Conditions: Dry Eye
Keywords: Dry Eye Soft Contact Lenses
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 32
Healthy volunteers: no

Brief summary:
This is a prospective, single site, randomized, double masked, comparator-controlled study designed to evaluate the efficacy of lifitegrast ophthalmic solution 5% in treating the symptoms of dry eye in soft contact lens wearers as compared to control. We hypothesize that there will be a significant improvement in dry eye symptoms in contact lens wearers using lifitegrast as compared to those being treated with control (lifitegrast vehicle).

Detailed description:

Arms:
arm 1: None arm 2: None

Interventions: intervention 1: Lifitegrast 5% Ophthalmic Solution intervention 2: Lifitegrast Ophthalmic Solution Vehicle
Intervention descriptions: intervention 1: Dosed twice a day for 8 weeks intervention 2: Dosed twice a day for 8 weeks

Protocol document:
Prot_SAP_000.pdf: 
 
 
 
LIFITEGRAST 5% FOR THE TREATMENT OF DRY EYE IN 
HABITUAL SOFT CONTACT LENS WEARERS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Principal Investigator:  Danielle Iacono, OD, FAAO 
Version Number:  v.5.0 
03AUG2021 
 
 
 
 
 


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V5.0 PROTOCOL CHANGE SUMMARY 
Control Treatment 
Changed from single use vials of Systane Original 
Preservative Free artificial tears to lifitegrast 
vehicle. 
Randomization and Masking 
Changed to explain labeling on lifitegrast vs vehicle. 
Minor Formatting Changes 
Minor changes for clarification. 
V4.0 PROTOCOL CHANGE SUMMARY 
Adverse Events 
Edited to add detail to adverse events section. 
V3.0 PROTOCOL CHANGE SUMMARY 
Sponsor 
Clarified that Novartis is not the sponsor of the 
study, but rather providing drug and budget. 
Study Duration 
Clarified Study Timeline 
Control Treatment 
Changed from lifitegrast vehicle to single use vials 
of Systane Original Preservative Free artificial tears. 
Overall Design 
Added language to require subjects who are currently 
using reusable contact lenses to use Clear Care 
solution to clean and disinfect the lenses.   
Eligibility Criteria 
Added Inclusion 10: Subjects currently wearing 
reusable contact lenses must be willing to use Clear 
Care 
solution 
for 
cleaning 
and 
disinfecting 
throughout the study.  
Added Exclusion 11: Punctal plug insertion in the last 
3 months, or presence of punctal plugs at the time of 
the exam. 
Randomization 
Edited to include information regarding updated 
randomization method.  
Sample Size Justification 
Updated sample size justification 
Statistics 
Updated statistical methods. 
Grammatical /Formatting Edits 
Minor grammatical/ formatting changes to clarify 
content.  
V2.0 PROTOCOL CHANGE SUMMARY 
Sponsor 
Changed from Shire Human Genetic Therapies, Inc. 
to Novartis Pharmaceuticals Corporation. 
Control Treatment 
Changed from single use vials of preservative free 
artificial tears to lifitegrast vehicle. 
Masking 
Changed wording from “branding” to “any labeling” 
in relation to how masking will be maintained. 
Study Procedures 
Added Monocular High Contrast, High Luminance 
Visual Acuity to each visit. 
Inclusion Criteria 
Clarified Inclusion 9 to specify that entrance Snellen 
visual acuity will be utilized to determine subject 
eligibility.   
 
 
 


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STATEMENT OF COMPLIANCE 
 
This clinical trial will be conducted in accordance with the principles of The Declaration of Helsinki, and 
will follow GCP guidelines. The protocol, informed consent form(s), recruitment materials, and all 
participant materials will be submitted to the IRB for review and approval.  Any amendment to the 
protocol will require review and approval by the IRB before the changes are implemented to the study. 
The study will be registered on clinicaltrials.gov.   
 
1 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
Title: 
Lifitegrast 5% for the Treatment of Dry Eye in Habitual Soft Contact Lens 
Wearers  
 
 
Principal Investigator: 
Danielle Iacono, OD 
 
Study 
Drug/ 
Budget 
Provided by: 
Novartis Pharmaceuticals Corporation 
 
Description 
of 
Study 
Intervention: 
This is a prospective, single site, randomized, double masked, 
comparator-controlled study designed to evaluate the efficacy of 
lifitegrast ophthalmic solution 5% in treating the symptoms of dry eye in 
soft contact lens (CL) wearers as compared to control. We hypothesize 
that there will be a significant improvement in dry eye symptoms in 
contact lens wearers using lifitegrast as compared to those being treated 
with control (lifitegrast vehicle). 
 
Objectives: 
 
Primary Outcome: To determine the efficacy of lifitegrast ophthalmic 
solution 5% in treating the symptoms of dry eye in contact lens wearers 
as measured by change in total score on the Contact Lens Dry Eye 
Questionnaire-8 (CLDEQ-8) after 8 weeks of treatment.  
Secondary and Exploratory Outcomes: 
a. Change in tear osmolarity at 8 weeks in the lifitegrast 5% group 
compared to the control 
b. Forced choice questionnaire at week 8 asking if the participant felt 
that their symptoms improved to the point that they would continue 
treatment outside of the study 
c. Change in total score on the CLDEQ- 8 at 2 weeks and 4 weeks 
d. Trends in responses to individual questions 
 
Estimated duration from 
FPFV to Study Report: 
14 months 
 
Participant Duration: 
Visit 1: Day 0 (Baseline Visit) 
Visit 2: Week 2 
Visit 3: Week 4 
Visit 4: Week 8  
 


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2 
STUDY DESIGN 
2.1 
STUDY RATIONALE  
 
Dry eye disease (DED) is commonly encountered as part of clinical practice. It has been estimated that 
more than 16 million adults in the United States have diagnosed DED.1 DED is defined as “a multifactorial 
disease of the ocular surface characterized by loss of homeostasis of the tear film, and accompanied by 
ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and 
damage, and neurosensory abnormalities play etiological roles.”2 DED can be associated with or induced 
by the use of contact lenses.2 Changes to the tear film in contact lens (CL) wearers with dry eye include a 
thinner lipid layer, tear film instability, lower basal tear turnover rate and decreased tear meniscus 
volume.2 
 
Lifitegrast ophthalmic solution 5% is an anti-inflammatory drug approved to treat both the signs and 
symptoms of DED. It acts as a lymphocyte function associated antigen-1 antagonist (LFA-1). This allows 
for inhibition of T-cell adhesion, migration and proliferation.3 This study will seek to determine if using 
lifitegrast ophthalmic solution 5% will help improve dry eye symptoms in subjects who are existing 
habitual soft CL wearers as compared to control (lifitegrast vehicle).  
 
The Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8) will be utilized to establish baseline symptoms and 
to monitor for changes with treatment. This questionnaire has been validated to reflect subject opinion 
of soft CLs in clinical trials.4 A score of greater than or equal to 12 has be shown to identify soft CL wearers 
who would benefit from management of their CL related symptoms, with a change of 3 identifying a 
clinically important difference on the CLDEQ-8 total score.5 For this study, subjects must have a score of 
12 or greater on at baseline in order to be eligible for participation.  
 
2.2 
OVERALL DESIGN 
 
This is a prospective, single site, randomized, double masked, comparator-controlled study designed to 
evaluate the efficacy of lifitegrast ophthalmic solution 5% in treating the symptoms of dry eye in soft 
contact lens wearers as compared to control. We hypothesize that there will be a significant improvement 
in dry eye symptoms in contact lens wearers using lifitegrast 5% as compared to those being treated with 
control (lifitegrast vehicle). 
 
Potential study candidates will sign an informed consent form prior to any clinical procedures or tests 
specific to the protocol are performed.  All screening examination procedures will be performed by the 
investigator or trained personnel working under the investigator’s supervision.  Subjects will undergo 
examination to determine eligibility at the Baseline visit.  A complete medical, ocular and medication 
history will be obtained.  Subjects who elect to participate will complete the study as outlined in Section 
2.4.  Signs and symptoms will be evaluated at baseline, 2 weeks, 4 weeks and 8 weeks. All tests and 
measurements will be obtained in accordance with the procedures specified in this protocol.  
 
If found to be eligible, subjects will be randomized in a 1:1 ratio to either the test product (lifitegrast 5%) 
or control (lifitegrast vehicle) arm. Subjects will be instructed to use the drops twice a day in each eye.  
Drops are to be instilled in the morning at least 15 minutes before CL insertion, and after CL removal in 
the evening.   


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Subjects who are currently using reusable contact lenses will be required to use Clear Care solution to 
clean and disinfect their lenses.   
 
Subjects will be asked to return to each visit with all of the used and unused vials dispensed at the prior 
visit.  Subject accountability will be assessed at each follow up visit by comparing the amount of used vials 
to the amount of expected days of use. Trends in compliance will be considered during analysis of study 
data.    
2.2.1 OUTCOME MEASURES 
The primary outcome measure is the efficacy of lifitegrast ophthalmic solution 5% in treating the 
symptoms of dry eye in contact lens wearers as measured by change in total score on the CLDEQ-8 after 
8 weeks of treatment. 
Secondary and exploratory outcomes include: 
a. Change in tear osmolarity (measured via Tear Lab) at 8 weeks in the lifitegrast 5% group compared 
to the control 
b. Forced choice questionnaire at week 8 asking if the participant felt that their symptoms improved 
to the point that they would continue treatment outside of the study 
c. Change in total score on the CLDEQ-8 at 2 weeks and 4 weeks 
d. Trends in responses to individual questions 
 
2.3 
RANDOMIZATION AND MASKING 
 
The randomization schedule will be generated by a biostatistician using simple random sampling. 
Participants will be randomized within center at the first visit. After all baseline assessments are 
completed, the delegated unmasked study coordinator will refer to the randomization scheme to assign 
each subject to one of the two study arms. All study participants who are randomized into the study will 
comprise the intent-to-treat population. Participants will be randomized into 1 of 2 different treatment 
arms.  
 
The labeling differences between the lifitegrast and the vehicle will be known to only the unmasked 
coordinator. The unmasked coordinator will dispense the appropriate treatment to the subject.  All drug 
dispensing and accountability will be done by an unmasked study coordinator so the investigator can 
remain masked.   
 
 


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2.4 
STUDY PROCEDURES 
a. Artificial Tear (AT)/ Rewetting drop use will include date of last use and average use per week. 
b. Amount of vials used will be compared to amount of expected vials used based on number of days since 
the subject’s last visit. 
c. 
Subjects are to report to each visit wearing their habitual lenses. Acuity will be recorded as the last line in 
which the subject was able to read at least half of the letters. Plus and minus notation will be used to 
indicate additional letters read beyond the recorded acuity line or missed on the recorded acuity line.   
d. TearLab will be used per manufacturer’s guidelines to measure tear osmolarity.  This procedure must be 
performed prior to any drops being instilled in the eye for at least 2 hours prior.  
e. Lenses must have an adequate fit (centration, limbal/corneal exposure and movement) as determined by 
the investigator.  Lens wettability and deposits will also be assessed.  
f. 
Slit lamp grading scale will be based on: Efron Grading Scale6 
g. 
Grading scale: NEI/Industry Grading System7 
h. TBUT will be recorded in number of seconds 0-15 or greater than 15 seconds 
i. 
Grading scale: NEI/ Industry Grading System7 
j. 
Schirmer testing will be performed without anesthesia for 5 minutes in each eye.  
k. 
The questionnaire will ask the subject if he/she felt their symptoms improved to the point that he/she 
would continue outside the study.  
Procedures 
Visit 1 (Baseline) 
Visit 2 
(2 weeks 3 days) 
Visit 3 
(4 weeks5 days) 
Visit 4 
(8 weeks 5days) 
Informed consent 
X 
 
 
 
Medical/ Ocular History (including artificial tear/ rewetting drop use, 
habitual contact lens information and typical wearing time, 
concomitant medications and allergies)a 
X 
X 
X 
X 
Drug Accountabilityb 
 
X 
X 
X 
Entering Acuity (Snellen)c 
X 
X 
X 
X 
LogMAR Visual Acuity, High Contrast, High Luminance, OD and OS 
X 
X 
X 
X 
CLDEQ-8 Administration 
X 
X 
X 
X 
Tear Osmolarityd 
X 
 
 
X 
Habitual Contact Lens Fit Assessmente 
X 
X 
X 
X 
Removal of Contact Lenses 
X 
X 
X 
X 
Slit lamp Biomicroscopyf 
X 
X 
X 
X 
Corneal Staining Assessment (NaFl)g 
X 
X 
X 
X 
Tear Break Up Time (TBUT) in secondsh 
X 
X 
X 
X 
Lissamine Green Stainingi 
X 
X 
X 
X 
Schirmer Testingj 
X 
X 
X 
X 
Randomization 
X 
 
 
 
Drug Dispensing 
X 
X 
X 
 
Forced Choice Questionnairek 
 
 
 
X 
Contact Lens Re-Insertion (with irrigation if necessary) 
X 
X 
X 
X 
Exit Acuity (Snellen) 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 


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2.5 
RISK/BENEFIT ASSESSMENT   
 
2.5.1 KNOWN POTENTIAL RISKS  
Lifitegrast ophthalmic solution 5% will be dispensed to subjects in the test arm and will be used for 8 
weeks. 
The common (5-25%) risks associated with lifitegrast 5% are8: 
 
Instillation site irritation 
 
Dysguesia 
 
Reduced Visual Acuity 
Less common (1-5%) side effects include8: 
 
Blurred vision 
 
Conjunctival hyperemia 
 
Eye irritation 
 
Headache 
 
Increased lacrimation 
 
Eye discharge 
 
Eye discomfort 
 
Eye pruritis 
 
Sinusitis 
 
As with any medication, allergic reactions are possible.  A serious, potentially life-threatening allergic 
reaction known as anaphylaxis is possible.  
Subjects will be required to wear their habitual contact lenses throughout the study. The most common 
risks associated with CL wear include: 
 
Burning, stinging, tearing, redness and/or itching of the eyes 
 
Contact lens related ocular discomfort 
 
Foreign body sensation 
 
Dryness 
More serious side effects of CL wear are less common, and include: 
 
Corneal infiltrates, ulcers or erosions 
 
Corneal edema  
 
Corneal neovascularization 
 
Iritis 
 
2.5.2 KNOWN POTENTIAL BENEFITS 
Subjects may experience an improvement in signs and symptoms of dry eye if they are in the treatment 
arm. They might not experience any benefits if they are in the control arm.  The efficacy of lifitegrast in 
contact lens wearers is not known.   
2.5.3 ADVERSE EVENTS  
An adverse event (AE) is “any untoward occurrence (physical, psychological, social, or economic) in a 
human subject participating in research”. The event is not necessarily unexpected.  The event may have 


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been described in the informed consent as a risk of the study.  Adverse events include abnormal laboratory 
findings, a symptom, or disease temporally associated with the use of an investigational agent, or the 
progression of disease, whether or not related to the investigational product. 
Anticipated Adverse Events:  Anticipated adverse events include those listed in the Known Potential Risks 
section, informed consent documents, the lifitegrast package insert and/or those known to be associated 
with contact lens wear or dry eye. 
Anticipated adverse events will be recorded in the appropriate source documents and case report forms. 
At a minimum, the following data will be collected:  
 
Description of the event 
 
Onset 
 
Location 
 
Seriousness 
 
Relation to study drug 
 
Expectedness 
 
Actions taken 
 
Follow up 
 
Resolution date and outcome    
Serious Adverse Event (SAE):  Serious adverse events are any untoward medical occurrences such as 
death, significant disability/incapacity, In-patient hospitalization or prolongation of existing 
hospitalization or congenital anomaly/birth defect. 
Unexpected Adverse Effect (UAE):  An unanticipated problem involving risk to human participants or 
others is one that was unforeseen at the time of its occurrence and indicates that participants or others 
are at an increased risk of harm. Unexpected adverse events are those that are not already described as 
potential risks in in the Known Potential Risks section, informed consent documents, the lifitegrast 
package insert and/or those known to be associated with contact lens wear or dry eye or not part of an 
underlying disease. 
SAE/UAE Reporting 
An event is considered reportable if it is unexpected or serious. Once an event is suspected by the 
investigator as reportable, the PI shall be consulted to determine how the event should be reported. When 
the event is determined to be reportable by the PI, the Novartis shall be contacted immediately (within 
24 hours) by e-mail or phone. A written report will then be submitted to the sponsor and the IRB as soon 
as possible, but no later than 5 working days after discovery of the event (or sooner, as specified by the 
sponsor or IRB). 


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 
The PI will report (within 24 hours) the SAE/UAE to the IRB and Novartis as per the “Safety Data 
Collection and Reporting Responsibilities” agreement with Novartis. This information will be 
reported as soon as it becomes available.  
 
The PI will also report any drug exposure during pregnancy and any instances of drug misuse or 
abuse to Novartis.   
 
At a minimum, the following will be reported: the person who reported the event, information 
about the patient, details of the study drug, and details on the safety events experienced by the 
patient. 
 
The PI or designee shall submit a SAE/UAE Initial Report to the IRB. 
 
For suspected unexpected SAEs (SUSARs), safety reports such as Investigator Notifications or 
SUSAR listings will be prepared as per the “Safety Data Collection and Reporting Responsibilities” 
agreement with Novartis.  
SAE/UAE Follow-up 
Follow up reports shall be made to Novartis and the IRB until resolution of the event. 
 
The SAE (or AE) follow-up information shall be submitted following the “Safety Data Collection 
and Reporting Responsibilities” agreement with Novartis. 
 
A Follow-up Report shall be submitted to the IRB as required. 
The source documents must indicate: 
 
The event being followed 
 
The current status of the event 
 
What treatment was provided 
 
Any follow-up action taken/recommended 
 
The outcome of the event 
Unmasking of Investigators and Subjects 
Unmasking will be performed on an as needing basis, such as in the following scenarios: 
 
Serious adverse event, where unmasking is relevant to either subject care or reporting 
 
Drug/device recall 
 
Potential safety or risk management concern 
 
The Investigator deems knowledge of the treatment group to be essential to subject care or safety 
 
3 
STUDY POPULATION 
3.1 
INCLUSION CRITERIA 
 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
1. Subjects must read, understand and sign the Statement of Informed Consent  
2. Subjects must be at least 18 years of age  
3. Subjects must be habitual soft contact lens (CL) wearers, with a daily, weekly, bi- weekly or  


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monthly replacement schedule 
4. Habitual contact lenses must have a suitable fit as determined by the investigator  
5. Subjects must report a history of dry eye symptoms, for which they have used rewetting drops or 
Artificial Tears (ATs) in the past 30 days 
6. Subjects must be willing to discontinue the use of Artificial Tears (ATs) and rewetting drops for 
the duration of the study  
7. Subjects must have a score of 12 or higher on the CLDEQ at baseline   
8. Subjects must have at least 2 of the following signs of dry eye disease:  
a. High tear osmolarity > 308mOsm/L, or a difference greater than 8 mOsm/L between eyes  
b. Any corneal staining  
c. Any bulbar conjunctival staining   
d. Low TBUT (<10s)  
e. Schirmer <10mm in either eye 
9. Subjects must be able to read at least half of the 20/25 (via entrance Snellen visual acuity) or 
better in each eye in their current contact lens prescription.  
10. Subjects currently wearing reusable contact lenses must be willing to use Clear Care solution for 
cleaning and disinfecting throughout the study.  
 
3.2 
EXCLUSION CRITERIA 
 
An individual will be ineligible to participate or continue in this study if: 
1. Currently pregnant or breastfeeding by self-report  
2. Allergy to lifitegrast ophthalmic solution 5% (Xiidra)  
3. Habitual extended wear contact lens schedule  
4. Any active ocular disease that may affect the ocular surface other than dry eye (significant 
blepharitis, allergic conjunctivitis, lagophthalmos, chalazia, hordeolum etc.)   
5. Any meibomian gland dysfunction, blepharitis, corneal neovascularization or papillary 
conjunctivitis that is grade 3 or higher using the Efron Grading Scale. 
6. Excessive corneal staining, that in the opinion of the investigator, is a contraindication to contact 
lens use.   
7. History of ocular surgery  
8. Any active ocular infection   
9. Use of any topical ophthalmic medications other than artificial tears or rewetting drops  
10. Inability to perform necessary visual function assessments 
11. Punctal plug insertion in the last 3 months, or presence of punctal plugs at the time of the exam. 
  
3.3 
SAMPLE SIZE JUSTIFICATION 
 
Assuming normality, we calculated the statistical power for various detectable effect sizes using unpaired 
t-test in a two-sided hypothesis test with a significance level, 0.05, where the ratio of sample size of 1:1 is 
assumed between study arms. Table 1 shows that our sample size will have adequate power to detect 
listed effect size. For example, we will achieve 84% power to detect a standardized mean difference of 
1.12 between two groups of a size of 15 for each, which corresponds to a difference of score change by 3 
with standard deviations 3.2 and 2.0 for each group5. Up to 40 subjects will be enrolled with the goal of 
randomizing 30 subjects (15 per arm). This will allow for a 25% screen-failure rate. Note that for each 


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domain score and the overall score, the power is the same for each effect size since they are standardized, 
but the mean change corresponding to a given effect size differs.  
 
Table 1 
Sample size (N) 
N1 vs. n2 
Unpaired t-test 
Effect size 1 
Power (%) 
15 vs. 15 
1 
75.3 
1.12 
84.4 
1.2 
87.5 
1 standardized mean difference of 2 groups  
 
3.4 
STRATEGIES FOR RECRUITMENT AND RETENTION 
 
Participants will be recruited from the patients, students, and faculty of the SUNY State College of 
Optometry without regard to gender, economic status, sexuality, or race. Subjects will also be recruited 
from outside sources via online recruitment efforts. It will be made clear to those recruited that their 
participation is completely voluntary, and that failure to participate will have no consequences with 
respect to their standing within the SUNY community. Participants may withdraw from the study at any 
time and need not give a reason for doing so. 
 
3.5 
ENROLLMENT OF VULNERABLE SUBJECTS 
 
Vulnerable subjects with the exception of employees of the site, and students of the respective university 
will not be recruited. Staff that is listed on the delegation form are excluded from participation. 
 
3.6 
SCREEN FAILURES 
 
Individuals who do not meet the criteria for participation in this trial (screen failure) will not be 
randomized.  There will be no opportunity for rescreening. 
 
4 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT DISCONTINUATION/ 
WITHDRAWAL 
 
Participants are free to withdraw from participation in the study at any time upon request.  An investigator 
may discontinue or withdraw a participant from the study for the following reasons: 
 
 
Cannot comply with instructions in the protocol 
 
Lost to follow up 
 
Subject no longer meets eligibility criteria 
 
Sustain a clinical adverse event (AE), laboratory abnormality, or other medical condition or 
situation occurs such that continued participation in the study would not be in the best interest 
of the participant 
 
The following actions must be taken if a participant fails to return to the clinic for a required study visit: 


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 
The site will attempt to contact the participant and reschedule the missed visit and ascertain if 
the participant wishes to and/or should continue in the study. 
 
Before a participant is deemed lost to follow-up, the investigator or designee will make every 
possible effort to contact the subject.   
 
Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
  
DATA SAFETY AND MONITORING 
4.1 
CONFIDENTIALITY 
 
All information obtained during the course of the study will be regarded as confidential. The Institutional 
Review Board (IRB), and/or the sponsor may inspect the investigator’s records pertaining to the subject 
as a participant in the clinical study.  The results of this study may also be used for medical and/or scientific 
publications but the subject’s identity will not be disclosed.  All data to be collected in accordance with 
HIPAA.  All data to be kept as a de-identified data set for subsequent analysis by the investigator.  
 
4.2 
HOW WILL CONFIDENTIALITY BE MAINTAINED? 
 
The Principal Investigator and research team will maintain research subject’s confidentiality by using 
coded identifiers on protocol-required information that is reported to the sponsor or leaves the 
designated research team in any form unless otherwise allowed by the subject through written consent. 
In order to maintain confidentiality and safety of the human subject, the Principal Investigator and 
research team will assure that a documented verifiable link exists to identify study subjects throughout 
the course of the research, including, maintaining the study- specific subject log in a secure location with 
other regulatory documents at the end of the research study. 
To protect the privacy interests of participants, the Clinical Vision Research Center (CVRC) adheres to the 
following guidelines: 
 
All study personnel are required to maintain research ethics certification.  
 
Paper study documents are kept in locked storage in the CVRC and are accessible only by study 
personnel.  
 
Electronic study documents are kept in password-protected computer files that are accessible 
only by study personnel.  
 
Discussions by study personnel and participants should occur only in the CVRC or in areas where 
non-study staff or other participants cannot overhear discussions.  
 
When communicating verbally, by email or by telephone with participants, study staff must 
ensure they are safeguarding subject confidentiality.  
 
Only information necessary for the research study is collected from study subjects. 
MONITORING 
 
Study initiation, routine and close-out visits are planned and conducted over the lifespan of a study. Study 
monitoring will be carried out by monitors of the CVRC.  
 
A Site Initiation Visit (SIV) will be conducted prior to site activation to confirm preparedness for protocol 
execution, satisfactory site facilities, clarify the applicable regulations and requirements of the protocol, 
carefully review the process of implementing the protocol at the site and conduct any necessary training 


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prior to the assigned Program Official activating the site for enrollment. The site initiation visit will be 
conducted as soon as all the necessary approvals have been obtained. 
 
Interim Monitoring Visits (IMVs) will be conducted to confirm subjects’ rights are being protected; the 
study is being conducted according to the protocol and applicable regulations, including GCP; confirm 
accurate reporting of subject safety data and study endpoints. The first routine monitoring visit will occur 
as soon as the first subject is recruited or within 2 weeks of the first subject being recruited. The frequency 
of monitoring will be established at the start of the study. 
 
A Close-Out Visit (COV) will be conducted to ensure that all study data and other study documentation is 
complete and accurate and that all study records have been reconciled. The COV is completed after data 
cleansing and data lock. 
 
4.3 
RECORD RETENTION 
 
At the end of the study, all study materials (i.e., source, regulatory documents) will be kept on site in a 
secure area at SUNY College of Optometry. Study materials will only be accessible by research personnel 
and will be kept for a minimum duration of seven (7) years or longer, if specified in the study contract. 
Any change to storage location off site will be communicated with the sponsor in advance. Sponsors will 
be contacted regarding destruction of study material at the end of the prescribed time. 
 
4.4 
ANALYSIS 
 
All source data will be collected on paper source documents. Data will be entered into an Excel 
spreadsheet with double data entry to check for error before locking the data set.   
 
5 
STATISTICS 
 
The clinical characteristics of subjects including demographics and lens modality will be first summarized 
using descriptive statistics in mean  SD for continuous variables or % (counts) for categorical variables, 
with attention to assessing balance in these characteristics by study arms, and with assessment of the 
distribution of variables, relevant to the choice of statistical tests. For the continuous outcomes, we will 
conduct the Kolmogorov-Smirnov or the Shapiro-Wilk test to confirm normality of measurements prior to 
performing statistical analyses. Detection of outliers will be done using histograms, box-plots, normal 
plots and summary statistics. Where appropriate, logarithmic transformation will be further done.   
 
All analyses will be conducted using the principle of “intent-to-treat” in which every participant is assumed 
to have received his/her assigned intervention, regardless of adherence. In order to assess for the 
significant difference between study arms for the primary outcomes of change in total score on the 
CLDEQ-8 after 8 weeks of treatment or continuous secondary outcomes (change in tear osmolarity), 
bivariate comparisons will be first conducted using t-tests. Alternatively Wilcoxon nonparametric 
counterpart will be used for continuous variables that deviate from normality. The forced choice 
questionnaire will be compared as a percentage of "yes" responses between the two groups by a two-
sample test of proportion. These univariate analyses will be followed by multivariable regression methods 
for an adjustment of all other potential confounding variables such as baseline clinical and demographic 
characteristics that differ by study arms.  


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Alternatively, we will use longitudinal linear models to analyze the difference of changes in total score 
between study arms from the baseline to the follow-up times across baseline, 2nd, 4th and 8th weeks (i.e., 
mixed-effects regression models with a random subject effect and GEE with exchangeable and 
independent correlations). The models will be specified with random intercepts and slopes such that a 
linear trajectory representing outcome will be compared between groups. Group (arm)-specific (as well 
as individual-level) intercepts and slopes over the period of follow-up will be included as random effects, 
while other covariates will be modeled as fixed effects. All models will be adjusted for other clinical or 
demographic confounders. Residual-based diagnostics will be used to evaluate validity of model 
assumptions. Two sided p-values <0.05 will be considered to be statistically significant.  All statistical 
procedures were performed using R statistical package (www.R-project.org). 
 
6 
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