Clinical trial NCT02472223
Conditions: Conjunctivitis Adenoviral Conjunctivitis
Keywords: "Pink Eye"
Sponsor: Washington University School of Medicine
Start date: 2015-03-23; Completion date: 2018-06-01
Enrollment: 28 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary aim of this pilot study is to generate data needed to design a definitive trial to compare the safety and efficacy of standard care with artificial tears vs. Betadine 5% (5% povidone-iodine) for the treatment of pink eye due to adenovirus. There is currently no FDA approved treatment for pink eye, a common and highly contagious eye infection caused by adenovirus. Standard care as recommended by the American Academy of Ophthalmology and American Optometric Association is instillation of artificial tears to relieve symptoms and possibly reduce the virus population. Betadine 5% is a commercially available, broad-spectrum antiseptic ophthalmic solution used for over 50 years to prepare the patient's eye and surrounding area for eye surgery. Because Betadine 5% kills bacteria and viruses, it may be useful in treating adenoviral conjunctivitis. Betadine 5% is inexpensive, safe, widely available, and immune to the development of bacterial/viral resistance. Betadine 5% has the potential to significantly impact the clinical management of "pink eye" worldwide.

This pilot study has received funding from the National Eye Institute. Participants who meet eligibility criteria will be randomized using a masked randomization packet to receive one-time, in-office treatment with either artificial tears or Betadine 5%.

Patients who agree to study participation will answer questions about their pink eye symptoms, medical and ocular history, have an eye examination and be tested to confirm "pink eye" due to adenovirus using a FDA approved "point of care" immunoassay. Participants testing positive for adenovirus will have a tear sample taken to measure viral load by qPCR. Randomization and a one-time treatment with either (standard care) artificial tears or Betadine 5% will be done on the first visit. Follow-up visits are at 1,4,7,14 and 21 days. At each visit, symptoms of pink eye are asked, a standardized study eye examination is given by the masked clinician and a sample of tears is taken to assess viral load by qPCR.

Detailed description:
Aim 1: To compare the safety and efficacy of 5% Betadine to artificial tears in reducing viral load in patients with adenoviral conjunctivitis.

Aim 2: To compare the efficacy of 5% Betadine to artificial tears in reducing patient reported bothersomeness of ocular symptoms.

"Pink eye" (adenovirus conjunctivitis Ad-Cs)is a common ocular condition, with afflicted patients comprising as much as 2% of a general practitioner's practice. Partly due to the ability of adenovirus to remain infectious in the desiccated state for weeks at room temperature, Ad-Cs is more contagious than other forms of conjunctivitis and it can be spread via both ocular or respiratory secretions. Owing to the highly contagious nature of this condition, Ad-Cs outbreaks occur where people congregate: schools, military units, nursing homes, workplaces, community and health-care facilities. With respect to the latter, the nosocomial spread of the condition is a significant public health issue as 17% of 145 cases, 44% of 192 cases and 85% of 132 cases were reported to originate at the place of eye examination. The infection spreads from the first affected eye to the fellow eye in a majority of patients, and secondary transmission of viral conjunctivitis to members of the same household is estimated to occur at a rate of 20%. Outbreaks of Ad-Cs spare no nationality, age, gender or social class and because of the epidemic potential of some adenoviral serotypes, Ad-Cs is a reportable condition in Germany and Japan. A treatment that decreases the duration of the infectious period could have substantial impact in reducing the spread of Ad-Cs outbreaks.

To insure timely completion of recruitment, especially since outbreaks are seasonal and episodic, the study has recruited 6 participating clinical sites nationally. To attain the overall sample target of 50 randomized patients, about 200 pts with pink eye will need to be screened. Each clinic will screen 30-40 patients and randomize 8-10 over a 12 month period.

Patients who present with presumed acute Ad-Cs, who are 19 years of age or older and report symptom onset of 4 days or less in the first affected eye will be invited to undergo eligibility screening.

Over a 12 month recruitment period, 10 Clinical Centers will screen at least 200 patients who present with presumed Ad-Cs, to enroll a target sample of 50 eligible patients. 10 Clinics include Illinois College of Optometry, Ohio State University, Northeastern State University and University of Alabama at Birmingham, Brooke Army Medical Center, University of California, Berkeley, Massachusetts Eye and Ear, New England College of Optometry, University of Illinois and Washington University School of Medicine. These clinics provide geographic diversity and multi-ethnic representation (including African American, Asian, Caucasian, Hispanic and Native American groups). Because patients with pink eye are more likely to see an optometrist than an ophthalmologist, PI's of Clinics are optometrists.

Patients who consent to participation:

* Participant completes eligibility screening about 30 minutes - confirmation of age and symptom duration, a symptom survey, an eye examination;
* AdenoPlus(TM) test to confirm adenoviral conjunctivitis (Screening/Baseline Form);
* Participants who test positive by AdenoPlus(TM) are "fully eligible" and a tear sample will be taken for qPCR testing.

Fully eligible participants

* Will be randomized using masked packets identified by serial numbers containing the randomized treatment with either artificial tears or Betadine 5%;
* "Treating" unmasked study certified clinician will administer treatment as randomized;
* Participants will rate the discomfort of treatment to assess treatment tolerability and asked to guess whether they received artificial tears or Betadine 5%.

Follow-up visits will be scheduled for 1, 4, 7, 14 and 21 days after randomization. Each follow-up visit is about 30 minutes.

* Participants will rate the discomfort of treatment to assess treatment tolerability on day 1 post treatment;
* Masked clinician/technician will ask the 10-question pink eye ocular symptom questionnaire;
* Masked clinician will perform the eye examination;
* Masked clinician/technician will take conjunctival tear sample for analysis of viral load by qPCR.
* Participants who miss f/up visits will be asked to complete the symptom checklist by telephone or by secure REDCap data entry.

All study-related encounters with potential study participants will be conducted in private, closed-door, "Red Eye" examination room in the clinical center. All study certified personnel will ensure patient confidentiality at all times. The minimum amount of information needed for the study will be collected from study participants. All research study data are coded as to clinic site and patient ID and do not include personal health data. Personal health data are kept physically separate from research study data. All data are kept in HIPAA compliant office spaces. All study data will be collected and maintained using a secure, password protected web-based data capture program (REDCap).

The study drug, Betadine 5% is FDA approved for topical ocular surface application to the cornea, conjunctiva and palpebral fornices and is used in this study at the recommended dose, age group, duration and method of application. Risk is minimized by limiting administration to a single, one-time, in-office application. A study certified optometrist/technician instills artificial tears or Betadine 5% in the study eye. If there are immediate untoward reactions, the patient is in a fully equipped and staffed eye care facility where appropriate expertise and treatment are available. Participants are closely monitored with follow-up eye examinations at 1, 4, 7, 14 and 21 days after treatment.

Potential nosocomial infections are minimized by asking the patient to use hand sanitizer before entering the examination room. Patient signs only the consent form and all other surveys are administered by the clinician/technician. We will observe strict adherence to current CDC disinfection protocol for Ad-Cs. Patients reporting marked symptoms will be withdrawn from the study and managed according to standard clinical care guidelines.

Arms: arm 1: One time in-office administration (4-5 drops) of Betadine 5% limited to 2 minutes, followed by saline lavage. arm 2: One time in-office administration (4-5 drops) of artificial tears limited to 2 minutes, followed by saline lavage.
Interventions: intervention 1: Betadine 5% intervention 2: Artificial Tears
Intervention descriptions: intervention 1: One time in-office administration (4-5 drops) of Betadine 5% limited to 2 minutes, followed by saline lavage.

Betadine 5% exposure to the ocular surface is limited to 2 minutes in-office administration, followed by saline lavage per labeling instructions. intervention 2: One time in-office administration (4-5 drops) of artificial tears limited to 2 minutes, followed by saline lavage.

Protocol documents:
Prot_SAP_ICF_000.pdf: 
09-17-2020 
 
Reducing Adenoviral Patient Infected Days (RAPID) 
 
https://clinicaltrials.gov/ct2/show/NCT02472223 
 
 


Chapter 2 
RAPID Protocol 
Table of Contents 
 
2.0 Study Design ........................................................................................................... 3 
2.1 Specific Aims ........................................................................................................... 4 
2.2 Study Organization ................................................................................................. 5 
2.3 Schedule of Visits, Tests and Measures ............................................................... 6 
2.4 Recruitment of Patients with “Pink Eye” .............................................................. 7 
2.5 Recruitment, Consent and Tear Sampling in Control Patients ........................... 7 
2.6 Screening Examination for Patients with “Pink Eye” .......................................... 8 
2.7 RPS AdenoPlusTM and Tear Samples for Molecular Diagnosis ........................... 9 
2.8 RPS AdenoPlus™ Testing ...................................................................................... 9 
2.9 Tear Sample for Molecular Diagnosis ................................................................. 10 
2.10 Randomization (Appendix 2-F, Randomization Form) ..................................... 11 
2.11 Discharge Instructions (Appendix 2-G, Discharge Instructions) .................... 12 
2.12 Follow-Up Visits (Appendix 2-H, Follow-up Visit Form) ................................... 12 
2.13 Missed Visits........................................................................................................ 13 
2.14 Participant Withdrawal (Appendix 2-I, Withdrawal Form) ................................ 13 
2.15 Infection Control Protocol .................................................................................. 14 
2.16 Reporting of Adverse Events (AE) (Appendix 2-J, Adverse Events Form) .... 14 
2.17.1 Participant Reimbursement ............................................................................. 15 
2.17.2 Clinic Reimbursement ..................................................................................... 15 
2.18 Methods to Minimize Bias................................................................................... 15 
2.19 Data Entry Software ............................................................................................ 15 
2.20 Timeline ................................................................................................................ 16 
 
 
 


2.0 Study Design 
 
Summary of Reducing Adenoviral Patient-Infected Days (RAPID) Study 
This is a double-masked, randomized pilot study to estimate planning parameters for a 
definitive large scale trial.  In the pilot study, we will randomize 50 participants with 
adenoviral conjunctivitis confirmed by qPCR in 1:1 ratio to either one-time, in-office 
treatment with artificial tears or povidone iodine 5% (5% PVP-I).  Follow-up care in both 
groups after treatment at baseline will be standard of care with single-use artificial tears 
4 times-a-day until resolution of symptoms.  The pilot study is funded by a NIH R-34 
Planning Grant. 
 
Key Eligibility Criteria 
   1. Ability to provide written informed consent; 
   2. At least 18 years of age, male or female, of any race; 
   3. Self-reported onset of symptoms in first affected eye < 4 days of presentation; 
   4. Adeno-viral conjunctivitis in study eye confirmed by RPS AdenoPlusTM; 
   5. Females capable of becoming pregnant must have negative urine pregnancy 
testing. 
 
Key Exclusion Criteria 
   1. History of hypersensitivity to iodine or Betadine™ or thyroid disease; 
   2. History of herpetic eye disease; 
   3. Ocular surgery in study eye within the past 3 months; 
   4. Presence of skin vesicles, corneal subepithelial infiltrates, corneal dendrites, 
traumatic corneal abrasion, corneal ulcer, foreign body, or conjunctival 
membrane/pseudomembranes, or anterior chamber cell or inflammation in study 
eye on slit lamp examination; 
   5. Females who are pregnant or lactating or have positive urine pregnancy test. 
 
Study Visits 
Screening/Baseline visit includes completion of RAPID symptom survey, a 
comprehensive eye examination including visual acuity, SLE, fluorescein staining, RPS 
AdenoPlusTM and tear sampling for molecular diagnosis. 
 
Eligible patients are randomized to receive one-time, in-office dose of 5% PVP-I or 
artificial tears at baseline and complete 5 f/up visits (1-2, 4, 7, 14 and 21 days).  Tear 
samples for molecular diagnosis are taken at each f/up visit and AdenoPlusTM testing 
continues til 2 consecutive negative tests. 
 
Ineligible patients will receive standard of care outside of the RAPID study. 
 
Unmasked clinician/technician administers randomized treatment. 
Masked clinician/technician completes all follow-up visits. 
 
 
 


2.1 Specific Aims 
There are no published clinical trials evaluating the efficacy of one-time, in-office 
administration of 5% PVP-I against a control group.  A definitive trial has the potential to 
alter clinical practice patterns whether 5% PVP-I is shown to be efficacious or not.  Our 
long-term goal is to conduct a definitive, randomized clinical trial (under an NEI UG1 
grant award) that evaluates whether or not a single, in-office application of 5% PVP-I is 
more effective than artificial tears alone at reducing viral load and improving symptoms 
in patients with Ad-Cs.  To optimize the design of such a large-scale clinical trial, we are 
conducting this R34-planning study.  We will use this planning study to address three 
specific aims that will yield information that is critical to the successful design of the 
UG1 RCT. 
 
Aim 1: Evaluate the performance of the RPS AdenoPlusTM detector in 
determining study eligibility by comparing the RPS AdenoPlusTM case positive 
eyes in patients presenting with conjunctivitis to molecular diagnosis such as 
PCR testing. 
While molecular diagnosis such as PCR is the gold standard for adenovirus detection, 
PCR is performed off-site and delays diagnosis by 24-48 hours.  The inaccuracy of 
clinical diagnosis of Ad-Cs based on patient signs and symptoms has been extensively 
documented.  We will use the RPS AdenoPlusTM, a rapid in-office detection system, to 
screen for Ad-Cs and will adjust sample size of the future UG1-funded study to reflect 
the false-positive rate associated with this device. 
 
Aim 2: Assess patient visit completion, change in patient-reported symptoms and 
PCR-determined viral load and masking during the 21 day follow-up period. 
We will assess participants over six visits, baseline (treatment randomization) and 
follow-up at 1-2, 4-5, 7, 14 and 21 days.  We will quantify rates of visit completion and 
changes in participant-reported symptoms and viral load by qPCR at these time-points.  
These data will be used to determine the necessity and feasibility of a shorter/longer 
follow-up period in the UG1 clinical trial.  We will also assess participant-reported eye 
discomfort due to treatment using a 10 point visual analog scale to assess participant 
tolerance of 5% PVP-I.  Masking of participants will be assessed at baseline and at visit 
day 4-5.  Success of clinician masking will be assessed at baseline and day 14. 
 
Aim 3: Correlate changes in PCR-determined viral load with changes in clinical 
signs and symptoms. 
Improvement in clinical signs and symptoms is the most important outcome from the 
participant’s perspective and a prerequisite for wide adoption of 5% PVP-I as Ad-Cs 
therapy.  The data collected in this planning study at baseline, 1-2, 4-5, 7, 14 and 21 
days will be used to start probing this relationship and to identify the key variables that 
could be more directly focused on and addressed fully in the larger UG1-funded Ad-Cs 
clinical trial. 
 
These Aims will provide key planning parameters for the preparation of a Manual of 
Procedures for a national, multi-site clinical trial to test definitively whether or not a 


single, in-office treatment of 5% PVP-I is more effective than artificial tears at reducing 
viral load and improving symptoms in participants with Ad-Cs. 2.2 Study Organization 
Steering Committee members include Clinical Center PI’s and Coordinating Center 
Director:  
1. Harthan, Jennifer  O.D., FAAO Illinois College of Optometry 
2. Hartwick, Andrew  O.D., Ph.D, Ohio State University 
3. Johnson, Spencer O.D., Northeastern State University 
4. Migneco, Mary O.D., FAAO, Washington University School of Medicine 
5. Shorter, Ellen O.D., University of Illinois 
6. Than, Tammy O.D., M.S., (Study Chair), University of Alabama at Birmingham 
7. Gordon, Mae Ph.D., (Director) Coordinating Center, Washington University 
School of Medicine 
 
The Steering Committee will meet weekly by teleconference as it has done since the 
summer of 2012, and in person 1-2 months within study funding and at 12-14 months to 
develop the UG1 study protocol.  The Steering Committee will be responsible for 
monitoring study progress semi-annually, completing planning studies, designing the 
UG1 collaborative study protocol, preparation of the Manual of Procedures, and UG1 
collaborative studies grant application. 
 
2.2 Study Organization 
Clinic Personnel 
To attain the overall target sample of 50 randomized participants who are qPCR 
positive, at least 200 patients who present with pink eye will need to be screened.  
Thus, each clinic is expected to screen at least 50 patients and randomize at least 8-9 
eligible patients who are qPCR positive by February 2018.  Each clinic must have at 
least one study certified person in each of the following positions:  1. unmasked treating 
clinician/technician, 2. masked clinician/technician and 3. study coordinator.  Supplies 
are distributed to clinics by the Coordinating Center. Participants receive a retention 
incentive of $20 by gift card or check for each follow-up visit completed. 
 
Data Safety and Monitoring Committee 
NIH does not require a Data Safety and Monitoring Committee for R-34 planning 
studies.  However, in this R-34 planning study, an external, unmasked committee will be 
needed to review interim outcome data to make timely interim protocol changes 
because clinicians are masked.  The Data Safety and Monitoring Committee will 
convene annually.  Its members include:  Sally Atherton, Ph.D, (Regents Professor 
Emeritus, Medical College of Georgia) specializing in the pathogenesis of herpes virus 
infections of the eye and brain and routes of virus spread, James Chodosh, M.D., 
M.P.H. (Massachusetts Eye and Ear Infirmary) a clinician scientist specializing in clinical 
and pre-clinical adenovirus research;  Thomas Freddo, O.D., Ph.D., (New England 
College of Optometry, Boston), an internationally recognized expert in ocular pathology; 
Thomas Leitman, M.D., clinician scientist specializing in community strategies for 
trachoma control and corneal ulcer prevention programs.  Dr. William Mather (2015-
2016) withdrew upon retirement from Oregon Health and Science University.  
 


Ex Officio members include Mae Gordon, Ph.D., Washington University, Director 
Coordinating Center, Mr. Donald Everett, National Eye Institute and Dr. Israel Goldberg, 
consultant. 
 
The Coordinating Center will monitor safety and efficacy in an ongoing fashion and 
generate semi-annual reports on study progress for review by the Steering Committee.  
Death and selected other serious adverse events will be reported to the local IRB and 
the Coordinating Center within 24 hours of notification.  The Coordinating Center will 
notify the Steering Committee and Data Monitoring and Oversight Committee within 24 
hours of its notification. 
 
2.3 Schedule of Visits, Tests and Measures 
 
Procedure 
Screening/Baseline Exam 
Pts.> 18 yrs. 
presenting w pink eye 
Follow-up Exam 
Randomized Pts. 
at 1-2, 4-5, 7, 14, 21 days 
 
Unmasked or Masked 
Clinician/Technician  
Masked Clinician or 
Masked Technician 
Pt. washes hands upon entering 
exam rm. 
X 
X 
Written Informed Consent 
X 
n/a 
Examiner-Administered Symptom 
Survey 
X 
X 
Medical and Ocular History 
X 
X 
Snellen Visual Acuity 
Pinhole if VA worse than 20/20 
X 
X 
Slit Lamp Examination 
X 
X 
Grading of Ocular Signs 
X 
X 
Subepithelial Infiltrate Check  
X 
X 
Lymph Node Palpation 
X 
X 
Pregnancy testing for women of 
childbearing age 
X 
n/a 
AdenoPlusTM Testing and 
photograph RPS test display 
X 
Continue RPS testing until 2 
negative results  
Tear sample for molecular diagnosis  
X 
X 
Fluorescein Grading 
X 
X 
Clinician Prediction of Cause of Pink 
Eye 
X 
n/a 
 
Randomization of   
Study Eye of Eligible Patients 
 
Randomization to artificial tears or 
5% PVP-I (BetadineTM5%) 
Unmasked Clinician/Technician 
Administers Randomized 
treatment 
n/a 
Repeat Fluorescein Grading 
X 
n/a 
Pt. receives artificial tears for 21 
days 
X 
X 
Staff gives gift card to pt. & 
completes check voucher for $20 
n/a  
X 
Complete disinfection protocol 
X 
X 


2.4 Recruitment of Patients with “Pink Eye” 
(Appendix 2-A “Recruitment Screening Script”) 
Participants who present with “pink eye” will be ushered directly to a designated “red 
eye” examination room.  If a designated room is not available, the patient will be 
ushered to a designated “red eye” chair in the waiting area.  Magazines adjacent to 
chair will be disposed of afterwards in a red biohazard bag.  The chair surface will be 
disinfected with hypochlorite bleach or cavicide wipes. 
 
Participants, who are ≥ 18 years of age and report symptom in the first affected eye 
onset ≤ 4 days, will be informed of the study by Clinical Center personnel and asked if 
they would be interested in learning more.  Patients expressing interest in the study will 
discuss study participation with a study certified clinician/coordinator in a specially 
designated “Red Eye” examination room.  (Appendix 2-B, “Sample Consent Form”) 
 
Upon entering the “red eye” examination room, the study certified clinician/technician 
will request the patient to wash their hands.  The clinician/technician will turn on the 
water and dispense soap.  The patient dries hands with paper and disposes of paper 
towels in red biohazard bag. 
 
The study certified clinician/coordinator will explain the study to the patient, answer all 
questions and provide a brochure (Appendix 2-C “RAPID Recruitment Brochure”). The 
brochure will include information about adenoviral conjunctivitis (public health impact 
and proper hygiene to reduce infection and diagnosis) and describe the RAPID study 
and provide Clinical Center contact information. 
 
Patients who decline study participation will be treated according to the standard of care 
with artificial tears as recommended by the American Academy of Optometry and 
American Ophthalmology Academy.  Patients who decline participation will not be 
assigned a study ID code.  The patient EXITS the study and no more questions need to 
be completed.  The visit date and gender of patients who decline participation will be 
maintained on a screening log.  No other data is retrieved on patients who decline 
participation. 
 
Patients who agree to study participation and will sign two copies of the consent form 
and will be assigned a study ID code.  The clinic files one in a red folder indicating 
biohazard.  The other copy is given to the patient along with the pen used to sign. 
 
All research data are identified only by study ID code.  No personal identifying data are 
collected as research data.  All subsequent study forms are completed by study 
personnel to reduce risk of infection transmission. 
 
2.5 Recruitment, Consent and Tear Sampling in Control Patients 
Approximately 50 normal, healthy adult controls (age > 18) at each clinic will be invited 
to provide a one-time tear sample for immunoassay and molecular diagnosis to 
describe ocular microbiome in the normal eye.  Control eyes will provide a baseline 
against which to compare microbiome in eyes that present with “pink eye” infected with 


adenovirus and/or other infectious agents including co-infection by bacteria.  A high 
prevalence of adenovirus co-infection with bacteria causing conjunctivitis could favor the 
use of a broad spectrum anti-microbial agent such as betadine rather than an anti-viral 
agent. 
 
A study certified clinician/technician will explain the study to healthy adults and answer 
all questions.  Individuals who agree to possible participation will sign a copy of a 
consent form for healthy, adult volunteers.  They will be assigned a study ID code and 
be asked to complete a form asking age, gender, race/ethnicity and if they have taken 
prescription medications for an ocular condition in the last 2 months.  Those who 
answer “yes” are excluded.  No other data will be collected from controls.  There is no 
follow-up beyond the day of presentation and there is no payment for participation.  The 
control volunteer receives a photocopy of the consent form and the original is filed at the 
clinic in a HIPAA compliant office. 
 
A study certified clinician/technician will instill a drop of 0.5% of proparacaine anesthetic 
to numb one eye.  After 5 minutes, a tear sample will be taken from the lower lid with an 
RPS flock for immunoassay and swab for molecular diagnosis.  
 
Potential adult controls who decline study participation will be treated according to the 
original purpose of their visit.  No patients will be specifically called in to serve as an 
ocular control. 
 
2.6 Screening Examination for Patients with “Pink Eye”  
(Appendix 2-D “Screening/Baseline Form”) 
 
Re-Confirm age > 18 years 
Study certified personnel will confirm patient age (> 18).  If age is less than 18, the 
patient EXITS the study, the examination stops here and no more questions need to be 
completed. 
 
Ocular Symptom Survey 
Study certified personnel will read ocular symptom questions in quotes “word-for-word”.  
Duration of symptoms (again) in first affected eye (<4 days) will be asked again as 
confirmation.  If symptom duration is greater than 4 days, the patient is ineligible but will 
complete the screening examination, but will not complete the Screening/Baseline Form 
for eligible patients. 
 
History and Eye Examination 
Study certified personnel will complete: 
1. Case history to determine history of allergy to iodine or Betadine, eye surgery 
within 3 months, thyroid disease, herpes related eye infection, pregnancy status; 
2. Snellen visual acuity-corrected or uncorrected, pinhole if < 20/20; 
3. Lymph node palpation; 
4. Skin vesicles; 
5. Slit lamp examination; 


a. grading of eyelid edema 
b. eye lid matting 
c. tearing 
d. purulent discharge 
e. bulbar conjunctival edema 
f. bulbar redness 
g. hemorrhage 
h. conjunctival papillary response 
i. conjunctival follicular response 
j. conjunctival membrane 
k. corneal subepithelial infiltrates 
l. corneal ulcer 
m. presence of foreign body 
n. corneal dendrites 
o. anterior chamber flare 
p. anterior chamber cell 
6. AdenoPlusTM testing; 
7. Tear Sample for molecular diagnosis 
8. Fluorescein staining. 
9. Urine pregnancy test for females of childbearing age who are eligible 
 
2.7 RPS AdenoPlusTM and Tear Samples for Molecular Diagnosis 
All patients > 18 years of age who present with “pink eye” and consent to study 
participation will be tested with AdenoPlusTM (Rapid Pathogen Screening, Sarasota FL).  
After a 5 minute interval to replenish tears, a tear sample will be taken for molecular 
diagnosis.  The first affected eye will be tested and defined as the “study eye”. 
 
If both eyes are clinically eligible and both eyes developed symptoms at the same time, 
the study eye will be selected randomly by coin toss.  Data from both eligible and 
ineligible patients will to enable exploration of the relationship between symptoms, 
clinical signs and Ad-Cs. 
 
2.8 RPS AdenoPlus™ Testing  
1. If patient is wearing contact lens in study eye, remove CL’s; 
2. Place disposable Chux pad on the counter; 
3. Instill 1 drop of proparacaine 0.5% in study eye; 
4. Instruct the patient to look up and expose the inferior palpebral conjunctiva 
by lowering the eyelid; 
5. Dab and drag the sampling fleece along the inferior palpebral conjunctiva 8 
times; begin temporally moving nasally with each dab/drag movement; 
6. Rest fleece against nasal palpebral conjunctiva for 5 additional seconds; 
7. Assemble the test by firmly placing the sample collector into the test cassette 
body; 
8. Remove the protective cap from the test cassette and place the absorbent tip 
into the buffer for 20 seconds; 


9. Remove the tip from the buffer, replace the protective cap and lay 
horizontally on a flat surface for 10 minutes, but not more than 1 hour; Set 
timer for 10 minutes and record time in military time. 
10. Write ID & date on cassette next to display window, photograph cassette 
with standard color chip with smart phone within 4 hours under ambient 
exam room lighting. 
 
2.9 Tear Sample for Molecular Diagnosis   
1. 5 minutes after AdenoPlus sampling, take tear sample with flocked swab for 
molecular diagnosis. 
2. Remove flocked-swab and vial of Universal Viral Transport Medium from sterile 
packaging. 
3. Confirm that it has been 5 min since 1 drop of proparacaine 0.5% was instilled in 
study eye. 
 
Tear Sample Collection 
4. Pull down lower lid and hold swab approximately parallel to conjunctival fornix, 
with handle of swab pointing temporally. 
5. Place swab on nasal palpebral conjunctiva and pull swab across palpebral 
conjunctiva until it reaches temporal angle. 
6. Rotate the swab 180° and then slide swab back across the palpebral conjunctiva 
going from temporal to nasal side. 
7. Hold the swab flat along the nasal palpebral conjunctival for 5 seconds. 
Storage 
8. Open vial and place swab in vial so that flocks are immersed in the medium. 
9. Snap off the excess handle by pulling the swab against the vial at the scored line. 
10. Screw cap tightly. 
Labeling 
11. Record date & participant ID# on label.  Affix bar code label.  Do not enter name 
or date of birth. 
12. Sample can be stored at room temperature until transport to -20 or -80 degree 
freezer within 4 hours of collection. 
 
 
 
10 minutes after RPS AdenoPlus test, Interpret RPS AdenoPlusTM 
 
No Blue Line – Invalid result 
If a blue line is not visible, then the test is not valid.  The test must be repeated. 


Only Blue Line – Negative 
If there is only a blue line, then AdenoPlusTM is negative for Ad-Cs.  Complete the eye 
examination, fluorescein staining grading and manage the patient according to the 
standard of care with artificial tears.  Patient EXITS the study at this point and no 
additional questions need to be completed. 
 
Red Line (Solid or partial) – Positive 
If there is partial or solid red line in addition to the blue line, then AdenoPlusTM is 
positive for Ad-Cs. 
 
Pregnancy Testing 
Female patients who are clinically eligible and RPS positive must complete urine 
pregnancy test to rule out pregnancy. 
Negative pregnancy test:  If the pregnancy test is negative, and the female 
patient is clinically eligible and RPS positive, will complete the “Randomization” 
Form for eligible patients, qPCR and treatment randomization. 
Positive pregnancy test:  if the pregnancy test is positive, the female patient is 
ineligible.  Complete the eye examination, fluorescein staining grading and 
manage the patient according to the standard of care with artificial tears.  Patient 
EXITS the study at this point and no additional questions need to be completed. 
 
Shipping of Tear Sample to Washington University 
 Sample can be stored at room temperature until transport to -40 or -80 degree 
freezer within 4 hours of collection. 
 All specimens for a participant should be sent in the same shipment using the 
shipping carton provided by the Coordinating Center with a shipping manifest.  
Follow shipping instructions for biohazard specimens for molecular testing at 
your institution. 
 
2.10 Randomization (Appendix 2-F, Randomization Form) 
Participants who meet eligibility criteria including an AdenoPlus positive test are eligible 
for randomization.  Randomization will be performed using a coded, sequentially 
numbered sealed envelope kept in the examination room.  Randomization plan will be 
stratified by clinic and use a permuted block design with small random sized blocks.  
Treating (UNMASKED) clinician or technician administers the randomized treatment 
packet which includes the randomization assignment and one bottle of treatment-
artificial tears or 5% PVP-I. 
 
Treatment Protocol 
Participant will not be informed of the treatment assignment.  If the fellow eye presents 
with symptoms of Ad-Cs, it will be treated according to the standard of care with artificial 
tears. 
 
Treating (UNMASKED) clinician or technician opens the randomization packet, 
completes randomization form and administers the randomized treatment - one bottle of 
either -artificial tears or 5% PVP-I. 


1. Instill 1 drop of proparacaine 0.5% in study eye. 
2. Open randomization package. 
3. Instill 4 to 5 drops of assigned treatment (either artificial tears or 5% Betadine™) 
in inferior fornix. 
4. Instruct participant to gently close his or her eyes and set timer for 2 minutes. 
5. Gently place gloved finger on closed treated eye. 
6. Ask participant to look up/down and left/right. 
7. With the participant’s eye closed, use 2x2 gauze moistened with assigned 
treatment and dab along the eyelid margins. 
8. Make a dam with Kleenex around treated eye. 
9. Lavage the ocular tissues with sterile saline irrigation solution. 
10. Take another 2x2 gauze moistened with sterile saline and dab along lid margins 
to remove all residual treatment solution and dispose in a red bag. 
11. Dispense in each eye 8-10 preservative-free, single use artificial tears q.i.d. for 2 
days. 
 
2.11 Discharge Instructions (Appendix 2-G, Discharge Instructions) 
Upon completion of the Baseline Visit, the participant will receive “Discharge 
Instructions” for eye care and prevention of adenovirus transmission. 
 
2.12 Follow-Up Visits (Appendix 2-H, Follow-up Visit Form) 
The masked clinician or masked technician, not the treating clinician/technician will 
perform follow-up examinations. 
 
Five follow-up visits should be scheduled + 3 days of the target date and at least 4 days 
apart as follows: 
1. 1-2 days (± 1); 
2. 4-5 days (± 1); 
3. 7 days (± 3); 
4. 14 days (± 3); 
5. 21 days (± 3).  If symptoms have not resolved by day 21, clinician will continue to 
follow the participant for further assessment. 
The masked clinician/technician completes follow-up visits as follows:  
1. Ocular symptom survey; 
2. Visual acuity; 
3. Lymph Node Palpation; 
4. Slit lamp examination; 
5. Tear sampling for qPCR. 
Conjunctival swabs for qPCR will be placed in a cooler immediately and stored in 
a -40 or -80 freezer.  When the participant has completed all follow-up visits, all 
swabs from baseline and follow-up visits will be batched and sent to Washington 
University (Dr. Sarah Chavez) for storage in a -80 freezer.  When samples for 6-
10 participants (6 samples per participant) have been received, the samples will 
be walked to the Washington University pediatrics virology laboratory (Dr. 
Richard Buller) for DNA extraction and molecular diagnosis including qPCR with 


the Focus Diagnostics cycler.  Samples of DNA and unprocessed samples will be 
returned to the Chavez lab for long-term storage. 
6. RPS testing of study eye until 2 consecutive negative test results. 
Photograph RPS display window labeled with ID/date along w standard color 
chip in ambient exam room lighting.  RPS is done after tear sampling for 
molecular diagnosis because molecular diagnosis provides quantitative measure 
of viral burden and is the primary outcome of the study.  Repeat RPS testing is 
done to determine consistency of RPS results and to identify sensitivity 
compared to molecular diagnosis. 
 
 
 
2.13 Missed Visits 
If participant misses a follow-up appointment, participant should be immediately 
rescheduled. 
 
If the participant is unable to be rescheduled, the participant should complete the 
RAPID survey by telephone or by a password protected REDCap link to the HIPAA 
compliant RAPID website.  Participant will receive $10 for completion of the RAPID 
survey. 
 
2.14 Participant Withdrawal (Appendix 2-I, Withdrawal Form) 
Participants will be free to withdraw from the study at any time with no penalty. 
 
Participants may be withdrawn from the study if the study clinician determines it is not in 
the best interest of the participant to continue. 
 
Participant may be withdrawn from the study if clinical features of the conjunctival 
infection change during follow-up in a manner to indicate a non-adenoviral infection 
(e.g. bacterial, herpetic).  Participants who develop known complications of adenoviral 
infections including corneal subepithelial infiltrates decreasing visual acuity two lines or 
more, a conjunctival pseudomembrane or a conjunctival membrane, will continue in the 
study and will be managed according to standard clinical care with the most appropriate 
therapy. 
 


2.15 Infection Control Protocol 
In compliance with the findings from the 2006 Rutala et al study and the CDC Guideline 
for Disinfection and Sterilization in Healthcare Facilities”,(66) hypochlorite bleach wipes 
(1:10 dilution) will be used to disinfect all counter-tops, chair surfaces, handled 
equipment, chin and forehead rests, and door knobs.  All surfaces will be disinfected 
immediately following each visit.  The 1:10 dilution complies with the CDC guidelines. 
 
1. Participants who present with “pink eye” will be ushered directly to a designated 
“red eye” examination room.  If one is not available, the patient will be ushered to 
a designated “red eye” chair in the waiting room. 
2. Magazines adjacent to chair will be disposed of afterwards in red biohazard bag.  
The chair surface will be disinfected with hypochlorite bleach or cavicide wipes. 
3. Upon entering the “red eye” examination room, the study certified 
clinician/technician will request the patient to wash their hands.  The 
clinician/technician will turn on the water and dispense soap.  The patient dries 
hands and disposes of paper towels in red biohazard bag. 
4. Two copies of the consent form are signed.  The clinic files one in a red folder 
indicating biohazard.  The other copy is given to the patient along with the pen 
used to sign. 
5. Label vial of Universal Viral Transport Medium and apply barcode prior to 
beginning examination.  Write patient ID and visit date on RPS test cassette with 
Sharpie® permanent marker prior to beginning examination. 
6. The clinician/technician dons gloves. 
7. After the examination is completed, the clinician/technician disposes of their 
gloves in the red biohazard bag and will request the patient to wash their hands 
again.  The clinician/technician will turn on the water and dispense soap.  The 
patient dries hands and disposes of paper towels in red biohazard bag. 
8. The clinician/technician disinfects all surfaces with hypochlorite bleach or 
cavicide wipes including: 
Chair 
Slit lamp microscope 
Handheld occluder  
Proparacaine bottle and paint chip 
 
2.16 Reporting of Adverse Events (AE) (Appendix 2-J, Adverse Events Form) 
Participants will be instructed to contact the study investigator immediately should an 
AE occur.  All AE’s will be documented on AE forms and entered into a computer-based 
log.  The masked clinician grades AE severity: 1) minimal discomfort 2) moderate 
discomfort limiting daily activities, or 3) major discomfort requiring medical care and 
judges “relatedness” of AE to treatment as “Definitely not related” “Possibly related”, 
“Definitely related”. 
 
Serious adverse events will be reviewed electronically within 24 hours of notification of 
the Coordinating Center by the Steering Committee and the Data Monitoring and 
Oversight Committee.  Routine review of AE’s will be done weekly by the Steering 
Committee and quarterly by the Data Monitoring and Oversight Committee. 


2.17.1 Participant Reimbursement 
Participants completing 5 F/U visits at 1-2 days, 4, 7, 14 and 21 days will be reimbursed 
$20 per completed visit for $100 total.  Parking costs, if applicable, will also be 
reimbursed.  Participants who miss a visit but complete RAPID survey questions on the 
follow-up form by phone or on the HIPAA compliant study website will be reimbursed 
$10 as well.  Clinical staff will complete reimbursement voucher for each completed visit 
within 3 working days and transmit the form via REDCap to the Coordinating Center.  
Reimbursement will be by a gift card in the amount of $20 or a check mailed directly to 
the participant for $10 for completion of the survey and/or $20 for each completed visit. 
 
2.17.2 Clinic Reimbursement 
Clinics may elect to forego or, if necessary, can request to receive up to $50 per follow-
up research visit to cover some of the costs of participant follow-up, data collection and 
data entry.  Clinic reimbursement does not include the screening/baseline visit nor 
follow-up visits that are considered standard of care.  Some clinics will charge off follow-
up research visits as “research” and not charge the study. 
 
2.18 Methods to Minimize Bias 
The following measures will be undertaken to reduce potential bias: 
1. Masked, centralized randomization; 
2. With the exception of the one-time, in-office application of artificial tears or 5% 
PVP-I at baseline, all participants will undergo the same follow-up treatment 
(artificial tears), measures and procedures during the follow-up visits; 
3. Study entry requires a positive AdenoPlusTM test, an unbiased and objective 
criteria compared to signs/symptoms assessed by clinicians; 
4. Separation of treating clinician/technician from the masked clinician/technician 
who conducts follow-up visits and records post-treatment clinical outcome 
measures; 
5. All eyes are lavaged with saline to reduce residual staining that could unmask 
participants who receive 5% PVP-I; 
6. The primary outcome is change in viral titers as measured by qPCR which is 
standardized, quantitative, performed by an independent laboratory and not 
subject to examiner bias. 
Missed visits will be minimized by giving participants the clinic contact information 
(telephone number, cell number of PI, e-m address), List of dates/times of F/U visits and 
by remuneration of $20 for each completed follow-up visit and $10 for completion of the 
survey by phone or by secure internet. 
 
2.19 Data Entry Software 
REDCap data entry system is a secure, web-based data capture and management 
system that is currently in use in over 1,311 active institutional partners involving over 
149,000 projects worldwide.  Data entry screens are customized for each project and 
study variables can be drawn from a large dictionary of standard clinical and 
demographic variables, names and formats.  The Division of Biostatistics is the 
Informatics Core that manages the system for the entire Washington University system.  
DES is installed on the private zone of the cluster of Linux servers in the Division of 


Biostatistics.  The private network is protected from the rest of the University by a Linux 
firewall, and the University system is protected from the world by another firewall.  The 
DES is password protected and uses a multi-level login system that regulates access 
corresponding to approval level. 
 
2.20 Timeline 
The Steering Committee has met by teleconference weekly since the fall of 2012 and 
will continue to do so. 
< Month 1 
February, 2015:  Complete provisional protocol and operational 
description for R-34 planning study, case report forms, web data entry and 
randomization system, IRB submission/approvals. 
Month 1-5 
February-June 2015:  Face-to-face Steering Committee meeting to finalize 
planning study and train/certify Clinical Center Clinicians, Coordinating 
Center completes programming for key progress and safety reports for 
monthly Steering Committee review, purchase & distribute supplies, clinics 
enroll patients. 
Month 6-12 July-January 2016:  Steering Committee will review pre-randomization 
data (recruitment, exclusions, baseline data, pre-post treatment 
fluorescein staining, treatment discomfort and masking at 4 days) and 
post-randomization data including retention, data quality and 
completeness.  Data Monitoring and Oversight Committee will review 
masked data semi-annually by randomization assignment including qPCR, 
clinical and pt. reported outcome data and safety data. 
 
Continue enrolling patients and generate quarterly reports on study 
progress and safety. 
Month 13-18 February-July 2016:  Close enrollment, analyses of AdenoPlusTM 
specificity and differences in viral load and symptoms over time by 
randomization groups. 
Month 18-24 August 2016-February 2017:  Face-to-face Steering Committee meeting to 
finalize protocol for UG1 clinical trial and MOP chapters. 
 
 
 
 


 
 
 


2.21 Statistical Analysis Plan:  Primary Efficacy Outcome 
 
RAPID is a National Eye Institute funded R-34 planning study.  The target sample size 
of 40 (20 per group) is selected assuming a large effect size of 0.80, power = 0.80, and 
a nominal two-sided alpha of 0.05.  To decrease the probability of failing to reject a null 
hypothesis, there is no correction for multiple comparisons. 
 
The primary efficacy outcome is reduction from peak viral load defined as the percent 
reduction of DNA copies per ml from the participant’s peak viral load.  The Data and 
Safety Monitoring Committee approved a modified intention to treat analyses (mITT) to 
test efficacy outcomes in participants with detectable viral load by qPCR at baseline.  
The mITT analysis should not bias efficacy results because samples for qPCR were 
taken from all screened patients prior to randomization and qPCR results were never 
disclosed to participants or study personnel.  Safety is assessed using all randomized 
participants per intention-to-treat. 
 
The primary outcome and other quantitative variables including symptoms and signs will 
be analyzed using nonparametric Wilcoxon rank order tests.  The exact p-value will be 
calculated by a computational network algorithm (Mehta and Patel, 1983) given that 
asymptotic results assuming a normal distribution cannot be assumed with small 
sample sizes.  Nominal variables will be analyzed using Fisher’s exact test.  Treatment 
“effect size” (PVP-I mean minus AT mean divided by their standard deviation) will be 
calculated for the primary outcome to supplement p-values.  Cohen has classified effect 
sizes of 0.2 as “small”, 0.5 as “medium” and 0.8 as “large”. (REF:  Cohen J. Statistical 
Power Analysis for the Behavioural Sciences. 2nd ed. Hillsdale, NJ: Erlbaum 
Associates; 1988.) 
 
 


 
FOR IRB USE ONLY 
IRB ID #: 201501128 
APPROVAL DATE: 04/23/20 
RELEASED DATE: 04/24/20 
EXPIRATION DATE: 04/22/21 
 
 
INFORMED CONSENT DOCUMENT – Pink Eye 
 
Project Title: 
Reducing Adenoviral Patient Infected Days (RAPID) Study 
 
Principal Investigator: 
 
 
Research Team Contact: 
  
        
  
 
         
      
 
 
This consent form describes the research study and helps you decide if you want to participate.  It 
provides important information about what you will be asked to do during the study, about the risks and 
benefits of the study, and about your rights and responsibilities as a research participant.  By signing this 
form you are agreeing to participate in this study. 
 You should read and understand the information in this document including the procedures, risks 
and potential benefits. 
 If you have questions about anything in this form, you should ask the research team for more 
information before you agree to participate. 
 You may also wish to talk to your family or friends about your participation in this study. 
 Do not agree to participate in this study unless the research team has answered your questions 
and you decide that you want to be part of this study. 
 
WHAT IS THE PURPOSE OF THIS STUDY? 
This is a research study.  We invite you to participate in this research study because you have had “pink 
eye” for 4 days or less and are 18 years of age or older. 
 
The purpose of this pilot research study is to improve the treatment of “pink eye”.  Currently there is no 
U.S. Food and Drug Administration (FDA) approved treatment for “pink eye”.  Standard care 
recommended by the American Academy of Optometry and American Ophthalmology Academy is with 
artificial tears to relieve symptoms and to possibly reduce adenovirus in the eye.  Another possible 
treatment is with Betadine 5%, an antiseptic ophthalmic solution used for over 50 years to prepare 
patient’s eye and surrounding area for eye surgery and to clean minor wounds.  Because Betadine 5% 
kills bacteria and viruses, it may be useful in treating adenoviral conjunctivitis.  This study will be 
among the first to test Betadine 5% for “pink eye”. 
 
Betadine is approved by the U.S. Food and Drug Administration for prepping of the periocular region 
(lids, brow, and cheek) and irrigation of the ocular surface (cornea, conjunctiva, and palpebral fornices). 
However, the use of Betadine is considered investigational in this study. 
 
WHAT WILL HAPPEN DURING THIS STUDY? 
In order to determine if you are eligible for this investigational treatment you will need to do the 
following as part of the screening process: 
 Complete questionnaires about symptoms of pink eye, lost days of work or school and 
transmission of “pink eye”.  You are free to skip questions that you would prefer not to answer. 
 Receive a comprehensive eye examination.  Give a sample of tears to confirm “pink eye” by 
genetic diagnosis and immunoassay. 
Appendix 2 B, “Sample Consent Form”
-


 
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Page 2 of 9 
 Ask a few questions about your past health history such as any allergies, problems with your 
thyroid and past eye conditions. 
 We will conduct a urine pregnancy test if you are a woman that is capable of becoming pregnant. 
 
TREATMENT 
If after completing the screening process you are eligible to continue in the study, you will receive 
treatment that day.  Steps in treatment are: 
 First, you will receive a drop of a topical anesthetic (numbing drop) in the infected eye. 
 50% of the patients will receive a one-time, in-office dose of artificial tears and 50% of the 
patients will receive Betadine 5%. 
 After approximately 2 minutes, the treatment will be flushed out of the eye with a sterile eye 
wash. 
 
This will be a double-blind study.  This means neither you nor your doctors conducting your follow up 
care will know whether you received Betadine 5% or not.  If medically necessary, the doctor can find 
out whether you received artificial tears or Betadine 5%.  Participants will be instructed to use one drop 
of artificial tears four times a day in the infected eye as long as symptoms persist. 
 
FOLLOW-UP VISITS 
It is important to know at what point in time you become free of pink eye symptoms and free of 
adenovirus.  For this reason, your pink eye symptoms and adenovirus levels will be measured at each 
visit at day(s) 1, 4, 7, 14 and up to 21 after today.  Each follow up visit is about 30 minutes.  At each 
follow-up visit, you will: 
 Complete a questionnaire about symptoms of pink eye, lost days of work or school and 
transmission of “pink eye.”  You are free to skip questions that you would prefer not to answer. 
 A comprehensive eye examination. 
 Give a sample of tears to measure adenovirus levels. 
 If you miss a follow up visit you will be asked to complete the symptom checklist by telephone 
or by a secure data entry website. 
 
HOW MANY PEOPLE WILL PARTICIPATE? 
Approximately 20 patients with pink eye will take part in this study conducted by investigators at 
Washington University.  Nationwide, there are 9 clinics that will enroll about 50 patients into the study. 
 
HOW LONG WILL I BE IN THIS STUDY? 
If you agree to participate in this study, your involvement will last up to 21 days. 
 
WHAT ARE THE RISKS OF THIS STUDY? 
You may experience one or more of the risks indicated below from being in this study. In addition to 
these, there may be other unknown risks, or risks that we did not anticipate, associated with being in this 
study.  
 
 
 
 


 
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APPROVAL DATE: 04/23/20 
RELEASED DATE: 04/24/20 
EXPIRATION DATE: 04/22/21 
 
 
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Use of temporary dye, topical anesthetic, betadine 5% may cause: 
Less Likely / Less Common(less than 50% of patients will experience) 
 Temporary stinging (for a few seconds to several minutes) 
 
Use of artificial tears may cause: 
Less Likely / Less Common(less than 50% of patients will experience) 
 Blurred vision (for a few minutes) 
 
Use of Betadine 5% may cause: 
Rare (less that 2 % of patients will experience) 
 Temporary discoloration (discoloration of the white part of your eye and eyelid)  
 
A risk of participating in this study is that confidential information about you may be accidentally 
disclosed.  We will use our best efforts to keep the information about you secure.  Please see the section 
in this consent form titled “How will you keep my information confidential?” for more information. 
 
There is a federal law called the Genetic Information Nondiscrimination Act (GINA). In general, this 
law makes it illegal for health insurance companies, group health plans and employers with greater than 
15 employees to discriminate against you based on your genetic information. However, it does not 
protect you against discrimination by companies that sell life insurance, disability insurance or long 
term-care insurance.  
 
WOMEN CAPABLE OF BECOMING PREGNANT 
If you are a woman capable of becoming pregnant, we will ask you to have a pregnancy test before 
beginning this study.  You must use effective birth control methods and try not to become pregnant 
while participating in this study.  If you become pregnant, there may be unknown risks to your unborn 
child, or risks to your unborn child that we did not anticipate.  There may be long-term effects of the 
treatment being studied that could increase the risk of harm to an unborn child.  You must tell the doctor 
if your birth control method fails while you are on the study.  If you believe or know you have become 
pregnant while participating in this research study, please contact the research team member identified at 
the top of this document as soon as possible.  Please discuss with the research team how long you need 
to wait before becoming pregnant after completing the treatment or procedures on this study. 
 
WHAT ARE THE BENEFITS OF THIS STUDY? 
You may or may not benefit from being in this study. 
However, we hope that, in the future, other people might benefit from this study because this study may 
help us better understand how to diagnose and treat adenoviral infections of the eye in the future. 
 
WHAT OTHER TREATMENT OPTIONS ARE THERE? 
Alternative therapies for the treatment of adenoviral conjunctivitis are available.  These include topical 
steroids, topical non-steroidal anti-inflammatory drugs, or topical ganciclovir.  None of these treatments 
have FDA approval for treatment of adenoviral conjunctivitis. 
 
Before you decide whether or not to be in this study, your doctor will discuss the other options that are 
available to you.  Instead of being in this study, you could be treated using artificial tears as 
recommended by the American Optometric Association and the American Academy of Ophthalmology. 


 
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RELEASED DATE: 04/24/20 
EXPIRATION DATE: 04/22/21 
 
 
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WILL IT COST ME ANYTHING TO BE IN THIS STUDY? 
As part of this study you will receive tests and procedures that are similar to what you would receive 
during routine clinical care of your condition.  Your health plan/insurance company will be billed for 
some or all of these costs, and you will be responsible for any co-pays and deductibles that are normally 
required by your health plan/insurance.  Not all insurance plans cover the costs associated with being in 
a study.  Even if they do, you may be responsible for more out-of-pocket expenses, such as co-pays and 
deductibles, when there are more tests and procedures or more expensive tests and procedures involved 
in the study than if you were to receive routine clinical care outside the study. 
 
If you wish to know whether there are more tests and procedures or more expensive tests and procedures 
in the study, you should ask your study doctor. 
 
If you wish to know whether your insurance will pay, you should contact them directly, or speak with 
the study team about obtaining a financial pre-certification prior to enrolling in the study. 
 
WILL I BE PAID FOR PARTICIPATING? 
You will be paid $20 for each visit or up to a total of $100 for 5 visits in this research study.  You will 
need to provide your social security number (SSN) in order for us to pay you.  You may choose to 
participate without being paid if you do not wish to provide your social security number (SSN) for this 
purpose.  If your social security number is obtained for payment purposes only, it will not be retained for 
research purposes. 
 
WHO IS FUNDING THIS STUDY? 
This research study is funded by the National Institutes of Health.  This means that Washington 
University is receiving payments from the National Institutes of Health to support the activities that are 
required to conduct the study.  No one on the research team will receive a direct payment or increase in 
salary for conducting this study. 
 
WHAT IF I AM INJURED AS A RESULT OF THIS STUDY? 
Washington University investigators and staff will try to reduce, control, and treat any complications 
from this research.  If you feel you are injured because of the study, please contact the investigator at 
314-362-6125, and/or the Human Research Protection Office at 1-(800)-438-0445. 
 
Decisions about whether payment for medical treatment for injuries relating to your participation in 
research will be made by Washington University and the National Institute of Health. If you need to 
seek medical care for a research-related injury, please notify the investigator as soon as possible.  
 
HOW WILL YOU KEEP MY INFORMATION CONFIDENTIAL? 
We will keep your participation in this research study confidential to the extent permitted by law.  
However, it is possible that other people such as those indicated below may become aware of your 
participation in this study and may inspect and copy records pertaining to this research.  Some of these 
records could contain information that personally identifies you. 
 Government representatives, (including the Office for Human Research Protections) to complete 
federal or state responsibilities. 
 The U.S. Food and Drug Administration. 
 National Institutes of Health. 


 
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APPROVAL DATE: 04/23/20 
RELEASED DATE: 04/24/20 
EXPIRATION DATE: 04/22/21 
 
 
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 Your primary care physician if a medical condition that needs urgent attention is discovered. 
 Hospital or University representatives, to complete Hospital or University responsibilities. 
 Information about your participation in this study may be documented in your health care records 
and be available to your health care providers who are not part of the research team. 
 Washington University’s Institutional Review Board (a committee that oversees the conduct of 
research involving human participants) and the Human Research Protection Office.  The 
Institutional Review Board has reviewed and approved this study. 
 
To help protect your confidentiality, research data are coded as to clinic site and patient numeric ID and 
do not include personal health data.  Study examinations are conducted in private, closed-door “Red 
Eye” examination rooms.  Only certified study personnel are authorized to conduct research measures or 
handle data.  Research data are transmitted to Washington University on secure, web-based data 
management systems protected by firewalls and passwords. 
 
If we write a report or article about this study or share the study data set with others, we will do so in 
such a way that you cannot be directly identified. 
 
To further protect your privacy, this research is covered by a Certificate of Confidentiality from the 
federal government. This means that the researchers can refuse to disclose information that may identify 
you in any legal or court proceeding or to anyone who is not connected with the research except if:  
 there is a law that requires disclosure, such as to report child abuse and neglect, or harm to self or 
others;  
 you give permission to disclose your information, including as described in this consent form; or 
 it is used for other scientific research allowed by federal law. 
You have the right to share your information or involvement in this study with anyone at any time. You 
may also give the research team permission to disclose your information to a third party or any other 
person not connected with the research.  
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law.  This Web site will not include information that can identify you.  You can search this Web site at 
any time. 
 
Are there additional protections for my health information? 
Protected Health Information (PHI) is health information that identifies you.  PHI is protected by federal 
law under HIPAA (the Health Insurance Portability and Accountability Act).  To take part in this 
research, you must give the research team permission to use and disclose (share) your PHI for the study 
as explained in this consent form.  The research team will follow state and federal laws and may share 
your health information with the agencies and people listed under the previous section titled, “How will 
you keep my information confidential?” 
 
Once your health information is shared with someone outside of the research team, it may no longer be 
protected by HIPAA. 
 
The research team will only use and share your information as talked about in this form or as permitted 
or required by law.  When possible, the research team will make sure information cannot be linked to 


 
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IRB ID #: 201501128 
APPROVAL DATE: 04/23/20 
RELEASED DATE: 04/24/20 
EXPIRATION DATE: 04/22/21 
 
 
Page 6 of 9 
you (de-identified).  Once information is de-identified, it may be used and shared for other purposes not 
discussed in this consent form.  If you have questions or concerns about your privacy and the use of your 
PHI, please contact the University’s Privacy Officer at 866-747-4975. 
 
Although you will not be allowed to see the study information, you may be given access to your health 
care records by contacting your health care provider. 
 
If you decide not to sign this form, it will not affect 
 Your treatment or the care given by your health provider. 
 Your insurance payment or enrollment in any health plans. 
 Any benefits to which you are entitled. 
However, it will not be possible for you to take part in the study. 
 
If you sign this form: 
 You authorize the use of your PHI for this research 
 This authorization does not expire. 
 You may later change your mind and not let the research team use or share your information 
(you may revoke your authorization). 
 To revoke your authorization, complete the withdrawal letter, found in the Participant section 
of the Human Research Protection Office website at 
https://hrpo.wustl.edu/participants/withdrawing-from-a-study/ or you may request that the 
investigator send you a copy of the letter. 
o If you revoke your authorization: 
 The research team may only use and share information already collected for 
the study. 
 Your information may still be used and shared as necessary to maintain the 
integrity of the research, for example, to account for a participant’s 
withdrawal from the research study or for safety reasons. 
 You will not be allowed to continue to participate in the study. 
 
CAN WE CONTACT YOU BY EMAIL? 
We would like to contact you by email for the purposes listed below.  Some of these emails may contain 
health information that identifies you. 
 
 If you miss a visit, you can opt to complete the questionnaire about “pink eye” symptoms on a 
secure website. 
 
Only the research team will have access to your email communications.  We will only communicate by 
email to send you the information listed above.  If you have any questions or need to contact us for an 
urgent or emergent situation, please contact the research team member identified at the top of this 
document. 
 
You should be aware that there are risks associated with sending your health information via email. 


 
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APPROVAL DATE: 04/23/20 
RELEASED DATE: 04/24/20 
EXPIRATION DATE: 04/22/21 
 
 
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 There is always a risk that the message could be intercepted or sent to the wrong email address.  
To avoid sending messages to the wrong email address, the first email we send you will be a test 
message to ensure we have the correct email address. 
 When using any computer you should be careful to protect your username and password.  Make 
sure you log-out before getting up from the computer. 
 If you share a home computer with other family members, and do not want them to know you are 
participating in this study make sure you provide an email address that only you can access. 
 Your employer will have access to any email communications sent or received on any electronic 
devices used for work or through a work server. 
Do you agree to allow us to send your health information via email? 
 
_____ Yes  
_____ No 
Initials  
Initials 
 
IS BEING IN THIS STUDY VOLUNTARY? 
Taking part in this research study is completely voluntary.  You may choose not to take part at all.  If 
you decide to be in this study, you may stop participating at any time.  Any data that was collected as 
part of your participation in the study will remain as part of the study records and cannot be removed. 
 
If you decide not to be in this study, or if you stop participating at any time, you won’t be penalized or 
lose any benefits for which you otherwise qualify. 
 
WHAT IF I DECIDE TO WITHDRAW FROM THE STUDY? 
You may withdraw by calling the study team 
 or e-mailing
 
 that you are no longer interested in participating in the study or you may send in 
a withdrawal letter.  A sample withdrawal letter can be found at  
https://hrpo.wustl.edu/participants/withdrawing-from-a-study/ under Withdrawing from a Research 
Study. 
 
WILL I RECEIVE NEW INFORMATION ABOUT THE STUDY WHILE PARTICIPATING?  
If we obtain any new information during this study that might affect your willingness to continue 
participating in the study, we’ll promptly provide you with that information. 
 
CAN SOMEONE ELSE END MY PARTICIPATION IN THIS STUDY? 
Under certain circumstances, the investigator might decide to end your participation in this research 
study earlier than planned.  This might happen because the study doctor decides it is not in the best 
interest of your health or because you became pregnant. 
 
WHAT IF I HAVE QUESTIONS? 
We encourage you to ask questions.  If you have any questions, concerns, or complaints about the 
research or a research- related injury including available treatments,
.  She will be 
glad to answer any of your questions.
 can be reached during office hours at 
 
  
 can also be reached after hours at 
. 
 
If you have questions, concerns, or complaints about your rights as a research participant, please contact 
the Human Research Protection Office at 660 South Euclid Avenue, Campus Box 8089, St. Louis, MO  


 
FOR IRB USE ONLY 
IRB ID #: 201501128 
APPROVAL DATE: 04/23/20 
RELEASED DATE: 04/24/20 
EXPIRATION DATE: 04/22/21 
 
 
Page 8 of 9 
63110, 1-(800)-438-0445, or email hrpo@wustl.edu.  General information about being a research 
participant can be found on the Human Research Protection Office web site, http://hrpo.wustl.edu.  To 
offer input about your experiences as a research participant or to speak to someone other than the 
research staff, call the Human Research Protection Office at the number above. 
 
 
This consent form is not a contract.  It is a written explanation of what will happen during the study if 
you decide to participate.  You are not waiving any legal rights by agreeing to participate in this study.  
As a participant you have rights and responsibilities as described in this document and including: 
 To be given enough time before signing below to weigh the risks and potential benefits and 
decide if you want to participate without any pressure from the research team or others. 
 To understand all of the information included in the document, have your questions answered, 
and receive an explanation of anything you do not understand. 
 To follow the procedures described in this document and the instructions of the research team to 
the best of your ability unless you choose to stop your participation in the research study. 
 To give the research team accurate and complete information. 
 To tell the research team promptly about any problems you have related to your participation, or 
if you are unable to continue and wish to stop participating in the research study. 
 
Your signature indicates that this research study has been explained to you, that your questions have 
been answered, and that you agree to take part in this study.  You will receive a signed and dated copy 
of this form. 
 
 
Do not sign this form if today’s date is after EXPIRATION DATE: 04/22/21. 
 
 
__________________________________________ 
_______________________________ 
(Signature of Participant) 
 
 
 
 
(Date) 
 
 
____________________________________________ 
(Participant's name – printed) 
 
 
 
STATEMENT OF PERSON WHO OBTAINED CONSENT 
 
The information in this document has been discussed with the participant or, where appropriate, with the 
participant’s legally authorized representative.  The participant has indicated that he or she understands 
the risks, benefits, and procedures involved with participation in this research study. 
 
 
__________________________________________ 
_______________________________ 
(Signature of Person who Obtained Consent) 
 
(Date) 


 
FOR IRB USE ONLY 
IRB ID #: 201501128 
APPROVAL DATE: 04/23/20 
RELEASED DATE: 04/24/20 
EXPIRATION DATE: 04/22/21 
 
 
Page 9 of 9 
 
 
___________________________________________ 
(Name of Person who Obtained Consent - printed)