Adaptive Deployment of DermAI to Evaluate Human Factor of Testing
Phase: NA
Conditions: Contact Dermatitis
Sponsor: Mayo Clinic

 
 
Adaptive Deployment of DermAI to Evaluate 
Human Factors of Testing 
 
NCT06387472 
 
15Sep2024 

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Adaptive Deployment of DermAI to Evaluate Human Factors of Testing 
 
 
Regulatory Sponsor: 
Matthew Hall, MD 
Department of Dermatology 
Mayo Clinic 
4500 San Pablo Rd 
Jacksonville, FL 32224 
 
Protocol Number: (IRBe) 
23-007636 
 
Clinical Trial Registration Number: 
NCT06387472 
Internal Study Number 
DermAI-005 
 
 
 
Initial version: January 16, 2024 
Revision number and date: Version 1.1 - March 29, 2024 
Revision number and date: Version 1.2 – September 15, 2024 
 
 

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Table of Contents 
 
1. 
INTRODUCTION............................................................................................................. 6 
1.1. 
BACKGROUND .................................................................................................................. 6 
1.2. 
INVESTIGATIONAL AGENTS .............................................................................................. 6 
1.3. 
PRELIMINARY DATA ........................................................................................................ 8 
1.4. 
RISKS AND BENEFITS ..................................................................................................... 10 
2. 
STUDY OBJECTIVES ................................................................................................... 11 
3. 
STUDY DESIGN ............................................................................................................. 11 
3.1. 
GENERAL DESCRIPTION ................................................................................................. 11 
3.2. 
NUMBER OF SUBJECTS ................................................................................................... 13 
3.3. 
DURATION OF PARTICIPATION ....................................................................................... 13 
3.4. 
IDENTIFICATION OF SOURCE DATA ................................................................................ 13 
4. 
SUBJECT SELECTION ENROLLMENT AND WITHDRAWAL .......................... 14 
4.1. 
INCLUSION CRITERIA ..................................................................................................... 14 
4.2. 
EXCLUSION CRITERIA .................................................................................................... 14 
4.3. 
SUBJECT RECRUITMENT, ENROLLMENT AND SCREENING .............................................. 14 
4.4. 
EARLY WITHDRAWAL OF SUBJECTS .............................................................................. 15 
4.4.1. 
When and How to Withdraw Subjects ................................................................... 15 
4.4.2. 
Data Collection and Follow-up for Withdrawn Subjects ..................................... 15 
5. 
TEST PATCH AND ALLERGEN DETAILS .............................................................. 15 
5.1. 
DESCRIPTION OF TEST PATCH VEHICLE ........................................................................... 15 
5.2. 
INVESTIGATIONAL ALLERGENS ...................................................................................... 15 
5.3. 
METHOD FOR ASSIGNING ALLERGENS TO TEST SITE REGIONS ......................................... 17 
5.4. 
PREPARATION AND APPLICATION OF TEST PATCHES ..................................................... 17 
5.5. 
SUBJECT COMPLIANCE MONITORING ............................................................................. 17 
5.6. 
MASKING/BLINDING OF STUDY ..................................................................................... 18 
6. 
STUDY PROCEDURES ................................................................................................ 18 
6.1. 
VISIT 1 ........................................................................................................................... 18 
6.2. 
VISIT 2 ........................................................................................................................... 19 
6.3. 
VISIT 3 ........................................................................................................................... 19 
7. 
STATISTICAL PLAN .................................................................................................... 22 
7.1. 
SAMPLE SIZE DETERMINATION ...................................................................................... 22 
7.2. 
STUDY ENDPOINTS ......................................................................................................... 22 
7.2.1. 
Primary Study Endpoints ...................................................................................... 22 
7.2.2. 
Secondary Study Endpoints................................................................................... 22 
7.3. 
ADDITIONAL STATISTICAL CONSIDERATIONS ................................................................ 24 
7.3.1. 
Descriptive Statistics ............................................................................................. 24 
7.3.2. 
Handling of Missing Data ..................................................................................... 24 
7.3.3. 
Multiplicity ............................................................................................................ 24 
7.3.4. 
Interim Analysis .................................................................................................... 24 

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7.3.5. 
Analysis Sets.......................................................................................................... 24 
8. 
SAFETY AND ADVERSE EVENTS ............................................................................ 25 
8.1. 
DEFINITIONS .................................................................................................................. 25 
8.2. 
RECORDING OF ADVERSE EVENTS ................................................................................. 26 
8.3. 
REPORTING OF SERIOUS ADVERSE EVENTS AND UNANTICIPATED PROBLEMS ............... 27 
8.3.1. 
Sponsor-Investigator reporting: notifying the Mayo IRB ..................................... 27 
8.3.2. 
Sponsor-Investigator reporting: Notifying the FDA ............................................. 27 
8.4. 
UNMASKING/UNBLINDING PROCEDURES ....................................................................... 28 
8.5. 
STOPPING RULES ............................................................................................................ 28 
8.6. 
MEDICAL MONITORING ................................................................................................. 28 
9. 
DATA HANDLING AND RECORD KEEPING ......................................................... 28 
9.1. 
CONFIDENTIALITY ......................................................................................................... 28 
9.2. 
SOURCE DOCUMENTS .................................................................................................... 28 
9.3. 
CASE REPORT FORMS .................................................................................................... 29 
9.4. 
RECORDS RETENTION .................................................................................................... 29 
10. 
STUDY MONITORING, AUDITING, AND INSPECTING ..................................... 30 
10.1. 
STUDY MONITORING PLAN ........................................................................................ 30 
10.2. 
AUDITING AND INSPECTING ....................................................................................... 30 
11. 
ETHICAL CONSIDERATIONS ................................................................................... 30 
11.1. 
CONFLICT OF INTEREST .............................................................................................. 30 
11.2. 
SUBJECT STIPENDS OR PAYMENTS ............................................................................. 31 
12. 
REFERENCES ................................................................................................................ 31 
 
 
 
 

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Study Summary 
Title 
Adaptive deployment of DermAI to evaluate human factors of testing 
Running Title 
User Adaptation 
Protocol Number 
DermAI-005 
Phase 
Other 
Methodology 
Prospective randomized controlled trial 
Overall Study 
Duration 
12 months 
Subject Participation 
Duration 
Participation will take approximately 1 week.  
Single or Multi-Site  
Single 
Objectives 
To develop the performance characteristics and human factor 
considerations to support fully remote patch testing. 
Number of Subjects 
Up to 10 pilot subjects followed by 150 Adaptive Patients 
Diagnosis and Main 
Inclusion Criteria 
The condition being studied is allergic contact dermatitis 
 
Inclusion Criteria:  
• Adults aged 18 or older  
• Able to provide consent 
 
Study Product, 
Dose, Route, 
Regimen 
Device: AI algorithm to evaluate photographs of skin test patch regions 
 
Drug: Allergens used in the testing protocol 
Statistical 
Methodology 
The analysis plan will focus on comparing the AI predictions of 
reactions with the interpretation of a human review of the photographs 
documented during the study visits.  The reference criterion will be the 
expert, in person review as is currently performed with standard clinical 
operations.  
 
 
 

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Summary of Protocol Changes 
Protocol Version 
Summary of Key Changes 
1.0 
• Original Protocol 
1.1 
• Addition of 10 pilot subjects 
• Minor refinements to protocol details throughout 
1.2 
• Addition of allergens and updates on Phase III activities. 
 
 

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1. Introduction 
 
This document is a protocol for a human research study. This study will be carried out in 
accordance with the applicable United States government regulations and Mayo Clinic research 
policies and procedures.  
1.1. Background 
 
Allergic contact dermatitis is a common inflammatory skin disorder. The disorder is characterized 
by pruritus, erythema, vesicles and scaling of the skin. Contact dermatitis can be further divided 
into allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD). ACD is a type of IV-
mediated hypersensitivity to a specific allergen, resulting in an inflammatory response with 
exposure. ICD is a non-immunologically driven, inflammatory reaction to an irritating substance.   
 
ACD is common, with some studies demonstrating prevalence rates as high as 20% of the general 
population (Alinaghi, Bennike, Egeberg, Thyssen, & Johansen, 2018). It can be difficult to 
distinguish ACD from other forms of dermatitis. History, patch testing, and other forms of 
assessments may help to clarify the diagnosis.  
 
The cause of allergic contact dermatitis is determined by patch testing performed by 
dermatologists. 
1.2. Investigational Agents 
 
This protocol is in preparation of the creation of an integrated test kit consisting of a novel physical 
patch design, custom allergen panels, digital photography, and a computer vision-based algorithm 
to interpret the patch test results.  These innovations represent a future state of technology.  Within 
scope of this protocol is an adaptation of existing patch testing supplies and a test of the 
performance of the AI algorithm performance in a manner that does not inform or alter the routine 
clinical diagnostic practice to minimize risk. 
 
The prospective data collection will involve multiple digital photography technologies. The 
primary photography device is an iOS-based custom application that allows for automated 
photograph capture and scheduling.  This smartphone application will be used by the participant 
enrolled in the study using a study-specific iPhone 12 or newer device.  The application in its 
current state only photographs the test site region and uploads the images to a secure, Firebase 
database on Google Cloud.  The software as a medical device aspect of the AI processing will not 
be involved in the capture or transfer of the data in the current configuration. The models will be 
run asynchronously using the data captured during the study.  In addition to this smart phone 
application, we will also use additional cameras, including a full-spectrum (infrared + ultraviolet 
+ visible light spectrums), to ensure the model performance is not contingent upon the iPhone 
model used in the study along with providing new data to potentially enhance the detection of 
contact dermatitis in the future.  
 

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1.2.1. Camera technologies under study 
 
Visible Light Digital Photography (“regular” photography): A standard iOS camera system will 
be the primary camera used in the study. This camera will be supplemented with cameras used 
during routine clinical documentation of the testing (i.e., a combination of Mayo Clinic owned and 
operated smartphones and interchangeable lens cameras.  
 
Full Spectrum Photography:  A full-spectrum digital photography system is one where the digital 
sensor has had the Bayer filter removed. This allows all wavelengths of light to reach the imagining 
sensor, including the ultraviolet spectrum (not visible with the unaided eye). A “Wood’s light” (or 
black light) uses ultraviolet light to accentuate different aspects of the skin, particularly 
pigmentation profiles. The study will also need to incorporate infrared light sources to best utilize 
the spectrum of light energy a camera can capture. A full spectrum camera can photograph the 
same wavelength of light, particularly if a glass filter that allows only a narrow range of 
wavelengths to pass is used. Likewise, infrared is used by many animals (and door sensor 
technologies) to identify subtle differences in heat profiles in objects. We are hypothesizing that 
the combination of ultraviolet and infrared spectra will improve the detection of allergic contact 
dermatitis by the computer vision algorithms.  
 
Photogrammetry: While a single photograph may characterize the appearance of raised textures 
on the skin surface, photogrammetry allows for direct modeling of the surface of the skin.  Briefly, 
photogrammetry is an established technique where an object (e.g., a suspicious skin lesion) is 
photographed from 30 or more angles. Computer algorithms assemble the set of photographs into 
a 3D mesh object that is a digital representation of the surface of the skin. We hypothesize that this 
3D representation of the skin lesion will convey important “tactile” information about the test sites 
that is not otherwise present in standard 2D digital photographs.  
 
1.2.2. Allergens 
The use of the allergens are in accordance with standard clinical practice. However, the allergens 
are not FDA approved for this purpose.  As such, they will be considered as investigational agents 
in the context of this study.   
 
1.2.3. Test Patch 
The physical patch test device is a clinical standard apparatus manufactured by Finn Chamber. The 
allergens are applied to the skin by means of direct contact when the patch test device is applied 
for testing.  Allergens are contained in an inert metal well.  For the purpose of this study, the paper-
like border surrounding these metal wells will be modified to allow for specific visual patterns to 
be drawn onto the skin using a standard surgical marker (blue shaded regions in the figure below). 
These markings will allow for the finalized AI workflow to identify unique allergen placement 
profiles based on markings drawn on the skin.  
 

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1.3. Preliminary Data 
1.3.1. Study #1: IRB 19-012164 
To-date, retrospective data collection under IRB  19-012164 has enrolled 310 subjects with 5,417 
reaction photographs (approximately 54,170 individual reaction sites) which includes images 
taken both from the prior patch design as well as the new, fiducial patch design. 
 
We have designed a deep learning classifier to predict the presence of allergic reaction from 
smartphone images of patch test reaction sites. The model was tested on a dataset of 260 patches 
(2,600 individual reactions) from several dozen individuals.  
 
On the test dataset, the model displayed area under the ROC curve of 0.877. At a prediction cutoff 
of 10%, the model had an accuracy of 0.942, a sensitivity (true positive rate) of 0.540, and a 
specificity (true negative rate) of 0.956. The ROC curve is shown below, along with several 
examples of correct and incorrect predictions. 
 

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ROC curve for model performance at the reaction level 
 
 
 
 
Examples of model prediction. For each of the four examples, the smartphone image of the 
reaction site is shown on the left, the true reaction label (based on the clinical report) is shown in 
the middle, and the model prediction is shown on the right. Positive and negative predictions are 
shown on a continuous color scale, where 1 (red) indicates the presence of reaction and 0 (blue) 
indicates the absence.  
 
1.3.2. Study #2: Prospective Clinical Trial (IRB 21-011596) 
 

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A prospective, pragmatic clinical trial was designed to advance the technologies associated with 
a democratized skin patch testing approach that leveraged novel patch designs and an integrated 
smartphone-based application to capture and upload photographs of the patch testing sites to the 
cloud. The study incorporated an in person, clinical assessment at all three study visits to 
establish the reference criterion according to current clinical protocol. Photographs were 
captured at each visit to provide means to evaluate a novel deep learning model for the detection 
of allergic contact dermatitis. While the deep learning algorithm’s performance could be 
established relative to the in-clinic reference reading, it was unknown just how well a human 
reader could function when only exposed to the photographs of the test sites (i.e., not able to 
palpate suspicious regions). To address this, the study incorporated a human reading protocol 
where the same photographs, void of any data collected about the patient or information obtained 
during the clinical visit, were reviewed by humans to determine what the accuracy of the 
machine learning approach in the context of human readers.  
 
A total of 232 participants consented to participate and 206 reached the day five assessment. A 
specific purpose of this study was to enroll 50% of participants with Fitzpatrick Skin Types IV – 
VI. This objective was achieved as the distribution of skin types over the six types were as 
follows: 46.6% were classified as types IV-VI. The mean (SD) participant age was 39.1 (13.5) 
years, and 66% (136/206) of the participants were female. A total of 32.0% (66/206) of 
participants self-identified as being Black or African American, 16.5% (34/206) as Asian 
(34/206), and 40.3% as White (83/206). A total of 23 participants self-identified as Other 
(11.2%) or of Hispanic origin (73.9%, 17/23).   
 
The overall incidence of allergic contact dermatitis in the sample was 6.4% (132/2,060) using the 
panel of allergens to be tested in the present study. The 206 images yielded 2060 test sites that 
were expertly evaluated during the in clinic (Day 5) evaluation. The only input to the neural 
network was the cropped image of the patch test site sites. The CNN model diagnosed the 
presence or absence of reaction with an AUROC of 0.861 (95% CI, 0.824 – 0.897). Using the 
previously selected cutoff of 4.88%, this generated an accuracy of 91.0% (95% CI, 89.7%-
92.2%), a sensitivity of 58.3% (95% CI, 49.4%-66.8%), and a specificity of 93.3% (95% CI, 
92.0%-94.3%). 
 
1.4. Risks and Benefits 
 
The risks of this research study are minimal. The most common side effect of skin testing is slightly 
swollen, red, itchy bumps (wheals). These wheals may be most noticeable during the test. In some 
people, though, an area of swelling, redness and itching may develop a few hours after the test and 
remain for a couple of days. 
Rarely, allergy skin tests can produce a severe, immediate allergic reaction.  
 
The patches are placed on the forearm for 48 hours. During this time, bathing and activities that 
cause heavy sweating need to be avoided. Irritated skin at the patch site may indicate an allergy. 

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As with all research, there is a chance that confidentiality could be compromised; however, we 
will take all appropriate precautions to minimize this risk.  
 
2. Study Objectives 
 
2.1. Primary Objective 
 
• To test if interpretation using novel AI algorithms analysis of photographs of skin patch 
tests is concordant with in person skin patch test interpretation.  
 
2.2. Secondary Objectives 
 
• To test if human review of photographs of skin patch tests are concordant with in person 
examination results. 
 
• To demonstrate performance of DermAI application usage by the participant. 
 
• To develop a database on novel photography modalities and explore performance 
advantages full spectrum photography and photogrammetry may bring to detecting 
contact dermatitis reactions. 
 
• To explore novel combinations of allergens to lessen the burden of testing. 
 
• To refine and optimize the lighting characteristics for photographing with visible 
spectrum and full spectrum lighting. 
 
 
 
3. Study Design 
3.1. General Description 
 
The overall adaptive study is designed to include three consecutive phases. Prior to the start of the 
adaptive study, a pilot cohort of up to 10 participants are planned to optimize the study protocol 
logistics, including camera usage, image capture parameters and documentation, and lighting 
conditions. This pilot phase is to ensure that the data captured during the adaptive study are as 
optimal as possible based on all study procedures. Pilot subjects will undergoing the same overall 
protocol scheme shown below and receive remuneration.  The data collected will be used to refine 
the protocol, with amendments as necessary.  
 

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Each of the phases in the adaptive study is intended to advance the technologies and evaluate how 
scalable the technologies will be outside the clinical practice.  The phases described below cover 
the primary intended workflow using the Mayo Clinic owned iPhone. Additional protocol actions 
including additional photography and ascertainment of other clinical study data (including adverse 
events) will occur to enrich the study data.  
 
Common study flow for all phases of the study: 
 
On day 1 a routine skin examination will be conducted. This will include photographic 
documentation of the condition of the skin region to be tested. Afterwards, the test patches will be 
applied to commence the testing. On day 3, the patients will return to remove the patch tests and 
document the test sites using the study iPhone app and the additional camera setups as specified 
in the protocol. On day 5, the final photographic documentation will be acquired and the final 
clinical assessment for allergic contact dermatitis will be provided by a medical professional with 
training in patch testing to establish the reference criterion.   
 
 
 
Specific adaptation according to each phase of the study: 
 
Phase 0 (n <=10): This pilot phase will study up to 10 participants to optimize the study manual 
of operations, ensuring the logistics and timing of all study visits to optimally conduct the three 
main phases of the study.  
 
Phase 1 (n=100): Phase 1 initiates where the prior pragmatic clinical trial (NCT053339750, IRB 
21-011596) concluded. This phase of the study will advance the technology in material ways 
through shifting day 3 (patch removal) and day 5 (final photographic documentation of test site) 
to the participant in the study.  Participants will be guided in the use of the application and primary 
iOS/iPhone photographic documentation; the study team will provide additional photographic 
documentation and review of the test site to establish the reference criterion.  
 
Phase 2 (n=25): For phase 2, the patch will be placed on the inside of the arm by the participant 
The study documentation will proceed identical to Phase 1.  
 
Quality Checkpoint Decision: Patch able to be successfully applied by patient in >90% of the cases 
(fewer than 3 placement errors). 
 

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Phase 3 (n=25): In phase 3, the entire study will be patient-led, although on-campus visits will be 
required to obtain the allergen panel and evaluate the reference criterion. This phase will use a 
prototype novel test kit with printed instructions and necessary supplies to clean the arm, assemble 
the patch application jig, install the app, and perform the patch testing. Human observation and 
patient surveys will be conducted to evaluate the human factors aspects of the test kit.  
 
For both Phases 2 and 3, participants will be invited to complete the Patient Journey questionnaire 
at least a week ahead of the scheduled visit 1 appointment by email. Responses will be summarized  
to suggest allergens that would be recommended based on past exposures. The recommendations 
will be constrained to only the set of allergens tested in this protocol (See Section 5.2). Participant 
will have the option to select the standard allergens used in Phase 1 of the study or use up to 10 of 
the recommended allergens based on the Patient Journey.  
3.2. Number of Subjects 
 
Up to a total of 160 participants will be enrolled and tested as part of the pilot (n<=10) or 
adaptive study (n=150). 
3.3. Duration of Participation 
 
An individual participant will require three visits to the study site on Days 1, 3 and 5.  
 
 
3.4. Identification of Source Data 
 
Study-specific case report forms (CRFs) will be used to document all of the following: 
1. Demographics and medical history including assessment of Fitzpatrick skin types 
2. Patient will be assigned to one of the randomized allergen templates that will be used for 
the study. 
3. Documentation of the randomized location of the allergens on the test patch used with the 
participant 
4. Documentation of the reference criterion (in person assessment by medical professional 
with training in patch testing Day 5) as well as the initial impression of reactions at Day 3 
immediately following the removal of the patches.  
5. Participant feedback on the user experience of the test patching 
6. Documentation of the blinded human review of the photographs acquired on Day 3 and 
Day 5 
7. Adverse events 
 
 
The following source data will not be directly collected in the CRFs, but will be integrated into the 
master database: 
• Test site photographs 
• AI predictions on the photographs 
 

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4. Subject Selection Enrollment and Withdrawal 
4.1. Inclusion Criteria 
• Adults aged 18 or older 
• Willing and able to provide informed consent 
 
4.2. Exclusion Criteria 
• Under 18 years of age 
• Has used topical or oral steroids two weeks prior to patch testing 
• Currently taking immunosuppression agents or is immunocompromised due to medical 
condition 
• No sunburn or rash at site of testing 
• Women who are breastfeeding or pregnant. 
• Treatment with ultraviolet (UV) light (including tanning) during the two weeks prior to 
visit. 
• Subjects unable to comply with patch test study requirements including multiple return 
visits and activity restrictions (e.g., protecting patch test area from excess moisture due to 
showering) 
 
4.3. Subject Recruitment, Enrollment and Screening 
 
The recruitment for this study will include participants from Mayo Clinic Florida patients and staff, 
and collaboration with the University of North Florida. 
In 2019, approximately 284 patients had skin patch tests performed at Mayo Clinic Department of 
Dermatology in Jacksonville Florida. Among these patients, 17 were identified Black or African 
American with a Fitzpatrick score of 5-6, and 32 were identified as Hispanic or Latino with a 
Fitzpatrick score of 3-6. 
Additionally, we will advertise for a healthy control group throughout Mayo Clinic Florida campus 
as well as the University of North Florida. In 2019, the University of North Florida student 
population enrollment was reported at approximately 17,117 students. The distribution of 
population for minority population of interest is 10% (1,684) Black or African American, 13.3% 
(2,280) Hispanic or Latino, and 5% (853) two or more races. Potential participants can contact the 
study coordinator listed in the flyer and/or electronic display to further inquire on eligibility criteria 
and study questions.  
Thus, we estimate that from a pool of 49 eligible patients in Mayo Clinic Florida per year, the 
robust minority population of employees at Mayo Clinic and student population at University of 
North Florida, we can achieve full enrollment. 
We will monitor enrollment bi-weekly and will hold calls with the study team to clarify questions 
about eligibility and ensure robust recruitment. If recruitment falls short of numerically defined 
targets, we will assess reasons for slow accrual and adjust the protocol accordingly.  

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Patients who have undergone previous patch testing will be screened by an experienced study 
coordinator for participants with a Fitzpatrick skin types 4 through 6 and eligibility criteria. This 
study coordinator will call the patient to discuss the study, eligibility, and study logistics, and then 
will plan to meet the patient at their next visit to the clinic to review and sign the consent (if the 
patient wishes to participate and is eligible).  
Potential participants who answer the advertisement will have a call scheduled with the study 
coordinator to discuss the study, eligibility, and study logistics. Based on the potential participant’s 
agreement, the study coordinator will schedule a research visit, as well coordinate with the 
Dermatology medical assistants to schedule the patch testing procedures.  
The study coordinators are skilled in presenting the trial information without bias or pressure and 
in a culturally appropriate manner. Translators will be used as needed. Study coordinators will ask 
those patients who remain initially undecided if they may contact them again at a determined 
timeframe to review again and ask further questions. Screening and enrollment failures and related 
reasons for same will be discussed at the monthly review meetings and potential actions will be 
taken as need. Attention will be paid to adhering to regulatory issues.  
4.4. Early Withdrawal of Subjects 
4.4.1. When and How to Withdraw Subjects 
 
Participants may withdraw at any point in the study. In the event the test patch is removed early   
due to possible reaction to an allergen or for another other reason (e.g., removed while bathing), 
the study team will be notified of the event.  
4.4.2. Data Collection and Follow-up for Withdrawn Subjects 
 
Participation is strictly voluntary. The participant will be followed according to protocol to 
document the reactions if the participant is willing. If the participant is unable or unwilling to 
continue with protocol procedures, the study records will be noted as such. 
 
5. Test Patch and Allergen Details  
5.1. Description of test patch vehicle 
 
The test patch (Finn Chamber) is a non-sterile aluminum chamber mounted on Scanpor tape, 
which is a hypoallergenic surgical tape with a non-latex adhesive.  The tape is made of rayon and 
polyester fibers.  
5.2. Investigational allergens 
5.2.1. Primary Test Site (arm 1) 
 
The following ten allergens manufactured by AllergEAZE will be used for patch testing during 
the study. Potential adverse reactions include pruritus, irritation, skin discoloration, erythema, 
induration, blistering and ulceration. Pruritus can be managed over-the-counter antihistamines. 

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While most reactions self-resolve, more severe skin reactions would be managed with topical 
steroids.    
 
 
1. Nickel sulfate hexahydrate, 2.5% (18.3%)  
2. M. Pereirae resin, 25% / Balsam of Peru (9.2%) 
3. Neomycin sulfate, 20% (7.8%)  
4. Fragrance mix, 8% (6.7%)  
5. Bacitracin, 20% (6.4%)  
6. Carba mix, 3% (5.8%) 
7. Quaternium-15, 1% (4.4%) 
8. Benzoic acid, 5% (3.7%) 
9. Propolis, 10% (3.5%) 
10. Thiuram mix, 1% (2.8%) 
 
5.2.2. Secondary Test Site (arm 2) 
 
As part of the technology development program, two secondary tests will be used. Each participant 
will be randomized to one of these two patches.  
 
Combination Patch #1: Standard Panel Array of 10 Allergens Combined into 4 Wells 
 
1: Metals: Nickel sulfate hexahydrate   
 
2: Fragrance & Taste Enhancers: M. Pereirae resin, 25% / Balsam of Peru  + Fragrance mix + 
Quaternium-15  
 
3: Topical/Homeopathic: Neomycin sulfate + Bacitracin + Propolis  
 
4: Fungicides:  carba mix + Thiuram mix + Benzoic acid  
 
  
 
 Combination Patch #2: Common Jewelry & Cosmetic Patch  
 
1: Common metal allergy: Nickel sulfate hexahydrate  
 
2: Cosmetics: M. Pereirae resin, 25% / Balsam of Peru   
 
3: Cleaners: Methylchloroisothiazinoline / methylisothiazinolone  
 
4: Fragrance: Fragrance mix   
 
Combination Patch #3: Patient Identified Allergen Profiles 
 

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For Phase II and III of the study, the following ten allergens will be added to the pool of 10 unique 
allergens tested in the primary patch and the combination of allergens offered as a part of the two 
combination patches.  
• Linalool 
• P-phenylenediamine 
• Benzisiothiazolinone, 0.1p 
• Methylchloroisothiazinoline / methylisothiazinolone 
• Paraben mix 
• Formaldehyde 
• Tea Tree Oil 
• Cobalt Chloride 
• Disperse Dye (Blue Mix) 
• Gold Sodium Thiosulfate 
 
This patient-driven combination of allergens can have between 1 and 10 individual test sites 
allowing for measurement of preference for “body burden” and patch test configurations.   
5.3. Method for Assigning Allergens to Test Site Regions  
 
To minimize complexity of the randomization process and preparation of the patch test for the 
primary test site, a total of four randomized placement sequences will be generated.  Participants 
will be assigned to these sequences in consecutive order. This same randomization sequence will 
be used to randomize the secondary patch option to the participants with participants holding an 
odd study number receiving Combination #1 and even study numbers receiving #2. Note these 
two patches are largely identical except for how the allergens are combined with the exception 
that Combination #2 has methylchloroisothiazinoline / methylisothiazinolone added to it.  
 
5.4. Preparation and Application of Test Patches 
 
The application of the allergens to the test patch will be conducted according to the Study 
Operation Manual. This manual will include the documentation of safe storage and handling 
practices of the allergens, templates of the randomized allergen locations, and guidelines for the 
application of the patch to the participant’s arm.  
5.5. Subject Compliance Monitoring 
 
The primary compliance consideration for this study is the maintenance of the test patch over the 
first three days. The participant will be given information on showering and other personal 
hygiene considerations while the patches are worn. Early removal or contamination of the test 
patch will be documented on Day 3 during the participant’s visit.  Deviations from the expected 
protocols will be documented on study case report forms.  
 

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5.6. Masking/Blinding of Study  
 
The medical professional that reads the photographs of the test sites will be blinded to all clinical 
information including, but not limited to, the allergen’s randomized locations, the in-person 
assessment of the reactions, and any AI predictions on the images. Effectively, the human read of 
the photograph will only have the photograph available to form all impressions about the 
reactions.  
 
The reading of the human interpretation of the photographs will occur at least 1 month after the 
clinical visit to maintain blinding and washout in the event study staff provide a visual 
impression of the reaction sites via photographic review. 
 
 
6. Study Procedures 
 
6.1. Prior to Visit 1 and after study consent, the participant will have an opportunity to 
complete the Patient Journey. For Phases II and III of the study, this patient 
journey will be distributed to the patient prior to Visit 1 to allow for the data to be 
summarized. The summarization will include qualitative and quantitative 
approaches to quantify the self-reported employment profiles, ancestry, and known 
allergens to identify which allergens that may be more allergenic to the participant. 
Visit 1 (Day 1) 
Informed consent will be obtained as well as demographic information, medical history, and 
current medications questionnaire (see Schedule of Events).  
 
A limited physical exam focused on the forearm will be conducted as well as assessment of 
participant's Fitzpatrick skin type.  
 
A baseline photo will be taken using the smart phone application and the additional camera systems 
including the full spectrum documentation and photogrammetry acquisition.  
 
A member of the study team will place the primary test patch on the volar aspect of participants’ 
forearm. The patch contains allergens placed in dime-sized wells. The location of the allergens 
within the patch will be randomized between participants. The study team member will document 
the location of each allergen.  
 
The smaller, 4 well patch, on the secondary arm will be placed similar manner to the primary test 
patch.  
 
Tape or waterproof dressing may be used to secure the patch strips. Participant will be given 
instructions to avoid water contact with patch, and avoidance of sun exposure.  
 
Participants will be allowed to take over the counter histamine blockers to alleviate pruritus.  

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6.2. Visit 2 (Day 3) 
Participant will be asked to return after 48 hours (Day 3) for patch removal and preliminary 
reaction assessment.  
 
Skin will be assessed and documented for reactions which may include irritation, redness, and/or 
swelling localized to the patch test area.  
 
The reaction will be documented as negative, irritation, or positive contact allergic reaction using 
the scale described below in section 6.6.  
 
Participant will be encouraged to let the study team know if there was any itching or burning while 
the patches were in place.  
 
A complete set of photos will be taken to document any reactions with the smart phone application 
and other camera systems. 
6.3. Visit 3 (Day 5) 
After about 96 hours (Day 5), the participant will return for a final assessment.  
 
This assessment time is the final (reference criterion) assessment as it is necessary to allow for up 
to five days for a skin reaction to appear.  
 
At the visit, the medical professional with training in patch testing will review the skin for any 
reaction and document in the CRF.  
 
A complete set of photos will be taken to document the reactions using the smart phone application 
and other camera systems.  
 
Participant feedback on the patch testing experience will be documented.  
 
Severe contact dermatitis will be treated with topical steroids if needed. 
 
 
6.4. Photographic Documentation 
 
At each study visit with photographs taken, a comprehensive set of images will be captured. This 
will include the primary acquisition using the study’s smartphone application but also novel 
imaging including: 
 
Full spectrum analysis:  
1. Unfiltered (clear) 
2. Filtered to specific wavelengths:  590nm, 665nm, 720nm, and 850nm  
3. Additional (wide range) filters: Blue IR (excluding visible light spectrum, except blue, and 
including infrared) and Hot Mirror (~100nm – 700nm; i.e., visible light) 

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4. Lighting conditions – routine clinical lighting, exposed with a Wood’s Lamp (“black 
light”), exposed with  
 
Live video clips: Short videos using the iPhone’s live capture 
 
Photogrammetry: A series of 20 or more images of each test site will be captured from all angles. 
These images are reconstructed using software to form a three-dimensional rendering of the test 
site.   
 
Tripod / camera assist device: The smartphone will be supported with a phone cradle during the 
photographic documentation.  This device includes a shell to block ambient light while allowing 
for the phone to be securely supported during the documentation process. This device is to 
standardize the distance and lighting while removing artifacts from the background of the image 
that could be identifiable data.  
 
 
6.5. Off study evaluation (post reaction care, if applicable) 
 
In the event of a positive allergic reaction that should be treated with topical steroids, the 
participant will be provided over-the-counter hydrocortisone.  If prescription strength steroids are 
required, a prescription will be made. 
 
6.6. Reaction Grading Scale 
Reactions will be graded as negative, irritant, or positive. Positive reactions will be rated as 
doubtful (1), weak (2), strong (3), or extreme (4) depending on their physical appearance. Doubtful 
reactions only have faint erythema, weak reactions are those with non-vesicular erythema, strong 
reactions are raised and have vesicular or non-vesicular erythema, extreme reactions are bullous 
or ulcerative in nature. 
 
(Spiewak et al)  
 

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(Johansen et al)  
 
 
 
6.7. Participant Remuneration 
Participants will be remunerated $125 / visit ($375 total for completing the study).  
Schedule of Events 
 
 
Study Activity 
Day 1  
Day 2 
Day 3  
Day 4 
Day 5 
Off Study 
Evaluation 
Informed consent 
X 
 
 
 
 
 
History a  
  X 
 
 
 
 
 
Concurrent meds 
  X 
 
 
 
 
 
Limited physical exam b  
  X 
 
 
 
 
 
Patch placement e 
  X 
 
 
 
 
 
Documentation of allergen 
location 
X 
 
 
 
 
 
Photographic Documentation c 
X 
 
X 
 
Xd 
 
Patch Removal 
 
 
X 
 
 
 
Reaction Assessment 
 
 
X 
 
X 
 
Participant feedback 
 
 
 
 
X 
 
Adverse Event Assessment 
 
 
X 
 
X 
X  

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a. Demographic information, medical history 
b. Fitzpatrick skin type assessment, arm inspection 
c. Photographic documentation of volar aspect of forearm (primary and optional secondary test sites)
taken with the approved photographic assessment  
d. In person assessment on Day 5 used as reference criterion 
e. Phase 1 & 2 will be done by provider. Phase 3 done by patient. 
 
 
7. Statistical Plan 
7.1. Sample Size Determination 
 
The primary sample size is determined based on Phase I of the study. With an expectation that 
15% of the test sites will be positive, based on the selection of allergens with the highest 
incidence of reactions, and a target sensitivity of 95%, 90% power, and a minimum clinically 
relevant difference of 5 percentage points, a total of 130 positive test sites needs to be present in 
the study to achieve the design specifications. Given the assumption that most participants will 
only exhibit 1 to 2 reactions and the intraclass correlation of detections remains unknown, the 
design effect (or variance inflation effect) is not applied to account for potential clustering of 
reactions per participant. Therefore, with the assumption that each participant will have 1.5 
positive reactions on average, we anticipate a requirement for 100 participants.  
 
The sample sizes for Phase  II and III have been administratively set based on feasibility of 
recruitment and testing.  
7.2. Study Endpoints 
7.2.1. Primary Study Endpoints 
 
The accuracy for the classification of regions within the test panel that either were a reaction 
(reaction grade 1+) or not (grade 0).  
7.2.2. Secondary Study Endpoints 
 
• The accuracy for the classification of the test site region using a 5-point scale: Grades 0 – 
4. 
• Sensitivity 
• Specificity 
• False positive rate 
• False negative rate 
• Percentage early termination of testing 
• Percentage of participants that removed patches early 
• Adverse events related to allergen exposure 
• Patient feedback on the testing process 

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Primary Hypothesis:  
 
The AI algorithm will provide non-inferior performance measured by binary classification 
accuracy relative to the human performance. 
 
To test the primary hypothesis, The primary hypothesis to be tested is the “agreement” between 
the clinical (in person) evaluation and the human review and AI predictions of the app captured 
images. Generalized estimating equations (GEE) will be structured to estimate the clustered 
accuracy using an identity link and robust variance estimator to account for the clustering within 
the database. The model will have a single predictor that indicates which reader (AI vs. human) 
is associated with the accuracy determination (a 1/0 with 1 indicating the “reader” reached the 
same conclusion as the expert, in person review). For the purpose of the primary outcome 
measure, the prediction from either the human or AI algorithm will be dichotomized into no 
reaction (grade 0) vs. any reaction (grades 1 – 4). The estimate and 95% CI for the “reader” 
effect will summarize the differential performance between the 
human and AI interpretations. For the AI algorithm to be 
considered non-inferior, a limit of inferiority of 5 percentage 
points will be used. The fitted model will be used to estimate 
the overall performance and 95% CI for the two readers. As 
shown in the figure, we desire both the human and AI 
performance to provide greater than 95% accuracy.  
 
To supplement this analysis, the area under the receiver operating characteristic curve (AUC 
ROC) will be computed using the visual analog scale by test site determined by the human 
observer and the AI model’s output. DeLong’s test will be used to compare the differences in 
performance between these two approaches.  
 
Secondary Hypothesis 1:  
 
For the secondary endpoint of agreement on the 5 point clinical scale, unweighted and weighted 
Kappa will be used to estimate the degree to which the human and AI interpretations agree. The 
unweighted analysis will focus on the direct match on grade assigned to each of the test sites.  
 
There is a block of standard measures of diagnostic performance (e.g., sensitivity, specificity).  
These statistics will be computed as is customary for similar studies.  The calculations will be 
performed two ways when possible.  First, each test site will be assumed to be statistically 
independent in the rating.  For the neural network, this is how the algorithm functions.  For the 
human reading, there may be some correlation among the ratings based on the reactions, if any, 
that are observed. To address this, an exploratory analysis will be conducted using generalized 
estimating equations to examine the impact empirically the intercorrelations may have on the 
estimated precision of the estimates (i.e., confidence interval width).   
 
Safety data will be summarized by tabulating adverse events for the study. These will be 
categorized according to allergen related or study protocol related. 

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The secondary test sites include allergens, in novel combinations, that were tested in the primary 
test site. A secondary analysis will be conducted to quantify the agreement of reactions to the 
same allergens alone (primary test patch) and in combination (secondary test patch).  Kappa will 
be used to quantify this agreement. 
 
Finally, participant feedback on the study including the wearability of the patch on the forearm 
will be summarized using standard qualitative methods. This will include the extraction of key 
themes as well as listing open ended feedback provided to the study team by the participants.  
7.3. Additional Statistical Considerations 
7.3.1. Descriptive Statistics 
 
Univariate descriptive statistics and frequency distributions will be calculated, as appropriate for 
all variables.  Baseline values for demographic, clinical, and outcome variables (primary and 
secondary) will be tabulated for the enrolled participants. These summaries will be summarized 
for the overall sample and by Fitzpatrick Skin Type.   
7.3.2. Handling of Missing Data 
 
Missing data may occur throughout the study.  The primary analysis, which is based on the AI 
and human interpretation of the images relative to the in-person assessment, will require that all 
test site regions have an interpretation of the reaction grade. If missing data is not able to be 
obtained by re-assessing the data, a “worst case” imputation strategy will be used. With this 
missing data will be included in the denominator of test sites tested but none of the regions will 
be included in the numerator for measurement of accuracy or concordance between AI and 
human interpretation (i.e., is counted as a “miss” in the analysis).  For demographic and medical 
history data, any missing data will be reported as such in the final analysis.  
7.3.3. Multiplicity 
 
There will be no adjustment to the level of significance for multiple testing.  All results will be 
reported unadjusted at the alpha=0.05 level of significance using estimates and 95% confidence 
intervals. 
7.3.4. Interim Analysis 
 
There is no planned interim analysis. 
7.3.5. Analysis Sets 
 
The analysis set for this study will follow the modified intention to treat principle.  To be included 
in the analysis, the participant needs to be randomized and complete at least the day 5 assessment 
(final documentation of the skin reactions).  Participants that study the allergen exposure challenge 
early are still eligible for the final analysis provided they consent to a day 5 assessment (see 
schedule of assessment early in the event the day 5 assessment occurs earlier).  

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8. Safety and Adverse Events 
8.1. Definitions 
Unanticipated Problems Involving Risk to Subjects or Others (UPIRTSO) 
Any unanticipated problem or adverse event that meets the following three criteria:  
• Serious: Serious problems or events that results in significant harm, (which may be 
physical, psychological, financial, social, economic, or legal) or increased risk for the 
subject or others (including individuals who are not research subjects). These include: (1) 
death; (2) life threatening adverse experience; (3) hospitalization - inpatient, new, or 
prolonged; (4) disability/incapacity - persistent or significant; (5) birth defect/anomaly; 
(6) breach of confidentiality and (7) other problems, events, or new information (i.e. 
publications, DSMB reports, interim findings, product labeling change) that in the opinion 
of the local investigator may adversely affect the rights, safety, or welfare of the subjects 
or others, or substantially compromise the research data, AND 
• Unanticipated: (i.e., unexpected) problems or events are those that are not already 
described as potential risks in the protocol, consent document, not listed in the 
Investigator’s Brochure, or not part of an underlying disease. A problem or event is 
"unanticipated" when it was unforeseeable at the time of its occurrence. A problem or 
event is "unanticipated" when it occurs at an increased frequency or at an increased 
severity than expected, AND 
• Related: A problem or event is "related" if it is possibly related to the research procedures. 
 
Adverse Event 
An untoward or undesirable experience associated with the use of a medical product (i.e., drug, 
device, biologic) in a patient or research subject. 
Serious Adverse Event 
Adverse events are classified as serious or non-serious.  Serious problems/events can be well 
defined and include; 
• death 
• life threatening adverse experience 
• inpatient hospitalization or prolongation of existing hospitalization 
• persistent or significant disability or incapacity 
• substantial disruption of the ability to conduct normal life functions 
• birth defect/congenital anomaly 
 
and/or per protocol may be problems/events that in the opinion of the sponsor-investigator 
may have adversely affected the rights, safety, or welfare of the subjects or others, or 
substantially compromised the research data. 
 
All adverse events that do not meet any of the criteria for serious, should be regarded as non-
serious adverse events.  
 

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Adverse Event Reporting Period 
 
Adverse events that occur between the time of the test patch application (Day 1) and Day 5 should 
be reported on the study CRFs. 
 
 
Preexisting Condition 
A preexisting condition is one that is present at the start of the study.  A preexisting condition 
should be recorded as an adverse event if the frequency, intensity, or the character of the 
condition worsens during the study period. 
 
General Physical Examination Findings 
At screening, any clinically significant abnormality should be recorded as a preexisting 
condition.  At the end of the study, any new clinically significant findings/abnormalities that 
meet the definition of an adverse event must also be recorded and documented as an adverse 
event.  
 
Post-study Adverse Event 
All unresolved adverse events should be followed by the sponsor-investigator until the events are 
resolved, the subject is lost to follow-up, or the adverse event is otherwise explained.  At the last 
scheduled visit, the sponsor-investigator should instruct each subject to report, to the sponsor-
investigator, any subsequent event(s) that the subject, or the subject’s personal physician, 
believes might reasonably be related to participation in this study.  
 
Hospitalization, Prolonged Hospitalization or Surgery 
Any adverse event that results in hospitalization or prolonged hospitalization should be 
documented and reported as a serious adverse event unless specifically instructed otherwise in 
this protocol.  Any condition responsible for surgery should be documented as an adverse event 
if the condition meets the criteria for an adverse event.  
  
8.2. Recording of Adverse Events 
At each contact with the subject, the study team must seek information on adverse events by 
specific questioning and, as appropriate, by examination.  Information on all adverse events 
should be recorded immediately in the source document, and also in the appropriate adverse 
event section of the case report form (CRF).  All clearly related signs, symptoms, and abnormal 
diagnostic, laboratory or procedure results should be recorded in the source document. 
 
All adverse events occurring during the study period must be recorded.  The clinical course of 
each event should be followed until resolution, stabilization, or until it has been ultimately 
determined that the study treatment or participation is not the probable cause.  Serious adverse 
events that are still ongoing at the end of the study period must be followed up, to determine the 
final outcome.  Any serious adverse event that occurs during the Adverse Event Reporting 
Period and is considered to be at least possibly related to the study treatment or study 
participation should be recorded and reported immediately. 

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8.3. Reporting of Serious Adverse Events and Unanticipated Problems 
 
When an adverse event has been identified, the study team will take appropriate action necessary 
to protect the study participant.  The sponsor-investigator will evaluate the event and determine 
the necessary follow-up and reporting required. 
8.3.1. 
Sponsor-Investigator reporting: notifying the Mayo IRB 
 
The sponsor-investigator will report to the Mayo IRB any UPIRTSOs and Non-UPIRTSOs 
according to the Mayo IRB Policy and Procedures. 
 
 
8.3.2. 
Sponsor-Investigator reporting: Notifying the FDA 
 
The sponsor-investigator will report to the FDA all unexpected, serious suspected adverse 
reactions according to the required IND Safety Reporting timelines, formats, and requirements. 
 
Unexpected fatal or life threatening suspected adverse reactions where there is evidence to 
suggest a causal relationship between the study drug/placebo and the adverse event, will be 
reported as a serious suspected adverse reaction.  This will be reported to the FDA-on-FDA 
Form 3500A, no later than 7 calendar days after the sponsor-investigator’s initial receipt of the 
information about the event. 
 
Other unexpected serious suspected adverse reactions where there is evidence to suggest a causal 
relationship between the study drug/placebo and the adverse event, will be reported as a serious 
suspected adverse reaction.  This will be reported to the FDA-on-FDA Form 3500A, no later 
than 15 calendar days after the sponsor-investigator’s initial receipt of the information about the 
event. 
 
Any clinically important increase in the rate of serious suspected adverse reactions over those 
listed in the protocol or product insert will be reported as a serious suspected adverse reaction.  
This will be reported to the FDA-on-FDA Form 3500A no later than 15 calendar days after the 
sponsor-investigator’s initial receipt of the information about the event. 
 
The sponsor-investigator must also notify the FDA (and sponsors must notify all participating 
investigators) in an IND safety report of potential serious risks, from clinical trials or any other 
source, as soon as possible, but in no case later than 15 calendar days after the sponsor determines 
that the information qualifies for reporting under § 312.32(c)(1)(i)-(iv). 
 
Findings from other studies in human or animals that suggest a significant risk in humans exposed 
to the drug will be reported.  This will be reported to the FDA-on-FDA Form 3500A, no later than 
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8.4. Unmasking/Unblinding Procedures 
 
In the event of a reaction to one of the allergens, the primary medical professional performing the 
in-person evaluation will have access to the unblinding information (i.e., identification of the 
allergens for each test site). The cause of any reactions will be denoted in the study records and 
communicated to the participant.  
 
8.5. Stopping Rules  
 
No study stopping rules are proposed based on the risk profile for the study.  In the event the 
feasibility of the study is not tenable due to challenges in recruitment or other study operational 
considerations, the study may be terminated at the request of the study sponsor in conjunction with 
the institutional review board of record.  
8.6. Medical Monitoring 
It is the responsibility of the Principal Investigator to oversee the safety of the study at his/her 
site.  This safety monitoring will include careful assessment and appropriate reporting of adverse 
events as noted above. 
9. Data Handling and Record Keeping 
9.1. Confidentiality 
Information about study subjects will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  
Those regulations require a signed subject authorization informing the subject of the following:  
1. What protected health information (PHI) will be collected from subjects in this study 
2. Who will have access to that information and why? 
3. Who will use or disclose that information? 
4. The rights of a research subject to revoke their authorization for use of their PHI  
 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by 
regulation, retains the ability to use all information collected prior to the revocation of subject 
authorization.  For subjects that have revoked authorization to collect or use PHI, attempts 
should be made to obtain permission to collect at least vital status (long term survival status that 
the subject is alive) at the end of their scheduled study period. 
9.2. Source Documents 
Source data is all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial.  Source 
data are contained in source documents.  Examples of these original documents and data records 
include: hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ 
diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated 
instruments, copies or transcriptions certified after verification as being accurate and complete, 
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records kept at the pharmacy, at the laboratories, and at medico-technical departments involved 
in the clinical trial. 
9.3. Case Report Forms 
 
The study case report form (CRF) is the primary data collection instrument for the study.  All data 
requested on the CRF is expected to be recorded.  All missing data must be explained.  If a space 
on the CRF is left blank because the procedure was not done or the question was not asked, write 
“N/D”.  If the item is not applicable to the individual case, write “N/A”.  All entries should be 
printed legibly in ink.  If any entry error has been made, draw a single straight line through the 
incorrect entry and enter the correct data above it.  All such changes must be initialed and dated.  
Do not erase or use “white-out” for errors.  For clarification of illegible or uncertain entries, print 
the clarification above the item, initial and date it.  If the reason for the correction is not clear or 
needs additional explanation, neatly include the details to justify the correction. 
 
Data Management 
 
Data recorded on CRFs will be entered into a password protected, change-audited electronic data 
management system (REDCap or equivalent). Data will be structured to document missing data, 
when appropriate. All changes to data saved to the database will have a timestamp indicating the 
user account that made the change to the data.   
 
Standard reports on data quality will be configured to identify possible errant data elements.  In 
the event a questionable data is identified, the data will be confirmed using original study records.  
9.4. Records Retention 
 
The sponsor-investigator will maintain records and essential documents related to the conduct of 
the study.  These will include subject case histories and regulatory documents. 
 
Case report forms will be designed to identify each subject-by-subject entry number and, where 
appropriate, subject's initials, the product being evaluated, and the results observed. All entries to 
the CRFs must be made as instructed by the study investigator. Data on subjects collected on 
CRFs during the study will be documented in an anonymous fashion, and the subject will only be 
identified by the subject number, and by his/her initials, if also required.  
 
All records will be kept in conformance to applicable national laws and regulations. The original 
signed ICF will be attached to each subject’s file. When the study treatment is completed, the 
ICF will be kept in the appropriate file folder; otherwise, a note indicating where the records can 
be located will be made. Documents will be stored in a password protected Mayo secure server 
as well as in a locked cabinet, where the study team is the only ones to have access to. 
 
The investigator will retain the specified records and reports for 
• Up to 2 years after the marketing application is approved for the drug; or, if a marketing 
application is not submitted or approved for the drug, until 2 years after shipment and 

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delivery of the drug for investigational use is discontinued and the FDA has been so 
notified OR 
• As outlined in the Mayo Clinic Research Policy Manual – “Retention of and Access to 
Research Data Policy”
   
whichever is longer. 
 
10. Study Monitoring, Auditing, and Inspecting 
10.1. 
Study Monitoring Plan 
 
The Investigator will allocate adequate time for such monitoring activities.  The investigator will 
also ensure the monitor or other compliance, or quality assurance reviewer has access to all 
study-related documents and study related facilities (e.g. pharmacy, diagnostic laboratory, etc.), 
and has adequate space to conduct the monitoring visit. 
10.2. 
Auditing and Inspecting 
The investigator will permit study-related monitoring, audits, and inspections by the IRB, the 
sponsor, and government regulatory agencies, of all study related documents (e.g., source 
documents, regulatory documents, data collection instruments, study data etc.).  The investigator 
will ensure the capability for inspections of applicable study-related facilities (e.g., pharmacy, 
diagnostic laboratory, etc.). 
 
Participation as an investigator in this study implies acceptance of potential inspection by 
government regulatory authorities and applicable compliance offices. 
11. Ethical Considerations 
This study is to be conducted according to United States government regulations and 
Institutional research policies and procedures. 
 
This protocol and any amendments will be submitted to a properly constituted local Institutional 
Review Board (IRB), in agreement with local legal prescriptions, for formal approval of the 
study.  The decision of the IRB concerning the conduct of the study will be made in writing to 
the sponsor-investigator before commencement of this study. 
 
All subjects for this study will be provided a consent form describing this study and providing 
sufficient information for subjects to make an informed decision about their participation in this 
study.  This consent form will be submitted with the protocol for review and approval by the IRB 
for the study.  The formal consent of a subject, using the approved IRB consent form, must be 
obtained before that subject undergoes any study procedure.  The consent form must be signed 
by the subject or the subject’s legally authorized representative, and the individual obtaining the 
informed consent. 
11.1. 
Conflict of Interest 
 

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Any study team member who has a conflict of interest with this study (patent ownership, royalties, 
or financial gain greater than the minimum allowable by their institution, etc.) must have the 
conflict reviewed by a properly constituted Conflict of Interest Committee with a Committee-
sanctioned conflict management plan that has been reviewed and approved by the study sponsor-
investigator prior to participation in this study. 
11.2. 
Subject Stipends or Payments 
 
Participants will receive $125.00 for each study visit completed. If the participant completes the 
entire study, they will receive payment up to $375.00 
 
12. References 
 
1. Spiewak R, Pietowska J, Curzytek K. Nickel: a unique allergen - from molecular structure to 
European 
legislation. 
Expert 
Rev 
Clin 
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