Conditions: Dry Eye
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 70
Healthy volunteers: yes

Brief summary:
Single site, prospective, double-masked, randomized-controlled, two-arm study of the dry eye symptoms as well as corneal and conjunctival staining in subjects using 2 different eyedrops. Subjects will be assessed at a screening visit, and 2 follow-up visits. Clinical evaluations will include patient questionnaire, tear-breakup time, and slit lamp exam.

Detailed description:

Arms:
arm 1: None arm 2: None

Interventions: intervention 1: Systane Complete Multi-Dose PF intervention 2: Walgreen's Lubricant Balance
Intervention descriptions: intervention 1: Eyedrop intervention 2: Eyedrop

Protocol document:
Prot_SAP_000.pdf: 
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Subjective and Objective Performance of Systane Complete Multi-Dose 
PF versus Walgreen’s Lubricant Balance  
An investigator-initiated clinical trial 
1.  TITLE PAGE 
 
Protocol Number: 
JM-23-02  
Amendment Number 
Version 1.0 
IRB / ERC 
Salus IRB 
2111 West Braker Lane, Suite 400 
Austin, Texas 78758 
 
 
Sponsor Name & Address: 
Jay Mashouf, OD 
Scripps Optometric Group 
10549 Scripps Poway Pkwy Ste G 
 San Diego, CA 92131 
 
(funding only, this is an investigator-initiated study 
IIT # 89908509) 
Alcon  
6201 South Freeway,  
Fort Worth, TX 76134-2099, USA  
 
 
Test Articles: 
Systane Complete Multi-Dose PF 
Walgreen’s Lubricant Balance 
 
  Investigator:  
 
  Jay Mashouf, OD 
 
 
 
 
 
 
 
 


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2 . INVESTIGATOR AGREEMENT 
 
I confirm that I have read and that I understand this protocol entitled “Subjective 
and Objective Performance of Systane Complete Multi-Dose PF versus Walgreen’s 
Lubricant Balance”, and understand the use of the study products. I agree to 
conduct this study in accordance with the requirements of this protocol and also 
protect the rights, safety, privacy, and well-being of study subjects in accordance 
with the following: 
 
• 
The ethical principles that have their origin in the Declaration of Helsinki. 
• 
All applicable laws and regulations, including, without limitation, data privacy 
laws and regulations. 
• 
Regulatory requirements for reporting serious adverse events defined in Section 
13 of this protocol.s 
 
 
 
 
Signature of Investigator  (Date) 
 
Investigator Name (print or type) 
 
Investigator’s Title 
 
Name of Facility 
 
Location of Facility (City) 


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3.  GENERAL INFORMATION 
 
Objective 
To compare dry eye symptoms as well as corneal and 
conjunctival staining of Systane Complete Multi-Dose PF, versus 
the Walgreen’s Lubricant Balance eye drop. 
 
The hypothesis is that mild to moderate dry eye subjects will 
exhibit less frequent and severe dry eye symptoms after using 
Systane Complete Multi-Dose PF versus those who use 
Walgreen’s Lubricant Balance. 
 
Test Article(s)   
Systane Complete Multi-Dose PF 
Walgreen’s Lubricant Balance 
Sample size  
70 subjects 
Study Population 
Subjects who currently have mild to moderate symptoms of dry 
eye. 
 
Number of sites 
One 
Study Design 
Single site, prospective, double-masked, randomized-controlled 
study with two arms 
 
Masking 
Double-masked 
Variables 
Primary:  Dry eye symptom frequency and severity as measured 
by the SANDE questionnaire change after 2 weeks of QID 
use. 
 
Exploratory: 
• Comparing corneal and conjunctival staining before and after 
2 weeks of QID use of their assigned drop. 
• Comparing Non-invasive TBUT times of the subjects in the 
two arms of the study, before and after 2 weeks of QID use of 
their assigned drop.  
• Dry eye symptom frequency and severity as measured by the 
SANDE questionnaire after 1 week of QID use. 
 
Duration / Follow-up 
Screening Visit to 2 weeks follow-up 
 
The study will be registered with clinicaltrials.gov.  
 
The study will be conducted in compliance with the protocol, GCP and applicable 
regulatory requirements 
 


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4.  TABLE OF CONTENTS 
1.  TITLE PAGE .............................................................................................................................. 1 
2 . INVESTIGATOR AGREEMENT .................................................................................................. 2 
3.  GENERAL INFORMATION ........................................................................................................ 3 
4.  TABLE OF CONTENTS .............................................................................................................. 4 
5.  INTRODUCTION ...................................................................................................................... 6 
6.  OBJECTIVE(S) .......................................................................................................................... 6 
7.  SUBJECTS ................................................................................................................................ 6 
7.1. Subject Population ...................................................................................................... 6 
7.2. Inclusion Criteria ......................................................................................................... 6 
7.3. Exclusion Criteria ......................................................................................................... 7 
8.  STUDY DESIGN ........................................................................................................................ 7 
8.1. Study Design ................................................................................................................ 7 
8.2. Methods Used to Minimize Bias .................................................................................. 8 
8.3. Method of Assigning Subjects to Treatment Arms ...................................................... 8 
9.  STUDY PROCEDURE ................................................................................................................ 8 
9.1. Informed Consent / Subject enrollment ..................................................................... 8 
9.2. Visits and Examinations ............................................................................................... 8 
9.3. Study Methods and Measurements .......................................................................... 10 
9.4.  Unscheduled Visits ................................................................................................... 11 
9.5.  Discontinued Subjects .............................................................................................. 11 
10.  ANALYSIS PLAN ................................................................................................................... 11 
10.1. Analysis Data Sets .................................................................................................... 11 
10.2. Statistical Methodology .......................................................................................... 11 
10.3. General Statistical Considerations .......................................................................... 12 
11.  SAMPLE SIZE JUSTIFICATION .............................................................................................. 12 
12. CONFIDENTIALITY/PUBLICATION OF THE STUDY ................................................................ 12 
13.  QUALITY COMPLAINTS AND ADVERSE EVENTS .................................................................. 13 
13.1. General Information ................................................................................................ 13 
13.2. Monitoring for Adverse Events ............................................................................... 13 
13.3. Procedures for Recording and Reporting AEs and SAEs .......................................... 13 


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13.4. Follow-Up of Adverse Events and Quality Complaints ............................................ 16 
13.5. Safety Analyses ........................................................................................................ 16 
14. GCP, ICH and ETHICAL CONSIDERATIONS ........................................................................... 16 
14.1 Confidentiality .......................................................................................................... 16 
15.  STANDARD EVALUATION PROCEDURES ............................................................................. 18 
Table 15.1. Proposed Visits and Study Assessments ........................................................ 18 
16. CONFIDENTIALITY ................................................................................................................ 18 
17. FINANCIAL AND INSURANCE INFORMATION/STUDY RELATED INJURIES ............................ 18 
18. STUDY ENDPOINT CRITERIA ................................................................................................ 19 
18.1. Patient Completion of Study ................................................................................... 19 
18.2. Patient Discontinuation ........................................................................................... 19 
18.3. Patient Termination ................................................................................................ 19 
18.4. Study Termination ................................................................................................... 19 
18.5. Study Completion .................................................................................................... 19 
19. SUMMARY OF RISKS AND BENEFITS .................................................................................... 19 
19.1. Summary of risks ..................................................................................................... 19 
19.2. Summary of benefits ............................................................................................... 19 
REFERENCES .............................................................................................................................. 20 
 
 
 


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5.  INTRODUCTION 
There are a vast array of lubricating eyedrops available on the market that can confuse 
and frustrate consumers. Many consumers view these the various products as “all the 
same” and often do not base their purchase on science or their doctor’s recommendation, 
but a variety of other factors including cost, store merchandising, and a potential view 
that all products are the same.  
 
However, even products that list the same active ingredient can have vastly different 
inactive ingredients resulting in a potentially different outcome for the patient. For 
example, Walgreen’s Lubricant Balance eyedrop and Alcon’s Systane Complete Multi-
Dose Preservative Free (PF) eyedrop has the same active ingredient (0.6% propylene 
glycol), however, Walgreen’s Lubricant Balance eyedrop is preserved in benzalkonium 
chloride (BAK), a known cause of ocular dryness and corneal and conjunctival staining.1 
To date, there is little data comparing the clinical outcomes between these two eyedrops.  
 
The purpose of this study is to compare dry eye symptoms as well as corneal and 
conjunctival staining of Systane Complete Multi-Dose PF, versus the Walgreen’s 
Lubricant Balance eye drop. 
6.  OBJECTIVE(S) 
To compare dry eye symptoms as well as corneal and conjunctival staining of Systane 
Complete Multi-Dose PF, versus the Walgreen’s Lubricant Balance eye drop. 
7.  SUBJECTS 
7.1. Subject Population  
Eligible test subjects will be 18-45 years of age who currently have mild to moderate 
symptoms of dry eye as defined by a screening SANDE score of 20 to 55 inclusive 
(equivalent to OSDI score of 12 to 32).2 
 
A total of 70 subjects at one site will be enrolled. Both eyes of a subject must be enrolled. 
Subjects must meet the inclusion criteria. Prior to enrollment, subjects will be provided 
information on the study and asked to sign a patient information and consent form to 
participate. The patient information and consent form will be approved by an appropriate 
ethics committee. 
7.2. Inclusion Criteria 
Subjects are eligible for the study if they meet the following criteria: 
Note: Ocular criteria must be met in both eyes. 
• Subjects who currently have mild to moderate symptoms of dry eye as defined by 
a screening SANDE score of 20-55 inclusive (equivalent to OSDI score of 12 -
32).2 
• Subjects between the ages of 18-65. 


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• Subjects willing to comply with the prescribed regimen and schedule of eye 
drops. 
• Subjects willing to attend all study visits. 
• Subjects willing to discontinue any current artificial tear use 24 hours prior to the 
baseline study visit. 
7.3. Exclusion Criteria 
If any of the following exclusion criteria are applicable to the subject or either eye, the 
subject should not be enrolled in the study. 
• Ocular anterior segment infection, inflammation, abnormality, or active disease. 
• History of herpetic keratitis or ocular surgery. 
• Recent (within 1 year) thermal meibomian gland expression procedure including 
Lipiflow, iLux, or TearCare. 
• Recent (within 1 year) blepharitis debridement procedure including BlephEx. 
• Screening SANDE score > 55 (equivalent to OSDI score of >32).2 This is 
indicative of a severe dry eye. 
• Screening SANDE score < 20 (equivalent to OSDI score of <12).2 This is 
indicative of a clinically normal eye. 
• Screening non-invasive TBUT < 2 seconds, or > 10 seconds.3 
• Screening NaFl score < 3 (clinically normal eye) or > 10 (severe dry eye).4 
• Pregnant or lactating. 
• Current use of contact lenses. 
• Any change in eye drop regimen, whether OTC or RX in the last 90 days. 
 
The principal investigator reserves the right to declare a patient ineligible or non-
evaluable based on medical evidence that indicates they are unsuitable for the trial.  
 
Pregnancy has a known effect on the stability of refractions and visual acuity. As such, 
subjects who become pregnant during the study will not be discontinued but their data may 
be excluded from analyses of effectiveness. 
8.  STUDY DESIGN 
8.1. Study Design  
Single site, prospective, double-masked, randomized-controlled, two-arm study of the dry 
eye symptoms as well as corneal and conjunctival staining in subjects using 2 different 
eyedrops. Subjects will be assessed at a screening visit, and 2 follow-up visits. Clinical 
evaluations will include patient questionnaire, tear-breakup time, and slit lamp exam. 
 
The primary outcome measure is Dry eye symptom frequency and severity as measured 
by the SANDE questionnaire change after 2 weeks of QID use. 
 
Exploratory outcome measures are as follows: 


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• Comparing corneal and conjunctival staining before and after 2 weeks of QID use of 
their assigned drop. 
• Comparing Non-invasive TBUT times of the subjects in the two arms of the study, 
before and after 2 weeks of QID use of their assigned drop.  
• Dry eye symptom frequency and severity as measured by the SANDE questionnaire 
after 1 week of QID use. 
8.2. Methods Used to Minimize Bias  
Patient selection will be based on the patient’s interest and the optometrist’s opinion as to 
whether they are a suitable candidate for eyedrops. Subjects will be randomized to 
treatment groups.  
 
All data collection will be completed through provided Case Report Forms (CRFs) or 
computer files generated by automated test equipment. All site personnel involved in the 
study will be trained in regard to conducting study-specific procedures. 
8.3. Method of Assigning Subjects to Treatment Arms 
Subjects will be assigned to Systane Complete Multi-Dose PF or the Walgreen’s 
Lubricant Balance treatment groups in a 1:1 ratio using the method of randomly 
permuted blocks.  
9.  STUDY PROCEDURE  
9.1. Informed Consent / Subject enrollment  
No subject will be enrolled into the study who does not meet the inclusion/exclusion 
criteria and does not sign the current approved informed consent document. Informed 
consent will be obtained prior to collecting any data for the study. The original signed 
documents will be maintained by the investigator as a permanent part of the subject's 
medical records. A signed copy will be provided to the subject.  
9.2. Visits and Examinations  
Subjects will participate in 3 study visits. Visits will include an uptake visit and 2 follow 
up visits (Visit numbers 1-3 below).  The visit schedule, complete with window and 
associated CRF forms, are displayed in Table 9.2-1.  Details of each study visit, including 
testing to be conducted, are provided below.  
 
 
 
 


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Table 9.2-1.  Visit Schedule 
 
Visit 
Number 
Visit Name 
Visit Window 
CRF 
Number 
1 
Recruitment 
Day 0  
1 
2 
Follow-Up Visit 1 
Day 7 ± 1 day 
2 
3 
Follow-Up Visit 2  
Day 14 ± 2 days 
3 
 
 
9.2.1. Recruitment 
 
At the recruitment visit, subjects will be consented, qualified for the study 
(compared with inclusion/exclusion criteria), and assigned a study ID/subject 
number.  Subject numbers will be assigned sequentially at each site in the order of 
enrollment.  
 
A medical history will be taken and exams will include the tests described below: 
§ slit lamp exam including evaluation of staining, 
§ non-invasive tear breakup time, 
§ SANDE questionnaire. 
In addition, all site-specific, routine, usual standard of care measures should be 
undertaken.   
 
Measurements should be made as described in section 9.3 below.  
 
9.2.2. Follow-Up Visit 1 
 
Exams will include the tests described below: 
§ SANDE questionnaire, 
§ compliance check. 
In addition, all site-specific, routine, usual standard of care measures should be 
undertaken.   
 
Any adverse events/serious adverse events (AEs/ SAEs) occurring during surgery 
will be noted at this visit. Any other problems during surgery and comments 
regarding surgery will be documented.  
 
9.2.3. Follow-Up Visit 2 
 
Exams will include the tests described below: 
§ slit lamp exam including evaluation of staining, 
§ non-invasive tear breakup time, 


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§ SANDE questionnaire, 
§ compliance check. 
In addition, all site-specific, routine, usual standard of care measures should be 
undertaken.   
 
Any adverse events/serious adverse events (AEs/ SAEs) occurring during surgery 
will be noted at this visit. Any other problems during surgery and comments 
regarding surgery will be documented.  
 
9.2.4. Exit Procedures 
In the event of premature exit from the study, all study related examinations 
should be completed where possible. The Exit CRF should be completed, noting 
that the subject did not complete the study and the reason for premature study 
exit.  If no premature exit from the study occurs, the Exit CRF should be 
completed at the end of Visit 3.  
 
9.3. Study Methods and Measurements 
All routine testing and basic eye examinations should be carried out at each study visit.  
Abnormalities should be recorded in the CRF “Comment” section.  Specific study 
examination procedures are outlined below.  
 
 
9.3.1. Non-Invasive Tear Breakup Time 
Non-invasive TBUT determined using the Topcon CA-800.  Subject will be 
instructed to blink 3 times and then hold eye open without blinking while test is 
being performed.  Three (3) consecutive readings will be taken, and the average 
will be recorded in seconds.  The Topcon CA-800 measuring is not able to be 
customized via software settings so the factory setting will be used.  Both eyes 
will be tested, but for the purposes of this study only a single, randomly selected 
eye will be used for statistical analysis. 
 
 
9.3.2. Staining 
Baseline corneal and conjunctival staining with sodium fluorescein and Wratten 
filter assessed OU using the Academy of Ophthalmology 5 quadrant scheme.  
Each quadrant will be graded (0-3) giving a total score of 0-15 per eye.  Again, 
both eyes will be evaluated, but only the total score of the single, previously 
selected eye in the TBUT measurement will be used for statistical analysis. 
 
9.3.3 Questionnaires 
The SANDE questionnaire, will be administered to subjects at all visits. The 
administrator should ensure the subjects understand the nature of the questions 
but should not interpret them for the subject.   


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9.4.  Unscheduled Visits 
Unscheduled exams may be conducted at the discretion of the Investigator with all 
relevant information from the exam recorded in the source documents and on the 
Unscheduled Visit pages within the CRF booklet. 
9.5.  Discontinued Subjects 
Discontinued subjects are those who do not have an exit visit or who come into the office 
to be exited prior to the scheduled final study visit. Subjects may be discontinued from 
the study at any time if, in the opinion of the investigator, their continued participation in 
the study poses a risk to their health. The reasons for discontinuation include: 
a. Adverse event; 
b. Lost to follow-up; 
c. Subject decision unrelated to an adverse event; 
d. Protocol violation; 
e. Treatment failure; 
f. Other. 
To ensure the safety of all subjects who discontinue prior to Visit 3, investigators should 
assess each subject and, if necessary, advise them of any therapies and/or medical 
procedures that might be needed to maintain their health. Any changes in medical health 
and/or use of concomitant medications should also be captured. 
10.  ANALYSIS PLAN 
10.1. Analysis Data Sets 
All subjects who are enrolled in the study will be evaluated for safety.  Efficacy analyses 
will be performed based on data from those eyes that complete the study.   
10.2. Statistical Methodology 
Analysis will be done on the per protocol population. For monocular outcomes, analysis 
will be performed on the study eye that was determined by randomization.  
 
Superiority of Systane COMPLETE relative to Walgreens will be established if the mean 
SANDE score is significantly lower in the Systane COMPLETE group vs. Walgreens 
group.  
 
Demographics, baseline characteristics, efficacy endpoints, and adverse events will be 
summarized descriptively. Summaries of these variables will include sample size, as well 
as the mean, median, standard deviation, minimum and maximum.   
 
Primary Endpoint: Dry eye symptom frequency and severity as measured by the SANDE 
questionnaire change after 2 weeks of QID use (subject level). Total scores will be 
compared using a two-sample t-test. 
 
The step-down methodology will be used on the other endpoints in the following order: 


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§ Comparing corneal and conjunctival staining in the study eye before and 
after 2 weeks of QID use of their assigned drop (eye level). The corneal 
and conjunctival staining scores will be totaled from the 5 evaluation 
zones for analysis. Total scores will be compared using a two-sample t-
test. 
§ Comparing Non-invasive TBUT times of the study eye in the two arms of 
the study, before and after 2 weeks of QID use of their assigned drop (eye 
level). Time will be compared using a two-sample t-test. 
§ Dry eye symptom frequency and severity as measured by the SANDE 
questionnaire after 1 week of QID use (subject level). Total scores will be 
compared using a two-sample t-test. 
10.3. General Statistical Considerations 
The statistical analyses will be performed using R, version 4.2.2 or higher.  Any 
statistical tests of hypotheses will employ a level of significance of alpha=0.05. 
11.  SAMPLE SIZE JUSTIFICATION 
Assuming a difference in means between groups of 7 (SANDE) and a pooled standard 
deviation of 6, the study would require a sample size of 16 subjects for each group (total 
sample size of 32 subjects) to achieve a power of 90% and a level significance of 5%. To 
increase the study power and account for dropout, the sample size is being increased to  
70 subjects (35 in each arm) to thoroughly characterize the performance of the drops. 
12. CONFIDENTIALITY/PUBLICATION OF THE STUDY 
The existence of this Study is confidential and should not be discussed with persons 
outside of the Study. Results will be submitted for publication and presentation at 
national and/or international meetings. A manuscript will be submitted to peer-review 
journals for publication but there is no guarantee of acceptance. 
 
All study data will be collected on appropriate Case Report Forms (CRFs). No protected 
health information will be included on the forms. CRFs will be retained in the patient’s 
file for a minimum period of 3 years. Collected information will only be used for 
purposes of this study and no information will be sold to third parties. The following 
people will have access to your study records:  
 
•    Study Doctor and staff involved with the study 
 
•    Study Monitor or Auditor 
 
•    Sponsor Company or Research Institution 
 
•    Review boards or accrediting agencies 
 
•    Other State or Federal Regulatory Agencies 
 


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The de-identified data may be shared with other researchers for future analysis. 
13.  QUALITY COMPLAINTS AND ADVERSE EVENTS 
All subjects will be monitored for adverse events over the course of the study. A place to 
record any adverse event is included on each case report form. 
13.1. General Information 
An Adverse Event (AE) is any untoward medical occurrence in a subject who is 
administered. a study treatment regardless of whether or not the event has a causal 
relationship with the treatment. An AE, therefore, can be any unfavorable or unintended 
sign (including an abnormal laboratory finding), symptom, or disease temporally 
associated with the study treatment, whether or not related to the treatment. In clinical 
studies, an AE can include an untoward medical occurrence occurring at any time, 
including run-in or washout periods, even if no study treatment has been administered. 
13.2. Monitoring for Adverse Events 
At each visit, after the subject has had the opportunity to spontaneously mention any 
problems, the Investigator should inquire about AEs by asking if the patient has any 
problems.  
13.3. Procedures for Recording and Reporting AEs and SAEs 
Subsequent to signing an informed consent form, all untoward medical occurrences that 
occur during the course of the study must be documented on an Adverse Event Form 
(AEF). A separate AEF must be filled out for each event. When possible, signs and 
symptoms indicating a common underlying pathology should be documented as one 
comprehensive event. For each recorded event, the AE documentation must include the 
onset date, outcome, resolution date (if event is resolved), intensity (i.e., severity), any 
action with study treatment taken as a result of the event, and an assessment of the 
adverse event’s relationship to the study treatment. 
Nonserious Adverse Events 
A nonserious AE is defined as any untoward change in a subject's medical health that 
does not meet serious criteria noted below (e.g., is not life-threatening, does not require 
hospitalization, does not prolong a current hospitalization, is not disabling, etc.). All 
adverse events must be reported regardless of whether or not they are related to the study 
treatment. 
 
For nonserious adverse events, an AEF containing all available information will be 
collected on a routine basis and submitted to the Medical Monitor at the close of the 
study.  
 
Serious Adverse Events 
A serious adverse event (SAE) is defined as any adverse experience that meets any of the 
following criteria: 
• 
Results in death. 
• 
Is life-threatening. 


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NOTE: Life-threatening means that the subject was at immediate risk of death 
from the reaction as it occurred; i.e., it does not include a reaction which 
hypothetically might have caused death had it occurred in a more severe form. 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization. 
NOTE: In general, hospitalization signifies that the individual remained at the 
hospital or emergency ward for observation and/or treatment (usually involving 
an overnight stay) that would not have been appropriate in the physician's office 
or an out-patient setting. Complications that occur during hospitalization are AEs. 
If a complication prolongs hospitalization or fulfills any other serious criteria, the 
event is serious. When in doubt as to whether “hospitalization” occurred, the 
event should be considered serious. 
• 
Results in persistent or significant disability/incapacity. Disability is defined as a 
substantial disruption of a person’s ability to conduct normal life functions. 
NOTE: The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. This definition is not intended to include 
experiences of relatively minor medical significance such as uncomplicated 
headache, nausea, vomiting, diarrhea, influenza, or accidental trauma (e.g., 
sprained ankle) which may interfere or prevent everyday life functions but do not 
constitute a substantial disruption. 
• 
Is an important medical event. An important medical event is an event that may not 
result in death, be life-threatening, or require hospitalization but may be considered 
an SAE when, based upon appropriate medical judgment, it may jeopardize the 
subject and may require medical or surgical intervention to prevent one of the 
outcomes listed in the definitions for SAEs. Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at 
home, blood dyscrasias or convulsions that do not result in subject hospitalization, or 
the development of drug dependency or drug abuse. 
All available information on a serious adverse event(s) and any other associated AE, 
if applicable, must be forwarded to the study coordinator for forwarding to the 
Medical Monitor immediately (i.e., within one working day of the Investigator’s or 
site’s knowledge of the event) as follows: 
o In studies utilizing EDC (electronic data capture), all available information for 
the SAE and any associated AE(s) must be entered immediately into the EDC 
system.  
o Additional information for any applicable event is to be reported as soon as it 
becomes available. 
 
In addition to the reporting of serious adverse events to the study Medical Monitor, the 
SAE must be reported to the IRB / IEC according to their requirements. 
 
The investigator must document all adverse device events (serious and nonserious but 
related) and all serious adverse events (related and unrelated) on the Adverse Device 
Effect and Serious Adverse Event Form. Any device quality complaints will also be 
documented.  
 


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• Both the Quality Complaint Form and the Adverse Device Effect and Serious 
Adverse Event Form must be e-mailed immediately to the study coordinator. 
• Additional relevant information is to be reported as soon as it becomes 
available.   
 
Study coordinator contact information is provided below. 
 
Table 13.3.-1:  
Contact Information for Study 
Study Staff 
Business Phone 
e-mail 
24-hour  
Office Phone 
Leslie Shan 
858-530-2800 
lshanod@gmail.com 
858-530-2800 
 
Further, depending upon the nature of the adverse event (serious or nonserious) or quality 
complaint being reported, the study sponsor may request copies of applicable portions of 
the subject’s medical records.  The investigator must also report all adverse events and 
quality complaints according to the relevant IRB requirements. 
 
12.3.1 Intensity and Causality Assessments  
For every adverse event and quality complaint, the investigator must assess the 
causality as Related or Not Related to the medical device under investigation. An 
assessment of causality will also be performed by the Medical Monitor utilizing 
the same definitions, as shown below: 
 
Causality 
Related 
An adverse event or quality complaint classified as related may be 
either definitely related or possibly related where a direct cause 
and effect relationship with the medical device has not been 
demonstrated, but there is a reasonable possibility that the adverse 
event or quality complaint was caused by the medical device. 
 
 
Not Related 
An adverse event or quality complaint classified as not related may 
either be definitely unrelated or simply unlikely to be related (i.e., 
there are other more likely causes for the adverse event or quality 
complaint). 
 
Where appropriate, the investigator must assess the intensity (severity) of the 
adverse event as mild, moderate, or severe based on medical judgment with 
consideration of any subjective symptom(s), as defined below:  
 
Intensity (Severity) 


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Mild 
An adverse event is mild if the subject is aware of but can easily 
tolerate the sign or symptom. 
Moderate 
An adverse event is moderate if the sign or symptom results in 
discomfort significant enough to cause interference with the 
subject’s usual activities. 
Severe 
An adverse event is severe if the sign or symptom is incapacitating 
and results in the subject’s inability to work or engage in their 
usual activities. 
 
The investigator must document any action taken (i.e., medication, intervention, 
or treatment plan) and outcome of the adverse event or quality complaint when 
applicable. 
13.4. Follow-Up of Adverse Events and Quality Complaints 
The investigator is responsible for adequate and safe medical care of subjects during the 
study and for ensuring that appropriate medical care and relevant follow-up procedures 
are maintained after the study.  Any additional data from these follow-up procedures 
must be documented and available to the study coordinator who, with the Medical 
Monitor, will determine when the data need to be documented on the CRFs.  
13.5. Safety Analyses 
The type, severity, duration, and frequency of reported ocular adverse events will be 
tabulated.  Adverse events will also be summarized for events that were considered 
treatment-related.   
14. GCP, ICH and ETHICAL CONSIDERATIONS 
This study will be conducted in compliance with Good Clinical Practices (GCPs), 
including International Harmonization (ICH) Guidelines, and in general, consistent with 
the 1996 version of the Declaration of Helsinki.  In addition, all applicable local, state 
and federal requirements will be adhered to. 
 
This study is to be conducted in accordance with Institutional Review Board regulations.  
The investigator will obtain appropriate IRB/ethics committee approval prior to initiating 
the study. 
 
The study will be registered with clinicaltrials.gov. 
 
14.1 Confidentiality 
The data collected will be data typical for the procedure(s) when performed on eyes 
outside the study. Any data collected will become part of the patient’s clinical record. 
The data will be subject to the same privacy and confidentiality as other data in the 
clinical record. 
 


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Only the principal investigator, research consultant and clinic staff will have access to the 
data collected. All data shared outside the practice will be de-identified; patients’ 
protected health information will not be available and will not be reported in any analyses 
or publications. No data will be sold to third parties. De-identified data may be used for 
future research.  


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15.  STANDARD EVALUATION PROCEDURES  
Table 15.1. Proposed Visits and Study Assessments 
                  (visits are by patient, with both eyes tested) 
 
 
Activity 
Recruit-
ment 
Follow-Up 
Follow-Up 
Visit 1 
Visit 2 
Visit 3 
 
 
 
Informed Consent 
X 
 
 
Demographics 
X 
 
 
General Information:   
Medical History 
X 
 
 
Non-Invasive Tear Breakup Time 
X 
 
X 
Slit Lamp Exam and Staining Evaluation 
X 
 
X 
SANDE Questionnaire 
X 
X 
X 
Compliance Check 
 
X 
X 
Monitor for Adverse Events  
 
X 
X 
Complete Exit Form1 
 
 
X 
 
1 Complete Exit Form upon termination of subject participation, or at Visit 3, whichever 
occurs first. 
16. CONFIDENTIALITY 
No protected health information (PHI), including the patient’s name and date of birth, 
will be collected; to ensure this, no PHI information is permitted to be entered on any of 
the Case Report Forms (CRFs). Subjects will only be identified by subject IDs and 
identities will be removed at the initial visit so that there is no further need to protect or 
destroy the information. Collected information will only be used for purposes of this 
study and no information will be sold to third parties. The non-PHI information collected 
may be used for future research, though there is currently no plan to do so.  
17. FINANCIAL AND INSURANCE INFORMATION/STUDY RELATED 
INJURIES 
Every effort to prevent study-related injury will be taken by the Study Doctor and staff. 
In the event a patient is injured as a direct result of the study while following the Study 
Doctor’s instructions and the study requirements, the patient will be instructed to contact 
his or her doctor immediately. The Study Doctor is to treat the injured subject as needed 
for those injuries caused directly by this research study. In the event of injury or illness 
caused by or occurring during a subject’s participation in this research study, all charges 
for medical care provided to the subject will be billed to his or her insurance company. 
The Study Doctor or Sponsor does not offer to cover the medical care costs for injuries or 
illnesses that are not caused directly by the research study. The Sponsor does not offer to 
provide any other compensation, unless specifically agreed to elsewhere in this 
document. This information will be provided to each study subject before the start of the 
study in the consent form. 


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18. STUDY ENDPOINT CRITERIA 
18.1. Patient Completion of Study  
If a study patient has completed the final visit (Visit 3) of the study, he/she is considered 
to have completed the study.  
 18.2. Patient Discontinuation  
Each study patient may voluntarily discontinue the study at any time they choose.  Study 
patients who cannot complete the study for administrative reasons (e.g., non-compliance, 
failure to meet visit schedule, etc.) will be discontinued from the study.  Study patients 
discontinued during the enrollment phase (prior to surgery) of the study will be replaced.  
 18.3. Patient Termination  
A study patient will be terminated if the study patient develops any severe adverse event 
that may be related to the study.  A study patient will receive appropriate treatment at the 
discretion of the investigator.  Notification of termination will be clearly documented.  
These study patients are considered to have completed the study and will not be replaced.   
18.4. Study Termination 
The investigator with appropriate notification may terminate the study.  If, after clinical 
observations, the investigator feels that it may be unwise to continue the study, he may 
stop the study.   
18.5. Study Completion  
The study will be complete when all enrolled patients have completed Visit 3 or have 
been terminated from the study.   
19. SUMMARY OF RISKS AND BENEFITS 
19.1. Summary of risks 
The risks with this study are similar to those for any patient using lubricating drops. 
There is no increased risk associated with the proposed study. 
19.2. Summary of benefits 
Patients who participate in the study may receive up to $75 reimbursement. 


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Amparo F, Schaumberg DA, Dana R. Comparison of Two Questionnaires for Dry 
Eye Symptom Assessment: The Ocular Surface Disease Index and the Symptom 
Assessment in Dry Eye. Ophthalmology. 2015;122(7):1498-1503. 
3. 
Yazdani M, Fiskadal J, Chen X, et al. Tear Film Break-Up Time and Dry Eye 
Disease Severity in a Large Norwegian Cohort. J Clin Med. 2021;10(4). 
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Muntz A, Marasini S, Wang MTM, Craig JP. Prophylactic action of lipid and 
non-lipid tear supplements in adverse environmental conditions: A randomised 
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