearable extremely 
easy to set up (100% found it “Very easy” to Wear and Charge, and 75% found it “Very 
Easy” to sync with their phone, with the remaining 25% rating it as “Fairly Easy.”). The 
most difficult hardware challenge was connecting the lightbulb, with one participant 
choosing not to set it up and one person marking it as “Neutral” difficulty. In summary, 
most participants did not find the hardware overly burdensome to set up. Clear daily 
patterns of activity and heart rate can be seen over the course of the collected data. While 
the feasibility of deploying wearables in a patient population was unclear before the 
usability trial, we found patients were willing and able to reliably wear the device.  

11 
1.7. 
Study Rationale. The scientific premise of this protocol stems from the literature 
presented in   the Background and Significance and the large body of prior work by the 
study PI and Co-Is who have extensive experience examining the information needs of 
cancer patients. The SYNC app has been tested in one-on-one user interviews and for 
ease-of-use with lighting and wearable hardware; the next stage of its development is to 
incorporate greater scientific rigor. The heterogeneity of cancer types and experiences 
means that an intervention may be effective for one population and not for another. The 
work proposed in this specific aim is to test the SYNC app, in three separate populations 
of cancer patients. Patients will be randomized either to use the SYNC app, with its tailored 
recommendations for use with blue-blocking glasses, or to a control app without tailored 
recommendations and clear glasses. 
1.8. 
SYNC 1.0 Development. The app was developed for iOS devices by Arcascope using a 
Phase I SBIR grant. A non-interventional version of the app was tested for usability in a 
prior study. The app was designed based on five in-depth interviews, assessed for 
usability in four recorded tests with the first prototype, and tested again by eight 
participants in a long-term study, along with hardware, including blue-blocking glasses 
and mobile-controlled smart-bulbs. The app was capable of syncing with smart-bulb 
devices, as well as registering when these devices were used. These features of the app 
were removed in response to user feedback that they did not like interfacing with the smart 
lightbulbs.  
1.9. 
Understanding circadian interventions. To better explain the recommendations by the 
app, consider the case where a user on a habitual 11:00 pm to 7:00 am sleep schedule 
has been disrupted by staying up later than normal. The model will track that user’s 
circadian state as disrupted, which is shown by the x variable from the limit cycle oscillator 
model in the figure above as a dashed red line, out-of-sync with the solid black line (again, 
x) of someone entrained to 16 hours of light and 8 hours of dark. Periods of light and dark 

12 
are marked as bands of yellow and black, respectively. Predicted windows of sleep 
(Phillips and Robinson 2007) are marked by purple bands. All simulations start at 11:00 
am 
local 
time. 
 
The app makes different recommendations based on the user’s predicted sleep drive. If 
the user followed no intervention (leftmost plot), they would end the 24-hour period still out 
of sync with their target rhythm. If they had accrued a relatively low sleep drive in the days 
leading up to the disruption, the app would recommend they put on blue-blocking glasses 
at 8:15 pm, with an anticipated sleep onset at 10:50 pm. If they had a significantly higher 
sleep drive, the app would recommend a maximum nap opportunity of 1.5 hours between 
12:30 and 2:00 pm, and a bedtime at 7:40 pm. For all these sample recommendations, 
times have been rounded to the nearest five-minute mark. While only two interventions 
are shown (for “low” and “high” sleep drive), there are many others that would be 
recommended for different sleep drives and different disruptions. 
1.10. Scientific Premise. Fatigue is a major problem for cancer patients, and one that can persist 
long after treatment ends. Recent work has demonstrated that light therapy may mitigate 
or reduce fatigue levels in both cancer patients and cancer survivors. This protocol seeks 
to assess how lighting interventions distributed through a mobile app affect fatigue, sleep, 
and quality of life across three populations of cancer patients. Our strong preliminary data, 
coupled with the need to deliver an effective intervention in a population with severe 
circadian disruption form the scientific premise. Our central hypothesis is that targeted, 
personalized light interventions will reduce fatigue in cancer patients. 
 
 

13 
1. 
STUDY DESIGN 
1.1. 
Study Overview. This study will use a two-arm randomized study design.  Participants will 
be recruited across three cancer types. Each of the participants will be randomized to an 
active “intervention” arm (using the full SYNC app) or to a control arm (using a “dummy” 
version of the SYNC app that gives recommendations for light at times that should not 
significantly affect the circadian clock). The random allocation of participants to the 
treatment arm or control arm establishes the basis for testing the statistical significance or 
difference between the groups in the measured outcome (patient fatigue, assessed by a 
daily 1-question fatigue survey and the PROMIS 4-item Fatigue). Patient age, gender, and 
other prognostic baseline characteristics that could potentially confound an observed 
association, including those that are unknown or unmeasured, will be distributed equally, 
except through chance alone, through random assignment. Thus, this design is well-suited 
to our goal of assessing the efficacy of a mobile health intervention, SYNC, on participants. 
1.2. 
Primary Hypothesis. The primary hypothesis is that a mobile-app delivered circadian 
intervention (SYNC) will reduce patient fatigue.  
1.3. 
Study Objectives 
1.3.1. Primary Objective.  To test the difference between the “intervention” (full SYNC 
app) arm and the control (limited SYNC app) arm in the measured outcome of 
patient fatigue, assessed by daily 1 question surveys and weekly 4-item PROMIS 
questionnaires over the course of 12 weeks.  
1.3.2. Secondary Objective. To determine the change in sleep disturbances, anxiety, 
depression, 
physical 
functioning, 
and 
global 
health 
through 
PROMIS 
questionnaires, between baseline and the 12-week assessment in both the control 
and intervention arms, and to look for differences in this change between the two 
arms.  
1.3.3. Exploratory Objectives 
1.3.3.1. Change in patient physical activity through physiological data capture 
using the wearable sensors in the control versus intervention arm. 
1.3.3.2. Change in patient health care utilization (e.g., total count of hospital days, 
readmissions, and ambulatory care clinic visits) in the control versus 
intervention arm 
1.3.3.3. Change in patient sleep aid usage in the control versus intervention arm. 
1.4. 
Participant Eligibility 
1.4.1.  Inclusion Criteria 
1.4.1.1. Able to provide informed consent and willing to sign an approved consent 
form that conforms to federal and institutional guidelines. 
1.4.1.2. Comfortable reading and speaking English. 
1.4.1.3. Must own an iPhone 6s or later (with iOS 14 or later or willing to update to 
iOS 14+) and be willing to complete surveys on it, per the protocol. 
Alternatively, patients without iPhones must be willing to use a loaner 
iPhone provided by the study team to use during the study and return at 
the end of the study. 
1.4.1.4. > 18 years of age.  

14 
1.4.1.5. Sleep aid usage will be allowed as long as the patient has been on a stable 
dose for at least 4 weeks prior to enrollment and agrees to continue the 
same dose during the study.  
1.4.1.6. A response of at least 4 on a 10-point scale (with 0 = not fatigued at all 
and 10 = extremely fatigued) to the question “How fatigued did you feel in 
the last four weeks?” 
1.4.1.7. Breast cancer population: Diagnosed with stage 1-3 breast cancer in the 
last 10 years, without metastatic disease. Chemotherapy or radiation 
therapy, if indicated, must have been completed at least 3 months prior to 
enrollment. Concomitant anti-HER2 therapy and/or anti-endocrine therapy 
is permitted. 
1.4.1.8. Prostate cancer population: Undergoing androgen deprivation therapy 
(ADT) for at least three months and are anticipated to remain on ADT for 
the duration of the trial. Concomitant additional anti-androgen therapy (e.g., 
enzalutamide) is permitted. 
1.4.1.9. HSCT population: Participants must be from the University of Michigan 
Blood and Marrow Transplant Program. 
1.4.2. Exclusion Criteria 
1.4.2.1. The patient cannot be undergoing chemotherapy at the time of enrollment 
unless it is post-transplant maintenance chemotherapy. Patients 
undergoing post-transplant maintenance chemotherapy are permitted to 
enroll. 
1.4.2.2. The patient must have no evidence of disease progression or recurrence. 
Specifically, for the prostate cancer population, the patient must have no 
evidence of disease progression on their current ADT regimen at the time 
of enrollment. 
1.4.2.3. The patient must not be a night shift worker, where night shift is defined 
as working a significant number of hours (i.e. more than half) between the 
hours of 11PM and 6AM on a regular basis. 
1.5. 
 Intervention Plan 
1.5.1. Participants will be consented, enrolled, and randomized remotely with a Research 
Coordinator prior to beginning the trial. A review of inclusion/exclusion criteria will 
be conducted to determine the patient’s eligibility for enrollment. Study procedures 
will be reviewed with the patient, and documentation of informed consent will be 
obtained. After signing the informed consent form (ICF) either in person or 
electronically using SignNow or other process approved by the University of 
Michigan IRBMED, patients will be assigned a unique study ID number in 
sequential order. Those who are found to be ineligible will be replaced. 
1.5.2. After providing informed consent, the participant will be provided, in the clinic or 
via mail, a wearable device and a pair of glasses, which will be either blue-blocking 
(intervention group) or clear (control group). Both of these are described in detail 
in Appendix A. When both are in the participant’s possession, the study 
coordinator will schedule a second meeting with the participant to onboard them 
to the specifics of the study.  

15 
1.5.3. The study coordinator will walk the participant through setting up the app and 
entering their Research ID number. They will ensure that the participant is able to 
connect to the wearable device via their phone and will explain to the subject that 
they should not wear the blue-blocking glasses while driving or if their vision will 
be impaired by them in a way that challenges their mobility.  
1.5.4. Participants will be allowed to use sleep aids over the course of the trial. There will 
be no restriction on their usage; however, subjects will be asked to report on a 
weekly basis what sleep aids they consumed, as well as the number of alcoholic 
drinks they consumed. This survey will be carried out in the app. 
1.5.5. Once the trial has begun, study coordinators will track completion of surveys, and 
in the event of missing data will follow-up with subjects to assess challenges to 
encourage survey completion. SYNC software will be maintained in collaboration 
with Arcascope, Inc. After randomization, subjects will complete baseline 
assessments, as outlined in the metrics Appendix. They will be asked to wear the 
wearable device day and night for twelve weeks. During this time, the app will 
deliver ecological momentary assessments of fatigue daily at random times of day 
and the validated 4-item PROMIS Fatigue questionnaire weekly to both the control 
and interventional groups. At the end of the twelve-week period, the subjects will 
remotely complete end-of-trial assessments. 
1.5.6. Intervention arm (SYNC app): Participants randomized to the intervention arm will 
be instructed on how to download the app on their mobile phones (iOS) and how 
to operate the wearable device. The app will record when the user opens the app, 
as well as when they check off having completed an assigned task; e.g. “getting 
bright light exposure”. Please see Appendix A to view the components of the 
wearable device. Please see Appendix B to view specifications of the mobile app. 
Any PHI information will be stored on University of Michigan servers in a secure 
way. Only non-PHI information will be stored and collected via the Sync app. The 
SYNC will be downloaded onto patient mobile phones and can be used freely 
throughout the intervention period because it contains no PHI data.  
1.5.7. Control arm: Participants randomized to the control arm will be instructed on how 
to download the SYNC app and how to operate the wearable sensor. Their 
research ID will trigger the “control” recommendations from SYNC, which are 
chosen to minimize circadian effect. Any PHI information will be stored on 
University of Michigan servers in a secure way. Only non-PHI information will be 
stored and collected via the Sync app. The SYNC will be downloaded onto patient 
mobile phones and can be used freely throughout the intervention period because 
it contains no PHI data.   
1.5.8. Light-blocking and “dummy” glasses: Participants will be provided either blue-
blocking glasses (intervention group) or clear glasses that do not block visible light 
(control). The blue-blocking glasses are meant to reduce the circadian effect of 
light at certain times for participants. Both pairs of glasses will be capable of being 
worn over regular glasses for vision impairment. Participants will be informed not 
to wear the glasses while driving, or when doing motor activity that risks injury with 
vision impairment. They will also be informed that they are not required to wear the 
glasses if doing so makes them feel uncomfortable; e.g. if they are out in public.  
1.5.9. Wearable sensor device: Each participant will be given a wearable sensor to wear 
throughout the treatment period, except while in water or when charging. The goal 
is to collect objective, continuous, multi-parameter physiological data (e.g., total 

16 
hours of sleep, sleep quality, total number of steps) on patients throughout the 
treatment period to correlate with their subjective, snapshot participant-reported 
outcomes collected over the course of the trial. The de-identified wearable data 
will be stored on servers purchased by the small business partner, Arcascope. For 
troubleshooting, detailed instructions will be provided for all participants, and 
customer support will be available 8AM – 5PM CST. Our team is available by pager 
after hours, if needed.  
 
 

17 
3. 
STUDY ENDPOINTS 
3.1. Primary Endpoint. The primary endpoint is fatigue, as assessed by a daily fatigue 
questionnaire and a weekly 4-item PROMIS fatigue questionnaire. 
3.2. Secondary Endpoint. The secondary endpoints are sleep disturbance, anxiety, 
depression, physical function and global health, as measured via the following PROMIS 
validated instruments: 
- PROMIS Sleep Disturbance (8-item) 
- PROMIS Anxiety (7-item)  
- PROMIS Depression (8-item) 
- PROMIS Physical Function (8-item)  
- PROMIS Global Health (10-item) 
3.3. Exploratory Endpoints. 
3.3.1. Activity data. Patient activity (steps) and sleep will be measured 
continuously from the start to the end of the trial through wearable sensors. 
3.3.2. Health care utilization data. Patient health care utilization data (e.g., total 
count of hospital days, emergency department visits, readmissions, and 
ambulatory care clinic visits) will be captured through the electronic health record 
as well as self-report (i.e., if the patient is readmitted at an outside hospital other 
than Michigan Medicine).  
3.3.3. Sleep aid utilization data will be collected via self-report in the app once a 
week.  
 
 

18 
 
4. 
PATIENT ENROLLMENT AND EVALUATION 
4.1. 
Study participants will be recruited through the following means: 
(1) The University of Michigan Rogel Cancer Center physicians, advanced practice 
providers, and nurse coordinators.  
(2) The University of Michigan health system’s electronic health record (EHR) is based 
on the Epic software (MiChart), which allows researchers, with IRB approval, to 
contact (via email, flyers, phone calls, or in-person) individuals who meet specific 
criteria and may be eligible to participate in the study. For example, with IRB-
approval, Drs. Choi, Alumkal, and Henry and their Research Staff can access the 
daily clinic schedules, which will enable them to identify potential participants and 
meet them in-person during a corresponding patient encounter.  
(3) With IRB-approval, we will distribute flyers in the outpatient clinics for our three 
cancer populations to inform potential individuals about the study. We will also 
distribute emails to potential study participants via the University of Michigan’s 
UMHealthResearch (https://umhealthresearch.org) service.  
(4) The Michigan Institute for Clinical and Health Research (MICHR), supported by 
the NIH Clinical and Translational Science Award Program, will assist our team 
with developing and reviewing recruitment materials, and identifying obstacles that 
may affect participant recruitment and retention. 
4.2. 
Randomization: Once the patient is deemed eligible and has provided written informed 
consent, the Research Coordinator will confirm eligibility. The study statistician, Walter 
Dempsey, will create a randomization list before the study begins enrollment using the 
statistical package R.  Dr. Dempsey will then forward the list to the Data Manager, who 
will be responsible for enrolling patients and assigning them to the correct study arm.   
4.3. 
Pre-Intervention Evaluation: PROMIS Patient-Reported Outcomes (PROs) – Well-being 
or HRQOL assessments will be obtained at baseline, pre-intervention. The surveys will be 
completed directly through the SYNC app on mobile phones. Based on prior work, our 
Study Team has experience administering PROMIS PROs on mobile devices. 
4.4. 
Post-Intervention Evaluation: PROMIS Patient-Reported Outcomes (PROs) – Well-being 
or HRQOL assessments will be completed at 12 weeks, post-intervention. This survey 
must be completed within two weeks after the 12-week intervention period.The surveys 
will be obtained directly through the SYNC app on mobile phones. Based on prior work, 
our Study Team has experience administering PROMIS PROs on mobile devices. 
4.5. 
Participant Withdrawal: At any time, a participant may request that her or his data no 
longer be collected. The participant may make this request to the Research Coordinator 
or to any member of the Study Team. A note will be made in the patient chart documenting 
the reason the patient withdrew from the study. Participants may also be removed for the 
following reasons: development of disease recurrence or progression, in the event that 
the IRB or sponsor decides to close the study, or if the treating physician thinks it is no 
longer in the best interest of the patient.  
4.6. 
Study Regulations: The trial will be performed in accordance with all applicable regulatory 
requirements and laws.  
4.7. 
Risks. 

19 
4.7.1. Wearable Sensor Device: Patient Subjects who agree to wear the device(s) for 
data collection may experience mild skin irritation, which will be monitored by the 
care team. The subject can decline to wear the device(s) or request to try a 
different device(s) that may be more comfortable. Subjects who decline to wear 
the wearable device will be replaced and not included in the statistical analysis. All 
subjects will be instructed to remove the device before any scans or radiation 
therapy. 
4.7.2. Confidentiality: There is a possible risk of loss of confidentiality. However, every 
effort will be made to keep your medical information confidential. We will code data 
by assigning a number to each individual patient and then store the data by that 
number. No mention of patient subject identities is made in analyses of the data or 
in any publications, which result from such research. 
4.8. 
Adverse Event Reporting Requirements.  
Adverse events related to this intervention are not expected, as the focus of this 
intervention (if randomized to the intervention group) is on lighting and minimal-risk 
behavioral interventions. However, any adverse events resulting from research 
procedures will be reported to IRBMED per institutional guidelines.  In the event an AE 
does occur, the PI will determine the attribution/relatedness of each AE. Expected side 
effects from anti-hormonal therapies, anti-HER2 therapy, GVHD will not be reported for 
this trial. 
4.9. 
Participant Data Security and Compliance. All identifiable information about the patient will 
be stored on a secure, password-protected core image laptop computer in Dr. Sung Won 
Choi’s Laboratory (MPB) following rules for secure data storage (e.g., M+Box or Dropbox). 
Research devices will not interface with MiChart. All study personnel will be HIPAA and 
PEERRS certified. All study information will be stored in password-protected encrypted 
files and identified by case number. The technologies proposed in this proposal have all 
been carefully reviewed, and approved by the governing bodies at Michigan Medicine. All 
regulatory and security requirements have been met and have been fully documented in 
accordance with the policies and best practices that govern the use of technology for 
patient care and research at Michigan Medicine. The MiChart web services were built and 
are supported by HITS, and their use for this project has been approved by HITS. All 
standard procedures and protocols for security and data integrity that apply to this project 
are being followed. All PHI will be stored in the HITS Oracle Database. 
4.10. Data Safety Monitoring Plan. This study will be monitored in accordance with the NCI 
approved University of Michigan Rogel Cancer Center Data and Safety Monitoring Plan. 
The study team will meet every six months or more frequently depending on the activity 
of the protocol. The discussion will include matters related to the safety of study 
participants (SAE/UaP reporting), validity and integrity of the data, enrollment rate relative 
to expectations, characteristics of participants, retention of participants, adherence to the 
protocol (potential or real protocol deviations) and data completeness. At these regular 
meetings, the protocol specific Data and Safety Monitoring Report form will be completed 
and signed by the Principal Investigator or by one of the co-investigators. Data and Safety 
Monitoring Reports will be submitted to the University of Michigan Rogel Cancer Center 
Data and Safety Monitoring Committee (DSMC) every six months for independent review. 
 

20 
5. 
STATISTICAL CONSIDERATIONS 
5.1. 
Study Design. The clinical trial is a two-arm randomized controlled trial. After 
completion of the intervention, data analysis will be conducted according to the 
statistical analysis plan outlined below. Descriptive statistics will be performed 
prior to conducting the statistical analyses. An intention-to-treat (ITT) analysis of 
the results will be based on the initial assignment of the randomized participants. 
With the ITT approach, participants will be analyzed according to the treatment 
assignment, even if the participant drops out of the study. The ITT approach 
minimizes biased comparisons among the treatment arms. Missing data will be 
imputed using the last collected data from the subject prior to dropout.  
5.2. 
Accrual. It is estimated that 18-months will be necessary to enroll the targeted     
sample size. Accrual will be reported by race, ethnicity, gender, and age.     
5.3. 
Study Duration. Survey results and wearable data will be actively collected from 
participants over the course of 12 weeks. At the conclusion of the 12 weeks, 
passive collection of wearable data through the app will continue for up to one 
year for each participant who opts-in to continue using the app. Medical records 
may be accessed for up to five years after the conclusion of the 12-week 
collection period. 
5.4. 
Randomization. Blocked randomization will be used to limit bias and achieve an 
equal distribution of participants to the intervention and control arms of the study 
(69 randomized, 69; with 23 from each cancer population in each arm). This 
approach will recruit participants in small blocks to ensure that half of the 
participants within each block will be allocated to the treatment and the other half 
to the control. The size of the blocks will be permuted to limit selection bias, and 
within each block, the order of patients will be random. The study statistician will 
create a randomization list before the study begins enrollment using the 
statistical package R.  This list will be used by the study group in assigning 
patients to the correct study arm. 
5.5. 
Blinding. Study arm assignments cannot be blinded to the investigators or the 
rest of the study team because it will be known whether participants have SYNC 
on their mobile device or not (due to technical purposes).  
5.6. 
Primary Endpoint. The primary objective of the study is to test the effects of 
SYNC in a randomized controlled clinical trial design. Patients will be randomly 
assigned to the treatment arm or the control arm. The primary objective is to 
quantify the effects of the light interventions delivered by SYNC on patient 
fatigue. 
5.7. 
Sample Size Considerations. We will enroll 138 cancer patients, with half in the 
intervention arm and half in the control arm. Our primary endpoint is the PROMIS 
4-item Fatigue Short Form.  The age- and sex-adjusted norm for the Fatigue 
scale is 50 points, with a standard deviation of 10 points. These statistics have 
been shown to be largely generalizable to the cancer patient population (mean: 
52, standard deviation 7.6). Our study will have power of 0.80, assuming a two-
sided Type I error rate of 0.05, to detect an effect size of half the standard 
deviation between the intervention and control arms if 64 cancer patients are 
enrolled in each of the control and intervention groups. A mean difference of one-
half a standard deviation is clinically meaningful and is considered a medium 
effect size for clinical trials. During the primary analysis, we will adjust for the fact 

21 
that there are three cancer populations in our data and will look for a well-defined 
effect that is marginal within each population. We will accrue a total of 69 patients 
in each arm to account for attrition of data, assuming a 7% dropout rate from the 
trial.  
5.8. 
PROMIS® measures use Item Response Theory (IRT), a family of statistical 
models that link individual questions to a presumed underlying trait or concept of 
global health represented by all items in the scale. PROMIS® instruments are 
scored using item-level calibrations. The most accurate way to score a 
PROMIS® instrument is to use the Health Measures Scoring Service, which our 
Study Team has experience with. This method of scoring uses “response pattern 
scoring,” which uses responses to each item for each participant. Response 
pattern scoring is especially useful when there is missing data (i.e., a respondent 
skipped an item), or different groups of participants responded to different items). 
 
There are four key features of the score for PROMIS® Fatigue: 
1. Reliability: The degree to which a measure is free of error. It can be estimated 
by the internal consistency of the responses to the measure, or by correlating 
total scores on the measure from two time points when there has been no true 
change in what is being measured (for z-scores, reliability = 1 – SE2). 
2. Precision: The consistency of the estimated score (reciprocal of error 
variance). 
3. Information: The precision of an item or multiple items at different levels of the 
underlying continuum (for z-scores, information = 1/SE2). 
4. Standard Error (SE): The possible range of the actual final score based upon 
the scaled T-score. For example, with a T-score of 52 and a SE of 2, the 95% 
confidence interval around the actual final score ranges from 48.1 to 55.9 (T-
score ± (1.96*SE) = 52 ± (1.96*2) = 48.1 to 55.9) 
 
The final score is represented by the T-score, a standardized score with a mean 
of 50 and a standard deviation of 10 points. 
 
5.9. 
Interim Analysis. There will be no interim analyses for efficacy or futility for this 
trial. 
5.10. Patient Characteristics. Patient characteristics will be summarized for all 
participants. Patient characteristics to be examined may include: age, gender, 
race/ethnicity, treatment and pathology information (including dates), and clinical 
outcomes; e.g. survival, relapse, and toxicities. 
5.11. Analysis Populations and General Analysis Guidelines. 
5.11.1. Primary Analysis Population. All participants enrolled, consented, and 
completing at least the baseline outcome measures will be included in the 
primary analysis population. Analyses for the primary and secondary 
endpoints will use the primary analysis population: The primary analysis 
will occur once all patients have been followed for the duration of the 12-
week trial, data adjudication completed, and data are locked. 
5.11.2. General Analysis Guidelines. Primary analyses for the primary, 
secondary, and exploratory endpoints will use the primary analysis 
population. Analyses of each endpoint in each population will follow the 

22 
analysis plans, as described below. We expect minimal missing data 
(<5%) for the primary endpoint and secondary endpoints based on past 
experience with mobile app studies. 
5.12. Analysis of Primary Endpoint. Analysis will be an intent-to-treat analysis that 
includes all participants. Mean Global Health scores at the end of the trial will be 
compared using a two-sample t-test (or Wilcoxon Rank Sum test if non-normality 
is apparent) with a significance level of 0.05. Linear regression models will be 
performed to complement the results of the t-test and adjust for specific baseline 
participant’s characteristics (e.g., demographic, social, environmental) to 
increase the precision of our inference. There is a possibility that patient 
characteristics will be unbalanced since our randomization scheme will be 
applied to participants. Thus, our models also will assess potential moderating or 
mediating effects. 
5.13. Analysis of Secondary Endpoint.  
Mean PROMIS scores (PROMIS sleep disturbances, anxiety, depression, 
physical function, and global health) for each arm at the end of the trial will be 
compared using a two-sample t-test (or Wilcoxon Rank Sum test if non-normality 
is apparent) with a significance level of 0.05. Linear regression models will be 
performed to complement the results of the t-test and adjust for specific baseline 
participant’s characteristics (e.g., demographic, social, environmental) to 
increase the precision of our inference. There is a possibility that patient 
characteristics will be unbalanced since our randomization scheme will be 
applied to participants. Thus, our models also will assess potential moderating or 
mediating effects. 
5.14. Analysis of Exploratory Endpoints. 
5.14.1. Patient activity. The accelerometer data of each subject will be 
transformed into a low-dimensional representation using motif discovery 
algorithms.79 Such techniques are completely data-driven, and search for 
motifs (i.e., patterns) in the data that occur more often than chance. A 
signal can then be represented by the number of times a particular motif 
occurs. Others have successfully used such techniques for representing a 
variety of waveform data, including accelerometer and continuous 
glucose data.80-82 The accelerometer data will be processed to derive 
estimates of total sleep duration (i.e., hours per night), wake after sleep 
onset, and sleep efficiency (i.e., ratio of sleep to wake). The variables will 
be compared between arms. 
5.14.2. Patient health care utilization. The total count of hospital days, ED visits, 
readmissions, and ambulatory care clinic visits during the trial, with 
adjustment for follow-up, will be compared between arms using a Poisson 
regression model, with adjustment for potential mediating or moderating 
effects of patient characteristics, if needed. The data will be captured at 
the time of PRO assessments. 
5.14.3. Patient sleep aid utilization. The total number of sleep aids being used by 
the patients, as well as the types, will be collected via weekly surveys 
over the course of the trial.  
 
 

23 
 
APPENDIX A: DESCRIPTION OF DEVICES  
Participants in both arms will be given a pair of glasses. In the control group, participants will be 
given a pair of clear safety glasses. They will be given one of two types of clear glasses, 
depending on whether or not they wear reading glasses and comfort considerations. 
 
The first type of glasses for the control group are those meant for participants who do not wear 
reading glasses. To account for changing availability of specific glasses models on the Amazon 
website, any pair of clear safety glasses that is similar to the model below may be used.  
 
Example of control glasses for participants who do not wear reading glasses: 
 
Crews BK310 BearKat 3 Polycarbonate Clear Lens Safety Glasses with Non-Slip Hybrid Black 
Temple Sleeve 
 
 
 
 
Manufacturer 
MCR Safety 
Part Number 
1 
Item Weight 
0.32 ounces 
Package Dimensions 
9 x 2.6 x 1.6 inches 

24 
Item model number 
BK310 
Color 
Clear Lens 
Style 
Duramass Coated Lens 
Finish 
Scratch-resistant 
Pattern 
Safety Glasses 
Item Package Quantity 
1 
Batteries Required? 
No 
 
The second type of glasses available to participants in the control group are larger and meant 
for participants who also wear reading glasses. To account for changing availability of specific 
glasses models on the Amazon website, any pair of clear safety glasses that is similar to the 
model below may be used. 
 
Example of control glasses for participants who do wear reading glasses: 
 
Safety glasses Industrial Goggles with Anti-fog Lens, Clear Safety glasses with Anti-Scratch 
Lens Goggles Inside Eyeglasses (Transparent)  
 
 
 

25 
 
Manufacturer 
MEIGIX 
Part Number 
MEIGIX-GOGGLES2 
Item Weight 
2.82 ounces 
Package Dimensions 
9.09 x 4.53 x 2.8 inches 
Finish 
Scratch-resistant, Anti-fog, Uv-
protection 
Material 
Plastic 
Batteries Required? 
No 
 
 
Participants in the intervention arm will be given a pair of blue-blocking glasses. This will be one 
of two types depending on whether they wear reading glasses or not, as well as comfort 
considerations. 
Participants in the intervention arm with reading glasses will receive blue-blocking glasses that 
fit over their other glasses. To account for changing availability of specific glasses models on 
the Amazon website, any pair of blue-blocking glasses that is similar to the model below may be 
used. 
 
Example of intervention glasses for participants who do wear reading glasses: 
 
Uvex ASTRO Over-The-Glass (OTG) Blue Light Blocking Computer Glasses with SCT-Orange 
Lens. 
 
 

26 
 
 
 
Manufacturer 
Honeywell 
Part Number 
S2515 
Item Weight 
2.32 ounces 
Package Dimensions 
6.81 x 2.83 x 2.6 inches 
Item model number 
S2515 
Style 
ASTRO OTG 
Item Package Quantity 
1 
Included Components 
1 safety eyewear 

27 
Batteries Required? 
No 
 
 
Participants in the intervention arm without reading glasses will receive smaller blue-blocking 
glasses that would not fit over other glasses. To account for changing availability of specific 
glasses models on the Amazon website, any pair of blue-blocking glasses that is similar to the 
model below may be used. 
 
Example of intervention glasses for participants who do not wear reading glasses: 
 
Uvex Skyper Blue Light Blocking Computer Glasses with SCT-Orange Lens. 
 
 
 
Manufacturer 
Uvex 
Part Number 
S1933X 
Item Weight 
1.6 ounces 

28 
Product Dimensions 
2.7 x 2.2 x 7 inches 
Item model number 
S1933X 
Is Discontinued By Manufacturer 
No 
Size 
1-Pack 
Color 
Sct-orange Lens 
Style 
Skyper 
Finish 
Anti-fog 
Item Package Quantity 
1 
Included Components 
1 Pair of Glasses 
Batteries Included? 
No 
Batteries Required? 
No 
Warranty Description 
Lifetime Frame Guarantee 
 
 
 
Participants in both arms will be given a wearable device. This device will be either a Fitbit 
Charge 3 or an Apple Watch.  
 

29 
In the event that Fitbit Charge 3s are the selected wearable device for the study, a description of 
the device follows below.  
The Fitbit Charge 3 is a smart watch capable of measuring heart rate, exercise amount, and 
sleep levels. There is a retail version available, and that is the model we will be using for our 
study. The data collected by the Fitbit Charge 3 is transferred from the smart watch to the Fitbit 
application installed on the patient’s phone via Bluetooth Low Energy (BLE), a form of Bluetooth 
specifically designed to lower power consumption without compromising range. The app then 
transmits the data to Fitbit’s information management system securely and without identifiable 
information. The smart watch can be worn on either wrist to give accurate measurements. The 
Charge 3 is made of safe-to-use aluminum and flexible, non-elastic elastomer material common 
in fitness watches. 
 
Participant Fitbits will be managed through Fitbit’s proprietary management system. The user will 
grant the SYNC app permission to access their heart rate and steps data during the onboarding 
step. The subject will wear the Charge 3 as often as they like. This will begin the collection of the 
subject’s data. The smart watch will upload the data to the patient’s phone every 15 minutes via 
BLE. The data is then sent to the Fitbit, where it is housed in secure Microsoft Azure servers, 
compliant with ISO/IEC 27001:2006 industry standards of encryption.  
In the event that the Apple Watch is the selected wearable device for the study, a description of 
the device follows below.  
The Apple Watch is a smart watch capable of measuring heart rate, steps, and sleep levels. The 
retail version will be used in the study. The data from the Apple Watch is transferred via 
Bluetooth Low Energy to the participant’s phone and stored in the Apple Health App. The smart 
watch can be worn on either wrist. The strap is made from liquid silicone rubber or nylon weave 
for wearing comfort.  
Information collected by the watch can be accessed by the app after the user has granted 
permission via the Apple Health app.  
The Apple Watch series used in this trial may range from Series 3 to Series 6 and may include 
Series SE. 
Detailed descriptions of both the Fitbit Charge 3 and the Apple Watch use and care are below.  

30 
Fitbit Charge 3 
Place Charge 3 around your wrist. If you need to attach a different size band, or if you 
purchased another band, see the instructions in "Change the band" on page 13. 
Placement for all-day wear vs. exercise 
When you're not exercising, wear Charge 3 a finger's width above your wrist bone. 
For optimized heart-rate tracking while exercising: 
During a workout, experiment with wearing your tracker a bit higher on your wrist for an 
improved fit. Many exercises, such as bike riding or weight lifting, cause you to bend your wrist 
frequently, which could interfere with the heart- rate signal if the tracker is lower on your wrist. 
Wear your tracker on top of your wrist, and make sure the back of the device is in contact with 
your skin. 
Consider tightening your band before a workout and loosening it when you’re done. The band 
should be snug but not constricting (a tight band restricts blood flow, potentially affecting the 
heart-rate signal). 
Handedness: 
For greater accuracy, you must specify whether you wear Charge 3 on your dominant or non-
dominant hand. Your dominant hand is the one you use for writing and eating. To start, the 
Wrist setting is set to non-dominant. If you wear Charge 3 on your dominant hand, change the 
Wrist setting in the Fitbit app: 
From the Today tab in the Fitbit app, tap your profile picture > Charge 3 tile > Wrist > Dominant. 
Change the band: 
Charge 3 comes with a small band attached and an additional large, bottom band in the box. 
Both the top and bottom bands can be swapped with accessory bands, sold separately on 
fitbit.com. For band measurements, see "Band size" on page 48. 
Remove a band: 
1. Turn over Charge 3 and find the band latches. 
2. To release the latch, press down on the flat button on the band. 
3. Gently pull the band away from the tracker to release it. 
4. Repeat on the other side. 
Attach a new band: 
To attach a new band, press it into the end of the tracker until you feel it snap into place. 
 
   

31 
If you have trouble attaching the band or if it feels loose, gently move the band back and forth to 
make sure it's attached to the tracker. 
Notifications: Charge 3 can show call, text, calendar, and app notifications from your phone to 
keep you informed. Keep your tracker within 30 feet of your phone to receive notifications. 
Set up notifications 
Check that Bluetooth on your phone is on and that your phone can receive notifications (often 
under Settings > Notifications). Then set up notifications: 
1. From the Today tab in the Fitbit app, tap your profile picture > Charge 3 
tile. 
2. Tap Notifications. 
3. Follow the on-screen instructions to pair your tracker if you haven't already. 
Call, text, and calendar notifications are turned on automatically. 
4. To turn on notifications from apps installed on your phone, including Fitbit and 
WhatsApp, tap App Notifications and turn on the notifications you want to see. 
Note that if you have an iPhone or iPad, Charge 3 shows notifications from all calendars synced 
to the Calendar app. If you have an Android phone, Charge 3 shows calendar notifications from 
the calendar app you choose during setup. 
 
See incoming notifications: A notification causes your tracker to vibrate. If you don't read the 
notification when it arrives, you can check it later by swiping down from the top of the screen. 
Manage notifications: Charge 3 stores up to 10 notifications, after which the oldest are replaced 
as you receive new ones. 
To manage notifications: 
Swipe down from the top of the screen to see your notifications and tap any notification to 
expand it. 
To delete a notification, tap to expand it, then swipe to the bottom and tap Clear. 
To delete all notifications at once, swipe to the top of your notifications and tap Clear All. 
Turn off notifications: Turn off certain notifications in the Fitbit app, or turn off all notifications in 
the quick settings on Charge 3. When you turn off all notifications, your tracker won't vibrate and 
the screen won't turn on when your phone receives a notification. 
To turn off certain notifications: 
1. From the Today tab in the Fitbit app on your phone, tap your profile 
picture > Charge 3 tile > Notifications. 
2. Turn off the notifications you no longer want to receive on your tracker. 
3. Sync your tracker to save your changes. 
To turn off all notifications: 

32 
1. Press and hold the button on your tracker and swipe left to reach the quick settings 
screen (on Fitbit Pay-enabled trackers). 
2. Tap DND to turn on do not disturb. The DND icon dims to indicate that all notifications, 
including goal celebrations and reminders to move, are turned off. 
Note that if you use the do not disturb setting on your phone, you don't receive notifications on 
your tracker until you turn off this setting. 
Answer or reject phone calls: 
If paired to an iPhone or Android (8.0+) phone, Charge 3 lets you accept or reject incoming 
phone calls. If your phone is running an older version of the Android OS, you can reject, but not 
accept, calls on your tracker. 
To accept a call, tap the check mark on your tracker's screen. Note that you can't speak into the 
tracker—accepting a phone call answers the call on your nearby 
phone. To reject a call, tap the icon on your tracker's screen. 
Respond to messages 
If paired to an Android (8.0+) phone, Charge 3 lets you respond directly to text messages and 
notifications from certain apps on your tracker with preset quick replies. 
To respond to a message: 
1. Tap the notification on your tracker. To see recent messages, swipe down from the clock 
face. 
2. Tap Reply. If you don’t see an option to reply to the message, replies aren’t available for 
the app that sent the notification. 
3. Choose a text reply from the list of quick replies or tap the emoji icon to choose an emoji. 
For more information, including how to customize quick replies, see help.fitbit.com. 
Activity and Sleep: 
Charge 3 continuously tracks a variety of stats whenever you wear it. Data automatically syncs 
when in range of the Fitbit app throughout the day. 
See your stats: 
Swipe up from the clock face on your tracker to see your daily stats, including: 
Core stats 
Steps taken today, distance covered, floors climbed, calories burned, and 
active minutes 

33 
Hourly 
steps 
Steps taken this hour, and the number of hours you met your hourly 
activity goal 
Heart rate 
Current heart rate and heart-rate zone, and resting heart rate 
Exercise 
Number of days you met your exercise goal this week 
Cycle track Information on the current stage of your menstrual cycle, if applicable 
Sleep Duration and quality of your sleep 
 
Find your complete history and other information detected by your tracker, such as sleep data, 
in the Fitbit app. 
Track a daily activity goal: Charge 3 tracks your progress toward a daily activity goal of your 
choice. When you reach your goal, your tracker vibrates and shows a celebration. 
Choose a goal: Set a goal to help you get started on your health and fitness journey. To begin, 
your goal is to take 10,000 steps per day. Choose to change the number of steps, or pick a 
different activity goal depending on your device. 
 
Track progress toward your goal on Charge 3. For more information, see "See your stats" on 
the previous page. 
Track your hourly activity:  
Charge 3 helps you stay active throughout the day by keeping track of when you're stationary 
and reminding you to move. 
Reminders nudge you to walk at least 250 steps each hour. You feel a vibration and see a 
reminder on your screen at 10 minutes before the hour if you haven't walked 250 steps. When 
you meet the 250-step goal after receiving the reminder, you feel a second vibration and see a 
congratulatory message. 
 
Track your sleep: Wear Charge 3 to bed to automatically track basic stats about your sleep, 
including your time asleep, sleep stages (time spent in REM, light sleep, and deep sleep), and 

34 
sleep score (the quality of your sleep). Charge 3 also tracks your estimated oxygen variation 
throughout the night to help you uncover potential breathing disturbances. To see your sleep 
stats, sync your tracker when you wake up and check the Fitbit app, or swipe up from the clock 
face on your tracker to check the Sleep tile in Fitbit Today. 
  
Fitness and Exercise 
Choose to automatically track exercise, or to track activity with the Exercise app and see real-
time stats and a post-workout summary. 
Sync Charge 3 with the Fitbit app and share your activity with friends and family, see how your 
overall fitness level compares to your peers, and more. 
Track your exercise automatically 
Charge 3 automatically recognizes and records many high-movement activities which are at 
least 15 minutes long. Sync your device to see basic stats about your activity in the Exercise tile 
in the Fitbit app. 
For more information, including how to change the minimum duration before an activity is 
tracked, see help.fitbit.com. 
Track and analyze exercise with the Exercise app 
Track specific exercises with the Exercise app on Charge 3 to see real-time stats, including 
heart-rate data, calories burned, elapsed time, and a post-workout 
summary on your wrist. For complete workout stats, and a workout intensity map if you used 
GPS, tap the Exercise tile in the Fitbit app. 
Note: Charge 3 uses the GPS sensors on your nearby phone to capture GPS data. 
 Check your heart rate 
Heart-rate zones help you target the training intensity of your choice. See your current zone and 
progress toward your maximum heart rate on your device next to your heart-rate reading. In the 
Fitbit app, you can see your time spent in zones during a particular day or exercise. Three 
zones based on American Heart Association recommendations are available, or you can create 
a custom zone if you have a specific heart rate you're targeting. 
Default heart-rate zones: 
Default heart-rate zones are calculated using your estimated maximum heart rate. Fitbit 
calculates your maximum heart rate with the common formula of 220 minus your age. 
 
 
 

35 
 
Icon Zone Calculation Description 
 
Below Zones 
Below 50% 
of your 
maximum 
heart rate 
Below the fat burn zone, your heart 
beats at a slower pace. You’re likely at 
rest or doing light activities such as 
taking a stroll. 
 
Fat Burn Zone 
Between 
50% and 
69% of your 
maximum 
heart rate 
In the fat burn zone, you’re likely in a 
moderate activity such as a brisk walk. 
Your heart rate and breathing might be 
elevated, but you can still carry on a 
conversation. 
 
Cardio Zone 
Between 
70% and 
84% of your 
maximum 
heart rate 
In the cardio zone, you’re likely doing a 
vigorous activity such as running or 
spinning. 
 
Peak Zone 
Greater 
than 85% of 
your 
maximum 
heart rate 
In the peak zone, you’re likely doing a 
short, intense activity that improves 
performance and speed, such as 
sprinting or high-intensity interval 
training. 
 
Custom heart-rate zones 
Instead of using these 3 heart-rate zones, you can create a custom zone to target a specific 
heart-rate range in the Fitbit app. 
 
 
 
 

36 
Apple Watch 
 
To use your Apple Watch Series 3 or later with watchOS 7, you need to pair your Apple Watch 
with an iPhone 6s or later with iOS 14 or later. Setup assistants on your iPhone and Apple 
Watch work together to help you pair and set up your Apple Watch. 
 
WARNING: To avoid injury, read Important safety information for Apple Watch before using your 
Apple Watch. 
 
Turn on, pair, and set up your Apple Watch 
1. Put your Apple Watch on your wrist. Adjust the band or choose a band size so your 
Apple Watch fits closely but comfortably on your wrist. 
For information about changing the band on your Apple Watch, see Remove, 
change, and fasten Apple Watch bands. 
2. To turn on your Apple Watch, press and hold the side button until you see the Apple 
logo. 
3. Bring your iPhone near your Apple Watch, wait for the Apple Watch pairing screen to 
appear on your iPhone, then tap Continue. 
Or open the Apple Watch app on your iPhone, then tap Pair New Watch. 
 
4. When prompted, position your iPhone so that your Apple Watch appears in the 
viewfinder in the Apple Watch app. This pairs the two devices. 
5. Tap Set Up Apple Watch. Follow the instructions on your iPhone and Apple Watch to 
finish setup. 
 
Tip: If you have difficulty seeing your Apple Watch or iPhone, VoiceOver or Zoom can help—
even during setup. See Set up Apple Watch using VoiceOver or Use Zoom on Apple Watch. 
While it’s pairing with your iPhone, your Apple Watch provides tips on how to interact with it. 
Tap Display, Digital Crown, and Side Button to learn more. 
 
You can activate cellular service on your Apple Watch during setup. If you don’t wish to, you can 
activate it later in the Apple Watch app on your iPhone. See Use Apple Watch with a cellular 
network. 
 
Your iPhone and Apple Watch must use the same cellular carrier. However, if you set up an 
Apple Watch for someone in your Family Sharing group, you may use a cellular carrier different 
from the one used on the iPhone you manage it with. 
Cellular service not available in all regions. 

37 
 
Trouble pairing? 
● If you see a watch face when you’re trying to pair: Your Apple Watch is already 
paired to an iPhone. You need to first erase all Apple Watch content and reset 
settings. 
● If the camera doesn’t start the pairing process: Tap Pair Apple Watch Manually at the 
bottom of the iPhone screen, and follow the onscreen instructions. 
● If Apple Watch isn’t pairing with iPhone: See the Apple Support article If your Apple 
Watch isn’t connected or paired with your iPhone. 
Unpair Apple Watch 
1. Open the Apple Watch app on your iPhone. 
2. Tap My Watch, then tap All Watches at the top of the screen. 
3. Tap 
 next to the Apple Watch you want to unpair, then tap Unpair Apple Watch. 
Pair more than one Apple Watch 
You can pair another Apple Watch in the same way you paired your first one. Bring your iPhone 
near your Apple Watch, wait for the Apple Watch pairing screen to appear on your iPhone, then 
tap Pair. Or follow these steps: 
1. Open the Apple Watch app on your iPhone. 
2. Tap My Watch, then tap All Watches at the top of the screen. 
3. Tap Pair New Watch, then follow the onscreen instructions. 

38 
See the Apple Support article Use more than one Apple Watch with your iPhone. 
To learn how to set up a watch for someone in your Family Sharing group, see Set up Apple 
Watch for a family member. 
Quickly switch to a different Apple Watch 
Your iPhone detects the paired Apple Watch you’re wearing and automatically connects to it. 
Just put on a different Apple Watch and raise your wrist. 
You can also choose an Apple Watch manually: 
1. Open the Apple Watch app on your iPhone. 
2. Tap My Watch, then tap All Watches at the top of the screen. 
3. Turn off Auto Switch. 
To see if your Apple Watch is connected to your iPhone, touch and hold the bottom of the watch 
screen, swipe up to open Control Center, then look for the Connected status icon 
. 
 
Pair Apple Watch to a new iPhone 
If your Apple Watch is paired to your old iPhone and you now want to pair it with your new 
iPhone, follow these steps: 
1. Use iCloud Backup to back up the iPhone currently paired to your Apple Watch (see 
the iPhone User Guide for more information). 

39 
2. Set up your new iPhone. On the Apps & Data screen, choose to restore from an 
iCloud backup, then select the latest backup. 
3. Continue iPhone setup and, when prompted, choose to use your Apple Watch with 
your new iPhone. 
When iPhone setup completes, your Apple Watch prompts you to pair it to the new iPhone. Tap 
OK on your Apple Watch, then enter its passcode. 
For more information, see the Apple Support article How to pair your Apple Watch with a new 
iPhone. 
Transfer an existing cellular plan to a new Apple Watch 
You can transfer your existing cellular plan from your Apple Watch with cellular to another Apple 
Watch with cellular by following these steps: 
1. While wearing your Apple Watch, open the Apple Watch app on your iPhone. 
2. Tap My Watch, tap Cellular, then tap 
 next to your cellular plan. 
3. Tap Remove [name of carrier] Plan, then confirm your choice. 
You may need to contact your carrier to remove this Apple Watch from your cellular 
plan. 
4. Remove your old watch, put on your other Apple Watch with cellular, tap My Watch, 
then tap Cellular. 
Follow the instructions to activate your watch for cellular. 
For more information about setup and pairing, see the Apple Support article Set up your Apple 
Watch. 
If you need to charge your Apple Watch before setup, see Charge Apple Watch. 

40 
 
Apple Watch SE 

41 
 
Apple Watch Series 4 and Apple Watch Series 5 

42 
 
Apple Watch Series 3 

43 
 
Charge Apple Watch 
Set up the charger 
1. In a well-ventilated area, place the included Apple Watch Magnetic Charging Cable 
or Apple Watch Magnetic Charging Dock on a flat surface. 
2. Plug it into the power adapter (sold separately). 
3. Plug the adapter into a power outlet. 
Begin charging Apple Watch 
Place the Apple Watch Magnetic Charging Cable on the back of your Apple Watch. The 
concave end of the charging cable magnetically snaps to the back of your Apple Watch and 
aligns it properly. 

44 
You hear a chime when charging begins (unless your Apple Watch is in silent mode) and see a 
charging symbol 
 on the watch face. The symbol is red when Apple Watch needs power and 
turns green when Apple Watch is charging. 
You can charge your Apple Watch in a flat position with its band open, or on its side. 
● If you’re using the Apple Watch Magnetic Charging Dock: Lay your Apple Watch on 
the dock. 
● If your battery is very low: You may see an image of the Apple Watch Magnetic 
Charging Cable and the low battery symbol 
 on the screen. For more 
information, see the Apple Support article If your Apple Watch won’t charge or it 
won’t turn on. 
Apple Watch Series 6 
 
Apple Watch SE 
 
Apple Watch Series 4 and Apple Watch Series 5 

45 
 
Apple Watch Series 3 
 
WARNING: For important safety information about the battery and charging Apple Watch, see 
Important safety information for Apple Watch. 
Check remaining power 
To see remaining power, touch and hold the bottom of the screen, then swipe up to open 
Control Center. To more quickly check the remaining power, add a battery complication to the 
watch face. See Customize the watch face. 

46 
 
Save power when the battery is low 
You can put your Apple Watch in Power Reserve mode to stretch the remaining battery power. 
Your Apple Watch still displays the time, but you can’t use apps. 
1. Touch and hold the bottom of the screen, then swipe up to open Control Center. 
2. Tap the battery percentage, then drag the Power Reserve slider to the right. 
 
Tip: If you have battery-powered devices such as AirPods connected to your Apple Watch 
through Bluetooth, their remaining charge appears on this screen. 
When battery charge drops to 10 percent or lower, your Apple Watch alerts you and gives you 
the opportunity to enter Power Reserve mode. 

47 
 
When your Apple Watch is almost out of power, it enters Power Reserve mode automatically. 
Tip: For tips on maximizing battery life, see Maximizing Battery Life and Lifespan at the Apple 
website. 
Return to normal power mode 
Restart your Apple Watch—press and hold the side button until the Apple logo appears. 
The battery must have at least 10 percent charge for your Apple Watch to restart. 
Check time since the last charge 
1. Open the Settings app 
 on your Apple Watch. 
2. Tap Battery. 
The Battery screen shows the remaining battery percentage, a graph that details the 
recent history of the battery charge, and information about when the battery was last 
charged. 
 
You can also check the time since last charge on iPhone. Open the Apple Watch app on 
iPhone, tap My Watch, then go to General > Usage. 
Check battery health 
You can find out the capacity of your Apple Watch battery relative to when it was new. 
1. Open the Settings app 
 on your Apple Watch. 

48 
2. Tap Battery, then tap Battery Health. 
To reduce battery aging, Apple Watch learns from your daily charging routines so it can wait to 
finish charging past 80 percent until you need to use it. 
Apple Watch alerts you if battery capacity is significantly reduced, allowing you to check your 
service options. 
Track important health information with Apple Watch 
Your Apple Watch can help you meet your sleep goals, track important information related to 
your heart, check your blood oxygen levels, and encourage you to wash your hands. 
 
Prioritize your sleep 
Apple Watch can help you create a sleep schedule, track your sleep, then report your sleep 
trends over time. To get started, open the Health app on iPhone and create a sleep schedule. 
Then wear your watch to bed and Apple Watch does the rest. 
 
Get heart health notifications 
You can enable notifications from the Heart Rate app on your Apple Watch to alert you to high 
or low heart rates. The irregular heart rhythm notification on the Apple Watch can also alert you 
if an irregular rhythm suggestive of Atrial fibrillation is identified. Open the Apple Watch app on 
your iPhone, go to My Watch, then tap Heart. Turn on High Heart Rate or Low Heart Rate, then 
set a heart rate threshold, also turn on irregular rhythm notifications. 

49 
 
Check your blood oxygen levels (Apple Watch Series 6 only) 
Use the Blood Oxygen app 
 to measure your blood oxygen levels directly from your wrist. 
See the most recent measurement on your Apple Watch and a record of all your readings in the 
Health app on iPhone. 
 
Wash your hands thoroughly 
Turn on Handwashing in the Apple Watch app on iPhone, and your Apple Watch encourages 
you to keep going for 20 seconds, the time recommended by global health organizations. Your 
watch can also notify you if you haven’t washed your hands within a few minutes of returning 
home. 

50 
 
Track your menstrual cycle 
Use the Cycle Tracking app 
 to log daily information about your menstrual cycle. The app 
uses that information to provide period and fertility window predictions. 
 
 
 
 
 
 

51 
APPENDIX B: SYNC COMPONENTS 
 
Study participants randomized to the Intervention Arm will use a version of SYNC that makes 
behavioral recommendations to correct circadian misalignment. Those in the Control Arm will use 
a “dummy” version of the app that makes behavioral recommendations that should minimally 
affect the circadian clock.  
 
The full version of SYNC has the following features:  
- 
Light exposure recommendations; e.g. times to sit near a window or go outside 
- 
Light avoidance recommendations; e.g. times to wear blue-blocking glasses 
- 
Caffeine avoidance recommendations  
- 
Ideal times to sleep 
- 
Ideal times to exercise for peak performance 
- 
Ideal times to exercise to shift the circadian clock 
- 
Surveys embedded for daily tracking of fatigue and other metrics 
- 
Personalized educational information about the circadian clock 
 
The dummy version of SYNC has the following features: 
- 
Light exposure recommendations, timed to avoid shifting circadian rhythms 
- 
Surveys embedded for daily tracking of fatigue and other metrics 
 
The abovementioned recommendations are calculated using mathematical models of the 
circadian clock which read in data from the user’s wearable device. The times are expected to 
shift every day, as the user’s circadian clock shifts.  
 
Sample 
behavioral 
recommendations 
from 
the 
full 
app 
include: 
 
- 
“Sit near a window or go outside from 8:30 am - 9:45 am” 
- 
“Put on your blue-blocking glasses at 7:05 pm” 
- 
“To fall asleep earlier tonight, do a workout between 6:45 am and 9:30 am” 
- 
“Your peak window of athletic performance is from 7:45 pm - 9:45 pm” 
- 
“Taking a nap from 1:00 - 1:45 pm today shouldn’t keep you from falling asleep tonight.”  
 
The dummy version of the app will make the following recommendations:  
- 
“Put on your study-provided glasses from 12:00 pm - 1:00 pm” 
- 
“Be in a room with normal lighting from 1:00 pm - 1:30 pm” 
 
A screenshot of the app, currently in revision, is provided below for context: 

52 
 
 
 
 
 
 
 

53 
APPENDIX C: USER-REPORTED OUTCOME MEASURES 
 
Baseline Survey/Exit Survey 
 

54 

55 
 

56 
 

57 
 
 
Morningness-Eveningness Questionnaire: 

58 
1. One hears about “morning” and “evening” types of people. Which one of these types do you 
consider yourself to be? 
a. Definitely a morning type 
b. More of a morning than evening type 
c. More of an evening than morning type 
d. Definitely an evening type 
2. Considering only your own “feeling best” rhythms, at what time would you get up if you were 
entirely free to plan your day? 
a. 5 am - 6:30 am 
b. 6:30 am - 7:45 am 
c. 7:45 am - 9:45 am 
d. 9:45 am - 11 am 
e. 11 am - 12 noon 
3. During the first half hour after awakening in the morning, how tired do you feel? 
a. Very tired 
b. Fairly tired 
c. Fairly refreshed 
d. Very refreshed 
4. At what time in the evening do you feel tired and in need of sleep?" 
a. 8 pm - 9 pm 
b. 9 pm - 10:15 pm 
c. 10:15 pm - 12:30 am 
d. 12:30 am - 1:45 am 
e. 1:45 am - 3 am 
5. At what time of the day do you think that you reach your “feeling best” peak? 
a. 10 pm - 5 am 
b. 5 am - 8 am 
c. 8 am - 10 am 
d. 10 am – 5 pm 
e. 5 pm – 10 pm 
 
 
 
 

59 
Daily Fatigue Survey 
 
 
 
 
 
 
 
 
 
 
 

60 
Weekly Survey 
PROMIS Fatigue Short Form 4a 
 
 
“How is your experience with the app?” questionnaire 
 
 
 
 
 
 
 

61 
Sleep aid usage survey 
 
 
 
Weekly travel questionnaire: 
 
1. Did you travel across time zones this week?" 
 
 
 

62 
APPENDIX D: REFERENCES 
 
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A. Parker, Susan Lawton, Paul Desan, and Lianqi Liu. 2012. “Light Treatment Prevents Fatigue 
in Women Undergoing Chemotherapy for Breast Cancer.” Supportive Care in Cancer: Official 
Journal of the Multinational Association of Supportive Care in Cancer 20 (6): 1211–19. 
 
Bowman, Clark; Huang, Yitong; Walch, Olivia; Fang, Yu; Frank, Elena; Goldstein, Cathy; 
Sen,Srijan; and  
Daniel B. Forger. “Characterizing the Human Heart Rate Circadian Pacemaker through Widely 
Available Wearable Devices.” In preparation.  
 
Burkhart, Kimberly, and James R. Phelps. 2009. “Amber Lenses to Block Blue Light and 
Improve Sleep: A Randomized Trial.” Chronobiology International 26 (8): 1602–12. 
 
Eckel-Mahan, Kristin, and Paolo Sassone-Corsi. 2013. “Metabolism and the Circadian Clock 
Converge.” Physiological Reviews 93 (1): 107–35. 
 
Huang, Yitong; Mayer, Caleb; Cheng, Philip; Siddula, Alankrita ; Burgess, Helen; Drake, 
Christopher; Goldstein, Cathy; Walch, Olivia; Forger, Daniel. “Predicting circadian phase across 
populations: a comparison of mathematical models and wearable devices.” In revision at Sleep. 
 
Jeste, Neelum, Lianqi Liu, Michelle Rissling, Vera Trofimenko, Loki Natarajan, Barbara A. 
Parker, and Sonia Ancoli-Israel. 2013. “Prevention of Quality-of-Life Deterioration with Light 
Therapy Is Associated with Changes in Fatigue in Women with Breast Cancer Undergoing 
Chemotherapy.” Quality of Life Research: An International Journal of Quality of Life Aspects of 
Treatment, Care and Rehabilitation 22 (6): 1239–44. 
 
Lely, Stéphanie van der, Silvia Frey, Corrado Garbazza, Anna Wirz-Justice, Oskar G. Jenni, 
Roland Steiner, Stefan Wolf, Christian Cajochen, Vivien Bromundt, and Christina Schmidt. 
2015. “Blue Blocker Glasses as a Countermeasure for Alerting Effects of Evening Light-Emitting 
Diode Screen Exposure in Male Teenagers.” The Journal of Adolescent Health: Official 
Publication of the Society for Adolescent Medicine 56 (1): 113–19. 
 
McClung, Colleen A. 2013. “How Might Circadian Rhythms Control Mood? Let Me Count the 
Ways.” Biological Psychiatry 74 (4): 242–49. 
 
Neikrug, Ariel B., Michelle Rissling, Vera Trofimenko, Lianqi Liu, Loki Natarajan, Susan Lawton, 
Barbara A. Parker, and Sonia Ancoli-Israel. 2012. “Bright Light Therapy Protects Women from 
Circadian Rhythm Desynchronization during Chemotherapy for Breast Cancer.” Behavioral 
Sleep Medicine 10 (3): 202–16. 
 

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Paganelli, Roberto, Claudia Petrarca, and Mario Di Gioacchino. 2018. “Biological Clocks: Their 
Relevance to Immune-Allergic Diseases.” Clinical and Molecular Allergy: CMA 16 (January): 1. 
 
Parsons, M. J., T. E. Moffitt, A. M. Gregory, S. Goldman-Mellor, P. M. Nolan, R. Poulton, and A. 
Caspi. 2015. “Social Jetlag, Obesity and Metabolic Disorder: Investigation in a Cohort Study.” 
International Journal of Obesity. https://doi.org/10.1038/ijo.2014.201. 
 
Phillips, A. J. K., and P. A. Robinson. 2007. “A Quantitative Model of Sleep-Wake Dynamics 
Based on the Physiology of the Brainstem Ascending Arousal System.” Journal of Biological 
Rhythms 22 (2): 167–79. 
 
Stone, Julia E., Xavier L. Aubert, Henning Maass, Andrew J. K. Phillips, Michelle Magee, Mark 
E. Howard, Steven W. Lockley, Shantha M. W. Rajaratnam, and Tracey L. Sletten. 2019. 
“Application of a Limit-Cycle Oscillator Model for Prediction of Circadian Phase in Rotating Night 
Shift Workers.” Scientific Reports 9 (1): 11032. 
 
Roenneberg, Till, Karla V. Allebrandt, Martha Merrow, and Céline Vetter. 2012. “Social Jetlag 
and Obesity.” Current Biology: CB 22 (10): 939–43. 
 
Wittmann, Marc, Jenny Dinich, Martha Merrow, and Till Roenneberg. 2006. “Social Jetlag: 
Misalignment of Biological and Social Time.” Chronobiology International 23 (1-2): 497–509.  
 
Woelders, Tom, Domien G. M. Beersma, Marijke C. M. Gordijn, Roelof A. Hut, and Emma J. 
Wams. 2017. “Daily Light Exposure Patterns Reveal Phase and Period of the Human Circadian 
Clock.” Journal of Biological Rhythms 32 (3): 274–86.