A Prospective, Randomized, Split-Arm Pilot Study Investigating the Efficacy and Safety of Sciton's Broad Band Light for Improving the Clinical Signs of Senile Purpura
Phase: NA
Conditions: Senile Purpura, Bateman's Purpura
Sponsor: Siperstein Dermatology

 
 
 
 
Advarra IRB Approval Date : August 27th 2018 
 
 
NCT03690375 
ID: Purpura001 
Robyn Siperstein, MD 
 
Documents Enlcosed: 
    
    
1. Statistical Analysis Plan  
2. Protocol 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
Primary Endpoint 
 
𝐻0:µ𝐶= 0  ;   𝐻1: µ𝐶> 0 
 
➢ The null hypothesis is the absolute mean difference in the change from baseline to 30 days after 
the last treatment on the treatment arm as compared to the non-treatment arm is zero. 
➢ The alternative hypothesis is the absolute mean change from baseline to 30 days after the last 
treatment on the treatment arm as compared to the non-treatment arm is greater than zero. 
 
1. Let µ𝐶 represent the absolute mean difference between the treated arm as compared to the 
non-treated arm in the difference in the number of ecchymoses from baseline to 30 days 
after the last treatment. 
 
2. Let µ𝐶 represent the absolute mean difference between the treated arm as compared to the 
non-treated arm in the difference in the size of ecchymoses from baseline to 30 days after 
the last treatment. 
 
 
A Paired t-test will be used to analyze the primary endpoint.   The results of the statistical 
analysis will be presented as an odds ratio with 95% Confidence intervals. A Shapiro-Wilk 
Test will be used to assess the normality of data. 
 
 
 
 
 
 
 
 
 
 
 
STATISTICAL ANALYSIS PLAN 

 
 
 
 
 
 
 
PROTOCOL 
 
 
A Prospective, Randomized, Split-
Arm Clinical Study Investigating 
the Efficacy and Safety of 
Sciton’s Broad Band for the 
Treatment and Prevention of 
Senile Purpura 
 
Pilot Study 
 
Robyn Siperstein M.D. 

 
  
A Prospective, Randomized, Split-Arm Clinical Study Investigating the Efficacy and Safety of Sciton’s 
Broad Band for the Treatment and Prevention of Senile Purpura 
 
Principal Investigator: Robyn Siperstein MD  
9897 Hagen Ranch Road 
Boynton Beach Florida 33472 
Phone: 954-494-1400 
Fax: 888-650-7801 
Email Address: Doctorsip@Sipderm.com 
 
Statistician: Kimoy Williams Kotun  
Phone: 786-469-9100 
Email Address: kimoywilliams@gmail.com 
 
Study Cooridnator: Stacy Stankiewicz  
Study Evaluator: Jennifer Richter  
9897 Hagen Ranch Road 
Boynton Beach Florida 33472 
Phone: 561-756-1538 
Fax: 888-650-7801 
 
 
 
 
 
 

 
  
 
  STATEMENT  OF COMPLIANCE
 
 
 
The trial will be conducted in accordance with the ICH E6 and the Code of Federal Regulations on 
the Protection of Human Subjects (45 CFR Part 46). The Principal Investigator will assure that no 
deviation from, or changes to the protocol will take place, 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:  Robyn Siperstein 
 
 
Signed:   
Date:    
 Signature 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
  
1.   1     PROTOCOL SUMMARY
 
       
Title: 
A Prospective, Randomized, Split-Arm Clinical Study Investigating the 
Efficacy and Safety of Sciton’s Broad Band for the Treatment and 
Prevention of Senile Purpura 
 
Précis: 
There will be ten subjects, 5 older subjects over 65 years of age with 
at least one ecchymotic lesion on each arm measuring at least one 
cm, and 5 subjects under 35 years of age. All subjects will be 
randomized to undergo 4 Sciton Broad Band Light (BBL) treatments 
on either their left or right arm one week apart. Subjects will fill out 
questionnaires, have pictures of their lower arms taken, and will be 
graded and measured by evaluators regarding the number and size of 
their ecchymoses as well as side effects such as blistering, pain, 
erythema, and swelling.  One day after their 4th treatment, subjects 
will have biopsies done to be analyzed for changes in histology and 
gene expression. The subjects will follow up at 30 days after their last 
treatments for final pictures of their lower arms and evaluations. 
 
Objectives: 
Primary Objectives: To assess the efficacy of BBL in improving the 
appearance of senile purpura  
 
 
Important Secondary Objectives:  
1. To assess the safety of a new BBL protocol for treating and 
preventing senile purpura  
2. To assess the efficacy of BBL in reducing skin tears  
3. To assess the efficacy of BBL to improve the histology of the skin 
4. To assess the efficacy of BBL to increase epidermal thickness 
5. To assess the efficacy of BBL to change gene expression  
 
Endpoint 
Primary Endpoints:  
1. Mean absolute difference in the BBL treated arms as compared 
to the non-treated arms of those with senile purpura in the total 
square area of purpuric lesions from the first treatment to 30 
days after the last treatment  
2. Mean absolute difference in the BBL treated arms as compared 
to the non-treated arms of those with senile purpura in the 
number of purpuric lesions from the first treatment to 30 days 
after the last treatment  
 
 
Important Secondary Endpoints:  
1. Measurement of pain, swelling, blistering, erythema, and all side-
effects immediately after each procedure, as well as 24 hours, 48 
hours, and 7 days after the procedure.  

 
  
2. Mean absolute difference in the number of skin tears at baseline and 
30 days after the last treatment 
3. The changes in collagen and elastin between untreated and treated 
skin 
4. Mean absolute difference in the change in epidermal thickness 
between treated and untreated skin 
5. Changes in gene expression between treated and untreated skin 
 
Population: 
Sample size 10 
 
Male and female adults over the age of 21 living in Palm Beach 
County Florida. 
 
 
Number of Sites 
1  
 
Study Agent: 
Sciton’s BBL 
 
Study Duration: 
51 days 
 
 
 
 

 
  
  SCHEMATIC  OF STUDY DESIGN 
 
 
 
•Total n=10 
•Obtain informed consent 
•Screen potential subjects by inclusion and exclusion criteria (Eligibility Questionnaire) 
 
 
•Subjects randomized to have BBL on either their left or right  
 
• Baseline Assessments: 
   Pre-procedure pictures of patient’s lower arms taken with a Digital Camera 
   Baseline assessment and measurement by evaluator 
   Baseline Medical History and Medication questionnaires completed by all subjects 
• Study Intervention #1: 
Sciton’s BBL done according to purpura protocol on one arm according to randomized assignment 
• Post-Procedure Assessments: 
   Post-procedure questionnaires filled out by all subjects 
 
 
• At Home Follow-up Assessments Questionnaire Regarding Side-Effects 
 
• At Home Follow-up Assessments Questionnaire Regarding Side-Effects 
 
• Follow-up assessments: 
 Evaluator assessment and measurement  
 Pictures taken of subject’s lower arms 
 Subject follow up questionnaires filled out by all subjects 
• Study Intervention #2: 
 Sciton’s BBL done a second time on the assigned arm according to protocol settings 
• Post-Procedure Assessments: 
Day 0: Randomization 
Day 1: Follow-up assessments 
Day -30 to 0  Screening 
Day 0: Baseline assessments/ Study Intervention 
Day 2: Follow-up assessments  
Day 7 +/- 2 Days: Follow-up assessments / Study Intervention 

 
  
Post-procedure questionnaires filled out by all subjects immediately after treatment 
 
• Follow-up assessments: 
Evaluator assessment and measurement  
Pictures taken of subject’s lower arms 
 
Subject follow up questionnaires filled out by all subjects 
• Study Intervention #3: 
 Sciton’s BBL  done a third time on the assigned arm according to protocol settings 
• Post-Procedure Assessments: 
Post-procedure questionnaires filled out by all subjects immediately after treatment 
 
 
• Follow-up assessments: 
 Evaluator assessment and measurement  
 Pictures taken of subject’s lower arms 
 Subject follow up questionnaires filled out by all subjects 
• Study Intervention #4: 
 Sciton’s BBL done a fourth time on the assigned arm according to protocol settings 
• Post-Procedure Assessments: 
Post-procedure questionnaires filled out by all subjects immediately after treatment  
 
• A 4mm punch biopsy will be done on both the treated and untreated arm approximately 4cm 
below the crease in the antecubital fossa 
 
• Follow-up assessments: 
 Evaluator assessment and measurement  
 Pictures taken of subject’s lower arms 
 Subjects follow up questionnaires filled out by all subjects 
 
Day 14 +/- 2 Days: Follow-up assessments / Study Intervention 
Day 21 +/- 2 Days: Follow-up assessments / Study Intervention 
Day 22 +/- 2 Days: Follow-up assessment via skin biopsy 
Day 51 +/- 2 Days: Follow-up assessment 

 
  
 
 
 
Senile Purpura is a benign common condition characterized by recurrent formation of ecchymosis on the 
extensor surfaces of forearms and hands following minor trauma. Other names of this condition are 
Bateman purpura, named after British dermatologist Thomas Bateman, who first described it in 1818, 
and actinic purpura, because of its association with sun damage (1). 
More recently in 2007, Kaya and Saurat coined the term dermatoporosis to describe the chronic 
cutaneous fragility of aging skin. Dermatoporosis features include thinning atrophic skin, purpura, skin 
lacerations and delayed healing (2). 
This condition affects over 10% of those aged over 65 years old and is equally common in males and 
females. Risk factors are known to include the use of oral or topical corticosteroids and anti-coagulants 
(3). 
With age and sun damage, the dermis becomes thin. As a result, this condition results from superficial 
vessels tearing even with negligible trauma. The subsequent extravasation of blood into the 
surrounding dermis results in the development of ecchymosis. Histologically, the epidermis is thinned 
and the dermis demonstrates significantly reduced amounts of collagen replaced by abnormal elastic 
fibers, as well as extravasated red blood cells (4).   
Intense pulsed light (IPL) is non-coherent, non-collimated, polychromatic light energy. IPL emits different 
wavelengths that target specific chromophores. This makes IPL a versatile therapy with many 
applications, from the treatment of pigmented or vascular lesions to hair removal and skin rejuvenation. 
Its large spot size ensures a high skin coverage rate and ease of use over large areas. The treatment has 
very little downtime given its non-ablative nature which makes it an attractive option. In many cases, IPL 
is similar to laser therapy in effectiveness, convenience, and safety and together with its versatility will 
lead to an expanded range of applications and possibilities in the future. 
Relevant Clinical Research 
 
Published studies on treatments for senile or actinic purpura or dermatoporosis are very limited. In one 
small double blinded study (N=14) published in 1995 in The Archives of Dermatology, they showed twice 
daily treatment with retinoic acid cream resulted in significant reduction in Bateman’s actinic purpura 
after two weeks, however there were no significant differences after that time (6). 
Multiple studies have shown the efficacy of topical Retinol and Tretinoin in increasing epidermal 
thickness and one study in particular in the Journal of Cosmetic Dermatology in 2016 showed not only 
an increased thickness in the epidermis but also up-regulated genes for Collagen Type 1 (COL1A1) and 
Collagen Type 3 (COL3A1) with corresponding increases in procollagen 1 and procollagen 3 protein 
expression (7). 
2.1 
BACKGROUND INFORMATION 
2 
INTRODUCTION: BACKGROUND INFORMATION  AND  SCIENTIFIC RATIONALE 

 
  
A very small study (N=6) on the effectiveness of human epidermal growth factor for the treatment of 
actinic purpura when applied twice daily for six weeks showed an increase epidermal thickness on 
ultrasound and the mean number of lesions decreased from 15 to 2.3 (8). 
More recently in 2017, Ceilley published his experience with DerMend in the Journal of Cllinical and 
Aesthetic Dermatology, reviewing why he thought a topical preparation with Retinol, Alpha hydroxyl 
acids, Arnica oil, Ceramindes, Niacinamide, and Phytonadione would be an optimal treatment for this 
condition (3).   
The current literature supports the ability of IPL to induce collagen neogenesis. Studies on mice showed 
that IPL treatments significantly increased the number of collagen and elastic fibers within the dermis 
and improved the parallel distribution of collagen fibers in relation to the epidermis. These results were 
only evident after three IPL treatments spaced 2 weeks apart and not after just one or two treatments 
(5).  In a study with rats, IPL increased dermal collagen fibers and collagen fiber diameter after 3 weeks 
(9) and in another study on rats, IPL increased dermal thickness, density of collagen, the hydroxyproline 
content, and the expression of III procollagen mRNA (18).  In one study in humans, 5 patients showed 
histological evidence of new collagen formation 6 months after four IPL treatments (19). The current 
literature not only supports the ability of IPL to induce collagen neogenesis but also microneedling and 
microneedling with radiofrequency. One study showed microneedling resulted in greater skin and 
dermal thickness than IPL and increased expression of Type 1 collagen and total collagen content (20).  
In Patrick Bitter’s pilot study published in 2015 in the Journal of Cosmetic Dermatology, they used 3'-end 
sequencing for expression quantification ("3-seq") to discover the gene expression associated with 
human skin aging and the impact of broadband light (BBL) treatment. In the study skin aging was 
associated with a significantly altered expression of 2,265 coding and noncoding RNAs, of which 1,293 
became "rejuvenated" after BBL treatment (more similar to expression levels in youthful skin). 
Rejuvenated genes (RGs) included several known key regulators of organismal longevity (16). Hence, 
according to this study, BBL treatment appears to be able to restore gene expression pattern of photo 
aged and intrinsically aged human skin to resemble young skin and therefore may be an ideal treatment 
option for senile or actinic purpura.  
In addition, though most cosmetic surgeons and injectors have seen firsthand the improvement of post 
procedural bruising with both pulse dye lasers or intense pulse light lasers, there are limited published  
studies on this topic. One study published in the Archives of Plastic Surgery in 2009 showed pulsed-dye 
laser was effective for treating ecchymoses after facial cosmetic procedures and resulted in a 63% mean 
improvement in ecchymosis scores within 48 to 72 hours (14), however there are no published studies 
to date using IPL. 
 
 
 
The current treatments of senile or actinic purpura include oral arnica, and topical arnica, vitamin K, 
retin-A, retinol, growth factors, alpha hydroxyl acids, ceramides, and niacinamide.  However, all of these 
have very limited results, if any, and there have been no large-scale studies proving their long-term 
efficacy for this condition.  
2.2 
RATIONALE 

 
  
If broadband light (BBL) is used to reduce photo-damage, decrease post-procedural purpura, is 
associated with a significantly altered expression of RNAs similar to that in youthful skin, and has been 
reported to increase collagen production and epidermal thickening, then it follows that this treatment 
may be an ideal option for reduction of senile purpura.  
 
 
 
Common potential risks of BBL include swelling, pain, scabbing, blistering, reduction of hair and 
lentigenes, erythema, pruritus, lightening and darkening of the skin, and reactivation of herpes 
infection. Rare but potential risks of BBL include severe burn, skin ulceration, scarring and infection. 
Common potential risks of a skin biopsy include bleeding and scarring while rare but potential risks 
include infection and allergy to the lidocaine, bandages, or sutures used in the procedure. 
 
 
 
Improvement of the subject’s ecchymoses leading to an aesthetic improvement. This aesthetic 
improvement may positively impact the subjects’ psychological well-being. In addition, the treatment 
may lead to less skin tears by increasing the epidermal thickness which would prevent bleeding, 
infection risk, and scarring.  
 
 
• 
A Prospective, Randomized, Split-Arm Clinical Study  
• 
Single Center 
• 
Study agent: Sciton’s BBL  
• 
Study Interventions: BBL Treatment on Day 0, Day 7, and Day 21 
• 
Evaluations on Day 0, Day 7, Day 14, Day 21, Day 22, Day 51. 
 
This will be a prospective, split-arm clinical study in which 5 subjects will be randomized to which arm 
will be treated with Sciton’s BBL. 
 
All subjects will have their arms shaved prior to the procedure and cleaned thoroughly with alcohol.  
After the procedure a zinc-based sunscreen will be applied to both arms.  
 
Before each of the four treatments and 30 days after the last treatment, the subjects’ number and 
square area of ecchymoses will be measured by an evaluator. Side effects will be measured on Day 0, 
1, 2, 7, 14, 21, 22 and 51. Digital photography of subject’s arms will be done on day 0, 7, 14, 21, and 
51.    
 
 
2.3 
POTENTIAL RISKS AND BENEFITS 
2.3.1 KNOWN POTENTIAL RISKS 
2.3.2 KNOWN POTENTIAL BENEFITS 
3.1 
DESCRIPTION OF THE STUDY DESIGN 
3.2 
STUDY OBJECTIVES & ENDPOINTS 
3 
STUDY  DESIGN, OBJECTIVES,  AND ENDPOINTS 

 
  
 
➢ Primary Objectives: To assess the efficacy of BBL in improving the appearance of senile purpura 
 
Important Secondary Objectives:  
➢ To assess the safety of a new BBL protocols for treating and preventing senile purpura  
➢ To assess the long-term efficacy 30 days after all treatments have stopped 
➢ To assess the efficacy of BBL in affecting histological changes such as epidermal thickness 
➢ To assess the changes in mRNA after treatment 
 
 
 
➢ Primary Endpoint: Mean absolute difference between the treated and non-treated arms in the 
change of total square area and number of ecchymoses from baseline to 30 days after the last 
treatment. 
 
 
 
1. Measurement of pain, swelling, blistering, erythema, and all side-effects immediately after each 
procedure, as well as 24 hours, 48 hours, and 7 days after the procedure.  
2. Mean absolute difference in the number of skin tears at baseline and 30 days after the last 
treatment 
3. The changes in collagen and elastin between untreated and treated skin 
4. Mean absolute difference in the change in epidermal thickness between treated and untreated 
skin 
5. Changes in gene expression between treated and untreated skin 
 
 
 
Through subject questionnaires, other variables that may affect study endpoints will be explored 
such as smoking, dominant hand, sex, medications, and time spent in the sun.  
 
 
 In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
• 
Provision of signed and dated informed consent form 
• 
Stated willingness to comply with all study procedures and availability for the duration 
of the study 
• 
Male or female, aged >22 
• 
In good general health as evidenced by medical history  
• 
Ecchymosis greater than 1cm on each arm 
 
 
 
An individual who meets any of the following criteria will be excluded from participation in this study: 
3.2.1 STUDY OBJECTIVE 
3.2.2 PRIMARY ENDPOINT 
3.2.3 SECONDARY ENDPOINTS 
3.2.4 EXPLORATORY ENDPOINTS 
4.1 
PARTICIPANT INCLUSION CRITERIA 
4.2 
PARTICIPANT EXCLUSION CRITERIA 
4 STUDY  ENROLLMENT  AND WITHDRAWAL 

 
  
• 
Subjects with a history of any arm swelling 
• 
Subjects with allergies to light  
• 
Subjects with auto-immune skin conditions such as lupus, or vitiligo 
• 
Subjects using topical retinol within the last 3 months  
• 
Subjects with any scheduled laser, light, or surgical procedures on the arm during the study 
• 
Subjects unwilling or unable to keep their arms still during digital pictures 
• 
Subjects who are pregnant or nursing  
• 
Subjects with a history of herpes simplex or zoster on their arms 
• 
Subjects with current skin infections, tumors, or dermatitis on the arm 
• 
Subjects with allergies to lidocaine 
• 
Subjects with a history of keloid formation 
• 
Subjects with a history of a bleeding disorder 
• 
Subjects with allergies to adhesives 
 
 
 
• 
Participants will be compensated by receiving $5 cash for each visit 
 
• 
Subjects will receive an email, text or phone call reminder for all their scheduled visits 
according to their preference 
 
• 
The source of the subjects will be those who visited Siperstein Dermatology Group 
and allowed their information to be used in order to be contacted for promotions 
and trials.  
 
 
  
 
Participants are free to withdraw from participation in the study at any time. 
 
An investigator may terminate participation in the study if: 
 
• 
The participant’s health declines  
• 
The participant needs any surgery or other serious medical interventions  
• 
The participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation. 
• 
The participant fails to show up for follow-up and final visits 
 
 
 
 
4.3 
STRATEGIES FOR RECRUITMENT AND RETENTION 
4.4 
PARTICIPANT WITHDRAWAL ORTERMINATION 
4.4.1 REASONS FOR WITHDRAWAL OR TERMINATION 
4.4.2 HANDLING OF PARTICIPANT WITHDRAWALS OR TERMINATION 

 
  
The primary investigator will attempt to visit all participants that have withdrawn or terminated from 
the trial if they are unable to make their follow-up visits to ensure as much data as possible has been 
collected and that all safety parameters have been met.  
 
 
 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. If the study is prematurely terminated or suspended, the primary investigator 
will promptly inform the IRB as well as provide the reason(s) for the termination or suspension. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Insufficient compliance to protocol requirements 
Study may resume once concerns about safety, protocol compliance, or data quality is 
addressed. 
 
 
 
 
 
 
• 
Sciton’s BBL, Joule Platform 
 
 
 
The Sciton BBL as described in the 510(k) summary for the Joule multi-platform system on which it is 
located, is described as a laser surgical instrument for use in general and plastic surgery and in 
dermatology. One of the intended uses is described as the treatment of vascular lesions. We are 
therefore using this device as per indication since a vascular lesion is a lesion relating to, affecting, or 
consisting of a vessel or vessels, especially those that carry blood and purpura is a lesion relating to 
the injury of blood vessels in which blood escapes into the surrounding skin. We will mainly be using 
the 560 and 590 cut off filters since these are the recommended filters to treat vascular lesions. 
 
 
   
• 
The BBL treatment will take approximately 15 minutes 
• 
The last treatment will be done on Day 21 
 
 
4.5 
PREMATURE TERMINATION OR SUSPENSION OF STUDY 
5 
STUDY AGENT 
5.1 
STUDY EQUIPMENT 
5.1.1 DEVICES FOR INTERVENTION 
5.1.2 DEVICE INDICATION 
5.1.2 DURATION OF THERAPY 

 
  
 
 
• 
Metal Goggles for participants and IPL specific wavelength goggles for investigator 
• 
Punch Biopsy Kit 
 
 
 
 
6.1 
STUDY PROCEDURES/EVALUATIONS 
 
 
• 
Medical history obtained and verbally verified 
• 
Assigned arm meeting inclusion criteria is shaved to remove all hair 
• 
Digital Pictures taken of bilateral hands and arms 
• 
Counseling the subjects on the treatment that they will be receiving and post-care 
instructions. 
• 
The study coordinator will check before the patient leaves that all appropriate photos and 
paperwork have been completed. 
• 
BBL study treatment will be done according the protocol below outlining specific settings 
 
BBL Only Protocol  
1st Treatment Settings 
1. SkinTyte Filter ST: 150 Joules, 15msec, 15 degrees for 10 continuous passes in alternating directions (5 
each direction) 
2. 590 Filter: 8J, 15msec, 15 degrees x 2 passes 
3. 590 Filter: 10J 15msec, 15 degrees x 2 passes  
4. 560 Filter: 8J, 15msec, 15 degrees x 2 passes 
2nd Treatment Settings 
If any answers on the post procedure side effects questionnaire from day 0,1, or 2 were SEVERE or if 
the patient had blisters from the previous treatment 
Decrease Step 3 & 4 by 2 Joules  
1. SkinTyte Filter ST: 150 Joules, 15msec, 15 degrees for 10 continuous passes in alternating directions  
5.1.3 OTHER EQUIPMENT NECCESARY 
6 
STUDY  PROCEDURES  AND SCHEDULE 
6.1.1 STUDY SPECIFIC PROCEDURES 

 
  
2. 590 Filter: 8J, 15msec, 15 degrees x 2 passes 
3. 590 Filter: 8J 15msec, 15 degrees x 2 passes  
4. 560 Filter: 6J, 15msec, 15 degrees x 2 passes 
If any answers on the post procedure side effects questionnaire on day 0,1, or 2 were MODERATE 
with NO blistering 
Decrease Step 3 & 4 by 1 Joule  
1. SkinTyte Filter ST: 150 Joules, 15msec, 15 degrees for 10 continuous passes in alternating directions  
2. 590 Filter: 8J, 15msec, 15 degrees x 2 passes 
3. 590 Filter: 9J 15msec, 15 degrees x 2 passes  
4. 560 Filter: 7J, 15msec, 15 degrees x 2 passes 
If all answers on the post procedure side effects questionnaire on day 0,1, or 2 protocol were 
MINIMAL 
Keep Settings the same as previous visit 
1. SkinTyte Filter ST: 150 Joules, 15msec, 15 degrees for 10 continuous passes in alternating directions (5 
each direction) 
2. 590 Filter: 8J, 15msec, 15 degrees x 2 passes 
3. 590 Filter: 10J 15msec, 15 degrees x 2 passes  
4. 560 Filter: 8J, 15msec, 15 degrees x 2 passes 
If all answers on the post procedure side effects questionnaire on day 0,1, or 2 protocol were NONE 
Increase Step 1 by 10 additional passes and Increase Step 3 & 4 by 1 Joule 
1. SkinTyte Filter ST: 150 Joules, 15msec, 15 degrees for 20 continuous passes in alternating directions (10 
each direction) 
2. 590 Filter: 8J, 15msec, 15 degrees x 2 passes 
3. 590 Filter: 11J 15msec, 15 degrees x 2 passes  
4. 560 Filter: 9J, 15msec, 15 degrees x 2 passes 

 
  
3rd and 4th Treatment Settings 
-If any answers on the post procedure side effect questionnaire were SEVERE or if the patient had 
blisters from the previous treatment 
Decrease Step 3 & 4 by 2 Joules from settings at previous visit 
-If any answers on the post procedure side effect questionnaire were MODERATE with NO blistering 
Decrease Step 3 & 4 by 1 Joule from settings at previous visit 
-If any answers on the post procedure side effect questionnaire were MINIMAL with NO blistering 
Keep Settings the same as previous visit 
-If all answers on the post procedure side effect questionnaire were NONE 
Increase Step 1 by 10 additional passes and Increase Step 3 & 4 by 1 Joule from settings at previous 
visit 
 
 
 
 
The patients will be cleaned with alcohol prior to treatment. After the treatment, a zinc-based 
sunblock will be applied and if there is any post-treatment pain a cold ice pack will be applied.  
 
The patient will be cleaned with alcohol prior to the skin biopsy and injected with lidocaine to numb 
the area. Sterile equipment will be used to take a 4mm punch biopsy from the same location on each 
arm. 
 
 
 
 
Screening Visit (Day -30 to 0) 
• 
Review subject questionnaire to determine eligibility based on inclusion/exclusion criteria 
• 
Schedule study visits for participants who are eligible and available for the duration of the 
study 
• 
Provide participants with specific instructions needed to prepare for all their visits 
 
 
 
 
Enrollment/Baseline Visit (Visit 1, Day 0) Treatment #1 
• 
Review in depth the study design with subjects and obtain informed consent of 
potential participants verified by signature 
• 
Perform examination and verbally review subject’s medications, medical history, and 
subject questionnaire to determine eligibility based on inclusion/exclusion criteria 
6.1.2 STANDARD OF CARE STUDY PROCEDURES 
6.2 
STUDY SCHEDULE 
6.2.1 SCREENING 
6.2.2 ENROLLMENT/BASELINE 

 
  
• 
Obtain demographic information 
• 
Shave the hair on the subjects’ lower arms  
• 
Take digital pictures of subjects’ lower arms 
• 
Have evaluator measure the size and number of bruises and skin tears  
• 
Perform the BBL treatment on assigned arm per protocol 
• 
Record adverse events as reported by participant or observed by investigator 
• 
Perform protocol adherence check by study coordinator 
• 
Expected post-procedure side effects and possible emergent situations 
reviewed with subjects and post-op written instructions given 
 
 
 
 2nd Treatment (Visit 2, Day 7 +/- 2 days)  
• 
Record adverse events as reported by participant or observed by investigator. 
• 
Subjects fill out adherence questionnaire and evaluator review to ensure continued eligibility 
• 
Evaluator measures the size and number of bruises and number of skin tears  
• 
Shave bilateral lower arms  
• 
Take digital pictures of subjects’ lower arms 
• 
Perform the BBL treatment the second time per protocol 
• 
Record adverse events as reported by participant or observed by investigator. 
• 
Perform protocol adherence check by study coordinator 
• 
Expected post-procedure side and post-op written instructions reviewed 
 
3rd Treatment (Visit 3, Day 14 +/-2 days)  
• 
Record adverse events as reported by participant or observed by investigator. 
• 
Subjects fill out adherence questionnaire and evaluator review to ensure continued eligibility 
• 
Evaluator measures the size and number of bruises and number of skin tears  
• 
Shave bilateral lower arms  
• 
Take digital pictures of subjects’ lower arms 
• 
Perform the BBL treatment a third time per protocol 
• 
Record adverse events as reported by participant or observed by investigator 
• 
Perform protocol adherence check by study coordinator 
• 
Expected post-procedure side and post-op written instructions reviewed 
 
4th Treatment (Visit 4, Day 21 +/-2 days)  
• 
Record adverse events as reported by participant or observed by investigator. 
• 
Subjects fill out adherence questionnaire and evaluator review to ensure continued eligibility 
• 
Evaluator measures the size and number of bruises and number of skin tears 
• 
Shave bilateral lower arms  
• 
Take digital pictures of subjects’ lower arms 
• 
Perform a BBL treatment on the assigned arm a fourth time per protocol 
• 
Record adverse events as reported by participant or observed by investigator. 
• 
Perform protocol adherence check by study coordinator 
6.2.3 FOLLOW UP TREATMENTS 

 
  
• 
Expected post-procedure side and post-op written instructions reviewed 
 
 
 
Follow Up Visit 1 (Visit 5, Day 22 +/-2 days)  
• 
Clean skin with alcohol 
• 
Perform protocol adherence check by study coordinator 
• 
Perform  4mm punch biopsy  
• 
One dissolving suture will be placed in the dermis along with a steri-strip on the top of the 
skin 
• 
Skin specimens will be bisected, and half will be placed in formalin and half will be placed in 
RNAlater. 
• 
Skin specimen bottles will be coded and sent for blinded evaluation 
• 
Expected post-procedure side and post-op written instructions reviewed 
 
 
 
 
Follow-up Visit 2 (Visit 6, Day 51 +/-2 days)  
• 
Record adverse events as reported by participant or observed by investigator. 
• 
Subjects fill out adherence questionnaire and evaluator review to ensure continued eligibility 
• 
Evaluator measures the size and number of bruises and number of skin tears  
• 
Shave bilateral lower arms   
• 
Take digital pictures of subjects’ lower arms 
• 
Provide final instructions 
 
 
 
• 
Record adverse events as reported by participant or observed by investigator. 
• 
Collect questionnaires 
• 
Take Digital Photos of subject’s lower arms 
• 
Record participant’s adherence to treatment program 
• 
Provide final instructions 
 
 
 
All unscheduled visits will be discouraged unless emergent. All unscheduled visits will be recorded and 
kept as brief as possible with no active intervention unless a vascular occlusion is suspected, or other 
emergent health condition is suspected. 
 
6.2.4 FOLLOW UP VISITS 
6.2.5 FINAL STUDY VISIT 
6.2.6 EARLY TERMINATION VISIT 
6.2.7 UNSCHEDULED VISIT 

 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Procedures 
Enrollment/Baseline/1st Treatment 
Visit 1, Day 0 
2nd Treatment Visit  
Visit 2, Day 7 
3rd Treatment Visit  
Visit 3, Day 14 
4th Treatment Visit 
Visit 4, Day 21 
Follow Up Visit 1 
Visit 5, Day 22 
Follow Up Visit 2 
Visit 6, Day 51 
Informed 
consent 
     X 
Demographics 
     X 
Medical history      X 
Subject 
Questionnaire 
     X 
     X 
     X 
     X 
      
    x   
Study 
Intervention 
     X 
     X 
     X 
 X 
  
  
Evaluation for 
adverse effects 
     X 
     X 
     X 
X 
 
x 
Digital photos 
     X 
     X 
    X 
     X 
 
x 
Evaluator 
Measurements      X 
     X 
    X 
     X 
 
x 
Skin Biopsy 
      
      
     
      
x 
 
 
 
 
 
6.2.8 SCHEDULE OF EVENTS TABLE 

 
  
 
 
Changes in any anti-coagulants and prednisone use are prohibited during the study as well as any 
procedures or surgeries on the treatment arm. 
 
In the event a subject makes changes to their medications or has treatments or procedures, the 
primary investigator will make the final decision regarding early termination from the study or 
disregarding certain data from final statistical analysis. 
 
 
 
None will be used 
 
 
 
 
If patients develop an infection during the trial, they will be prescribed the appropriate anti-viral or 
anti-bacterial medication but will continue in the study. 
  
 
 
7.1 
SPECIFICATION OF SAFETY PARAMETERS
 
 
 
 
 
Adverse event means any untoward medical occurrence associated with the use of an 
intervention in humans, whether or not considered intervention-related (21 CFR 312.32) 
 
Serious adverse event or serious suspected adverse reaction. 
 An adverse event or suspected adverse reaction is considered "serious" if, in the view of either the 
investigator or sponsor, it results in any of the following outcomes: death, a life-threatening adverse 
event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant 
incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital 
anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or 
require hospitalization may be considered serious when, based upon appropriate medical judgment, 
they may jeopardize the patient or subject and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition. 
  
 
 
6.3 
PROHIBITED MEDICATIONS, TREATMENTS, AND PROCEDURES 
6.4 
PROPHYLACTIC MEDICATIONS, TREATMENTS, AND PROCEDURES 
6.5 
RESCUE MEDICATIONS, TREATMENTS, AND PROCEDURES 
7 ASSESSMENT  OF SAFETY 
7.1.2 DEFINITION OF SERIOUSADVERSE EVENTS (SAE) 
7.1.3 DEFINITION OF UNANTICIPATED PROBLEMS (UP) 

 
  
Unanticipated problems involving risks to participants or others to include, in general, any 
incident, experience, or outcome that meets all of the following criteria: 
• 
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 participant 
population being studied; 
• 
Related or possibly related to participation in the research (“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 
• 
Suggests that the research places participants or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was previously known 
or recognized. [4] 
 
With these events the following will occur: 
• 
Modification of inclusion or exclusion criteria to mitigate the newly identified risks 
• 
Implementation of additional safety monitoring procedures 
• 
Suspension of enrollment of new participants or halting of study procedures for 
enrolled participants 
• 
Modification of informed consent documents to include a description of newly recognized risks 
• 
Provision of additional information about newly recognized risks to previously 
enrolled participants. 
 
7.2 
CLASSIFICATION OF AN ADVERSE EVENT
 
 
 
• 
Mild – Events require minimal or no treatment and do not interfere with the participant’s 
daily activities. 
• 
Moderate – Events result in a low level of inconvenience or concern with the 
therapeutic measures. Moderate events may cause some interference with 
functioning. 
• 
Severe – Events interrupt a participant’s usual daily activity and may require systemic 
drug therapy or other treatment. Severe events are usually potentially life-threatening 
or incapacitating. 
 
 
 
All AEs will have their relationship to study agent or study participation assessed. 
Evaluation of relatedness will consider etiologies such as natural history of the underlying disease, 
concurrent illness, concomitant therapy, study-related procedures, accidents, and other external 
factors.   
 
The clinician’s assessment of an AE's relationship to study agent is part of the documentation 
process, but it is not a factor in determining what is or is not reported in the study. If there is any 
doubt as to whether a clinical observation is an AE, the event will be reported. All AEs must have 
their relationship to study agent assessed. In a clinical trial, the study product will always be suspect. 
To help assess, the following guidelines are used. 
7.2.1 SEVERITY OF EVENT 
7.2.2 RELATIONSHIP TO STUDY AGENT 

 
  
 
• 
Related – The AE is known to occur with the study agent, there is a reasonable possibility 
that the study agent caused the AE, or there is a temporal relationship between the study 
agent and event. Reasonable possibility means that there is evidence to suggest a causal 
relationship between the study agent and the AE. 
• 
Not Related – There is not a reasonable possibility that the administration of the study agent 
caused the event, there is no temporal relationship between the study agent and event onset, 
or an alternate etiology has been established.  
 
 
 
The primary investigator will be responsible for determining whether an AE is expected or 
unexpected. An AE will be considered unexpected if the nature, severity, or frequency of the event 
is not consistent with the risk information previously described for the study agent. 
 
  7.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP
 
 
 
The occurrence of an AE or SAE may come to the attention of study personnel during study visits 
and interviews of a study participant presenting for medical care, or upon review of subject 
questionnaires. 
 
 Information to be collected on al AE or SAE includes event description, time of onset, clinician’s 
assessment of severity, relationship to study product, and time of resolution/stabilization of the 
event. All AEs occurring while on study must be documented appropriately regardless of 
relationship. All AEs will be followed to adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened will be 
considered as  
baseline and not reported as an AE. However, if the study participant’s condition deteriorates at 
any time during the study, it will be recorded as an AE. UPs will be recorded in the data collection 
system throughout the study. 
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the 
event at each level of severity to be performed. AEs characterized as intermittent require 
documentation of onset and duration of each episode. 
 
The primary investigator will record all reportable events with start dates occurring any time after 
informed consent is obtained until 7 (for non-serious AEs) or 14 days (for SAEs) after the last study 
intervention. At each study visit, the investigator will inquire about the occurrence of AE/SAEs since 
the last visit. Events will be followed for outcome information until resolution or stabilization. 
 
7.2.3 EXPECTEDNESS 

 
  
 
  7.4 
REPORTING PROCEDURES
 
 
 
The IRB will receive notification of any UP, AE, or SAE within 24 hours of discovery by the primary 
investigator. 
 
All SAEs will be followed until satisfactory resolution or until the site investigator deems the event to 
be chronic or the adherence to be stable. The primary investigator will be responsible for notifying 
FDA of any unexpected fatal or life-threatening suspected adverse reaction as soon as possible but 
in no case later than 7 calendar days after the investigator’s initial receipt of the information. 
 
 
 
If it is discovered that a subject is pregnant, the subject will discontinue any interventions and 
continue in the study while continuing safety follow-up until the conclusion of her pregnancy. 
 
  7.5 
STUDY  HALTING RULES
 
 
 
Administration of the study agent will be halted when two SAEs determined to be related  
are reported. The primary investigator will inform the FDA of the temporary halt and the 
disposition of the study. 
 
  7.6 
SAFETY OVERSIGHT & CLINICAL MONITORING
 
 
 
An independent medical expert (medical monitor) will advise the study investigator and monitor 
participant safety. The role of the Medical Monitor is to 1) Review all AEs on a regular basis 
throughout the trial; 2) be available to advise the investigators on trial-related medical questions or 
problems, and 3) evaluate cumulative participant safety data and make recommendations 
regarding the safe continuation of the study. The Medical Monitor will remain blinded throughout 
the conduct of the clinical trial unless un-blinding is warranted to optimize management of an 
adverse event or for other  
 
safety reasons. Clinical site monitoring is conducted to ensure that the rights and well-being of 
human  
subjects are protected, that the reported trial data are accurate, complete, and verifiable, and that 
the conduct of the trial is in compliance with the currently approved protocol/amendment(s), with 
GCP, and with applicable regulatory requirement(s). 
7.4.1 ADVERSE EVENT REPORTING 
7.4.2 REPORTING OF PREGNANCY 

 
  
 
 
  8.1 
STATISTICAL HYPOTHESES 
 
 
Primary Endpoint 
 
𝐻0:µ𝐶= 0  ;   𝐻1: µ𝐶> 0 
 
➢ The null hypothesis is the absolute mean difference in the change from baseline to 30 days after 
the last treatment on the treatment arm as compared to the non-treatment arm is zero. 
➢ The alternative hypothesis is the absolute mean change from baseline to 30 days after the last 
treatment on the treatment arm as compared to the non-treatment arm is greater than zero. 
 
1. Let µ𝐶 represent the absolute mean difference between the treated arm as compared to 
the non-treated arm in the difference in the number of ecchymoses from baseline to 30 
days after the last treatment. 
 
2. Let µ𝐶 represent the absolute mean difference between the treated arm as compared to 
the non-treated arm in the difference in the size of ecchymoses from baseline to 30 days 
after the last treatment. 
 
 
A Paired t-test will be used to analyze the primary endpoint.   The results of the 
statistical analysis will be presented as an odds ratio with 95% Confidence intervals. A 
Shapiro-Wilk Test will be used to assess the normality of data. 
   8.3   ADDITIONAL SUB GROUP ANALYSIS  
The primary and secondary endpoint will be analyzed based on age, sex, race/ethnicity or other 
variable such as subjects behavior (smoking, diet, handedness, exercise, etc..) 
 
8.4   SAMPLE SIZE  
N/A – Pilot Study 
 
8.5 MEASURES TO MINIMIZE BIAS  
 
In order to avoid bias, the subjects will be randomized to receive treatment on either their left or 
right arm. All evaluators of pictures will be blinded as to which technique was used on which side.  In 
order to avoid bias, the evaluator will not be the primary investigator. 
To ensure only the clinical investigator performing the procedures and the study coordinator know 
8 
STATISTICAL CONSIDERATIONS 
ENROLLMENT/ RANDOMIZATION/ MASKING PROCEDURES  

 
  
the assignment of arms, each subject will have an envelope assigned to them to be held by the study 
coordinator with the subject’s name on the outside and the assignment on the inside. Only during 
treatments does the study coordinator allow the clinical investigator to see the inside of the 
envelope.  
 
The skin biopsy samples will be coded to ensure blinded analysis. 
 
 
 
9.1 
ETHICAL STANDARD
 
 
 
 The investigator will ensure that this study is conducted in full conformity with Regulations for 
the Protection of Human Subjects of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 CFR 
Part 56, and the ICH E6. 
 
 
9.2 
INFORMED CONSENT PROCESS
 
 
 
Informed consent is required for all participants. In obtaining and documenting informed consent, 
the investigator will comply with applicable regulatory requirements and will adhere to 45 CFR Part 
46, 21 CFR Part 50, 21 CFR Part 56, and ICH GCP. Prior to the written informed consent, the consent 
forms will be provided to the participants. Consent forms describing in detail the study agent, study 
procedures, and risks will be given to the participant and written documentation of informed 
consent is required prior to starting intervention/administering study product.  
 
The investigator will explain the research study to the participant and answer any questions that 
may arise. All participants will receive a verbal explanation in terms suited to their comprehension 
of the purposes, procedures, and potential risks of the study and of their rights as research 
participants. Participants will have the opportunity to carefully review the written consent form and 
ask questions prior to signing. The participants will have the opportunity to think about being a 
participant prior to agreeing to sign. The participant will sign the informed consent document prior 
to any procedures being done specifically for the study. The participants may withdraw consent at 
any time throughout the course of the trial. A copy of the informed consent document will be given 
to the participants for their records. The rights and welfare of the participants will be protected by 
emphasizing to them that the quality of their medical care will not be adversely affected if they 
decline to participate in this study. 
 
9.3 
PARTICIPANT AND DATA CONFIDENTIALITY
 
 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, and 
the sponsor(s) and their agents. Therefore, the study protocol, documentation, data, and all other 
information generated will be held in strict confidence. No information concerning the study or the 
data will be released to any unauthorized third party without prior written approval of the 
sponsor. 
9 ETHICS/PROTECTION  OF  HUMAN SUBJECTS 

 
  
 
The study monitor, other authorized representatives of the sponsor, representatives of the IRB or 
pharmaceutical company supplying study product may inspect all documents and records required 
to be maintained by the investigator, including but not limited to, medical records for the 
participants in this study. The clinical study site will permit access to such records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal 
use during the study. At the end of the study, all records will continue to be kept in a secure 
location for as long a period as dictated by local IRB and Institutional regulations. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, 
will be transmitted to and stored at the Siperstein Dermatology Group Boynton research office. 
This will not include the participant’s contact or identifying information. Rather, individual 
participants and their research data will be identified by a unique study identification number. The 
study data entry and study management systems used by clinical sites and by Siperstein 
Dermatology Group research staff will be secured and password protected. At the end of the study, 
all study databases will be de-identified and archived at the Siperstein Dermatology’s Boynton 
Beach research office. 
 
 
 
Pictures and data collected under this protocol may be used in future publications. Access to 
stored pictures and data will be stored using codes assigned by the investigators. Data will be 
kept in password protected computers.  Only investigators will have access to the samples and 
data. 
 
 
10.1 
DATA  COLLECTION  AND  MANAGEMENT RESPONSIBILITIES
 
 
 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the 
site PI. The investigator is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported. 
 
All source documents will be completed in a neat, legible manner to ensure accurate 
interpretation of data. Black ink is required to ensure clarity of reproduced copies. When making 
changes or corrections, cross out the original entry with a single line, and initial and date the 
change.  
 
Clinical data (including AEs, concomitant medications, and expected adverse reactions data) will 
be entered into a 21 CFR Part 11-compliant data capture system. The data system includes 
password protection and internal quality checks, such as automatic range checks, to identify data 
9.3.1 RESEARCH USE OF STORED HUMAN DATA 
10 
DATA HANDLING AND RECORD KEEPING 

 
  
that appear inconsistent, incomplete, or inaccurate. Clinical data will be entered directly from the 
source documents. 
 
10.2 STUDY RECORDS RETENTION 
 
Study documents will be retained for a minimum of 2 years after the formal discontinuation of the 
clinical study. These documents will be retained for a longer period, however, if required by local 
regulations. No records will be destroyed without the written consent of the sponsor, if applicable. 
It is the responsibility of the sponsor to inform the investigator when these documents no longer 
need to be retained. 
 
10.3 PROTOCOL DEVIATIONS 
A protocol deviation is any noncompliance with the clinical trial protocol. The noncompliance may 
be either on the part of the participant, the investigator, or the study site staff. As a result of 
deviations, corrective actions are to be developed by the site and implemented promptly. It is the 
responsibility of the site to use continuous vigilance to identify and report deviations within 7 
working days of identification of the protocol deviation, or within 7 working days of the scheduled 
protocol-required activity. All deviations must be addressed in study source documents, reported 
to the IRB and sponsor. The site PI/study staff is responsible for knowing and adhering to their IRB 
requirements.  
 
 
 
 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical. Therefore, any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a 
way that is appropriate to their participation in the trial.   
 
 
 
1. https://grants.nih.gov/clinicaltrials_fdaaa/definitions.htm 
2. https://osp.od.nih.gov/clinical-research/clinical-research-policy 
3. FDA Guidance for Clinical Investigators, Sponsors, and IRBs, Adverse Event Reporting to IRBs – 
Improving Human Subject Protection 
 
FDA: Regulations Relating to Good Clinical Practice and Clinical Trials 
 
HHS:  The HIPAA Privacy Rule 
 
ICH Guidance for Industry, E6 Good Clinical Practice: Consolidated Guidance 
 
OHRP: Guidance on Reviewing and Reporting Unanticipated Problems Involving Risks 
to Subjects or Others and Adverse Events 
 
OHRP: Human Subject Regulations Decision Charts 
 
OHRP: Informed Consent Checklist 
 
OHRP: IRBs and Assurances 
 
OHRP:  Policy & Guidance Index 
11 CONFLICT  OF  INTEREST POLICY 
12 
REFERENCES 

 
  
 
OHRP:  Vulnerable Populations 
 
OHRP: Tips on Informed Consent 
 
21 CFR Part 11: Electronic Records, Electronic Signatures 
 
21 CFR Part 50: Protection of Human Subjects 
 
45 CFR Part 46; Protection of Human Subjects Research 
 
 
 
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