Optive Brand For Day And Night Dry Eye Management
Phase: NA
Conditions: Dry Eye
Sponsor: Allergan

NCT03208673 
 
Study ID: CMO‐EAME‐EYE‐0485 
 
Title:  Optive Brand For Day And Night Dry Eye Management 
 
 
Protocol Date: 18 May 2017 

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CMO-EAME-EYE-0485  
Clinical Investigational Plan, v1.0, 18th May 
2017 
Page 2 of 30 
 
 
 Clinical Investigational Plan 
 
OPTIVE BRAND FOR DAY AND NIGHT DRY EYE MANAGEMENT 
 
OTG-i Study Number and Version: ID17-04 Version 1.0 
Study Sponsor Number: CMO-EAME-EYE-0485 
Issue Date: 18th May 2017 
 
 
Protocol Signature Page 
 
 
  
As Principal Investigator, I agree to conduct this study in accordance with all applicable laws and regulations 
and in compliance with the provisions of this Clinical Investigational Plan. 
 
I am responsible for ensuring that the investigation is conducted according to this plan and for protecting the 
rights, safety, and welfare of the research participants. 
 
 
 
_____________________________ 
 
______________________ 
  _______________ 
Principal Investigator Name (printed) 
 
Signature 
 
 
   Date 
 
 
Confidentiality Statement 
The information in the following document is provided to you as an investigator, potential investigator, or 
consultant, for review by you, your staff, and applicable Ethics Committee or Institutional Review Board, and 
is considered confidential.  It is understood that the information will not be disclosed to others without written 
authorization from OCULAR TECHNOLOGY GROUP - International, except to the extent necessary to obtain 
informed consent from the study participants. 
 
Each party shall keep confidential all information which is received from the other party and which is 
specified by the disclosing party to be confidential at the time of disclosure, and direct its employees, agents 
and sub-contractors to do the same. This obligation shall not apply to information which (i) either at the time 
of disclosure or after disclosure is published or generally available to the public other than through a breach 
(ii) is already in the receiving party's possession at the time of receipt and which was not acquired directly 
or indirectly from the disclosing party (iii) is acquired by the receiving party in good faith from a third party 
(iv) is required to be disclosed by law or (v) has been authorised to be disclosed in writing, by the disclosing 
party

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Clinical Investigational Plan, v1.0, 18th May 
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DOCUMENT CHANGE HISTORY 
 
Revision 
Originator 
Description of Change(s) 
Date 
1.0 
 
Original document 
18th May 2017 
1.1 
 
 
 
1.2 
 
 
 
1.3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table of Contents 
1 
Overall Synopsis .......................................................................................................................... 7 
2 
Introduction and Rationale ........................................................................................................... 11 
2.1 
Background ..................................................................................................................... 11 
2.2 
Objectives ....................................................................................................................... 11 
2.3 
Hypothesis ...................................................................................................................... 11 
2.4 
Endpoints ........................................................................................................................ 12 
3 
Study Sponsor and Investigators ................................................................................................. 12 
3.1 
Study Sponsor ................................................................................................................. 12 
3.2 
Clinical Research Organization ....................................................................................... 12 
3.3 
Study Site(s) .................................................................................................................... 12 
3.4 
Clinical Investigators ....................................................................................................... 13 
3.5 
Medical Monitor ............................................................................................................... 13 
3.6 
Data Controller ................................................................................................................ 13 
3.7 
Independent Ethics Committee ....................................................................................... 13 
4 
Test Materials ............................................................................................................................... 14 
4.1 
Test Products .................................................................................................................. 14 
4.2 
Run-in Product ................................................................................................................ 14 
4.3 
Adjunct Products ............................................................................................................. 14 
5 
Test Population ............................................................................................................................ 14 
5.1 
Recruitment Procedure ................................................................................................... 14 
5.2 
Number of Participants ................................................................................................... 14 
5.3 
Inclusion and Exclusion Criteria ...................................................................................... 15 
5.3.1 
Inclusion Criteria ................................................................................................ 15 
5.3.2 
Exclusion Criteria ............................................................................................... 15 
5.4 
Premature Withdrawal..................................................................................................... 15 
5.5 
Informed Consent ............................................................................................................ 16 
6 
Study Design & Procedures ......................................................................................................... 16 
6.1 
General Description ........................................................................................................ 16 

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6.2 
Experimental Routine ...................................................................................................... 16 
6.3 
Measures to Avoid Bias .................................................................................................. 17 
6.3.1 
Randomization ................................................................................................... 17 
6.3.2 
Masking .............................................................................................................. 17 
6.4 
Test Procedures .............................................................................................................. 17 
6.4.1 
Efficacy Procedures ........................................................................................... 17 
6.4.2 
Safety Procedures ............................................................................................. 17 
6.4.3 
Population Profiling Procedures ......................................................................... 18 
7 
Statistical Analysis and Sample Size Determination ................................................................... 19 
7.1 
Determination of Sample Size ........................................................................................ 19 
7.1 
Statistical Analysis Plan .................................................................................................. 19 
8 
Risk Analysis ................................................................................................................................ 20 
8.1 
Benefits ........................................................................................................................... 20 
8.2 
Risks ............................................................................................................................... 20 
9 
Adverse Events and Reporting .................................................................................................... 20 
9.1 
Adverse Events ............................................................................................................... 20 
9.1.1 
Adverse Event Definitions .................................................................................. 20 
9.2 
Procedures for Adverse Events ...................................................................................... 21 
9.3 
Reporting Adverse Events .............................................................................................. 22 
9.4 
Pregnancy ....................................................................................................................... 22 
10 
Device Deficiencies ...................................................................................................................... 22 
11 
Investigator, Sponsor and Medical Monitor Responsibilities ....................................................... 22 
11.1 
Investigator Responsibilities ........................................................................................... 22 
11.2 
Sponsor Responsibilities ................................................................................................. 23 
11.3 
Medical Monitor Responsibilities ..................................................................................... 23 

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12 
General Clinical Management ...................................................................................................... 24 
12.1 
Data Recording ............................................................................................................... 24 
12.2 
Clinical Monitoring ........................................................................................................... 24 
12.3 
Study Product Accounting ............................................................................................... 24 
12.4 
Participant Compliance Monitoring ................................................................................. 25 
12.5 
Unmasking of Study Information ..................................................................................... 25 
12.6 
Participant Payments ...................................................................................................... 25 
13 
Administration Management ........................................................................................................ 25 
13.1 
Relevant Standards......................................................................................................... 25 
13.2 
Deviations from the Protocol ........................................................................................... 25 
13.2.1 Major Protocol Deviations .................................................................................. 25 
13.2.2 Minor Protocol Deviations .................................................................................. 26 
13.3 
Modifications to the Clinical Investigational Plan ............................................................ 26 
13.4 
Termination of the Study ................................................................................................. 26 
13.5 
Data Protection ............................................................................................................... 26 
13.6 
Data Handling and Record Keeping ............................................................................... 27 
13.7 
Reporting ......................................................................................................................... 27 
13.8 
Study Registration ........................................................................................................... 27 
13.9 
Publication Policy ............................................................................................................ 27 
 
 
13.11 
Indemnity ......................................................................................................................... 27 
14 
References ................................................................................................................................... 28 
15 
List of Abbreviations ..................................................................................................................... 28 
16 
Appendices .................................................................................................................................. 29 
16.1 
Appendix A: ..................................................................................................................... 29 
16.2 
Appendix B: ..................................................................................................................... 30 
 
 
 
 
 

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1 
Overall Synopsis 
 
Study Sponsor 
Allergan Pharmaceuticals International Ltd.  
Clonshaugh Industrial Estate, Coolock, Dublin 17, Ireland. 
Title of Study 
Optive Brand For Day And Night Dry Eye Management 
Protocol Number 
CMO-EAME-EYE-0485 
Phase or type of study 
The study will be an open label, bilateral, prospective, interventional 
post marketing, clinical study.  
Investigator(s) / Site(s) 
OCULAR TECHNOLOGY GROUP - International (OTG-i), 66 
Buckingham Gate, London, SW1E 6AU UK. 
Planned Duration of Study 
6 months 
Study Population  
Up to 40 participants to have 35 participants enrolled into the 
investigational phase at the end of Visit 2 to achieve a cohort of 30 
participants completing the study. 
Inclusion Criteria 
The inclusion criteria will include the following: 
• Age at least 18 years; 
• OSDI score of ≥ 23; 
• Ocular comfort at waking <65 on 100-point scale; 
• Conjunctival staining Grade ≥ 2 (scale 0 to 4) in at least one eye; 
• Use of eyedrops for the relief of dry eye symptoms for at least one 
month. 
Exclusion Criteria 
The exclusion criteria will include the following: 
• Use of Benzalkonium Chloride (BAK) preserved eyedrops in the 
last month;    
• Use of Optive brand eyedrops in the last month; 
• Contact lens wear during the study; 
• Known pregnancy or lactation during the study period; 
• Enrolment of investigator’s office staff, relatives, or members of 
their respective households; 
• Participation in any clinical trial within 30 days of the enrolment 
visit. 
 
Planned Start Date 
July 2017 

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Objective(s) 
The primary objectives of the study will be to: 
i. 
Quantify the effect of a one-month treatment involving an eyedrop 
/ gel combination on overall dry eye symptomatology on moderate 
to severe dry eye sufferers; 
ii. 
Evaluate the effect of a one-month treatment involving an eyedrop 
/ gel combination on conjunctival staining moderate to severe dry 
eye sufferers. 
The secondary objective of the study will be to quantify the effect of a 
one-month treatment involving an eyedrop / gel combination on 
symptomatology upon waking on moderate to severe dry eye sufferers. 
Hypotheses 
The primary hypotheses that will be tested will be that: 
i. One-month treatment of moderate to severe dry eye sufferers with 
an eyedrop / gel combination will reduce overall dry eye 
symptomatology; 
ii. One-month treatment of moderate to severe dry eye sufferers with 
an eyedrop / gel combination will decrease conjunctival staining. 
The secondary hypotheses that will be tested will be that a one-month 
treatment of moderate to severe dry eye sufferers with an eyedrop / 
gel combination will reduce symptomatology upon waking. 
Efficacy Endpoint(s) 
The primary end points will be: 
i. OSDI total score; 
ii. Measured lissamine green bulbar conjunctival staining (mm2). 
The secondary end points will be symptomatology upon waking (VAS 
scale). 

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Efficacy Procedure(s) 
The primary response procedures will be: 
i. OSDI questionnaire; 
ii. Digital photography of lissamine green staining of the exposed 
bulbar conjunctiva. 
The secondary response procedures will be: 
i. VAS comfort & symptomatology questionnaire; 
Safety Procedure(s) 
The safety procedures will be biomicroscopy, identification of adverse 
events, measurement of Snellen Visual Acuity and identification of 
prevalence of adverse events. 
Population Profiling 
Procedure(s) 
 The procedures to profile the population key characteristics will be: 
i. Demographics and ocular history questionnaire (including 
concomitant treatment);  
ii. OSDI questionnaire; 
Experimental Design 
 Retrospective 
X Prospective 
X Non-Randomized  
 Randomized  
 Single masked (participant) 
 Single masked (investigator) 
 Double masked 
 Sponsor masked 
X Open label 
 
X Single group 
 Parallel group 
 Crossover 
 Contralateral 
 

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Run-in Product(s) 
REFRESH® Contacts® Unitdose, a CE marked eye lubricant eyedrop, 
manufactured by Allergan Pharmaceuticals Ireland, containing 0.5% 
carboxymethylcellulose sodium. 
Test Product(s) 
The treatment regimen to be tested will be: 
i. Optive® Fusion™ a CE marked eyedrop, manufactured by Allergan 
Pharmaceuticals Ireland, containing 0.1% sodium hyaluronate, 
0.5% carmellose sodium and 0.9% glycerol for daytime use. The 
eyedrop will be used as needed up to four times a day but at least 
twice a day. 
ii. Optive® Gel Drop a CE marked gel manufactured Allergan 
Pharmaceuticals Ireland, containing 0.5% carboxymethylcellulose 
sodium and 0.9% glycerol for night time use.  The eyedrop will be 
used once in the evening; the gel drop being instilled any time 
during the last hour prior to sleep 
Study Visits 
Three scheduled visits over a five-week period.  
i. Enrolment visit; 
ii. Baseline / Dispensing visit (7 ± 1 days from enrolment); 
ii. One month follow-up visit (30 ± 3 days from dispensing. 
Keywords 
Optive Fusion, Optive Gel Drops, Refresh Contacts Unitdose, OSDI, 
Conjunctival Staining, Tear Film Kinetics, Dry Eyes 
Regulatory Status 
This trial requires Ethics Committee (EC) approval prior to initiation.  
Responsibilities 
Sponsor 
Name: 
Allergan 
Pharmaceuticals 
International Ltd. 
 
CRO and Data Management 
OCULAR TECHNOLOGY GROUP - 
International 
 
Legal Representative (where 
applicable) 
 
 
 
 

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2 
Introduction and Rationale 
2.1 
Background 
Tear film physiology differs greatly between the waking and sleeping periods.  During the waking period the 
tear film is an aqueous based film produced by the lacrimal gland and connected to the ocular surface via the 
inner mucin layer, and protected from evaporation by the outer lipid layer.  Aqueous, which accounts for 98% 
of the overall tear film, is distributed onto the ocular surface and a proportion of the aqueous is eliminated 
with each blink.  In contrast, during sleep aqueous production stops and the tear film becomes a gel like 
structure dominated by mucin and lipids [1]. 
Anomalies of any of the layers of the tear film lead to dry eye complaints which vary greatly not only in their 
level of severity but also in their diurnal characteristics.  Typically, dry eye complaints are least during the day 
and most marked either in the evening or upon waking, suggesting different potential mechanisms [2]. 
The physiological characteristics of the tear film would suggest that a different dry eye treatment should be 
implemented for the waking and sleeping phases of the day: aqueous supplementation and surface protection 
from the atmosphere during waking hours and gel supplementation during sleep; the latter being particularly 
important for those sufferers with highest level of complaints upon waking. 
In addition to symptomatology, dry eyes are characterised by changes in the tear film and / or the ocular 
surface depending upon the patients.  Reported tear film anomalies include destabilisation (shorter tear film 
break up time), poorer ocular surface coverage (decreased tear film kinetics) and increased tear film 
evaporation. The ocular surface modifications are corneal fluorescein staining and conjunctival (exposed 
bulbar and palpebral) lissamine green staining, the latter being the most prevalent.  Another ocular tissue 
change reported is increased redness due to the inflammatory process associated with dry eye [3].     
2.2 
Objectives 
The primary objectives of the study will be to: 
i. 
Quantify the effect of a one-month treatment involving an eyedrop / gel combination on overall dry eye 
symptomatology on moderate to severe dry eye sufferers; 
ii. 
Evaluate the effect of a one-month treatment involving an eyedrop / gel combination on conjunctival 
staining on moderate to severe dry eye sufferers. 
The secondary objective of the study will be to: 
Quantify the effect of a one-month treatment involving an eyedrop / gel combination on symptomatology 
upon waking on moderate to severe dry eye sufferers. 
 
 
 
 
 
 
 
 
2.3 
Hypothesis 
The primary hypotheses that will be tested will be that: 

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i. 
One-month treatment of moderate to severe dry eye sufferers with an eyedrop / gel combination will 
reduce overall dry eye symptomatology; 
ii. 
One-month treatment of moderate to severe dry eye sufferers with an eyedrop / gel combination will 
decrease conjunctival staining. 
The secondary hypothesis that will be tested will be that: 
One-month treatment of moderate to severe dry eye sufferers with an eyedrop / gel combination will 
reduce symptomatology upon waking. 
2.4 
Endpoints 
The primary end points will be: 
i. 
OSDI total score. 
ii. 
Measured lissamine green bulbar conjunctival staining (mm2). 
The secondary end points will be symptomatology upon waking (VAS scale). 
3 
Study Sponsor and Investigators 
3.1 
Study Sponsor 
The Sponsor for this investigation will be Allergan Pharmaceuticals International Ltd. Clonshaugh Industrial 
Estate, Coolock, Dublin 17, Ireland. 
3.2 
Clinical Research Organization 
The investigation will be carried out by OCULAR TECHNOLOGY GROUP - International (OTG-i), Lower 
Ground Floor, 66 Buckingham Gate, London SW1E 6AU (Study Director
 
  
3.3 
Study Site(s) 
The study site will be OCULAR TECHNOLOGY GROUP - International (OTG-i), Lower Ground Floor, 66 
Buckingham Gate, London SW1E 6AU  

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3.4 
Clinical Investigators 
The study Chief Investigator will be 
 
 
3.5 
Medical Monitor 
The medical monitor at the OTG-i Research Clinic will be 
; the medical 
monitor is contracted to OTG-i Research Clinic for this activity   
3.6 
Data Controller 
The statistical analysis and data management control will be conducted by OCULAR TECHNOLOGY GROUP 
– International. The data controller will be 
  
3.7 
Independent Ethics Committee 
Before clinical study initiation, this protocol, the informed consent form any other written information given to 
participants, and any advertisements planned for participant recruitment will be approved by an Independent 
Ethics Committee (IEC). The Investigator will provide documentation of the IEC approval to the Sponsor. The 
approval will be dated and will identify the applicable protocol, amendments (if any), informed consent form, 
all applicable recruiting materials, written information for participants, and participant compensation 
programs. The IEC will be provided with all information as required by local regulations and/or the IEC. At the 
end of the study, the Investigator will notify the IEC about the study’s completion. The IEC also will be notified 
if the study is terminated prematurely. Finally, the Investigator will report to the IEC on the progress of the 
study at intervals stipulated by the IEC.  
Voluntary informed consent will be obtained from every participant prior to the initiation of any screening or 
other study-related procedures. The Investigator has a defined process for obtaining consent. Specifically, 
the Investigator, or designee, will explain the clinical study to each potential participant and the participant 
must indicate voluntary consent by signing and dating the approved informed consent form. The participant 
will be provided an opportunity to ask questions to the Investigator, and if required by local regulation, other 
qualified personnel. 
The Investigator will provide participants with a copy of the consent form written in a language the participant 
understands; in this study all documentation will be in English and only participants fluent in English will take 
part. The consent document will meet all applicable local laws and will provide participants with information 
regarding the purpose, procedures, requirements, and restrictions of the study, along with any known risks 
and potential benefits associated with participating, the available compensation, and the established 
provisions for maintaining confidentiality of personal, protected health information. Participants will be told 
about the voluntary nature of participation in the study and will be provided with contact information for the 
appropriate individuals should questions or concerns arise during the study. Participants also will be told that 
their records may be accessed by appropriate authorities and Sponsor-designated personnel. The 
Investigator must keep the original, signed copy of the consent and must provide a duplicate copy to each 
participant. 
The study will be submitted to the IRAS centralized National Research Ethics Service (for proportionate 
review). The investigation will not start until approval has been received by the site. 

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4 
Test Materials 
4.1 
Test Products 
The treatment regimen will be: 
i. 
Optive® Fusion a CE marked eyedrop, manufactured by Allergan Pharmaceuticals Ireland, containing 
0.1% sodium hyaluronate, 0.5% carmellose sodium and 0.9% glycerol for daytime use. The eyedrop will 
be used as needed up to four times a day but at least twice a day; 
ii. 
Optive® Gel Drop a CE marked gel manufactured by Allergan Pharmaceuticals Ireland, containing 0.5% 
carboxymethylcellulose sodium and 0.9% glycerol for night time use.  The eyedrop will be used once in 
the evening; the gel drop being instilled any time during the last hour prior to sleep. 
The treatment regimen will be used for one month (30 ± 3 days). 
4.2 
Run-in Product 
The run-in product will be REFRESH® Contacts® Unitdose, a CE marked eye lubricant eyedrop, 
manufactured by Allergan Pharmaceuticals Ireland, containing 0.5% carboxymethylcellulose sodium.  The 
eye drop will be used as needed up to four times a day but at least twice a day for one week (7 ± 1 days) 
4.3 
Adjunct Products 
No other system will be used and the products will be used according to their indication and discarded at the 
completion of the period of use. 
5 
Test Population 
5.1 
Recruitment Procedure 
The prospective participants will be selected from the existing clinical population of the OTG-i Research Clinic 
or recruited my means of an advertisement if necessary. The participants fulfilling the criteria for inclusion 
and none of the exclusion criteria will be invited in a random fashion to participate in the study until the test 
population is achieved. 
The prospective participants will initially be contacted by telephone, the investigation will be explained in detail 
and if interested an enrolment / test visit will be scheduled. The prospective participants will be sent a copy 
of the Participant Information Sheet and Informed Consent by email prior to the visit, upon arrival at the clinic 
the participants will be given a printed copy of the consent form and the study will be explained to them.  The 
participants will be asked to read and sign the Informed Consent prior to any evaluation. 
5.2 
Number of Participants 
Up to 40 participants will be screened for 35 participants to be enrolled into the investigational phase at the 
end of Visit 2 with a view to achieve a cohort of 30 participants completing the study as per the protocol. 

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5.3 
Inclusion and Exclusion Criteria 
5.3.1 Inclusion Criteria 
There are no requirements as to participant race, gender or occupation. 
In order to be enrolled, each participant shall meet the following criteria: 
i. 
At least 18 years old; 
ii. 
Moderate to severe dry eye symptomatology based up an OSDI score of ≥ 23; 
iii. 
Ocular comfort at waking <65 on 100-point scale; 
iv. 
Conjunctival staining Grade ≥ 2 (scale 0 to 4) in at least one eye; 
v. 
Use of eyedrops for the relief of dry eye symptoms for at least one month. 
vi. 
Have read and understood the Participant Information Sheet; 
vii. 
Have read, signed and dated the Informed Consent; 
viii. 
Best corrected visual acuity in each eye of at least 20/25 
ix. 
Have normal eyes with the exception of the need for visual correction; subjects must be willing to 
cease contact lens wear for the duration of the study; 
x. 
Be willing and able to adhere to the instructions set in the clinical protocol and maintain the 
appointment schedule. 
5.3.2 Exclusion Criteria 
To be eligible as a participant, each candidate shall be free of any ocular or medical condition that may affect 
the results of this study. 
The following are specific criteria that exclude a candidate from enrolment in this study: 
i. 
Use of Benzalkonium Chloride (BAK) preserved eyedrops in the last month;     
ii. 
Use of Optive brand eyedrops in the last month; 
 
 
 
iv. 
Use of systemic or ocular medications for which test products could be contraindicated as 
determined by the investigator; 
v. 
Monocular participants (only one eye with functional vision). 
vi. 
Subjects unwilling or unable to cease contact lens wear for the duration of the study; 
 
 
 
viii. 
History of herpetic keratitis, ocular surgery or irregular cornea; 
ix. 
Known pregnancy or lactation during the study period; 
 
 
xi. 
Participation in any clinical trial within 30 days of the enrolment visit; 
5.4 
Premature Withdrawal 
A participant will be withdrawn from the investigation before completion if: 
i. 
The participant withdraws his/her consent to be included in the trial;  
ii. An adverse event takes place that is considered by the participant or the investigator to warrant 
withdrawal; 

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iii. Any event that leads the investigator to believe that it is not in the best interest for the participant to 
continue in the study; 
iv. The study is prematurely terminated by the Principal Investigator, local research ethics committee or the 
Sponsor; 
v. The participant is lost to follow-up; 
vi. The participant no longer meets the eligibility criteria; 
vii. The participant dies. 
5.5 
Informed Consent 
Each participant must give written consent according to local requirements after the nature of the study has 
been fully explained. The consent form must be signed before performance of any study-related activity. The 
consent form that is used must be approved by both the Sponsor and by the reviewing IEC. The informed 
consent must be in accordance with principles that originated in the Declaration of Helsinki, current ICH and 
GCP guidelines, applicable regulatory requirements, and sponsor policy. 
Before entry into the study, the Investigator or an authorized delegated member of the investigational staff 
must explain to potential participants the aims, methods, reasonably anticipated benefits, and potential 
hazards of the study, and any discomfort it may entail. Participants will be informed that their participation is 
voluntary and that they may withdraw consent to participate at any time. They will be informed that choosing 
not to participate will not affect the care the participants will receive.  Finally, they will be told that if needed 
their records may be accessed by health authorities and authorized sponsor staff without violating the 
confidentiality of the participant, to the extent permitted by the applicable law(s) or regulations.  
The participants will be given sufficient time to read the informed consent form and the opportunity to ask 
questions. After this explanation and before entry into the study, consent must be appropriately recorded by 
means of the participant's dated signature. After having obtained the consent, a copy of the informed consent 
form must be given to the participants. 
In the event that additional investigators / sites are added to the protocol, the informed consent will be modified 
to include the Investigator’s name, address, phone number and 24-hour emergency number.  
6 
Study Design & Procedures 
6.1 
General Description 
The study will be a conducted as an open label, bilateral, prospective, interventional single arm clinical study, 
however, the investigator carrying out the tear film kinetics and tissue staining analyses post-hoc will be 
masked for these activities.  
6.2 
Experimental Routine 
The participants will attend a total of three scheduled visits over a five-week period.  
i. 
Enrolment visit; 
ii. 
Baseline / Dispensing visit (7 ± 1 days from enrolment); 
ii. 
One month follow-up visit (30 ± 3 days from dispensing). 
The participants will attend an initial Enrolment visit to obtain their informed consent, evaluate their suitability 
to take part in the investigation and collect their baseline information. The participants who fulfil the 
investigation inclusion and exclusion criteria will be dispensed with the run-in eyedrops to be used for one 

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week. Subjects who wear contact lenses will be required to cease wear during this run-in period (and continue 
to do so for the duration of the study).  At the completion of the one-week run-in period the participants will 
attend the clinic for baseline measurements and dispensing of the study products.  The participants will use 
the study products as per the study protocol for the reminder of the study. The Baseline and One-month visits 
will be scheduled in the morning. The participants will not take part in any concomitant investigation of any 
type or take concomitant medications not allowed by the exclusion criteria. 
The participants will complete weekly time stamped questionnaires sent in electronic format using 
 secure electronic survey software using either a personal computer, Apple Mac, tablet or 
smart phone to characterise the time scale of the improvement that may be achieved. 
Two visual analogue scale questionnaires will be sent on each occasion: one overnight to capture 
symptomatology upon waking and one late afternoon to be completed prior to sleep to capture daytime and 
evening symptomatology. In addition, the participants will complete the OSDI questionnaire one and four 
weeks after test product dispensing. 
6.3 
Measures to Avoid Bias 
6.3.1 Randomization 
There is no randomization in this study. 
6.3.2 Masking  
All videos and images will be anonymized and randomized by an unmasked technician prior to analysis. The 
investigators conducting the post hoc analyses of the Tearscope videos and digital images will be masked 
with respect to the participant ID and visit. 
6.4 
Test Procedures 
6.4.1 Efficacy Procedures 
The primary response procedures will be: 
i. 
OSDI questionnaire; 
ii. 
Digital photography of lissamine green staining of the exposed bulbar conjunctiva. 
The secondary response procedure will be: 
i. 
VAS comfort & symptomatology questionnaire ; 
 
 
 
 
 
 
 
 
 
 
 
 
6.4.2 Safety Procedures 
The procedures to monitor safety will be: 
i. 
Identification and prevalence of adverse events; 
ii. 
Measurement of Snellen visual acuity; 

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iii. 
Safety ocular integrity (biomicroscopy). 
6.4.3 Population Profiling Procedures 
The procedures to profile the population key characteristics will be: 
i. 
Demographics and ocular history questionnaire (including concomitant treatment). 
ii. 
OSDI questionnaire. 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
aire 
xiii. Scheduling 
                                                                                                                                                                              
1 The participants will be given full details of the investigation at the time of making the appointment for the enrolment visit.  The 
explanation at the time of the visit will be to reinforce the information given during the initial telephone contact and answer any questions 
the participants may have. 

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7 
Statistical Analysis and Sample Size Determination 
7.1 
Determination of Sample Size 
A sample size of 27 achieves 81% power to detect superiority using a one-sided t-test when the OSDI margin 
of equivalence is 7.5 and the true difference between the baseline and the follow-up value is 10.0, the data 
being drawn from a single population with a within participant standard deviation of 5.0 and with the 
significance level (alpha) of the test being set at 0.050.  Based upon the intended cohort sample it is proposed 
to screen 40 participants to have 35 participants enrolled into the investigational phase at the end of Visit 2 
to achieve a cohort of 30 participants completing the study as per the protocol. 
7.1 
Statistical Analysis Plan 
All data summaries and statistical analysis will be performed using SPSS Basic, Advanced and Regression 
modules (IBM SPSS Statistics). Throughout the data analysis the results for each participant/eye will be used 
when available. 
Summary tables (descriptive statistics and/or frequency tables) will be produced for all the variables recorded. 
The variables will be summarized by the following statistics: 
i. 
Parametric variables: n, mean, standard deviation (SD), median, minimum and maximum; 
ii. 
Non-parametric variables: n, median, mode, minimum, maximum and categorical distribution. 
A detailed statistical analysis Plan (SAP) will be developed as a start-up document prior to database closure 
and subsequent analysis will include comparative statistics for all primary and secondary variables. 
All participants who meet the eligibility criteria, adhere to the protocol, and successfully complete the full study 
assessment will be available for the per-protocol analysis.  Participants with missing data will be included in 
the analysis unless there is some non-response-related reason to exclude them, such as a protocol 
violation/invalid data. 
 
 

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8 
Risk Analysis 
OCULAR TECHNOLOGY GROUP - International has conducted an analysis of the benefits and risks of this 
study.  OCULAR TECHNOLOGY GROUP - International has determined that this clinical investigation is 
justified as the overall potential benefit to the population outweighs its risks. 
8.1 
Benefits 
There might not be direct benefits to the participants in this study. However, participation in a study may 
contribute to scientific research information that may be used in the development of new dry eyes 
management products. In addition, participants will receive an examination of the front part of their eyes and 
may have the opportunity to try different types of eyedrops products at no cost to them.  
8.2 
Risks 
All the assessments are routine clinical procedures or specialized procedures and none present any 
increased risk to participants compared with normal clinical routine. The risks associated with using the study 
products are similar to those of using any approved eyedrops for similar indication, such as the participants’ 
own eyedrops. These may include eye irritation, burning and discomfort, eye pain and eye irritation, visual 
disturbance. Less common side effects include allergic reactions (including eye allergy), blurred vision, sticky 
eye, watery eye, redness of the eye, eye injury to the surface of the eye due to tip of bottle touching the eye 
during use. 
Since all participants will be dry eyes sufferers, the risks of taking part in the study are no greater than those 
associated with doing nothing or continuing to use their habitual eyedrops. In addition, this is a five-week 
study and participants will be under the care of the research investigators closely while they are using the 
study products and their eyes will be examined at one week and one month post enrolment. 
9 
Adverse Events and Reporting 
9.1 
Adverse Events 
Adverse events including serious adverse events and quality complaints will be reported in accordance with 
MEDDEV 2.12.1 rev 8 Guideline on a Medical Devices Vigilance System.  
9.1.1 Adverse Event Definitions 
An Adverse Event (AE) is defined in accordance with ISO 14155 as “any untoward medical occurrence, 
unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in subjects, 
users, or other persons, whether or not related to the investigational medical device.” This definition includes 
events related to the investigational medical device or comparator and events related to the procedures 
involved.  
 
Disease signs and symptoms present prior to the study product being utilised are not considered AEs, unless 
the condition re-appears or worsens in intensity or frequency during the study. 
All adverse events and clinically significant abnormal laboratory findings will be documented on the CRF.  

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Classification 
Definition 
Serious 
Adverse Event 
(SAE) 
A SAE is defined in accordance with ISO 14155 as an AE that: 
a. Led to death 
b. Led to serious deterioration in the health of the participant, that either resulted in 
1. A life-threatening illness or injury, or 
2. A permanent impairment of a body structure or a body function, or 
3. Inpatient or prolonged hospitalization, or 
4. Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function, 
c. Led to fetal distress, fetal death or a congenital abnormality or birth defect 
 
NOTE: Planned hospitalization for a pre-existing condition, or a procedure required by 
the protocol, without serious deterioration in health, is not considered an SAE. 
Adverse 
device 
effect 
(ADE)  
An adverse device effect (ADE) is defined in accordance with ISO 14155 as “an adverse 
event related to the use of an investigational medical device.” This definition includes any 
AEs resulting from insufficient or inadequate instructions for use, deployment, 
implantation, installation, or operation, or any malfunction of the investigational medical 
device as well as any event resulting from use error (per ISO 62366) or from intentional 
misuse of the investigational medical device. 
Unanticipated 
Adverse 
Device 
Effect 
(UADE) 
An unanticipated adverse device effect (UADE) is defined in accordance with 21 Code 
of Federal Regulations (CFR) 812.3 as “any serious adverse effect on health or safety or 
any life-threatening problem or death caused by, or associated with, a device, if that 
effect, problem, or death was not previously identified in nature, severity, or degree of 
incidence in the investigational plan or application (including a supplementary plan or 
application), or any other unanticipated serious problem associated with a device that 
relates to the rights, safety, or welfare of subjects.” 
Serious 
adverse 
device effect 
(SADE) 
A serious adverse device effect (SADE) is defined in accordance with ISO 14155 as “an 
adverse device effect that has resulted in any of the consequences characteristic of a 
serious adverse event.” 
 
9.2 
Procedures for Adverse Events 
Treatment of an adverse event will depend on its nature and severity. Based upon the clinical judgment of 
the investigator the participant may be referred to an ophthalmologist for treatment. The investigator will 
attempt to determine whether the reaction is related to the eyedrops or a result of other factors. An Adverse 
Event Form will be completed for each adverse event. If both eyes are involved, each eye will be counted as 
one adverse event and Adverse Event information will be completed for each eye. Whenever possible, the 
adverse event will be photo-documented. 
Expenses incurred for medical treatment as part of study participation will be paid by the sponsor (bills and 
prescription receipts kept). The participant must be followed until resolution and a written report completed 
indicating the subsequent treatment and resolution of the condition. 

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9.3 
Reporting Adverse Events 
All safety events and device deficiencies, regardless of causality, will be reported to the principal investigator 
within 24 hours of the investigator becoming aware of the event.  
All SAEs and SADEs occurring during the study period (from signing ICF) through the last subject visit are to 
be immediately reported to Allergan at a fax number/email address listed on the cover page and recorded on 
the appropriate eCRFs within 24 hours of awareness. All subjects with an SAE/SADE must be followed up 
and the outcomes reported. The principal investigator is to supply Allergan and the Independent Ethics 
Committee with any additional requested information (e.g. hospital discharge summary, autopsy reports and 
terminal medical reports). Allergan shall evaluate all SADEs and determine and document in writing whether 
they meet the definition of a UADE. These shall be reported to all participating principal investigators, the 
regulatory authorities, and IRBs/ECs as required by national regulations. 
In the event of an SAE/SADE, the principal investigator must: 
1. Notify Allergan immediately by fax/e-mail using the SAE/SADE reporting forms. 
2. Obtain and maintain in his/her files all pertinent medical records, information, and medical judgments 
from colleagues who assisted in the treatment and follow-up of the subject. 
3. Provide Allergan with a complete, written case history which includes a statement as to whether the 
event was or was not related to the use of the investigational device. 
Promptly inform the Independent Ethics Committee of the event, if it is treatment-related. For other 
SAEs, notify the Independent Ethics Committee as required by local regulations, and the governing 
health authorities.  
9.4 
Pregnancy 
If a female becomes pregnant during the study, the investigator will notify the sponsor immediately after the 
pregnancy is confirmed. The investigator must document the outcome of the pregnancy and provide a copy 
of the documentation to Allergan. The pregnancy reporting form, which contains details of where to send the 
report, can be found in Appendix B. 
10 Device Deficiencies 
A device deficiency is defined in accordance with ISO 14155 as “inadequacy of a medical device with respect 
to its identity, quality, durability, reliability, safety, or performance.” Device deficiencies include malfunctions, 
use errors, and inadequate labelling. If a device deficiency occurs, the principal investigator will notify Allergan 
within 24 hours using the fax number or email on the front page of the protocol. Device deficiencies shall be 
documented throughout the study and appropriately managed by Allergan. Allergan shall review all device 
deficiencies and determine and document in writing whether they could have led to a SADE. These shall be 
reported to the regulatory authorities and IRBs/ECs as required by national regulations.  
11 Investigator, Sponsor and Medical Monitor Responsibilities 
11.1 Investigator Responsibilities 
The investigator is responsible for ensuring participant safety and data quality by: protocol compliance, 
adherence to GCP and local regulatory requirements, and the Declaration of Helsinki. The investigator should 

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be appropriately qualified and legally entitled to practice, and be trained in the proper method of obtaining 
informed consent. 
The investigator must have the appropriate resources to conduct the clinical trial, be familiar with the protocol 
and agree to adhere to it, support monitoring and auditing activities, communicate with the Sponsor regarding 
any clinical trial issues or need for protocol modifications, make the necessary arrangements to ensure proper 
conduct and completion of the clinical trial, and ensure the protection and welfare of the participant, including 
arranging any emergency treatment as needed. 
The investigator must ensure written Ethics Committee / IRB approval is received prior to the start of the 
clinical trial, that the Ethics Committee / IRB and sponsor is kept informed of the clinical trial progress, 
including serious/adverse events and deviations as required by them, and that any changes to the protocol 
are notified to the Ethics Committee / IRB and review written approval prior to implementation. 
The investigator must try to ensure adequate participant recruitment; that all necessary and appropriate 
information is given to potential participants to ensure informed consent is taken and documented; and that 
clinical records indicate the participant is enrolled in a clinical trial. The investigator must ensure that 
participants are provided with emergency contact details along with a procedure to follow in the case of an 
emergency, and that participants are kept informed as pertinent new information becomes available that may 
affect their decision to participate. 
The investigator has primary responsibility for the accuracy, legibility and security of all clinical investigation 
data, documents and participant records at the Investigator site during and after the clinical trial. CRFs are to 
be signed by the investigator, and any alterations to data are to be made by authorized personnel, initialled 
and dated by same or, in the instance of electronic data, an audit trail must be in place, with no obstruction 
of the original data. 
The investigator must ensure that data be kept for the minimum time as specified by this protocol. The test 
product must be accounted for (the quantity of the devices received must be reconciled with the quantities of 
the device used, discarded or returned), and must also be responsible for the supervision and assignment of 
duties to all responsible for the conduct and evaluation of the clinical trial for the Investigator centre involved. 
11.2 Sponsor Responsibilities 
The Sponsor has delegated the selection of the Investigator and study site to the CRO. The Sponsor will, 
select and appoint a monitor. The Sponsor has the ultimate responsibility for monitoring. The Sponsor is to 
supply and keep an up-to-date signed protocol and protocol amendments. 
The sponsor should ensure: appropriate information is provided to the Investigators to conduct the clinical 
trial; that deviations are reviewed with the Investigator as needed and included in the final report. Adverse 
events are reported by the investigator, and the sponsor in turn will then notify their applicable regulatory 
authorities, and other investigators as appropriate. The Sponsor is to maintain Sponsor-specific clinical trial 
documentation as required by the regulatory authorities and to ensure the investigator is aware of their record 
keeping responsibilities. 
11.3 Medical Monitor Responsibilities 
The Medical Monitor will be a physician specialising in ophthalmology. To reduce study bias concerns, the 
Medical Monitor will not have any real or potential conflict of interest with the Sponsor, Study Investigator or 
participating Investigative.          

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The primary purpose of the Medical Monitor is to ensure an independent review all Serious Adverse Events 
(SAE), device-related Adverse Events and AE related to the safety endpoints. When reviewing SAE and 
device-related adverse events, the Medical Monitor will report the relationship between the AE and the study 
device and the study procedure. The results of all events reviewed by the Medical Monitor will be documented.  
The Medical Monitor for the OTG-i Research Clinic will be 
 
 
12 General Clinical Management 
12.1 Data Recording 
The clinical data will be recorded on dedicated electronic case report forms (eCRFs) specifically designed to 
match the testing routine for each visit.  
 will be used for data 
recording. All data captured with this software will be stored in a secure SQL database. The eCRFs will be 
reviewed for accuracy and comprehensiveness once completed and signed by the investigator. 
 time stamped, secure electronic survey software will be used to weekly remotely collect the 
participants ‘subjective impression.  A summary of the data will also be recorded in the participants’ clinical 
records. These constitute the participants’ source documents, which will be signed by the investigator.  The 
content and structure of the eCRFs are compliant with ISO14155:2011. 
12.2 Clinical Monitoring 
The Sponsor will monitor the study in a manner consistent with ICH GCP E6, EN ISO 14155:2011 and the 
Declaration of Helsinki.  The study monitor will maintain close contact with the Principal Investigator and the 
Investigator’s designated staff. The monitor’s responsibilities will be laid out in the Protocol Specific Monitoring 
Plan (PSMP), which includes: 
i. 
Ensuring that the investigation is being conducted according to the protocol; 
ii. 
Ensuring the rights and wellbeing of participants are protected; 
iii. 
Ensuring that protocol deviations are documented with corrective action plans, as applicable; 
iv. 
Clarifying questions regarding the study; 
v. 
Addressing study issues at the site that may arise with site personnel and/or study team; 
vi. 
Reviewing the study records to ensure completeness and accuracy; 
vii. Study and patient source document records reviewed will include: 
a. The Information and Consent Form  
b. Source documentation including consenting, medical history, concomitant medications, and adverse 
event information as applicable.   
c. Study related Regulatory documents as per ICH E3 section 8 
The clinical monitor will review study data as per the PSMP and will perform, at a minimum, one Interim and 
one Close-Out Visit on site. 
12.3 Study Product Accounting 
Study product records include the study eyedrops shipping orders, dispensing logs and the physical count 
and disposition of the remaining unused study eyedrops.  The clinical monitor will ensure product is reconciled 
and any discrepancies are investigated and either corrected or documented. At study conclusion, all study 
eyedrops will be reconciled. 

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12.4 Participant Compliance Monitoring 
Throughout the course of the study the clinical monitor will review study data for participant compliance to the 
protocol.  Non-compliances will be documented as protocol deviation(s).  If a deviation is determined to be 
major, the deviation will be reported to the Ethics Committee as per their requirements. 
12.5 Unmasking of Study Information 
The study is an open label study. The only documents that will be masked will be the digital videos of the tear 
film and the digital photos of the ocular tissues.  Masking will only take place post hoc for the purpose of 
carrying out the analysis in an unbiased manner.  Once the analysis is complete unmasking will be 
implemented.  Masking in this study, therefore does not interfere with the participants’ safety management. 
 
 
 
 
 
 
 
 
 
13 Administration Management 
13.1 Relevant Standards 
This clinical study will be conducted in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki, and in compliance with the International Conference on Harmonization (ICH) E6 Good 
Clinical Practice (GCP) Consolidated Guideline, the International Standards Organization (ISO) Clinical 
investigation of medical devices for human participants – Good clinical practice (ISO 14155:2011(E)), and 
other regulations as applicable. The Investigator and all clinical study staff will conduct the clinical study in 
compliance with the protocol. The Investigator will ensure that all personnel involved in the conduct of the 
study are qualified to perform their assigned responsibilities through relevant education, training, and 
experience. 
13.2 Deviations from the Protocol 
Protocol deviations are unanticipated or unintentional changes to a study after it has received prior sponsor 
approval and ethics clearance. Protocol deviations can be major or minor.  
13.2.1 Major Protocol Deviations 
Major protocol deviations may impact the research protocol, information consent document or other study 
materials, usually cannot be anticipated ahead of time and are often necessary to ensure the safety and 
welfare of the participants. 
The following are examples of protocol deviations that must be reported to the EC: 
i. 
Changes in procedures initiated to eliminate immediate risks/hazards to participants; 

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ii. 
Enrolment of participants outside the protocol inclusion/exclusion criteria whether agreed to or not by 
the sponsor; 
iii. 
Inadvertent deviation in specific research intervention procedures or timing of the research intervention 
which could impact upon the safety or efficacy of the study-related intervention or upon the 
experimental design; 
iv. 
Information consent documentation violations: no documentation of informed consent; incorrect version 
of, or incomplete, informed consent documentation used. 
13.2.2 Minor Protocol Deviations 
Protocol deviations caused by or which originate with research participants are generally considered minor, 
and normally are not reported to the Independent Ethics Committee unless these result in increased risk to 
the participants). 
The following are examples of protocol deviations that are considered minor and do not require reporting to 
the Independent Ethics Committee: 
i. 
Logistical or administrative aspects of the study (e.g., study participant missed appointment, change in 
appointment date); 
ii. 
Inadvertent deviation in specific research intervention procedures or timing of the research intervention 
which would not impact upon the safety or efficacy of the study-related intervention or upon the 
experimental design (i.e., missing a measurement during a session that is not considered critical for 
the study).  
13.3 Modifications to the Clinical Investigational Plan 
Any modifications to the clinical investigational plan that are considered necessary can only be effected after 
approval from the principal investigator, the Sponsor and the Independent Ethics Committee.  In an 
emergency situation, as indicated in ISO14155, the clinical investigator will exercise his judgement to 
safeguard the participant's interest and may deviate from the clinical investigation plan without the prior 
approval of the Independent Ethics Committee.  In that case, the deviation will not be considered as a breach 
of agreement but will be reported to the ethics committee. 
13.4 Termination of the Study 
The Sponsors reserve the right to terminate the study at any time for any reason.  The Investigator should 
promptly notify the IEC of the termination or suspension and of the study and the reason. 
13.5 Data Protection 
All information obtained during the course of the investigation will be regarded as confidential. All personal 
data gathered in this trial will be treated in strictest confidence by investigators, monitors, OTG-i personnel, 
the sponsor and the independent ethics committee.  No data will be disclosed to any third party without the 
express permission of the participant concerned, with the exception of OTG-i personnel (monitor, auditor), 
the sponsor, the independent ethics committees and regulatory organisations in the context of their 
investigation related activities which, as part of the investigation will have access to the CRFs and source 
documents. 

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13.6 Data Handling and Record Keeping 
The data analysis will be carried out by OTG-i. 
All records, including CRFs, will be kept in the files of the Principal Site Investigators for the latter of the two 
dates a period of two years after the date on which the investigation is terminated or completed, or the date 
that the records are no longer required for legal clinical requirements.   
13.7 Reporting 
OTG-i shall submit a final report to the sponsor as per the terms in the Statement of Work. 
OTG-i shall also submit a summary one-year update and/or a summary final report to the Independent Ethics 
Committee. 
13.8 Study Registration 
Since this study is an interventional clinical study, it is considered as an applicable clinical trial for clinical 
trials registry (www.ClinicalTrials.gov or equivalent); the National Research Ethics Service (NRES) requires 
that clinical investigations involving medical devices are registered on a publicly accessible register in 
compliance with the HRA registration requirements for the UK. Therefore, the study will be registered with 
www.ClinicalTrials.gov. The National Research Ethics Service (NRES) will also publish the research 
summary wording that is submitted on the Integrated Research Application System (IRAS) Research Ethics 
Committee Application Form. 
13.9 Publication Policy 
The study data will be wholly owned by the Sponsor.  The results of the study may not be used in publications 
or presentations without the prior written permission of the Sponsor. 
 
 
   
13.11 Indemnity 
The Sponsor will take out indemnity to cover the participants and research staff involved in the study and the 
ethics committee.  This will NOT cover the research staff for clinical negligence.  Investigators will have their 
own professional indemnity. 
 
 

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14 References 
1. Bitton E, Keech A, Jones l, Simpson T. Subjective and Objective Variation of the Tear Film Pre- and 
Post-Sleep Optom Vis Sci. 2008. 85: 740–744 
2. Dumbleton KA, Guillon M, Theodoratos P, Patel T. Diurnal Variation in Comfort in Contact Lens and 
Non-contact Lens Wearers. Optom Vis Sci 2016. 93: 820 - 827 
3. Lemp MA, Baudoin C, Baum J et al. The Definition and Classification of Dry Eye Disease: Report of 
the Definition and Classification Subcommittee of the International Dry Eye Workshop. Ocular 
Surface. 2007. 5: 75 – 92 
• 
ISO 14155:2011(E) Clinical investigation of medical devices for human participants – Good clinical 
practice 
• 
ISO 19980:2012 (E) Ophthalmic optics – Contact lenses and contact lens care products – Guidance 
for clinical investigations 
• 
MEDDEV 2.12/1 Rev 8 - Guidance document - Market surveillance - Guidelines on a Medical Devices 
Vigilance System 
• 
International Conference on Harmonization (ICH), Guideline for Good Clinical Practice (GCP) 
• 
Code of Federal Regulations: 21CFR11 (Electronic Records; Electronic Signatures), 21CFR50 
(Protection of Human Participants), 21CFR56 (Institutional Review Board), 21CFR812 
(Investigational Device Exemptions), 21CFR54 (Financial Disclosure by Clinical Investigators) 
 
15 List of Abbreviations 
AE 
Adverse Event 
BAK 
Benzalkonium Chloride 
CRO 
Contract Research Organization 
EC 
Ethics Committee 
e.g. 
For example 
FDA 
US Food and Drug Administration 
GCP 
Good Clinical Practice 
HRA 
Health Research Authority 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
ID 
Identification 
IEC 
Independent Ethics Committee 
IRAS 
Integrated Research Application System 
IRB 
Investigational Review Board 
ISRCTN 
International Standard Randomised Controlled Trial Number 
mm2 
Millimeter square 
NRES 
National Research Ethics Service 
OSDI 
Ocular Surface Disease Index 
PIS 
Participant Information Sheet 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
VAS 
Visual Analog Scale 
 
 
 

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16 Appendices 
16.1 Appendix A:  
 
INTERVENTIONAL STUDY: SERIOUS ADVERSE EVENT FORM FOR CLINICAL TRIALS 
 
 
 
 

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16.2 Appendix B:  
 
CLINICAL TRIAL PREGNANCY REPORT FORM