Validation of SHADE a Mobile Technology for Monitoring of Ultraviolet Exposure
Phase: NA
Conditions: Skin Cancer, Actinic Keratoses, Ultraviolet-Induced Change in Normal Skin, Behavior, Health, Behavior, Risk Reduction
Sponsor: Weill Medical College of Cornell University

 
 
IRB Protocol Number: 1609017593  
Clinicaltrials.gov ID: NCT03315286  
NIH/NCI  contract: HHSN261201700005C 
Study design, Procedures and Statistical 
 Analysis Plan (SAP): 6/21/2017 
  
Title: Validation of SHADE a Mobile Technology for Monitoring of Ultraviolet Exposure 
Coordinating Center: Weill Cornell Medical College, Department of Dermatology 
Collaborating Sponsor: YouV Labs, Inc. d/b/a Shade 
  
IRB Protocol Version and Date: Version 3: 08/14/2018 
Original, Version 1 dated June 21st, 2017 
Amendment 1: 4/28/2018 – Updating the CRF to include a page for patients to 
document the medication they are currently taking, to change the order of documents 
within the CRF to assist with filing and to update the inclusion/exclusion criteria on the 
CRF to reflect the IRB 
 
 
 

 
p.2 
 
Table of Contents 
LIST OF ABBREVIATIONS 
7 
STATEMENT OF COMPLIANCE 
7 
PROTOCOL SUMMARY 
8 
SCHEMATIC OF STUDY DESIGN 
9 
1 
KEY ROLES 
9 
2  
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE 
10 
2.1 
Background Information 
10 
2.2 
Rationale 
10 
2.3 
Potential Risks and Benefits 
11 
2.3.1 
Known Potential Risks 
11 
2.3.2 
Known Potential Benefits 
11 
3 
OBJECTIVES AND PURPOSE 
11 
4 
STUDY DESIGN AND ENDPOINTS 
12 
4.1 
Description of the Study Design 
12 
4.2.1 
Primary Endpoint 
12 
4.2.2 
Secondary Endpoints 
12 
4.2.3 
Exploratory Endpoints 
13 
5 
STUDY ENROLLMENT AND WITHDRAWAL 
13 
5.1 
Participant Inclusion Criteria 
13 
5.2 
Participant Exclusion Criteria 
13 
5.3 
Strategies for Recruitment and Retention 
13 
5.4 
Participant Withdrawal or termination 
14 
5.4.1 
Reasons for Withdrawal or Termination 
14 
5.4.2 
Handling of Participant Withdrawals or termination 
14 
5.5 
Premature Termination or Suspension of Study 
14 
6 
STUDY AGENT 
14 
6.1 
Study Agent(s) and Control Description 
14 
6.1.1 
Acquisition 
14 
6.1.2 
Appearance, Packaging, and Labeling 
14 
Application User Interface 
15 
Alarms 
17 
6.1.3 
Product Storage and Stability 
17 

 
p.3 
 
6.1.4 
Preparation 
17 
6.1.5 
Dosing and Administration 
17 
6.1.6 
Route of Administration 
17 
6.1.7 
Starting Dose and Dose Escalation Schedule 
17 
6.1.8 
Dose Adjustments/Modifications/Delays 
17 
6.1.9 
Duration of Therapy 
17 
6.1.10 
Tracking of Dose 
17 
6.1.11 
Device Specific Considerations 
17 
6.2 
Study agent Accountability Procedures 
18 
7 
STUDY PROCEDURES AND SCHEDULE 
18 
7.1 
Study Procedures/Evaluations 
18 
7.1.1 
Study specific procedures 
18 
7.1.2 
Standard of care study procedures 
18 
7.2 
Laboratory Procedures/Evaluations 
19 
7.2.1 
Clinical Laboratory Evaluations 
19 
7.2.2 
Other Assays or Procedures 
19 
7.2.3 
Specimen Preparation, Handling, and Storage 
19 
7.2.4 
Specimen Shipment 
19 
7.3 
Study Schedule 
19 
7.3.1 
Screening 
19 
7.3.2 
Enrollment/Baseline 
20 
7.3.3 
Follow-up 
20 
7.3.4 
Final Study Visit 
20 
7.3.5 
Early Termination Visit 
20 
7.3.7 
Schedule of Events Table 
21 
7.4 
Justification for Sensitive Procedures 
21 
7.5 
Concomitant Medications, Treatments, and Procedures 
21 
7.5.1 
Precautionary Medications, Treatments, and Procedures 
21 
7.6 
Prohibited Medications, Treatments, and Procedures 
22 
7.7 
Prophylactic Medications, Treatments, and Procedures 
22 
7.8 
Rescue Medications, Treatments, and Procedures 
22 
7.9 
Participant Access to Study Agent At Study Closure 
22 
8 
ASSESSMENT OF SAFETY 
22 
8.1 
Specification of Safety Parameters 
22 

 
p.4 
 
8.1.1 
Definition of Adverse Events (AE) 
22 
8.1.2 
Definition of Serious Adverse Events (SAE) 
22 
8.1.3 
Definition of Unanticipated Problems (UP) 
23 
8.2 
Classification of an Adverse Event 
23 
8.2.1 
Severity of Event 
23 
8.2.2 
Relationship to Study Agent 
23 
8.2.3 
Expectedness 
23 
8.3 
Time Period and Frequency for Event Assessment and Follow-Up 
24 
8.4 
Reporting Procedures 
24 
8.4.1 
Adverse Event Reporting 
25 
8.4.2 
Serious Adverse Event Reporting 
25 
8.4.3 
Unanticipated Problem Reporting 
25 
8.4.4 
Events of Special Interest 
25 
8.4.5 
Reporting of Pregnancy 
25 
8.5 
Study Halting Rules 
25 
8.6 
Safety Oversight 
25 
9 
CLINICAL MONITORING 
26 
10 
STATISTICAL CONSIDERATIONS 
26 
10.1 
Statistical and Analytical Plans 
26 
10.2 
Statistical Hypotheses 
26 
10.3 
Analysis Datasets 
26 
10.4 
Description of Statistical Methods 
26 
10.4.1 
General Approach 
27 
10.4.2 
Analysis of the Primary Efficacy Endpoint(s) 
27 
#1 (Primary): Quantify the impact of Shade on the cumulative number of new actinic 
keratoses developed over the study period. 
27 
10.4.3 
Analysis of the Secondary Endpoint(s) 
27 
#2 (Secondary): Quantify the impact of Shade on the numbers of new AK’s observed at 
the final visit 
27 
#3 (Secondary): Quantify the impact of Shade on the numbers of new cutaneous 
squamous cell carcinomas confirmed by histology during follow up over the study period.
 
27 
#4 (Secondary): Quantify the impact of Shade on the number of new nonmelanoma skin 
cancers (basal cell carcinomas, cutaneous squamous cell carcinomas) confirmed by 
histology over the study period. 
28 

 
p.5 
 
#5 (Secondary): Test the correlation between measured UV exposure and the number of 
new actinic keratoses. 
28 
#6 (Secondary): Test the correlation between measured UV exposure and the number of 
new nonmelanoma skin cancers. 
28 
#7 (Secondary): Quantify the impact of Shade on keratinocyte DNA damage approximated 
by the measurement of cyclobutane pyrimidine dimers by ELISA. 
28 
#8 (Secondary): Quantify the impact of Shade on patients’ quality of life assessed by 
PROMIS (Patient-Reported Outcomes Measurement Information System) in the fields of 
anxiety (Mental Health), depression (Mental Health), and Ability to Participate in Social 
Roles and Activities (Social health). 
28 
#9 (Secondary): Assess sensor usage in the study patient population and compare 
characteristics of observant vs non-observant and responsive vs non-responsive patients.
 
29 
#10 (Secondary): Assess feasibility of the intervention for kidney transplant recipients 
through report of their rates for compliance and retention. 
29 
10.4.4 
Safety Analyses 
29 
10.4.5 
Adherence and Retention Analyses 
29 
10.4.6  
Baseline Descriptive Statistics 
29 
10.4.7 
Planned Interim Analyses 
30 
10.4.7.1 
Safety Review 
30 
10.4.7.2 
Efficacy Review 
30 
10.4.8 
Additional Sub-Group Analyses 
30 
10.4.9 
Multiple Comparison/Multiplicity 
30 
10.4.10 
Tabulation of Individual Response Data 
30 
10.4.11 
Exploratory Analyses 
31 
10.5 
Sample Size 
31 
10.6 
Measures to Minimize Bias 
32 
10.6.1 
Enrollment/ Randomization/ Masking Procedures 
32 
10.6.2 
Evaluation of Success of Blinding 
32 
10.6.3 
Breaking the Study Blind/Participant Code 
32 
11 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 
33 
12 
QUALITY ASSURANCE AND QUALITY CONTROL 
33 
13 
ETHICS/PROTECTION OF HUMAN SUBJECTS 
33 
13.1 
Ethical Standard 
33 
13.2 
Institutional Review Board 
33 
13.3 
Informed Consent Process 
33 

 
p.6 
 
13.3.1 
Consent/assent and Other Informational Documents Provided to Participants 
33 
13.3.2 
Consent Procedures and Documentation 
33 
13.4 
Participant and data Confidentiality 
33 
13.4.1 
Research Use of Stored Human Samples,Specimens or Data 
34 
13.5 
Future Use of Stored Specimens 
34 
14 
DATA HANDLING AND RECORD KEEPING 
34 
14.1 
Data Collection and Management Responsibilities 
34 
14.2 
Study Records Retention 
34 
14.3 
Protocol Deviations 
34 
14.4 
Publication and Data Sharing Policy 
34 
15 
STUDY ADMINISTRATION 
35 
15.1 
Study Leadership 
35 
16 
CONFLICT OF INTEREST POLICY 
35 
17 
REVISION HISTORY 
35 
17.1 Versions 
35 
17.2 Managing Protocol Changes for continuing subjects 
36 
APPENDIX 1  User Instructions 
37 
 
 
 

 
 
1300 York Avenue, New York, NY 10065
LIST OF ABBREVIATIONS 
 
AE 
Adverse Event 
AK 
Actinic Keratosis 
BT 
Bluetooth low energy 
CAT 
Computer Adaptive Test 
CFR 
Code of Federal Regulations 
CPD 
cyclopyrimidine dimer 
CRF 
Case Report Form 
ELISA 
Enzyme Linked ImmunoSorbent Assay 
IC 
Informed Consent 
ICF 
Informed Consent Form 
IRB 
Institutional Review Board 
IS 
Immunosuppressive 
LN2 
Liquid nitrogen 
NCI 
National Cancer Institute 
NIH 
National Institutes of Health 
PI 
Principal Investigator 
NMSC 
Non-Melanoma Skin Cancer 
PROMIS 
Patient Reported Outcome Measurement Information System 
SAE 
Significant Adverse Event 
SCC 
Squamous Cell Carcinoma 
SPF 
Sun Protection Factor 
UV 
Ultraviolet Light 
UVI 
Ultraviolet Index 
WC 
Weill Cornell Medical College 
 
STATEMENT OF COMPLIANCE 
The trial will be conducted in accordance with the ICH E6, the Code of Federal Regulations on the Protection of Human 
Subjects (45 CFR Part 46), and the Terms of Subcontract to Weill Cornell from the prime contract HHSN261201700005C 
to YouV Labs, Inc. The Principal Investigator will assure that no deviation from, or changes to the protocol will take place 
without prior agreement from the sponsor and documented approval from the Institutional Review Board (IRB), except 
where necessary to eliminate an immediate hazard(s) to the trial participants. All personnel involved in the conduct of 
this study have completed Human Subjects Protection Training. 
I agree to ensure that all staff members involved in the conduct of this study are informed about their obligations in 
meeting the above commitments. 
 
Principal Investigator: George I. Varghese, M.D. 
 
Signed: _____________________________________ Date: ______________ 
 
 

 
 
8
PROTOCOL SUMMARY 
Title: 
Validation of shade, a wearable ultraviolet light monitor, for reduction of actinic 
keratosis 
Summary: 
The incidence of non-melanoma skin cancers, due to increased ultraviolet (UV) 
exposure, has increased by 300% over the past 2 decades. The innovative UV 
sensor, Shade, is designed to help people manage their UV exposure by 
quantifying their UV exposure levels through a linked smartphone application. In 
order to validate the effectiveness of Shade, we propose conducting a study 
communicating the level of UV exposure and correlating it with the development 
of actinic keratosis (AK), a precancerous lesion of the skin. We will recruit patients 
with multiple AK¿s.   We will include renal transplant patients as this population 
develop AKs as well.  We will evaluate the UV monitor's effectiveness in decreasing 
the number of AKs over a summer. This randomized partially blinded study will 
recruit 120 patients with a recent history of AKs and evaluate the incidence of new 
AKs after one summer. We will perform a control versus study group analysis. Half 
of the subjects (study group) will be randomly assigned to use the sensor along 
with its smartphone application, while the other half (control group) will receive 
standard of care treatment involving counseling to avoid sun exposure. Subjects 
will have regular standard of care visits with the dermatologist who will follow the 
number of actinic keratosis via clinical exam and photography. The primary 
outcome will be a statistically significant reduction by at least 25% of the 
cumulative number of newly occurred AK lesions between the control and the 
study group over one summer, counted at enrollment and follow-up. In subjects at 
one study site, skin DNA damage will also be assessed using cyclobutane 
pyrimidine dimers (CPD) levels measured by ELISA in both sun exposed (nose) and 
sun protected skin (buccal mucosa) in both the study and control groups. 
Secondary outcomes will look at clinical decreases by 25% in CPD levels after using 
the sensor. 
 
 
 

 
 
9
SCHEMATIC OF STUDY DESIGN 
 
 
 
1 
KEY ROLES 
 
Weill Cornell Medical College 
 
Name 
Title 
Degrees 
Unit 
Role 
George I. Varghese Assistant Prof. 
M.D. 
Dermatology 
Principal Investigator 
Jonathan H. Zippin Assistant Prof.-
Clinical 
M.D., Ph.D. 
Dermatology 
Protocol design, laboratory 
analytics 
Darshana Dadhania Assoc. Prof., 
Assist. Dir. 
M.D., M.S. 
Nephrology 
Rogosin Institute 
Co-investigator 
 
Melissa Platt 
Physician Assistant MMS 
Dermatology 
Study coordinator 
Susan Koshy 
Administrator 
M.B.A. 
Dermatology 
Administrative Contact 
The following physicians are associated with the study mainly with the role of recruiting appropriate subjects. 
Clinical Co-Investigators 
Name 
Title 
Degrees 
Unit 
Role 
Meredith Anull 
Associate Prof. –
Research 
Pharm D. 
Surgery 
Screen subjects 
Choli Hartono 
  
M.D. 
Nephrology & Hypertension 
Screen subjects 
Joseph Jorizzo 
Prof. – Clinical 
M.D. 
Dermatology 
Screen subjects 
Sandip Kapur 
Prof. 
M.D. 
Surgery 
Screen subjects 
Jim Kim 
Assistant Prof. 
M.D. 
Surgery 
Screen subjects 
John Richard Lee 
Assistant Prof. 
M.D. 
Nephrology & Hypertension 
Screen subjects 
Jun Lee 
  
M.D. 
Nephrology & Hypertension 
Screen subjects 
Kira Minkis 
Assistant Prof. 
Ph.D., M.D. 
Dermatology 
Screen subjects 
Patrice Robin 
Powell 
Staff Associate 
B.S., M.S. 
Nursing 
Screen subjects 
David Serur 
  
M.D. 
Nephrology & Hypertension 
Screen subjects 

 
 
10 
Manikkam 
Suthanthiram 
Prof. 
M.B., B.S. 
Nephrology & Hypertension 
Data analysis 
Muthukumar 
Thangamani 
Associate Prof. M.D., M.B., 
B.S. 
Nephrology & Hypertension 
Screen subjects 
  
 
2  
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE  
 
2.1 
BACKGROUND INFORMATION  
The incidence of non-melanoma skin cancers (NMSC) has increased by 300% over the past 2 decades. Increasing 
ultraviolet (UV) exposure from the sun has been largely recognized as the primary risk factor for the development of 
these NMSCs. Actinic keratosis (AK) is a frequent pre-cancerous skin lesion caused by damage from ultraviolet exposure. 
Without treatment, 1-2% of these lesions evolve into squamous cell carcinoma (SCC)[1].  Therefore, the number of AKs 
reflects the effect of UV exposure and the risk for SCC. The burden of SCC is especially high in immunosupressed patients 
such as transplant patients who are at high risk of skin cancer because of their immunosuppressive medications. 
Morbidity/mortality of SCC in transplant patients can be as high as 25%[2]. Sunscreen use has been demonstrated to 
decrease the number of actinic keratosis from 24%-44%[3]. However, despite, counseling and protection, UV exposure 
can still be difficult to control due to a variety of factors including the lack of real time UV intensity monitoring, 
incomplete adherence to preventive measures, and misuse of sunscreen.  
 
2.2 
RATIONALE  
 
The incidence of non-melanoma skin cancers (NMSC) has increased by 300% over the past 2 decades. 
Increasing ultraviolet (UV) exposure from the sun has been largely recognized as the primary risk factor for the 
development of these NMSCs. Actinic keratosis (AK) is a frequent pre-cancerous skin lesion caused by 
damage from ultraviolet exposure. Without treatment, 1-2% of these lesions evolve into squamous cell 
carcinoma (SCC)[1]. 
Therefore, the number of AKs reflects the effect of UV exposure and the risk for SCC. Transplant patients are 
at high risk of skin cancer because of the immunosuppressive medications required to 
prevent organ rejection. Morbidity/mortality of SCC in this patient population can be as high as 25%[2]. 
Sunscreen use has been demonstrated to decrease the number of actinic keratosis from 24%-44%[3]. However, 
despite, counseling and protection, UV exposure can still be difficult to assess and control due to a variety of 
factors including UV intensity, shade, the use of protective clothing and the amount of sunscreen used. A new 
innovative ultraviolet (UV) sensor, Shade, helps quantify daily UV exposure and can enable users to manage 
their UV exposure through alerts and self-reporting through a smartphone app. In order to validate the 
effectiveness of Shade, we propose conducting a study looking at amount of UV exposure and the 
development of actinic keratosis over a 12 month period in transplant patients with a history of AKs. The 
study protocol will be similar to the 2015 Chen et al. NEJM paper[4] which observed a difference between 11% 
and 20% between their study group (nicotinamide) and the control group (placebo) in the number 
of actinic keratoses at 3, 6, 9, and 12  months after randomization. In addition, we will test the effect of UV 
exposure on cyclobutane pyrimidine dimers (CPD). These are biological markers that are increased 
immediately with UV exposure in a dose dependent fashion. Measurement of CPD following the delivery of a 
known UV dose allows for a biological readout of UV effects. In addition, CPD levels represent an equilibrium 
between UV induced formation and DNA repair; therefore, they can also reflect chronic UV exposure[5]. The 

 
 
11 
control group will not wear a sensor. This choice of control group allows us to provide standard  of care advice 
to these subjects. The behavior change in the treatment group is expected to be a result of both the decision to 
engage with the device, for example by putting it on and opening the App as well as due to the knowledge of 
personal UV exposure reported by the device. We expect to gather information on the cumulative UV exposure 
of all subjects by using an ELISA assay for cyclopyridimine dimers (CPD) from photoexposed skin.  
 
References: 
1. Criscione, V. D. et al. Actinic keratoses: Natural history and risk of malignant transformation in the Veterans 
Affairs Topical Tretinoin Chemoprevention Trial. Cancer 115, 2523-2530 (2009).  
2. Zavos, G. et al. Nonmelanoma skin cancer after renal transplantation: a single-center experience 
in 1736 transplantations. Int. J. Dermatol. 50, 1496-1500 (2011).  
3. Thompson, S. C., Jolley, D. & Marks, R. Reduction of solar keratoses by regular sunscreen use. N. Engl. J. 
Med. 329, 1147-1151 (1993).  
4. Chen, A. C. et al. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. N. Engl. J. 
Med. 373, 1618-1626 (2015).  
5. Yamaguchi,Y. et al. Cyclobutane pyrimidine dimer formation and p53 production in human skin 
after repeated UV irradiation. Exp. Dermatol. 17, 916-924 (2008). 
 
2.3 
POTENTIAL RISKS AND BENEFITS  
 
2.3.1 KNOWN POTENTIAL RISKS  
This is a minimal risk study. All subjects will, over the duration of the study, have one dermatology visit and skin check 
beyond the standard of care. Subjects in the treatment group will have additional information and interaction on their 
UV exposure to help them make the choice to minimize such exposure. 
 
2.3.2 KNOWN POTENTIAL BENEFITS  
The incidence of non-melanoma skin cancers (NMSC) has increased by 300% over the past 2 decades. Vulnerable 
populations, such as transplant patients, have a 65 times higher risk for developing squamous cell carcinoma (SCC), and 
once diagnosed they have a far higher rate of developing metastases and higher mortality rate. Modification of UV 
exposure is difficult to teach because the rays are invisible, intuition about their intensity is demonstrably poor, and the 
ability to recollect exposure events is generally poor. In addition, a sudden medical change, such as immunosuppression 
following transplantation, can make some patients, especially skin types III-IV, become more susceptible to UV exposure 
and vulnerable due to limited knowledge of their daily UV requirement. The use of the UV sensor, Shade, is designed to 
help people manage their UV exposure by quantifying their UV exposure and alerting them of their levels through a 
smartphone app. The sensor is small, easy to use, and user friendly. Therefore, this device would provide an immediate 
benefit to study participants. In addition, if the study due to the use of Shade can demonstrate a 25% reduction in the 
levels of actinic keratosis (AK), and hence SCC risk, then we can extrapolate that the use of this device may decrease the 
morbidity and mortality of SCCs. In addition, by including a cohort of transplant patients, this study will help assess 
feasibility for groups at high-risk of SCC. 
 
3 
OBJECTIVES AND PURPOSE 
This study will evaluate the safety and effectiveness of Shade for the management of UV-induced skin complications and 
data collected from this study will be used to support the proposed indications for use. 
 
The purpose of this investigation is to demonstrate the safety and effectiveness of the Shade UV sensor and mobile 

 
 
12 
phone application product to reduce actinic keratosis. 
 
4 
STUDY DESIGN AND ENDPOINTS 
4.1 
DESCRIPTION OF THE STUDY DESIGN 
This randomized partially blinded study will recruit 120 patients with a history of actinic keratosis (AK) lesions. A control 
versus study group analysis will be performed where 50% of the subjects will be randomly assigned (balanced by 
Fitzpatrick skin type, separate randomization lists will be made for type I&II and types III-VI, at time of first visit subjects 
will be assigned to study or control group by giving them the next assignment on the appropriate list) to use the SHADE 
sensor and its app (study group), while 
the other 50% (control group) will receive standard of care UV  ounseling(placebo). Subjects will have 3 visits. The first 
and last visit will be standard of care visits at 0 month (enrollment), and the conclusion 
of their involvement. The second visit will be scheduled 3 months after the enrollment visit. The final visit will be 
scheduled be as soon as practical, but at least 3 months after  isit 2 and after September 30. On arrival at each visit, study 
personnel will pre-screen patients to ensure that the sensor is not visible to physician prior to examination, for example by 
placing it in their pocket. At each follow up visit, the number of actinic keratosis on the face and hands will be counted and 
photographed. They will be treated as per standard of care protocol with cryotherapy or curettage. General use of field 
therapies will not be permitted during the trial. Any lesions suspicious of 
non-melanoma or melanoma skin cancer will be photographed and biopsied as part of the standard of care algorithm. 
Cyclobutane pyrimidine dimers (CPD) levels will be measured by ELISA from exposed (cheek) and unexposed (buccal 
mucosa) skin scrapings collected at the first and 
last visit. For each patient, the CPD level from exposed skin will be  normalized to the sun protected CPD level measured 
from unexposed skin. We will compare the normalized CPD level of control versus study participants at each timepoint 
and  their average CPD change over time. 
We will then compare these levels with Shade UV measurements. Finally, patients will also answer questions in PROMIS 
(Patient-Reported Outcomes Measurement Information System) in the fields of anxiety, depression and ability to 
participate socially to gauge their attitudes toward the sensor 
4.2.1 PRIMARY ENDPOINT 
1. Quantify the impact of Shade on the cumulative number of new actinic keratoses developed over the study 
period. 
4.2.2 SECONDARY ENDPOINTS 
2. Quantify the impact of Shade on the cumulative number of new actinic keratoses observed at the final study 
visit. 
3. Quantify the impact of Shade on the cumulative numbers of new cutaneous squamous cell carcinomas 
confirmed by histology over the study period. 
4.  Quantify the impact of Shade on the cumulative number of new nonmelanoma skin cancers (basal cell 
carcinomas, cutaneous squamous cell carcinomas) confirmed by histology over  the study period. 
5. Test the correlation between measured UV exposure and the number of new actinic keratoses. 
6. Test the correlation between measured UV exposure and the number of new nonmelanoma skin cancers. 
7. Quantify the impact of Shade on keratinocyte DNA damage approximated by the measurement of cyclobutane 
pyrimidine dimers by ELISA. 
8.  Quantify the impact of Shade on patients’ quality of life assessed by PROMIS (Patient-Reported Outcomes 
Measurement Information System) in the fields of anxiety (Mental Health), depression (Mental Health), and 
Ability to Participate in Social Roles and Activities (Social health). 
9.  Assess sensor usage in the study patient population and compare characteristics of observant vs. non-
observant and responsive vs. non-responsive patients. 

 
 
13 
10. Assess feasibility of the intervention for kidney transplant recipients through report of their rates for 
compliance and retention. 
 
4.2.3 EXPLORATORY ENDPOINTS 
None 
 
5 
STUDY ENROLLMENT AND WITHDRAWAL 
 
5.1 
PARTICIPANT INCLUSION CRITERIA 
1. Open to men and women of all skin types between the ages of 18-80 
2. Prior history of actinic keratosis. Specifically,  
a. Was given a diagnosis of actinic keratosis in the past year and/or has had a history of 5 or more actinic 
keratosis in the past 5 years. 
b. If the patient has received a kidney transplant, the date of transplant  should be longer than 6 months 
and should be currently on transplant immunosuppression therapy. 
3. Has a smartphone that support Bluetooth low energy using a compatible operating system (iOS 8+ or Android 4+) 
4. Able to commit to dermatology visits three times during the study period. 
5.2 
PARTICIPANT EXCLUSION CRITERIA 
1. Has received UV therapy in the past 6 months.  
2. Has had field therapy (e.g., entire face or scalp) for the treatment of actinic keratosis (e.g. topical imiquimod, 5-
fluorouracil, photodynamic therapy) in the past 3 months. 
3. Patient's work and or their lifestyle is not compatible with wearing a UV sensor. 
4. Has difficulty controlling their own UV exposure (nursing home, long term hospitalization). 
5. Has a medical condition judged incompatible with the study by the enrolling physician including the presence of 
an ICD or an existing plan for an extended inpatient treatment. 
6. Is an employee or direct relative of an employee of the investigational site or study sponsor. 
7. Must have a smartphone that is compatible with the Shade app and is comfortable using a new app (the Shade 
app) on their smartphone. 
a. Jitterbug and the Samsung Galaxy J3 are not compatible with the app 
Ongoing exclusion criteria: 
If subject is not able to meet the commitment to ongoing visits or their answer to the exclusion criteria questions 
changes the subject will be removed from the study. If the change in status is temporary, less than three months, the 
decision to remove a subject from the study will be at the discretion of the PI. 
 
5.3 
STRATEGIES FOR RECRUITMENT AND RETENTION 
Recruiting will be performed mainly at Weill Cornell Medical Center which is closely affiliated with HSS and MSKCC 
providing additional access to patients.  Dermatologists at Weill Cornell Medicine will be primary sources of referral 
within the department.  In addition, Darshana Dadhania MD, MS, Transplant Nephrologist and Medical Director, 
Histocompatible Transplant Program will help recruit transplant patients from their transplant center. 
Each patient regarding of study arm will receive $50 for each visit for a maximum of 3 visits.  Patients in the study arm 
who use the device on a consistent basis (>40% of days per month with no gaps longer than seven days) will receive $20 
per month for up to 12 months.  
The sponsor may offer additional prize based motivations for use which will not exceed $1,000 for any single subject in a 
given month. 
 

 
 
14 
5.4 
PARTICIPANT WITHDRAWAL OR TERMINATION 
Participants may withdraw for any reason during the study. 
5.4.1 REASONS FOR WITHDRAWAL OR TERMINATION 
Participants who can not comply with the requirement for quarterly visits will be dropped from the study. 
5.4.2 HANDLING OF PARTICIPANT WITHDRAWALS OR TERMINATION 
Subject compensation will not be affected by study withdrawal or termination. Each endpoint will be analyzed using only 
data for which there is a complete data set relevant to that analysis. 
 
5.5 
PREMATURE TERMINATION OR SUSPENSION OF STUDY 
Study will be terminated if the PI or IRB feels that the rate of adverse events warrants termination or suspension. Study 
will be suspended if recruiting targets are not met, specifically, if fewer than 70 subjects are recruited at the end of three 
months, the study will be suspended. 
  
6 
STUDY AGENT 
 
6.1 
STUDY AGENT(S) AND CONTROL DESCRIPTION 
 
6.1.1 ACQUISITION 
Shade sensors will be delivered to the study coordinator by the sponsor. 
 
6.1.2 APPEARANCE, PACKAGING, AND LABELING 
Device: 
Figure 6.1.2.1 Shade device 
 
 
Specifications : 
Size: 1.58” diameter, 0.49” height 
Weight: 0.48 oz 
Battery Life: 4 days (from a full charge); low battery notifications[JC3]  
Magnet: Neodynium 
Notifications: Light and vibrations 
Connectivity: Bluetooth Low Energy 
Compatibility: iPhone 5 and above | Android 4.4 and above 
Charging: Micro-USB cable included 
Recharge time: 1.5 hours 

 
 
15 
Materials: plastic case 
UV Measurement Sensitivity: 
Wavelength range: 280-400 nm erythemally weighted 
Limit of detection: 0.01 UVI. The UV Index is the unit of intensity recommended by the World Health 
Organization’s INTERSUN working group. 
Maximum UV: 16 UVI 
Dosimetry: accuracy and precision 1.5 J/cm2 
 
Software 
The software consists of firmware in the device, a mobile application, and backend servers to support it. The mobile 
application has been designed based on user feedback to highlight issues important to people concerned about their 
exposure to UV light. Specifically it reports the devices estimate of the current UV Index as well as the user’s cumulative 
exposure for the day in units of J/m2. The software keeps a history of the exposure and allows the user to set a daily limit 
of UV exposure at which they will receive alerts. The backend manages each user account and stores their historical data 
to allow retrieval and analysis.  
When the device is charged, it indicates connection by momentarily glowing green, then it indicates charging by glowing 
red. When the device is fully charged, and connected to power, it indicates green. Once powered up, it sends a Bluetooth 
(BT) signal advertises its presence. In this state it can be paired to a phone using app set to the pairing function. If the 
device is covered, for example by a jacket, it provides a vibration alert and a mobile phone alert periodically until it is 
uncovered. 
 
APPLICATION USER INTERFACE 
  
When the device is first activated and paired with a new mobile device an onboarding protocol is run through (see 
Attachment 4). The application contains five tabs:  dashboard, history, symptoms, chat, and settings. 
Dashboard: 
The dashboard allows the user to visualize their current exposure, total exposure for the day, as well as an estimate of 
the time remaining during the day that the user can be exposed to the sun at current intensity levels. From the 
dashboard the user is also capable of logging their sunscreen (SPF) usage during the day.  For a period of time after 
logging the sunscreen (90 minutes) the reported UV dose is reduced by an amount corresponding to the reported SPF. 
The history tabs allows the user to visualize their daily UV exposure over the last 12 days. 
Symptoms: 
From the symptom tab the user is capable of inputting their symptoms with a timestamp that could provide useful 
feedback to the user on the correlation between symptoms and UV exposure. 
Chat: 

 
 
16 
Chat enables users to receive real-time feedback from the company regarding the Shade device and the mobile 
application usage. This is also a platform for providing feedback to the company, application troubleshooting, or any 
other questions, comments, or queries the users may have. 
Settings: 
The user can manage general application settings from this tab. For example: it is from this tab that a user can pair their 
Shade sensor to their mobile phone. 
Figure 2-3: Shade Application Key Screenshots 
 
 

 
 
17 
ALARMS 
In use, the device uses two methods to notify the user. (1) shade device vibration and (2) mobile phone alerts. 
Notifications are triggered by the following events: 
1) 
UV exposure reaches a 20 percent interval of the user’s specified daily limit. 
2) 
The sensor has been covered making it insensitive to UV. 
Additionally, the user can trigger both alert methods by covering the proximity sensor with their finger or the vibration 
alert by triple tapping the battery indicator on the app’s dashboard screen (Figure 2-3, first screen). 
 
Packaging: 
The device and user guide are supplied in a white  4.7 x 6.25 x 1.5 inch cardboard box labeled ‘Shade.’ 
 
Labeling: 
User instructions are attached as Appendix 1. The device packaging will be labeled with a sticker indicating ‘For 
Investigational Use Only.’ 
 
6.1.3 PRODUCT STORAGE AND STABILITY 
Store indoors (0-40°C). Product is stable indefinitely. 
  
6.1.4 PREPARATION 
Prior to use, subject must install a device specific application on their mobile phone. The Study Coordinator or a sponsor 
representative will assist them in this process. As part of the use of this application the user enters an email address. 
Subjects will not enter their own email address and will instead enter a non-functional study email address assigned by 
the study coordinator. See data management sections for details. 
 
6.1.5 DOSING AND ADMINISTRATION 
N/A 
 
6.1.6 ROUTE OF ADMINISTRATION 
N/A 
 
6.1.7 STARTING DOSE AND DOSE ESCALATION SCHEDULE 
N/A 
 
6.1.8 DOSE ADJUSTMENTS/MODIFICATIONS/DELAYS 
N/A 
 
6.1.9 DURATION OF THERAPY 
9-12 months 
 
6.1.10 TRACKING OF DOSE 
N/A 
 
6.1.11 DEVICE SPECIFIC CONSIDERATIONS 
The device is worn externally, magnetically affixed to the subject’s clothing. The device vibrates to communicate to 

 
 
18 
subjects when they have accumulated UV dosage and when the device is covered. The mobile application provides 
similar alerts with accompanying explanatory text. 
6.2 
STUDY AGENT ACCOUNTABILITY PROCEDURES 
Product will be delivered to the study coordinator by the sponsor. The delivery slip will include a receipt with a list of 
device serial numbers. The study coordinator will acknowledge receipt and return the signed packaging invoice to 
sponsor. Supplies should be kept in a secure area.  
The study coordinator will maintain a device disposition table with the columns: S/N, Subject ID, Date dispensed, 
Dispensed by (name of study personnel), Date returned, Returned to (name of study personnel), Comments (e.g. 
working/broken/lost). The device disposition table is considered confidential and should be viewed only by the study 
coordinator and study monitors, physicians must remain blinded to the device disposition table. 
7 
STUDY PROCEDURES AND SCHEDULE 
7.1 
STUDY PROCEDURES/EVALUATIONS 
7.1.1 STUDY SPECIFIC PROCEDURES  
Cyclobutane pyrimidine dimers (CPD) levels will be measured by ELISA from exposed (cheek) and unexposed (buccal 
mucosa) skin scrapings. The area from which the cutaneous scraping is collected will be cleaned with an alcohol swab. 
Using a 15 blade, the epithelial cell will be lightly scraped on the cutaneous cheek and the buccal mucosa.  The skin cells 
will be placed in an eppendorf tube and put on ice. These eppendorf tubes will be transported to a research lab where 
ELISA testing will be performed by a technician. For each patient, the CPD level from exposed skin will be normalized to 
the sun protected CPD level measured from unexposed skin. A physician will compare the normalized CPD level of 
control versus study participants at each timepoint and their average CPD change over time.   
 
Clinical counting of AKs: The physician will identify actinic keratosis based on a visual and textural examination. If the 
actinic keratosis is large and continuous it will be counted as one actinic keratosis.  The actinic keratosis will then be 
circled and photographed. The photograph will be available in the patient medical record but will not be copied to the 
CRF. The areas that are identified during the visit will be treated. Photos will be taken at each visit. At subsequent visits, 
the previous visits, photos will be reevaluated to prevent double counting. All lesions suspected of malignancy will be 
biopsied and subject to histological examination. These lesions will be reclassified according to histology diagnosis if 
necessary. 
 
7.1.2 STANDARD OF CARE STUDY PROCEDURES  
Skin Check 
A standard skin examination will be performed by a dermatologist. The scalp, face, mucous membranes, chest, back 
abdomen, arms, legs, genitalia, digits will be examined at the first and last visit (V1 and V3). A focused examination of the 
scalp, face, hands and any other pertinent areas will be performed at the second visit (V2).   
 
Treatment of actinic keratosis 
When an actinic keratosis (AK) is identified, the area will be identified with a marking pen. The areas will be 
photographed and the photos attached to the patient’s chart. The areas will then be treated with a destructive modality. 
The most common technique that will be employed is cryotherapy with liquid nitrogen or curettage of the actinic 
keratosis. Any AK that is suspicious or resistant to treatment will be biopsied via shave technique. Shave technique is 
described as the removal of entire lesion using a dermablade with 1-2 mm margins. 
 
Ultraviolet Exposure Counseling 
The dermatologist will make the following recommendations to each patient having a skin cancer screening.  

 
 
19 
-Always use a sunscreen product with a minimum SPF of 30 when going outdoors, even on a cloudy day. 
-Avoid exposure to the sun during the peak hours between 10 AM and 4 PM and to stay in the shade when possible. 
-Wear protective eyewear during peak sun hours.   
-If sunscreen is not available, always wear protective clothing, such as long-sleeved shirts and pants, wide-brimmed hats, 
and sunglasses with UV protection. 
-Routinely examine skin at least once a month for any visible changes or changing lesions. 
-Avoid the use of tanning products or tanning beds. 
-See your dermatologist yearly for a professional skin exam 
 
7.2 
LABORATORY PROCEDURES/EVALUATIONS 
 
7.2.1 CLINICAL LABORATORY EVALUATIONS  
7.2.1.1 CPD Assay 
The CPD Assay will employ a commercial ELISA based test. It will be carried out following a detailed written protocol 
developed by the investigating laboratory based on the manufacturer’s published procedure. The validation of this 
procedure will be presented by the laboratory manager and this validation along with the protocol will be reviewed by 
the PI and the sponsor. Once implemented, the procedure will be carried out on clinical samples with attention to good 
laboratory practice. 
 
7.2.2 OTHER ASSAYS OR PROCEDURES 
N/A 
 
7.2.3 SPECIMEN PREPARATION, HANDLING, AND STORAGE 
Skin scraping will be collected as described in 7.1.1 Study specific procedures. 
The tubes containing the samples and any secondary containers will be labeled by:  ###-S and visit number 
- study subject number ### 
- site S which is one of  B (buccal mucosa) or S (skin) 
- visit number # = 1,2,3  
The specimens will be stored in liquid nitrogen or at -80°C in the clinic in a labeled separate container for materials for 
this study. Samples will remain in this container until collected by laboratory staff.  
 
7.2.4 SPECIMEN SHIPMENT 
Skin scrapings will be transferred to the New York Presbyterian Laboratory at 525 East 68th Street,  
New York, NY 10065.  Staff will carry the samples to the clinical lab in an insulated container immersed in liquid nitrogen 
and then samples will be stored in liquid nitrogen or at -80°C prior to being processed by the laboratory technical staff.  
 
7.3 
STUDY SCHEDULE 
 
7.3.1 SCREENING 
A pre-screening/recruiting phone call will occur before scheduling the screening visit. This call will establish the subjects 
probable eligibility for the study. 
At the screening visit the study coordinator will assess eligibility by checking for inclusion and exclusion criteria and 
entering these results in the CRF. 
Following inclusion/exclusion questions, the study coordinator will obtain informed consent from the subject. 
Only subjects who satisfy all screening criteria and provide consent will be enrolled in the study. 

 
 
20 
 
7.3.2 ENROLLMENT/BASELINE 
During the enrollment visit the physician will complete a medical history including an assessment of Fitzpatrick skin type. 
The enrollment visit will include standard of care counseling on the importance of UV avoidance. For transplant 
recipients, condition appropriate information will be included. 
 
Ultraviolet Exposure Counseling: as described in 7.1.2 Standard of Care Study Procedures 
 
The enrollment visit will include the skin check described in 7.1.2 Standard of Care Study Procedures. 
 
Skin Check: as described in 7.1.2 Standard of Care Study Procedures 
 
Treatment of Actinic Keratoses as described in 7.1.2 Standard of Care Study Procedures. 
 
At the conclusion of the enrollment visit the study coordinator will discuss with enrolling physician for  for determination 
of Fitzpatrick skin type. The coordinator will then assign the subject to treatment or control groups following the 
procedure in section 10.6.1. The subject’s assignment will be noted on the randomization table to be kept confidential to 
the coordinator and study monitors.  
 
The coordinator will meet with the subject in a separate room to schedule the first follow up visit. If the subject is in the 
treatment arm, in this meeting the subject will be given the box with the Shade sensor. The coordinator or a sponsor 
representative will observe and support the subject in the process of opening the box and installing the application on 
their phone. At this time the coordinator will assign a study email address to the subject and enter that address in the 
randomization table and an electronic table along with the subject’s actual email address. 
 
7.3.3 FOLLOW-UP 
 A focused examination of the scalp, face, hands and any other pertinent areas will be performed at the follow up visit(s). 
AKs will be identified and photographed.  Any other suspicious lesions will be biopsied as described as above.  AKs will be 
treated as previously described.  
 
The study coordinator will maintain the schedule of follow up visits and will contact subjects via phone or email. In the 
event that a subject in the treatment arm is having difficulty achieving compliance, the study coordinator will be 
available for counseling, training, to provide replacement of broken or lost devices, and encouragement. Calls will be 
logged in the study binder. 
 
7.3.4 FINAL STUDY VISIT 
For the final visit, a standard skin examination will be performed by a dermatologist.  The scalp, face, mucous 
membranes, chest, back abdomen, arms, legs, genitalia, digits will be examined.  Any AKs will be identified, 
photographed and treated as previously described.  Any suspicious lesions will be biopsied.  If the patient is in the study 
arm, the device will be collected by the study coordinator at this visit.   
 
7.3.5 EARLY TERMINATION VISIT 
Subjects who withdraw consent or otherwise voluntarily leave the study will be offered the opportunity to participate in 
the next visit scheduled for the study.  
 

 
 
21 
Subjects who are dropped from the study for any reason will be contacted by phone to explain the reason they have 
been dropped from the study. An early termination visit is not required. 
 
Subjects who terminate early will be asked to return their Shade device and will be given the same offer to obtain a new 
device of their own as subjects who complete the study. 
 
The study coordinator will fill out a study termination form for all subjects including those who leave early. 
 
7.3.7 SCHEDULE OF EVENTS TABLE 
 
Procedures 
Prior to 
enrollmen
t 
Enrollme
nt 
Visi
t 1 
Befor
e  
visit 2 
Visi
t 2 
Befor
e  
visit 3 
Visit 
3 
AE 
Visit 
Screening call 
X 
 
 
 
 
 
 
 
Screening questions 
 
x 
 
 
 
 
 
 
Informed consent 
 
x 
 
 
 
 
 
 
Medical history 
 
x 
 
 
 
 
 
 
Patient survey 
 
 
x 
 
x 
 
x 
 
Dermatology Visit 
 
 
x 
 
x 
 
x 
 
UV counseling 
 
 
x 
 
x 
 
x 
 
Full Skin Check 
 
 
x 
 
x 
 
x 
 
Focused Skin Check 
 
 
x 
 
x 
 
x 
 
Collect skin scraping (WCM only) 
 
 
x 
 
x 
 
x 
 
Randomization 
 
 
x 
 
 
 
 
 
Compliance engagement 
 
 
 
x 
 
x 
 
 
Return study materials 
 
 
 
 
 
 
x 
 
Condition driven medical exam 
 
 
 
 
 
 
 
x 
 
Screening call: 
Screening questions: These are listed in the CRF 
Informed consent: As approved by IRB 
Medical history: Key questions listed in CRF 
Patient survey:  
Dermatology visit: 
Collect skin scraping: 
Randomization: 
Compliance engagement: 
Return study materials:  See section 7.9 
 
7.4 
JUSTIFICATION FOR SENSITIVE PROCEDURES 
There are no sensitive procedures in this study. 
 
7.5 
CONCOMITANT MEDICATIONS, TREATMENTS, AND PROCEDURES  
Concomitant medications, treatments and procedures will be recorded in the CRF.  
 
7.5.1 PRECAUTIONARY MEDICATIONS, TREATMENTS, AND PROCEDURES 
None 

 
 
22 
 
7.6 
PROHIBITED MEDICATIONS, TREATMENTS, AND PROCEDURES  
The use of topical and oral medications prescribed as field treatment for actinic damage (i.e., imiquimod, acitretin, etc.) 
would be prohibited during this study.  Targeted topical treatment of biopsy-proven non melanoma skin cancer (e.g. 
imiquimod) would be allowed at the provider’s discretion.   Any treatment of actinic keratoses or any biopsies of 
suspected malignancies by an outside dermatologist would be prohibited during the study 
 
7.7 
PROPHYLACTIC MEDICATIONS, TREATMENTS, AND PROCEDURES  
None 
 
7.8 
RESCUE MEDICATIONS, TREATMENTS, AND PROCEDURES  
None 
 
7.9 
PARTICIPANT ACCESS TO STUDY AGENT AT STUDY CLOSURE  
At the conclusion of the study subjects in the treatment arm will 
1. Return the Shade device used in the study.  
2. Receive a printout of their UV history from the study coordinator. 
3. Delete the shade mobile application from their phone. 
All subjects will 
4. Choose between receiving the final study compensation at the visit or a coupon usable to purchase a new sensor. 
The coordinator will explain that if they use the coupon, Shade will know that they participated in the study. But 
Shade will not know their subject ID and will therefore not be able to connect their identity to medical records 
provided in the study. 
 
8 
ASSESSMENT OF SAFETY 
 
8.1 
SPECIFICATION OF SAFETY PARAMETERS 
The primary safety endpoint is the number of adverse events related or possibly related to the device or sun exposure 
experienced within the study period. To test this hypothesis the number of adverse events related or possibly related to 
the device or sun exposure experienced by the treatment group should not be significantly greater than the number of 
adverse events related or possibly related to the device or sun exposure experienced by the control group throughout 
the duration of the study. Adverse events will be categorized by type, duration, severity, relationship to the study device 
and need for treatment. 
 
8.1.1 DEFINITION OF ADVERSE EVENTS (AE) 
An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical 
product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any 
unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated 
with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product 
(see the ICH guidance for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting). 
 
8.1.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE) 
● Any untoward medical occurrence that at any dose: 
● Results in death, 

 
 
23 
● Is life-threatening, 
● Requires inpatient hospitalization or prolongation of existing hospitalization, 
● Results in persistent or significant disability/incapacity, or 
● Is a congenital anomaly/birth defect. 
 
8.1.3 DEFINITION OF UNANTICIPATED PROBLEMS (UP) 
Unanticipated problems include any incident, experience, or outcome that meets all of the following criteria: 
1) unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in 
the protocol-related documents, such as the IRB-approved research protocol and informed consent document; 
and (b) the characteristics of the subject population being studied; 
2) related or possibly related to participation in the research (in this guidance document, possibly related means 
there is a reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
3) suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, 
economic, or social harm) than was previously known or recognized. 
 
8.2 
CLASSIFICATION OF AN ADVERSE EVENT 
 
8.2.1 SEVERITY OF EVENT 
Classifications often include the following: 
·      Mild: Awareness of signs or symptoms, but easily tolerated and are of minor irritant type causing no loss of time 
from normal activities. Symptoms do not require therapy or a medical evaluation; signs and symptoms are transient. 
·      Moderate: Events introduce a low level of inconvenience or concern to the participant and may interfere with daily 
activities, but are usually improved by simple therapeutic measures; moderate experiences may cause some interference 
with functioning 
·      Severe:  Events interrupt the participant’s normal daily activities and generally require systemic drug therapy or 
other treatment; they are usually incapacitating 
Severity is not synonymous with seriousness. A severe rash is not likely to be an SAE. Likewise, a severe headache is not 
necessarily an SAE.  However, mild chest pain may result in a day’s hospitalization and thus is an SAE. 
 
8.2.2 RELATIONSHIP TO STUDY AGENT 
Adverse events may be caused by one or more of the following: 
1. the procedures involved in the research; 
2. an underlying disease, disorder, or condition of the subject; or 
3. other circumstances unrelated to either the research or any underlying disease, disorder, or condition of the 
subject.  
In general, adverse events that are determined to be at least partially caused by (1) would be considered related to 
participation in the research, whereas adverse events determined to be solely caused by (2) or (3) would be considered 
unrelated to participation in the research. 
 
8.2.3 EXPECTEDNESS  
AEs must be assessed as to whether they were expected to occur or unexpected, meaning not anticipated based on 
current knowledge found in the protocol, investigator brochure, product insert, or label. Categories are:  
·      Unexpected - nature or severity of the event is not consistent with information about the condition under study or 
intervention in the protocol, consent form, product brochure, or investigator brochure.  

 
 
24 
·      Expected - event is known to be associated with the intervention or condition under study.  
Relatedness  
The potential event relationship to the study intervention and/or participation is assessed by the site investigator. A 
comprehensive scale in common use to categorize an event is: 
·      Definitely Related:  The adverse event is clearly related to the investigational agent/procedure – i.e. an event that 
follows a reasonable temporal sequence from administration of the study intervention, follows a known or expected 
response pattern to the suspected intervention, that is confirmed by improvement on stopping and reappearance of the 
event on repeated exposure and that could not be reasonably explained by the known characteristics of the subject’s 
clinical state. 
·      Possibly Related:  An adverse event that follows a reasonable temporal sequence from administration of the study 
intervention follows a known or expected response pattern to the suspected intervention, but that could readily have 
been produced by a number of other factors. 
·      Not Related:  The adverse event is clearly not related to the investigational agent/procedure. -  i.e. another cause of 
the event is most plausible; and/or a clinically plausible temporal sequence is inconsistent with the onset of the event 
and the study intervention and/or a causal relationship is considered biologically implausible. 
Mild sunburns, not requiring medical treatment, are expected to be over reported in the treatment group because of 
their constant communication with the application. These will not be considered AE’s for the purposes of the safety 
endpoint. 
 
8.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
Adverse events reported will be assessed and followed up as soon as practical. Subjects reporting adverse events will be 
contacted by the study coordinator to schedule an assessment. Follow up timing will be sufficient to meet the following 
reporting requirements. 
 
Unexpected fatal or life-threatening suspected adverse reaction reports: 
The sponsor (or sponsor-investigator) must notify the FDA of any unexpected fatal or life-threatening suspected adverse 
reaction as soon as possible but no later than 7 calendar days after the initial receipt of the information. 
 
Other reporting requirements: 
The sponsor (or sponsor-investigator) must also notify the FDA and all participating Principal Investigators (in multi-site 
studies) in an safety report about potential serious risks, from clinical trials and any other source, no later than 15 days in 
the following cases: 
·      Serious and unexpected suspected adverse reactions. Any suspected adverse reaction that is both serious and 
unexpected must be reported. The report must proceed only if there is evidence to suggest a causal relationship 
between the drug and the adverse event. 
·      Finding from other studies. Any findings from epidemiological studies, pooled analysis of multiple studies, or clinical 
studies (other than those reported under serious and unexpected adverse reactions above) must be reported whether or 
not conducted under an IND or whether or not conducted by the investigator, that suggest a significant risk in humans 
exposed to the drug. 
·      Increased rate of occurrence of serious suspected adverse reactions. Any clinically important increase in the rate of 
serious suspected adverse reactions over that listed in the protocol must also be reported. 
 
8.4 
REPORTING PROCEDURES 

 
 
25 
8.4.1 ADVERSE EVENT REPORTING  
If any medical event reaches the threshold of an adverse event (AE) as judged by a treating physician, the AE will be 
reported by study staff or medical staff within 24 hours using both email and telephone to the clinical PI, the study PI and 
the IRB.   
Appropriate action will be taken by the clinical PI and reported in writing to Shade and the IRB within 72 hours.   
A written summary of any Adverse Events and their disposition will be submitted by the study PI (E. Dumont) to the 
funding NIH I/C within two weeks of receiving the written disposition from the clinical PI. 
 
8.4.2 SERIOUS ADVERSE EVENT REPORTING  
As in 8.4.1 
 
8.4.3 UNANTICIPATED PROBLEM REPORTING  
Unanticipated problems with the device or application will be reported to the study coordinator who will relay the 
reports to Sponsor. These will be managed by the sponsor using their process for Corrective and Preventive Actions. If a 
device is lost or becomes inoperable, a new device will be shipped to the subject by the study coordinator. Sponsor and 
study coordinator will communicate regularly about the inventory of devices and resupply as needed. 
 
8.4.4 EVENTS OF SPECIAL INTEREST  
The study team has not defined any events of special interest. 
 
8.4.5 REPORTING OF PREGNANCY  
Pregnancy will be noted on the CRF as a change in health status. Pregnancy will not result in exclusion from the study. 
 
8.5 
STUDY HALTING RULES  
The study can be halted at the request of the sponsor, the funding organization, the principal investigator or the IRB. It is 
expected that the study would be halted in the event that one or more of these reach the conclusion that as result of 
reported AE’s it is unethical to continue the study. 
 
8.6 
SAFETY OVERSIGHT 
 
 
 
 
 
Study staff will record all visits (regularly scheduled and others) and any hospitalization events.  
 
Safety Monitoring 
a. Adverse events: If any medical event reaches the threshold of an adverse event (AE) it will be reported and handled as 
described in 8.4.1. 
b. Overall rates of hospitalization and occurrence of AK will be reported by Shade to the clinical PI and the IRB every six 
months until the study closes. 
c. Final rates of hospitalization and occurrences of AK will be included in the final study report. 
d. The Shade device does not require an FDA issued IDE. Shade, in consultation with its legal consultants, has determined 
that is a non-significant risk device because it is not an implant, is not used to sustain human life and is not used in the 
diagnosis or treatment of disease, and does not otherwise present a significant health risk. As such the device is subject 
to abbreviated requirements under 21 CFR 812.2(b) 
 
 
 
 
 
•It will only be used in at risk-populations with IRB approval including monitoring and consent.  
•The devices will be labeled ‘Investigational Use Only’ 
•All FDA requirements concerning data reporting, monitoring and promotion will be observed. Shade will 
request an IRB determination that the device is not significant risk prior to the submission of the study protocol. 

 
 
26 
Shade may also request an FDA determination of non- significant risk prior to initiation of this study.  
 
 
 
 
9 
CLINICAL MONITORING 
All clinical data will be recorded on CRFs and monitored by a representative of Shade who may be an employee or an 
external study consultant. Monitors will perform source-data verification prior to study analysis. The data monitor will 
ensure that subject confidentiality is not breached by reviewing each CRF for the presence of identifying information. 
Monitoring visits will be held within two weeks of  the first day of scheduled subject visits and continue periodically at 
the discretion of the sponsor but in no case less than at at six month intervals until study closeout. To facilitate an orderly 
and timely analysis and to avoid an accumulation of data queries at closeout, there will be a monitoring visit four to six 
weeks before the end of data collection. At the conclusion of each monitoring visit a report indicating any issues with 
data, outstanding queries or protocol compliance issues. This report will be shared with Shade and the clinical PI. The 
results of monitoring visits and queries will be made available to the funding agency’s project officer. 
 
10 
STATISTICAL CONSIDERATIONS  
 
10.1 STATISTICAL AND ANALYTICAL PLANS 
The statistical analysis of the study is the responsibility of the study statistician. Intermediate data reviews will be 
conducted after 6 months to check for potential problems with data integrity. 
 
10.2 STATISTICAL HYPOTHESES 
The general hypothesis is that sun damage will be lower in the treatment group. The null hypothesis is that sun damage 
is the same or higher. Below there is a more precise statement of the hypothesis for each study aim. 
 
10.3 ANALYSIS DATASETS 
Datasets will be prepared by the study coordinator from case report forms. The tables will be formatted as requested by 
the study statistician and will be monitored. 
 
10.4 DESCRIPTION OF STATISTICAL METHODS 
Actinic keratosis (AK) is a frequent pre-cancerous skin lesion caused by damage from ultraviolet exposure. 
Without treatment, 1-2% of these lesions evolve into squamous cell carcinoma (SCC).19 Therefore, the number 
of AKs reflects the effect of UV exposure and the risk for SCC.  Transplant patients are at high risk of skin 
cancer because of their immunosuppressive medications required to prevent organ rejection. 
Morbidity/mortality of SCC in this patient population can be as high as 25%. 
  
The primary outcome of this trial will be a statistically significant reduction by at least 25% in the cumulative number of 
newly developed AK lesions between the control and the study group. 
  
AK lesions on sun exposed skin areas (scalp, face, hands) will be counted and reported by dermatologists at enrollment 
and at each subsequent visit. AKs are defined as keratotic macule(s) or papule(s) on an erythematous base by 
dermatological examination. In addition to the enrollment visit, this study will include a follow up dermatological visit 
after the summer. For each patient, the number of newly occurred AKs will correspond to the cumulative AK counts 
during the study period. To insure that only new occurrences of AK lesions after V1 will be counted, data from 
subsequent study visits will include the location of AK lesions and pictures of the lesions. 
 

 
 
27 
10.4.1 GENERAL APPROACH 
All tests will be two-tailed with the significance level set at 0.05. Analysis will be performed using STATA statistical 
software (StataCorp. 2015) or R (R: A language and environment for statistical computing. R Foundation for Statistical 
Computing,  Vienna, Austria). 
 
10.4.2 ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
#1 (Primary): Quantify the impact of Shade on the cumulative number of new actinic keratoses developed over the study period. 
   
To test our primary aim, we will perform a control versus study group analysis. The study group will receive a Shade 
sensor and Shade app while the control group will standard of care sun avoidance counseling. The study will be 
randomized and single-blinded as described in section 10.6.1. This will also allow us to control for the effect of UV level 
variation on the primary outcome since the two groups will have balanced enrollment dates. All the patients will receive 
recommendations about UV exposure protection as defined by the recommendations of the American Academy of 
Dermatology and the National Cancer Institute. 
  
Patients who will have used the Shade sensor for less than 15% of the days over the study period will be excluded from 
these analyses. We will use a Student’s t-test with the following null and alternative hypothesis: 
H0: mean C
t12 (AK) = meanI
12 (AK) 
Ha: meanC
t12 (AK) ≠ meanI
t12 (AK) 
where meanC
t12 (AK) is the averaged cumulative number of AK between enrollment follow up of controls and meanC
t12 
(AK) is the averaged cumulative number of AK  of intervention patients. 
  
In this analysis, demographic and clinical factors such as gender, age, baseline count of AKs, skin type, 
immunosuppressive treatment and comorbidity can be confounding factors. To test and control for confounding, 
demographic and clinical data (skin type, living area, gender, age, count of AK at enrollment, immunosuppressive (IS) 
treatment, level of immunosuppression  and comorbidity) will be collected. We will use a stepwise multivariate approach 
with backward selection: 1) the effect of potential confounding factors will be tested using the same statistical tests, 2) 
factors with p-value <0.2 and less than 25% of missing values will be included in the multivariate model and 3) only 
covariates with significant adjusted p-value (<0.05) will be kept in the final model. Clinically relevant interactions will also 
be tested (e.g. skin type, gender, age) and kept in the final model if significant. The adjusted effect of Shade use will be 
estimated using a multivariate linear regression. 
 
10.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
#2 (Secondary): Quantify the impact of Shade on the numbers of new AK’s observed at the final visit 
This analysis will follow the same procedure as the primary analysis but will only include AK data from the final visit. 
#3 (Secondary): Quantify the impact of Shade on the numbers of new cutaneous squamous cell carcinomas confirmed by histology 
during follow up over the study period. 
  
To test the early effect of Shade on skin cancer risk and the robustness of our findings, we will perform a longitudinal 
analysis to test a reduction by at least 25% of squamous cell carcinoma. The effect of Shade use will be estimated using a 
single mixed linear model (with random intercept and slope) for repeated (longitudinal) data including study group and 
time since enrollment as explanatory variables. A similar stepwise multivariate approach with backward selection as 
described in the primary aim will be perform to take into account confounding factors. 

 
 
28 
  
#4 (Secondary): Quantify the impact of Shade on the number of new nonmelanoma skin cancers (basal cell carcinomas, cutaneous 
squamous cell carcinomas) confirmed by histology over the study period. 
To test the early effect of Shade on skin cancer risk and the robustness of our findings, we will compare the cumulative 
numbers of new nonmelanoma skin cancers between the control and study group and  test a reduction by at least 25% of 
non-melanoma skin cancer s as secondary outcome, using a t-test.  A similar stepwise multivariate approach with 
backward selection as described in the primary aim will be perform to take into account confounding factors. 
#5 (Secondary): Test the correlation between measured UV exposure and the number of new actinic keratoses. 
We will test the correlation between the cumulative UV exposure and the number of AK lesions at each time point using 
a Pearson correlation test or a non-parametric Spearman test if the requirements for the parametric test are not met. A 
significant correlation will be defined as ⍴ > 0.2 and p-value < 0.05. UV exposure will be defined as the cumulative UV 
exposure in erythemally-weighted J/m2 at each time point since enrollment. 
#6 (Secondary): Test the correlation between measured UV exposure and the number of new nonmelanoma skin cancers. 
We will test the correlation between the cumulative UV exposure and the number of new nonmelanoma skin cancers 
using a Pearson correlation test or a non-parametric Spearman test if the requirements for the parametric test are not 
met. A significant correlation will be defined as ⍴ > 0.2 and p-value<0.05. UV exposure will be defined as the cumulative 
UV exposure in erythemally-weighted J/m2 at each time point since enrollment.  
#7 (Secondary): Quantify the impact of Shade on keratinocyte DNA damage approximated by the measurement of cyclobutane 
pyrimidine dimers by ELISA. 
Cyclobutane Pyrimidine Dimers (CPD) are induced by UV exposure in a dose dependent fashion.6 UV exposure can lead to 
immediate CPD increase; therefore measurement of CPD following the delivery of a known UV dose allows for a 
biological readout of UV effects. In addition, CPD levels represent an equilibrium between UV induced formation and 
DNA repair; therefore, they can also reflect chronic UV exposure.21 
  
CPD level will be measured from ELISA from exposed (cheek) and unexposed (buccal mucosa) skin samples collected. For 
each patient, the level from exposed skin will be normalized to the basal CPD level measured from unexposed skin. 
Correlation  of CPD level to Shade UV measurement 24 hours prior to collection will allow for an acute UV biological 
validation that Shade measured UV levels correspond to levels of CPD damage (using Pearson correlation test or a non-
parametric Spearman test). We will also compare the normalized CPD level of control versus study participants at each 
timepoint and their average CPD change over time using a t-test. These comparisons will assess the accuracy of Shade 
measurements as it relates to chronic UV exposure. 
  
The outcome will be a statistically significant reduction by at least 25% of the normalized CPD level of exposed 
keratinocytes. 
#8 (Secondary): Quantify the impact of Shade on patients’ quality of life assessed by PROMIS (Patient-Reported Outcomes 
Measurement Information System) in the fields of anxiety (Mental Health), depression (Mental Health), and Ability to Participate 
in Social Roles and Activities (Social health).  
To assess the impact of Shade on quality of life, patients will be surveyed using short form paper versions of PROMIS 
(Patient-Reported Outcomes Measurement Information System) scores in the fields of depression, anxiety, and the 
ability to participate in social roles and activities.  PROMIS survey will be performed at each visit. We will compare the 
change in PROMIS scores between group and study using a t-test at each time-point. 

 
 
29 
  
The outcome will be assessed for statistical significance (p-value of change in PROMIS score between groups) and clinical 
significance (changes of 3 points on a single score are generally considered meaningful to subjects). 
#9 (Secondary): Assess sensor usage in the study patient population and compare characteristics of observant vs non-observant 
and responsive vs non-responsive patients. 
To assess sensor usage, we will estimate the overall percentage (and 95% confidence interval) of days used in the study 
patient population, the average (and standard deviation) and median (and quartile) of the daily UV threshold set by the 
patients and the percentage of days below and above the UV threshold. 
  
The Shade sensor and the mobile application enables users to decide, by looking at self-reported symptoms and daily 
cumulative UV exposure over 15 and 30 days, how much UV exposure in J/m2 they would like to manage per day, which 
we call the daily UV threshold. Users can select a daily UV threshold that is lower than their previous maximum daily UV 
exposure. Of course, users are free to go beyond this threshold if they chose to and the app will let them know in real 
time by how much they have exceeded their threshold. The threshold can be adjusted at any time through the app. The 
Shade app does not make any recommendation regarding the daily threshold. Note that each subject will be individually 
counseled to minimize UV exposure. 
  
We will also quantify the percentage of observant and non observant patients, as well as the percentage of responsive 
and non-responsive patients. While observance will be based on the use of the sensor, responsiveness will be based on 
“safe” UV behaviors. Observance will be defined as at least 50% of days used, poor observance between 15% to 50% and 
non-observance as inferior to 15%. Responsiveness will be defined as less than 15% days over the UV threshold and more 
than 85% of days with an UV threshold set within one standard deviation of the study group’s average UV threshold. 
Conversely, non-responsiveness is defined as more than 15% days over the UV threshold or more than 85% of days with 
an UV threshold set above one standard deviation of the study group’s average UV threshold. 
  
The sociodemographic and clinical characteristics of observant, poorly observant, non-observant, responsive and non-
responsive patients will be assessed separately and compared using Student’s t-tests for quantitative characteristics and 
𝝌2 for categorical characteristics. These comparisons will provide useful information to better understand the 
determinants of UV behaviour change. 
  
To be conservative, only non-observant subjects (<15% of days use) will be excluded from the analyses while poorly and 
non-responsive patients will be included. The comparison of their characteristics will rule out a selection bias.  
#10 (Secondary): Assess feasibility of the intervention for kidney transplant recipients through report of their rates for compliance 
and retention. 
Rates will be reported but are not expected to be analyzed for significance. 
 
10.4.4 SAFETY ANALYSES 
No safety analyses are planned. 
10.4.5 ADHERENCE AND RETENTION ANALYSES 
See specific Aim #8. 
10.4.6  BASELINE DESCRIPTIVE STATISTICS 
Demographic statistics (# and % male/female, %ethnicity, % race) will be collected and reported. 

 
 
30 
 
10.4.7 PLANNED INTERIM ANALYSES  
 
10.4.7.1 SAFETY REVIEW 
As this is a low-risk study, no specific safety review will be conducted. See the handling of Adverse Events for 
mechanisms for safety assurance. 
 
10.4.7.2 EFFICACY REVIEW 
N/A 
 
10.4.8 
ADDITIONAL SUB-GROUP ANALYSES 
N/A 
10.4.9 MULTIPLE COMPARISON/MULTIPLICITY 
The planned analyses do not include multiple comparisons.  
 
10.4.10 
TABULATION OF INDIVIDUAL RESPONSE DATA 
Clinical data tables will be reduced into a table of individual responses for analysis as follows: 
 
Column 
Source (name of CRF with data) 
SubjectID 
N/A 
AK  baseline (count) 
Actinic Keratosis 
AK  follow up (cumulative count) 
Actinic Keratosis 
NMSC  baseline (count) 
NMSC 
NMSC  follow up (cumulative count) 
NMSC 
Observant  % of days 
Compliance database 
Responsive Y/N 
Shade database: days with UV limit below 90% of 
exposures 
CPD  R 0 
Lab data 
CPD  R 12 month 
Lab data 
MHA 1 
PROMIS MHA visit 1 
MHA 2 
PROMIS MHA visit 2 
MHA 3 
PROMIS MHA visit 3 
MHD 1 
PROMIS MHD 
MHD 2 
PROMIS MHD 
MHD 3 
PROMIS MHD 
SHP 1 
PROMIS SHP 
SHP 2 
PROMIS SHP 
SHP 3 
PROMIS SHP 
UV Ave 
Sensor data 
AE (count) 
CRF 
comment 
 

 
 
31 
group 
Randomization 
exclude 
 
 
 
10.4.11 
EXPLORATORY ANALYSES 
None 
 
10.5 SAMPLE SIZE 
The most efficient approach to performing the power calculation for this study via Monte Carlo simulation as the 
underlying phenomenon, AK rate, is best modeled by a Poisson distribution.22 
  
As a starting point, we took the distribution of AK rates from actual clinical data. The data were assembled by querying 
EPIC on 2014 visits of kidney transplant patients to dermatology (this subset of the population will have fewer AK’s than 
the non-transplant subjects and therefore use of this distribution will err on the side of caution toward overpowering the 
study). For each visit in which the dermatologist chose to treat by LN2 destruction, the query retrieved the number of 
procedures performed. This approach is conservative as the input data potentially underestimates AK count as some AK’s 
may not have been treated. 
  
The structure of the Monte Carlo was straightforward. A set of potential study sizes (N recruited) and effect sizes were 
chosen. For each input condition, two thousand random experiments were performed. In each of these interactions, 
baseline AK rates were drawn from the clinically observed distribution of AK’s. Subjects were sequentially assigned to 
treatment or control groups. Observed AK rates were generated using a Poisson distribution for each visit. The analysis 
expected for the study was then performed. In this analysis the total count of AK’s for each subject was obtained and the 
means and distributions compared for directionality (AK_treated < AK_control) and significance (p-value from a one-
tailed t-test). 
  
Analysis was performed in R (R Open 3.2.3) with statistical calculations and random number generation using the base 
and stat libraries. 
 
Figure 10.5.1. With an effect size of 0.25 and recruitment of 100 patients (50 treatment, 50 control) we predict a power 
of 0.81. 
 

 
 
32 
10.6 MEASURES TO MINIMIZE BIAS 
This study will be partially blinded.  We will divide study participants into 2 groups.  The experimental group will wear an 
ultraviolet sensor which will record their UV exposure.  The control group will receive  standard of care counseling about 
photoprotection from their dermatologist.   The study coordinator will spend the first 10 minutes of the visit with each 
patient reviewing any  issues related to the study, including sensor related issues.   The study coordinator will remind the 
patient at each visit to put the sensor away from view and to not discuss any sensor related questions to the 
dermatologist.   The dermatologist will then come in and perform a total body skin examination.  Actinic keratosis will be 
identified, circled and photographed.  The actinic keratosis will then be treated via a destruction method.  Any potential 
skin cancers will be biopsied and sent for pathology.  Cyclopyridimine butane dimer (CPD) analysis will be obtained via 
light curettage of the skin and mucosa.  They will be sent to a lab and the data will be  processed.  A different physician 
will evaluate the results and will not have access to clinical data. This physician will remain completely blinded to the 
study. 
 
10.6.1 ENROLLMENT/ RANDOMIZATION/ MASKING PROCEDURES 
The randomization schedules will be developed prior to the enrollment of the first subject. There will be one schedule for 
Fitzpatrick types I-II and a second schedule for Fitzpatrick types III and higher. The randomization schedule is a simple list 
of assignments to the groups ‘Treatment,’ meaning that the subject will be given the Shade device and mobile 
application and ‘Control,’ meaning that the subjects will be given only the standard of care counseling to avoid UV. 
The following sequence of events at enrollment will ensure that the treating physician will be blinded to the subject 
assignment: 
(1) visit with study coordinator for screening, informed consent, and medical history.  
If the subject passes screening and grants consent 
(2) physician visit. 
During the physician visit, the study coordinator will take the next randomization from the randomization schedule. This 
schedule will be prepared by the sponsor in such a manner that the coordinator remains blind to the next assignment 
until it is requested. The sponsor has latitude to implement this using any reasonable physical or computational system. 
The subject assignment will be entered on the randomization schedule available only to the study coordinator and the 
study monitor. 
(3) wrap up conversation with study coordinator. 
After the physician visit the study coordinator will sit with the subject in a separate room. The next visit or visits will be 
tentatively scheduled. If the subject is in the treatment group, the device will be provided and either the coordinator or a 
sponsor representative will work with the subject to setup the mobile application and ensure that subject understands 
how to use the device. 
 
At subsequent visits subjects in the treatment group will be instructed to  
(1) avoid discussing their assignment with the physician. 
(2) place the shade sensor in a purse or pocket out of view of the physician 
(3) mention to the study coordinator if the subject of the assignment came up in conversation with the physician. 
 
10.6.2 EVALUATION OF SUCCESS OF BLINDING  
The study coordinator will note any failures of blinding in the randomization table.  
 
10.6.3 BREAKING THE STUDY BLIND/PARTICIPANT CODE 
The study blind will be broken after PI and sponsor agree that the clinical data tables are complete and that all remaining 
data queries have been followed to their logical conclusion. 

 
 
33 
Just prior to breaking the study blind, the study data tables will be frozen. 
The blind will be broken by the study coordinator who will provide the full team with a copy of the randomization table. 
 
11 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 
Sources of data for the CRF include: 
Medical records created by the examining physician 
Survey data filled in by the subjects 
Other medical records stored in the study site electronic medical records system 
 
The study coordinator will have access to all of these data sources. 
The examining physician and the PI will have access to all of these data sources. 
The study monitor will have supervised access to these sources during monitoring visits. It is the responsibility of the 
study coordinator to assist study monitors in source data verification. Study monitors will record only non-identifying 
information in their queries. 
 
Data queries will include the subject ID and the nature of the query. 
 
12 
QUALITY ASSURANCE AND QUALITY CONTROL 
The study team will implement quality assurance and quality control measures documented in this protocol. The intent 
of the protocol and the commitment of all staff is to be in compliance with good clinical practice, including its 
requirements for quality management. 
 
13 
ETHICS/PROTECTION OF HUMAN SUBJECTS  
 
13.1 ETHICAL STANDARD  
This study is conducted under the ethical standards described in ICH E6. Please see the compliance statement on the PI 
sign-off page at the beginning of the protocol for details. 
 
13.2 INSTITUTIONAL REVIEW BOARD  
This study will be under the review of the Weill Cornell Institutional review board. 
 
13.3 INFORMED CONSENT PROCESS  
Informed consent will be obtained at the beginning of the screening phase of the first visit. No subjects will be enrolled in 
the study unless they have completed the screening and provided consent. 
 
13.3.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO PARTICIPANTS 
See Appendix 2 Informed Consent, and Appendix 3 Advertising Material 
 
13.3.2 CONSENT PROCEDURES AND DOCUMENTATION 
At the initiation of the screening and consent process, a subject ID will be assigned, and the subject ID entered into the 
central table of subjects. Once consent is provided, the IC form will be added to the study binder. At this point the 
subject table value, ‘Screen passed’ will be entered in the table. 
 
13.4 PARTICIPANT AND DATA CONFIDENTIALITY  

 
 
34 
At the study site, medical and research staff will have access to patient information for the purpose of transferring this 
information to non-identifiable CRFs. Study data monitors will match clinical data to CRFs under supervision of the study 
coordinator. Sponsor will maintain, any identifiable private information will be encrypted and stored in Shade’s HIPAA 
compliant storage. No identifying information will be available to sponsor except during monitoring activities. 
 
13.4.1 RESEARCH USE OF STORED HUMAN SAMPLES,SPECIMENS OR DATA 
The study team may use any stored samples, specimens or data for future research or analysis. All future analyses will 
respect subject confidentiality. Non-identifying study data will be retained by the sponsor and made available to any 
qualified researcher upon request as described in section 14.4. 
 
13.5 FUTURE USE OF STORED SPECIMENS  
Stored specimens may be subject to future analysis for research purposes related to or unrelated to the purpose of this 
study. Such analyses will respect subject confidentiality.  
 
14 
DATA HANDLING AND RECORD KEEPING  
 
14.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
Clinical data collection is the responsibility of the Weill Cornell team with the PI having overall responsibility for 
supervision and the study coordinator having responsibility for execution of data collection. Study coordinator will 
prepare monthly reports summarizing progress on data completion. 
 
The sponsor will review and monitor data periodically. 
 
14.2 STUDY RECORDS RETENTION  
IRB records will be retained by WMC for no less than three years, and research records will be retained by WMC for no 
less than three years after the completion of the research. 
 
14.3 PROTOCOL DEVIATIONS  
Protocol deviations will be reported to the sponsor and the IRB within 72 hours. The following events are expected and 
should be marked on the CRF but do not require reporting as deviations: 
1. Rescheduled visit. While visits should be scheduled within 7 days of the target visit date, visits may be 
rescheduled within 21 days of the visit target date. 
2. Screen fail. A subject may be enrolled based on passing screening questions but subsequently dropped if there is 
evidence in their medical record that they have failed screening. In that event the subject’s CRF will indicate a 
screen fail (by initialing the appropriate CRF) and the subject will be dropped from the study.  
 
14.4 PUBLICATION AND DATA SHARING POLICY 
Sponsor and Investigators are committed to enhancing the value of research and furthering the advancement of public 
knowledge as well as to the development of its commercial products and the protection of its intellectual property. We 
recognize that this project will result in the collection of data useful to the research community. Therefore, final research 
data will be shared openly and timely in accordance with the most recent NIH guidelines 
(http://grants.nih.gov/grants/policy/data_sharing) while being mindful that the confidentiality and privacy of 
participants in research must be protected at all times. Timelines for distribution of data will vary depending on any 
required restrictions in accordance with federal and/or institutional policies and guidelines. In general, we expect the 

 
 
35 
data will be available through publications, presentations at scientific symposia and seminars. In some cases, Shade may 
determine that a licensing program may be necessary to better serve the public and the research community whether or 
not patents have been filed. Efforts will be made to publish our research findings in scientific journals. All final peer-
reviewed manuscripts that arise from this proposal will be submitted to the digital archive PubMed Central. 
 
In order to protect the identity of subjects in this study, a more detailed discussion of the clinical data collected in this 
project is required. Data will come from two sources which will be handled differently. 
Data collected from the clinic itself will include subject demographics including race, gender, Fitzpatrick skin type, in 
addition to key metadata related to the study hypothesis including transplant status, prior cancer history and prior 
history of actinic keratosis. These data will be published in an appropriately aggregated tabular form. 
 
The second source of data will be from the Shade device and software. While more specific, and potentially identifying, 
data may be collected by the device, as discussed in the human subjects protection section, potentially identifying data 
will not be available to study staff. Device data will include usage data, sun exposure, self-reported adherence to sun 
protection guidelines, self- reported symptoms of sun exposure including erythema. Subject level device data is likely to 
include subgroups of fewer than 20 people with specific combinations of metadata. For that reason, there will no release 
of subject level device data with direct links to metadata. Subject level data will be linked to Fitzpatrick skin type, gender 
and age rounded to the nearest multiple of 10 as well as the assignment of the subject to the test or control group. These 
data will be plotted, statistically analyzed and tabulated for publication. To encourage use of the data, subject level 
device data will be made available on request to qualified researchers including to NIH staff who agree to restrictions 
against public release of the data, attempts to identify study participants, destruction of the data after analyses are 
completed, reporting responsibilities, restrictions on the redistribution of the data to third parties, and proper 
acknowledgement of the data resource. Requests will be made directly to Shade by email through contact information to 
be provided on its web site and included in each publication based on these data. These data will be shared without fee 
through a single use web link which will enable the secure download of subject level device data in .csv format. 
 
 
15 
STUDY ADMINISTRATION 
 
15.1 STUDY LEADERSHIP 
N/A 
 
16 
CONFLICT OF INTEREST POLICY 
The WC conflict of interest policy applies to all personnel involved in this study. The policy is available at 
https://www.dfa.cornell.edu/policy/azindex/conflicts 
It is expected that all personnel will complete training in this policy which is available through the CITI program with links 
available at http://researchintegrity.weill.cornell.edu/conflicts_management_office/ 
 
17 
REVISION HISTORY 
17.1 VERSIONS 
2017A1_v1 
 
Approved date: 
2017A_v2_1 
 
Submitted date: 
Change summary: remove requirement for subjects to be kidney transplant recipients. 
motivation: on examination, the recruiting pool of KTR is small and there is not an underlying medical belief that the risk 

 
 
36 
or mechanism is different for the non KTR pool, with significant and recurring AK’s. 
 
17.2 MANAGING PROTOCOL CHANGES FOR CONTINUING SUBJECTS 
All subjects who signed consent forms prior to the protocol change will be reconsented at their next visit. 
Visits one and two are unchanged. Visits 3 and 4 have been removed from the protocol. At the time of this protocol 
change some subjects have completed visit 2. These subjects, who were scheduled to have a visit that is no longer part of 
the study design will be informed that this visit is no longer required. As no action is required of these subjects there will 
be no need to reconsent until their final study visit. For subjects who have not yet had their 3 month visit, reconsent at 
visit 2 will be appropriate. 
 
 
 

 
 
37 
APPENDIX 1  USER INSTRUCTIONS