Microbial Contamination Rates on the Back Surface of Soft Contact Lenses in Two Short-term, Randomized, Contralateral Non-dispensing Studies
Phase: NA
Conditions: Optometry
Sponsor: The University of New South Wales

 
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CLINICAL TRIAL PROTOCOL 
 
 
 
Protocol Title - Long: 
Microbial contamination rates on the back surface of soft contact lenses in short-
term, randomized, contralateral non-dispensing studies. 
Protocol Title - Short: 
Smart Touch non-dispensing handling studies 
Protocol ID Number: 
SOVS-2017-050 
Amendment Number: 
N/A 
Version Date: 
18th December 2018 
 
 
 
 

 
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CONFIDENTIALITY 
This document is confidential and the property of the Eye Research Group at the School of Optometry and Vision Science 
(ERG@SOVS), UNSW. 
 
No part of it may be transmitted, reproduced, published, or used without prior written authorization from the Head of the ERG@SOVS, 
UNSW.  
 
 
 
 
 
APPROVALS 
 
 
 
 
 
 
 
 
 
Jacqueline Tan, Author/Sub-investigator 
 
Date 
 
 
 
 
 
 
Ajay Kumar Vijay, Sub-investigator  
 
Date 
 
 
 
 
 
 
 
Fiona Stapleton, Head of School, Principal 
Investigator  
 
Date 
 
 
 
 
 
 
 
Steve Newman, Menicon  
 
Date 
 
 
 
 
 
 
 
 
 
 
 

 
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SPONSOR 
Sponsor: 
 
Address: 
 
University of New South Wales (UNSW) 
 
Sydney, NSW 2052 
Australia 
CO-SPONSOR 
Co-Sponsor: 
 
Address: 
 
Menicon Co. Ltd. 
 
21-19, AOI 3, Naka-ku, Nagoya, 460-0006, Japan 
 
SUMMARY OF FINAL PROTOCOL & AMENDMENTS 
Initial/ 
Amend # 
Version Date 
Author 
Main Changes 
Final 
1st September 
2017 
Jacqueline Tan 
N/A 
A1 
10th October 2017 
Jacqueline Tan 
Section 3 Medical Expert and Section 12.6 Referrals – 
changed to “Emergency Department” 
Section 4.1 Table 4 –contact lens details corrected 
Section 6 Trial Design – clarification in regards to 
“aseptic lens removal” has been added 
Section 6.1.2 Randomization and masking and 
Section 10.1 Administration of study lenses – changed 
the lens handling technique for lenses extracted from 
the conventional blister pack, and added practice for 
participants to familiarize themselves with the lens 
handling technique to remove a contact lens from the 
Smart Touch Technology blister pack   
A2 
18th December 2018 
Jacqueline Tan 
Addition of evaluation of the impact of EDTA in the 
packaging solution on microbial contamination rates. 
Revisions made to Tables 4 and 5, Sections 1, 4, 5, 6,  
A3 
 
 
 

 
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TABLE OF CONTENTS 
 
 
 
CONFIDENTIALITY ...................................................................................................................................... 2 
 
APPROVALS ................................................................................................................................................ 2 
 
SPONSORS .................................................................................................................................................. 3 
 
SUMMARY OF FINAL PROTOCOL AND AMENDMENTS ......................................................................... 3 
 
TABLE OF CONTENTS ................................................................................................................................ 4 
 
1.  
PROTOCOL SYNOPSIS .................................................................................................................. 7 
 
2.  
INVESTIGATOR(S) .......................................................................................................................... 9 
 
3.  
MEDICAL EXPERT ........................................................................................................................ 10 
 
4.  
BACKGROUND INFORMATION .................................................................................................. 11 
 
4.1 
Product .............................................................................................................................. 11 
 
4.2 
Summary ........................................................................................................................... 11 
 
 
4.2.1 
Risks and Benefits................................................................................................ 11
 
 
4.2.2 
Treatment Rationale ............................................................................................. 12 
 
 
4.2.3 
Guidelines and Regulations ................................................................................. 12 
 
 
4.2.4 
Trial Population .................................................................................................... 13 
 
 
 
5.  
TRIAL OBJECTIVES AND CLINICAL HYPOTHESIS .................................................................. 14 
 
5.1 
Trial Objective ................................................................................................................... 14 
 
5.2 
Clinical Hypothesis ............................................................................................................ 14 
 
6.  
TRIAL DESIGN. ............................................................................................................................. 15 
 
6.1 
Methodology / Study Visits ................................................................................................ 15 
 
 
6.1.1 
Data Requirements per Visit ................................................................................ 15 
 
 
6.1.2 
Randomisation and Masking ................................................................................ 16 
 
 
6.1.3 
Clinical Trial Population ........................................................................................ 18 
 
 
6.1.4 
Trial Duration ........................................................................................................ 18 
 
 
6.1.5 
Enrollment ............................................................................................................ 18 
 
6.2 
Primary Endpoint ............................................................................................................... 18 
 
6.3 
Secondary Endpoint(s) ...................................................................................................... 18 
 
7.  
SELECTION AND WITHDRAWAL OF PARTICIPANTS .............................................................. 19 
 
7.1 
Participant Selection.......................................................................................................... 19 
 
 
7.1.1 
Inclusion Criteria................................................................................................... 19 
 
 
7.1.2 
Exclusion Criteria ................................................................................................. 19 
 
7.2 
Participant Withdrawal....................................................................................................... 20
 
7.3 
Withdrawal and Follow-Up Procedure............................................................................... 20 
 
7.4 
Early Termination of Trial .................................................................................................. 20 
 
 
 
 

 
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TABLE OF CONTENTS - cont 
 
8.  
NUMBERING / RANDOMISATION ............................................................................................... 20 
 
9.  
EQUIPMENT TO BE USED / STANDARD & NON-STANDARD PRACTICE PROCEDURES ... 21 
 
9.1 
Standard Equipment and Procedures ............................................................................... 21 
 
9.2 
Non-standard Equipment and Procedures ........................................................................ 21 
 
9.3 
Maintenance and Calibration of Equipment ...................................................................... 21 
 
10.  
TREATMENT OF PARTICIPANTS ............................................................................................... 22 
 
10.1 
Administration of Study Lenses ......................................................................................... 22 
 
10.2 
Study Lens Storage and Accountability ............................................................................ 22 
 
 
10.2.1 Storage Requirements ......................................................................................... 22 
 
 
10.2.2 Accountability ....................................................................................................... 22 
 
10.3 
Concomitant Therapy ........................................................................................................ 23 
 
10.4 
Participant Instructions ...................................................................................................... 23 
 
11.  
ASSESSMENT OF EFFICACY ..................................................................................................... 24 
 
11.1 
Parameters  ....................................................................................................................... 24 
 
11.2 
Methods ............................................................................................................................. 24 
 
12.  
ASSESSMENT OF SAFETY ......................................................................................................... 25 
 
12.1 
Parameters  ....................................................................................................................... 25 
 
12.2 
Methods ............................................................................................................................. 25 
 
12.3 
Definitions .......................................................................................................................... 25
 
 
12.3.1   Adverse Events .................................................................................................... 25 
 
 
12.3.2 Serious Adverse Events ....................................................................................... 26 
 
 
12.3.3 Significant Adverse Events .................................................................................. 27
 
 
12.3.4 Non-Significant Adverse Events ........................................................................... 27
 
 
12.3.5 Unanticipated Adverse Events ............................................................................. 28 
 
 
12.3.6   Event Severity ...................................................................................................... 28 
 
12.4 
Reporting ........................................................................................................................... 28 
 
 
12.4.1 Expedited Reporting ............................................................................................. 28 
 
 
12.4.2 Foreseeable Adverse Events and Adverse Device Events ................................. 29
 
 
12.4.3 Other Observations .............................................................................................. 29 
 
12.5 
Follow-Up .......................................................................................................................... 29 
 
12.6 
Referrals ............................................................................................................................ 30 
 
13.  
STATISTICS 
.............................................................................................................................. 31 
13.1 
Description ........................................................................................................................ 31 
 
13.1.1 Number of Participants ......................................................................................... 31 
 
13.1.2 Significance .......................................................................................................... 31 
 
13.1.3 Analysis ................................................................................................................ 31 
13.2 
Criteria for Termination of the Trial ................................................................................... 32 
13.3 
Accountability of Data........................................................................................................ 32 
 
14.  
DATA HANDLING AND RECORD KEEPING ............................................................................... 33 
14.1 
Source Data ...................................................................................................................... 33 
14.2 
Direct Access to Source Data/Documents ........................................................................ 33 
14.3 
Database Management ..................................................................................................... 33 
14.4  
Data Archiving  .................................................................................................................. 33 
14.5 
Retention of Essential Documents .................................................................................... 34 
 
 

 
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TABLE OF CONTENTS - cont 
 
15.  
QUALITY CONTROL AND QUALITY ASSURANCE ................................................................... 35 
15.1 
Ethical Considerations....................................................................................................... 35
 
15.1.1 Confidentiality ....................................................................................................... 35 
 
15.1.2 Informed Consent ................................................................................................. 35 
 
15.1.3 Protocol Amendments .......................................................................................... 36 
 
15.1.4 Investigator Responsibilities ................................................................................. 36 
 
 
 
16.  
FINANCING AND INSURANCE .................................................................................................... 38 
 
17.  
PUBLICATION POLICY ................................................................................................................ 38 
 
18.  
INVESTIGATOR AGREEMENT .................................................................................................... 39 
 
APPENDIX 1: Declaration of Helsinki....................................................................................................... 40 
 
APPENDIX 2: CCLRU Grading Scales .................................................................................................... 44 
 
APPENDIX 3: CIBA Grading Scales ........................................................................................................ 46 
 
 
 
 

 
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1. PROTOCOL SYNOPSIS 
 
Table 1 
Protocol Title 
Microbial contamination rates on the back surface of soft contact 
lenses in short-term, randomized, contralateral non-dispensing 
studies. 
Protocol ID Number 
SOVS2017-050 
Trial Classification 
Evaluation 
Investigator(s)/Site(s) 
Eye Research Group @ SOVS 
The University of New South Wales 
Sydney, Australia 
Overall Duration of Trial 
4 months 
Number of Trial Participants 
Planned 
25 to complete each arm 
Planned Start Date 
May 2017 
Primary Objective 
To compare the microbial contamination rates on the back surface of 
hydrogel and silicone hydrogel contact lenses extracted from Smart 
Touch Technology blister packs versus conventional lens packaging, 
and the impact of EDTA in the packaging solution after short-term 
placement on the eye. 
Secondary Objectives 
o 
To compare the microbial contamination rates of the worn contact 
lenses to those on the participants’ hands/fingers used to conduct 
lens insertion 
o 
To determine the sample size required to conduct Phase 2 of the 
study (a randomized, bilateral cross-over, dispensing study to 
evaluate ocular redness, comfort and lens contamination rates) 
based on the detection limits for microbial contamination rates on 
the back surface of worn contact lenses 
Primary Safety Variable(s) 
Visual acuity 
Biomicroscopy: ocular redness, corneal details and staining 
Primary Efficacy/Performance 
Variable 
Level of microbial contamination of on the back surface of worn soft 
contact lenses 
Experimental design  
 Retrospective 
 Prospective 
 Single masked (Trial Participant) 
 Single masked (Investigator) 
 Double masked 
 Sponsor masked 
 Open label 
 Other 
 Single group 
 Multiple group 
 Parallel group 
 Cross over 
 Contralateral 
Study product details 
Name 
Smart Touch Technology 
 
Manufacturer 
Menicon Co. Ltd. 
Inclusion criteria 
Participants enrolled in the trial must be:  
 
Able to read and comprehend English and give informed consent 
as demonstrated by signing a record of informed consent; 
 
Be at least 18 years old; 

 
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 
Experienced soft contact lens wearer; 
 
Willing to refrain from wearing contact lenses for 24 hours prior to 
the scheduled study visits. 
Exclusion criteria 
 
 
Participants enrolled in the trial must NOT: 
 
Have any active corneal infection, ocular disease or systemic 
disease that would affect wearing of contact lenses; 
 
Use or have a need for any systemic or topical medications which 
may alter normal ocular findings/are known to affect a participant’s 
ocular health/physiology either in an adverse manner or risk 
providing a false positive; 
 
Have had eye surgery within 12 weeks immediately prior to 
enrolment for this trial; 
 
Have contraindications to contact lens wear; 
 
Have a greater than 2 line reduction in habitual visual acuity while 
wearing the study contact lenses; 
 
Be currently enrolled in another clinical trial; 
 
Be pregnant (verbal self-report); 
The Investigator may, at his/her discretion, exclude anyone else who 
they believe may not be able to fulfil the study requirements, or if it is 
believed to be in the participant’s best interests. 
 
Human Research Ethics 
Committee Status /  
Regulatory Status  
This trial requires Human Research Ethics Committee approval prior 
to study initiation, any advertising, and participant consent/enrolment. 
This trial requires approval from the Therapeutic Goods 
Administration. 
 

 
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2. INVESTIGATOR(S) 
 
Table 2 
Name: 
Jacqueline Tan 
Title: 
Senior Research Fellow  
Site Address: 
 
Eye Research Group @ SOVS 
The University of New South Wales 
Level 3, North Wing, RMB 
Gate 14, Barker Street 
Sydney  NSW  2032 
Telephone: 
+61 2 9385 6551 
 
Name: 
Ajay Kumar Vijay 
Title: 
Research Fellow 
Site Address: 
 
Level 2, North Wing, RMB 
Gate 14, Barker Street 
The University of New South Wales 
Sydney  NSW  2032 
Telephone: 
+61 2 9385 4503 
 
Name: 
Katherine Wong 
Title: 
Research Optometrist 
Site Address: 
 
Level 1, North Wing, RMB 
Gate 14, Barker Street 
The University of New South Wales 
Sydney  NSW  2032 
Telephone: 
+61 2 9385 4721 
 
Name: 
Fiona Stapleton 
Title: 
Head of School 
Site Address: 
 
Level 3, North Wing, RMB 
Gate 14, Barker Street 
The University of New South Wales 
Sydney  NSW  2032 
Telephone: 
+61 2 9385 4375 
 

 
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3. MEDICAL EXPERT 
 
Table 3 
Name: 
Emergency Department 
Title: 
Ophthalmologist 
Address: 
Sydney Eye Hospital 
South Block  
Number 8 Macquarie Street 
Sydney  NSW  2000 
Telephone: 
+61 2 9382 7111 
 

 
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4. BACKGROUND INFORMATION 
 
4.1. Product 
 
 
Following lens manufacture, disposable soft contact lenses are packaged in blister packs, 
with lenses free floating in solution. Extracting the contact lens from the blister pack 
involves removing the lens and manipulating the lens with both hands to ensure the lens is 
of the correct orientation prior to inserting the lens on the eye. 
 
Contact lens manufacturer Menicon have developed Smart Touch Technology blister 
packaging designed to minimize the amount of lens handling prior to lens insertion. Contact 
lenses are pinched from the blister pack such that only the front surface of the lens is 
handled for insertion directly onto the eye. 
 
The potential benefits of reduced handling of contact lenses during insertion include: 
minimizing the transfer of microbes to the eye, which may reduce the incidence of contact 
lens-related adverse events, reduced ocular redness and improved ocular comfort.  
 
Details of the contact lenses to be evaluated in this trial are shown in Table 4. 
 
Table 4 
Visit 
Contact Lenses 
Material 
Type 
Material 
Power 
(D) 
Diameter 
(mm) 
Base 
Curve 
(mm)  
TGA 
Approved 
(for sale in 
Australia) 
EDTA 
1 or 2 
Miru 1day UpSide 
in Smart Touch™ 
Silicone 
hydrogel 
midafilcon A 
-0.50 
14.2 
8.4 
No 
Yes 
1 or 2 
Miru 1day UpSide 
in conventional 
Silicone 
hydrogel 
midafilcon A 
-0.50 
14.2 
8.4 
No 
Yes 
1 or 2 
Miru 1day 
Menicon Flat Pack 
in Smart Touch™ 
Hydrogel 
hioxifilcon A 
-0.50 
14.2 
8.4 
Yes 
No 
1 or 2 
Miru 1day 
Menicon Flat Pack 
in conventional 
Hydrogel 
hioxifilcon A 
-0.50 
14.2 
8.4 
Yes 
No 
3 
Miru 1day UpSide 
in Smart Touch™ 
Silicone 
hydrogel 
midafilcon A 
-0.50 
14.2 
8.4 
No 
No 
3 
Miru 1day 
Menicon Flat Pack 
in Smart Touch™ 
Hydrogel 
hioxifilcon A 
-0.50 
14.2 
8.4 
Yes 
Yes 
 
 
4.2. Summary 
 
 

 
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4.2.1. Risks and Benefits 
 
Risks of the Clinical Trial 
 
As this will be a short-term non-dispensing study with three visits, all participants 
will be fitted with the same lens power (-0.50D) in each eye. This low power has 
been selected such that study participants with a habitual spectacle correction can 
wear their regular spectacles over the study contact lenses and still achieve similar 
vision. For study participants who do not require any habitual spectacle correction, 
this low power optical correction should still provide comparable and adequate 
vision for the short duration of lens wear (45 minutes). However, to ensure safety, 
participants’ vision will be measured and only those who can achieve visual acuity 
within 2 lines with the study contact lenses compared to their habitual visual acuity 
without the contact lenses will be included in the study.  
 
It is possible but unlikely that study participants will experience minor headaches 
associated with visual fatigue while wearing the low power contact lenses, unless 
they are engaging in highly visually demanding tasks. Therefore, participants will be 
advised to refrain from engaging in highly visually demanding tasks for the short 
duration of lens wear (45 minutes).  
 
Potential problems associated with normal contact lens wear, such as discomfort, 
redness of the eyes, light sensitivity or blurry vision still apply and may occur during 
this study. However, any risks associated with the study are very minor given the 
short-term duration of contact lens wear in this non-dispensing study.  
 
 
Benefits of the Clinical Trial 
 
There is no guarantee or promise that the participants will receive any benefits from 
this clinical trial.  
 
However, understanding microbial contamination rates of contact lenses extracted 
from Smart Touch Technology blister packaging compared to conventional contact 
lens packaging, and the impact of EDTA in the packaging solution, will provide vital 
information as to the potential benefits of reduced handling of contact lenses during 
insertion to: minimize the transfer of microbes to the eye; reduce the incidence of 
contact lens-related adverse events; reduce ocular redness and; improve ocular 
comfort.  
 
4.2.2. Treatment Rationale 
 
Contact lens manufacturer Menicon have developed Smart Touch Technology 
blister packaging designed to minimize the amount of lens handling prior to lens 
insertion. Contact lenses are pinched from the blister pack such that only the front 
surface of the lens is handled for insertion directly onto the eye. 
 
The purpose of this randomized, contralateral, investigator-masked non-dispensing 
study, is to investigate the microbial contamination rates on the back surface of soft 
hydrogel and silicone hydrogel contact lenses extracted from Smart Touch 
Technology blister packs versus conventional lens packaging, and the impact of 
EDTA in the packaging solution after short-term placement on the eye, and to 

 
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compare the microbial contamination rates of the worn contact lenses to those on 
the participants’ hands/fingers used to conduct lens insertion.  
 
The detection limits for microbial contamination rates on the back surface of worn 
soft contact lenses will be determined, in order to calculate the sample size which 
would be required to conduct a dispensing study to evaluate the effect on ocular 
redness, ocular comfort and lens contamination rates in a bilateral, randomized 
cross-over study. 
 
 
4.2.3. Guidelines and Regulations 
 
 
The clinical trial will be conducted in accordance with the protocol, the Declaration 
of Helsinki (see Appendix 1), ICH GCP and local regulations as applicable including 
TGA and NH&MRC guidelines. 
 
 
4.2.4. Trial Population 
 
25 participants are required to complete each arm of the study.  
 
 
 

 
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5. TRIAL OBJECTIVES AND CLINICAL HYPOTHESIS 
 
 
 
5.1. Trial Objective 
 
The objective of this study is to investigate the microbial contamination rates on 
the back surface of hydrogel and silicone hydrogel contact lenses extracted from 
Smart Touch Technology blister packs versus conventional lens packaging, and 
the impact of EDTA in the packaging solution after short-term placement on the 
eye (45 minutes), in a randomized, contralateral, investigator-masked non-
dispensing study comprising of two visits. 
 
5.2. Clinical Hypothesis 
 
The microbial contamination rates on the back surface of soft contact lenses 
extracted from Smart Touch Technology blister packs will be lower compared to 
the microbial contamination rates on the back surface of contact lenses extracted 
from conventional lens packaging. 

 
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6. TRIAL DESIGN 
 
 
This will be a prospective, single centre, randomized, contralateral, investigator-masked 
non-dispensing study. This study requires three visits of approx. 1 hour duration each.  
 
At the first visit, if possible, the order in which the hydrogel and silicone hydrogel contact 
lenses are allocated to the study participants will be randomized. At the second visit, 
participants will be crossed over to the alternate lens type (hydrogel or silicone hydrogel).   
 
At each visit, participants will be instructed to: 
 
o Wash their hands prior to handling the contact lenses; 
o Swab their thumb and two index fingers of the hand routinely used to conduct contact 
lens insertion using a sterile cotton swab moistened with sterile preservative free 
saline for the evaluation of skin microbiota; 
o Follow the manufacturer’s guidelines for lens insertion; 
o Open the blister pack and insert the contact lens randomly assigned for the right eye; 
o Open the blister pack and insert the contact lens assigned for the left eye; 
o Contact lenses will be removed aseptically by a masked investigator wearing sterile 
latex gloves, who is experienced in this technique, after 45 minutes of lens wear. All 
contact between the contact lens with the eyelids and eyelashes during lens removal 
will be avoided. 
Lenses and finger swabs will be analysed for microbial contamination using established 
routine microbiology protocols. The number and species of organisms will be determined.  
 
A minimum washout period of 48 hours will occur between the two study visits.  
 
All proposed procedures conform to the NHMRC Statement on Human Experimentation.   
 
Participants are considered enrolled when they have signed the informed consent form 
and are regarded as part of the clinical trial population. 
 
  
 
6.1. Methodology / Study Visits 
 
6.1.1. Data Requirements per Visit 
 
This study requires three visits of approx. 1 hour duration each. The data 
requirements for this visit are shown in Table 5. 
  
 

 
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Table 5 
Procedure 
Visit 1 
Visit 2 
Visit 3 
Informed Consent 
X 
 
X 
Demographics, ocular and medical history 
X 
 
 
Update ocular and medical history 
 
X 
X 
Spectacle vision 
X 
X 
X 
Slit lamp examination including fluorescein 
assessment 
X 
X 
X 
Randomization to contact lens material type* 
X 
 
 
Randomization – assign eye in which to insert 
contact lenses retrieved from the two types of 
lens packaging  
X 
X 
 
Randomization – assign eye in which to insert 
each contact lens material extracted from the 
Smart Touch Technology blister packs 
 
 
X 
Study participant to wash hands and undergo 
finger swab 
X 
X 
X 
Study participant to insert contact lenses 
(including practice removing the contact lenses 
from the lens packages) 
X 
X 
X 
Vision with spectacles worn over contact lenses 
X 
X 
X 
Aseptic contact lens removal 
X 
X 
X 
Adverse event 
* 
* 
* 
 
* If applicable 
 
 
 
    
 
6.1.2. Randomisation and Masking 
 
Prior to initiation of study treatment, each subject who provides informed consent 
will be assigned to a subject number that will serve as the subject identification 
number on all study documents.  Subject numbers will be assigned in ascending 
order and should not be omitted or reused.  
 
Participants will be randomly assigned to the lens packaging type to be inserted on 
each eye. A randomization scheme will be prepared in advance. In addition, if 
possible (dependent upon lens availability), participants will also be randomized as 
to the order in which the hydrogel and silicone hydrogel contact lenses are 
allocated at the first and second study visits. 

 
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Participants will practice the lens handling technique to remove a contact lens from 
the Smart Touch Technology blister pack. Once the participant is proficient with this 
technique, they will be instructed to follow the manufacturer’s guidelines for 
insertion of the Smart Touch Technology contact lens, and to open the blister pack 
of the contact lens in the conventional lens packaging, scoop the lens out of the 
blister pack by placing a finger on the lens and sliding the lens up the side of the 
lens package until it is free of the container, and insert the contact lens on their eye.  
 
The Investigator will provide instructions to the study participants as to the lens 
insertion technique but will not be cognizant to the randomisation schedule and will 
not be present during the lens insertion procedure to maintain masking.   
 

 
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6.1.3. Clinical Trial Population 
 
A total of 25 experienced soft contact lens wearers (hydrogel or silicone hydrogel) 
will be required to complete each arm of the study. 
 
Trial participants will be recruited from the local population at the investigational 
site. An e-mail invitation will be circulated to all SOVS staff, the Brien Holden Vision 
Institute, the Centre for Eye Health, SOVS post-graduate students, and previous 
study participants and/or Optometry Clinic patients who have indicated their 
willingness to be contacted to participate in future research studies. Advertisements 
may also be posted in University newsletters, notice boards, websites, local 
newspapers, social media (e.g. Facebook), on the SOVS clinic TV screen and other 
local advertising and community websites. . 
6.1.4. Trial Duration 
 
This study requires three visits of approx. 1 hour duration each. 
 
6.1.5. Enrolment 
 
A study participant is considered enrolled when they have signed the Participant 
Information Statement and Consent Form.  
 
 
6.2. Primary Endpoint 
 
Microbial contamination rate of the back surface of worn soft contact lenses. 
 
 
 
6.3. Secondary Endpoint(s) 
 
Microbial contamination rate of participants’ hand swabs compared to the worn contact 
lenses. 
 

 
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7. SELECTION AND WITHDRAWAL OF PARTICIPANTS 
 
7.1. Participant Selection  
 
Only experienced soft contact lens wearers will be enrolled. Informed consent will be 
obtained prior to any clinical trial procedures being conducted.  
 
All participants will conform to the clinical trial entry criteria listed below: 
 
 
7.1.1. Inclusion Criteria  
 
 
Able to read and comprehend English and give informed consent as 
demonstrated by signing a Participant Information Statement and Consent 
Form; 
 
Be at least 18 years old; 
 
Experienced soft contact lens wearer; 
 
Willing to refrain from wearing contact lenses for 24 hours prior to the scheduled 
study visits. 
 
 
7.1.2. Exclusion Criteria  
 
 
Under 18 years old; 
 Have any active corneal infection, ocular disease or systemic disease that would 
affect wearing of contact lenses; 
 Use or have a need for any systemic or topical medications which may alter 
normal 
ocular 
findings/are 
known 
to 
affect 
a 
participant’s 
ocular 
health/physiology either in an adverse manner or risk providing a false positive; 
 Have had eye surgery within 12 weeks immediately prior to enrolment for this 
trial; 
 Have contraindications to contact lens wear; 
 Have a greater than 2 line reduction in habitual visual acuity while wearing the 
study contact lenses; 
 Be currently enrolled in another clinical trial; 
 Be pregnant (verbal self-report).  
 
 
 
 

 
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7.2. Participant Withdrawal 
 
Participants may be permanently discontinued from the clinical trial for any of the following 
reasons: 
 
If, in the Investigator’s opinion, it is in the best interest of the participant; 
 
Persistent clinical trial-related symptoms/complaints that are not correctable; 
 
Has a serious adverse event/serious adverse device event that is eye/lens related 
and/or which, in the Investigator’s opinion, requires withdrawal of the participant; 
 
Participant voluntarily withdraws consent from the clinical trial (i.e. Revocation of 
Consent); 
 
If a participant is not compliant with the clinical trial requirements and instructions; 
 
Protocol violations/deviations. 
 
 
 
7.3. Withdrawal and Follow-up Procedure  
 
 
This study comprises two visits for each participant. Any participants who wish to be 
withdrawn from the study will be exited upon request. 
 
 
 
7.4. Early Termination of Trial 
 
The trial may be stopped early for any one or more of the following reasons: 
 
If the monitoring of the clinical trial reveals unacceptable levels of device-related 
adverse events, even though some of the participants may not be affected; 
 
If the Investigator does not adhere to the protocol or decides to stop the study for any 
reason, with appropriate notification. 
 
In the event of early termination of the trial, the HREC will be notified. 
 
 
 
 
 
 
8. NUMBERING 
 
Participant numbering will occur sequentially commencing with ‘01’.   
 
 
 

 
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9. EQUIPMENT TO BE USED / STANDARD & NON-STANDARD 
PRACTICE PROCEDURES 
 
9.1. Standard Equipment and Procedures: 
 
 
 
Visual Acuity:  Measurement of the standard of vision achieved with 
spectacles or contact lenses using standard letter charts. Measurements are 
taken under monocular and/or binocular conditions. 
 
 
Slit-Lamp Biomicroscopy:  A specialised microscope with its own light 
source is used to examine the anterior eye. 
 
 
Fluorescein Assessment:  The ocular surface is assessed by instilling a 
harmless fluorescent dye called ‘fluorescein’ directly to the inferior bulbar 
conjunctiva using a sterile strip impregnated with fluorescein and moistened 
with sterile saline. The eye is assessed with the slit-lamp biomicroscope using 
a cobalt blue filtered light and a Wratten 12 filter. 
 
 
 
 
9.2. Non-Standard Equipment and Procedures: 
 
 
Non-standard procedures that may be performed include: 
 
 
Finger swabs for microbial evaluation: The thumb and two index fingers of 
the hand routinely used to conduct contact lens insertion will be swabbed by 
the study investigator using a sterile cotton swab moistened with sterile 
preservative free saline. The swab will be rolled over each finger twice – once 
in a forward direction, and once in the reverse direction. 
 
 
Collection of used contact lenses for microbial evaluation:  Study lenses 
will be collected from participants’ eyes aseptically using sterile powder-free 
gloves. The study lenses will be sent to the microbiology laboratory for 
analysis of microbial contamination rates on the back surface of lenses. 
 
 
Photography/Video:  A photograph and/or video recording of any 
interesting/unusual findings may also be made for documentation and/or 
follow-up purposes. 
 
 
9.3. Maintenance and Calibration of Equipment 
 
Equipment will be monitored regularly for maintenance and calibration as per 
relevant company and product manuals. 

 
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10. TREATMENT OF PARTICIPANTS 
 
10.1. Administration of Study Lenses 
 
Participants will practice the lens handling technique to remove a contact 
lens from the Smart Touch Technology blister pack. Once the participant is 
proficient with this technique, they will be instructed to follow the 
manufacturer’s guidelines for insertion of the Smart Touch Technology 
contact lens, and to open the blister pack of the contact lens in the 
conventional lens packaging, scoop the lens out of the blister pack by placing 
a finger on the lens and sliding the lens up the side of the lens package until 
it is free of the container, and insert the contact lens on their eye.  
 
The Investigator will provide instructions to the study participants as to the 
lens insertion technique but will not be cognizant to the randomisation 
schedule and will not be present during the lens insertion procedure to 
maintain masking.   
 
  
10.2. Study Lens Storage and Accountability 
 
10.2.1. Storage Requirements 
 
Study lenses will be stored at room temperature in a secure 
storeroom/cupboard. The storage facility should be kept locked to prevent 
unauthorized access and to ensure accountability of the study lenses at all 
times. 
 
 
10.2.2. Accountability 
 
A Lens Tracking spreadsheet is used for keeping track of who, where and 
when lenses have been issued or dispensed to.  
 
 
Receipt of Lenses:  Once invoice has been checked, the lenses will be 
entered into the Lens Tracking spreadsheet. 
 
 
Issue of Lenses to Clinical Trial Participants:  The Optometrist is 
responsible for documenting the dispensing of the lenses on the Lens 
Tracking spreadsheet. 
 
Disposal of Unused Supplies:  Instruction will be obtained from 
Menicon as to how to handle returned, unused lenses. 
 

 
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10.3. Concomitant Therapy 
 
Whilst participating in this clinical trial participants are not permitted to enrol in other 
clinical trials.   
 
Participants must not use or have a need for any systemic or topical medications 
which may alter normal ocular findings/are known to affect a participant’s ocular 
health/physiology either in an adverse manner or risk providing a false positive. 
 
Participants will be instructed to refrain from wearing contact lenses for 24 hours 
prior to the study visits. 
 
 
10.4. Participant Instructions 
General instructions to all participants  
 Contact the clinic immediately if problems are experienced or if they have any 
questions or concerns. 
 
 

 
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11. ASSESSMENT OF EFFICACY 
 
11.1. Parameters  
 
 
Microbial contamination rate on the back surface of worn soft contact lenses. 
 
 
11.2. Methods 
 
Used study contact lenses will be collected after 45 minutes of wear for evaluation 
of microbial contamination rates on the back surface of the lenses. 

 
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12. ASSESSMENT OF SAFETY 
 
12.1. Parameters 
 
 
Visual acuity  
 
History 
 
Ocular redness: bulbar and limbal conjunctiva 
 
Corneal staining 
 
 
12.2. Methods 
 
Visual acuity will be measured using standard letter charts. The study participant’s 
habitual visual acuity will be assessed as well as study contact lens acuity (with 
the study participant’s habitual spectacle correction worn over the contact lenses 
where applicable). 
 
History (including medical and general health) will be recorded at the study visit. 
 
Ocular redness (bulbar and limbal), and corneal staining will be assessed and 
recorded using the CCLRU (Appendix II) and CIBA Grading scales (Appendix III).   
 
An optometrist will be available for the duration of the study. Participants will be 
advised to contact the Optometrist immediately of any event not normal for lens 
wear e.g. unusual redness, pain, irritation, etc. At the clinic, the Optometrist will 
briefly assess the eye on a slit-lamp under low illumination to ascertain the nature 
of the condition, if any. If an adverse event occurs, the appropriate procedures will 
be conducted, including referral for medical treatment if necessary. Any adverse 
events will be followed until complete resolution to the reasonable satisfaction of 
the participant and the investigator. 
 
 
12.3. Definitions 
 
12.3.1. Adverse Events 
 
Adverse Event: Any undesirable clinical occurrence in a participant, 
whether it is considered to be device-related or not, that includes a clinical 
sign, symptom or condition and/or observation of an unintended technical 
performance or performance outcome of the device. 
 
Adverse Events may be classified as Serious, Significant, Non-significant or 
Unanticipated as defined further on. 
 

 
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Adverse Device Event: A clinical sign, symptom or condition that is 
causally related to the device or the performance of the device system. 
 
 
 
12.3.2. Serious Adverse Events 
 
Any adverse medical occurrence that: 
 
led to death. 
 
led to a serious deterioration in health of a Participant user or other.  
This would include: 
-    a life threatening illness or injury. 
- 
a permanent impairment of body function or permanent damage to 
a body structure. 
- 
a condition requiring hospitalisation or increased length of existing 
hospitalisation. 
-    a condition requiring unnecessary medical or surgical intervention. 
-    foetal distress, foetal death or a congenital abnormality/birth  
 
   defect. 
 
might have led to death or a serious deterioration in health had 
suitable action or intervention not taken place.  This includes: 
-   a malfunction of a device such that it has to be modified or 
temporarily/permanently taken out of service. 
-   a factor (a deterioration in characteristics or performance) found on 
examination of the device. 
 
Specifically for the eye, Serious Adverse Events include but are not limited 
to: 
 
permanent decrease in best-corrected visual acuity (≥2 lines) 
 
central corneal opacities 
 
central corneal neovascularisation – in the central 4mm of the 
 
cornea 
 
central corneal opacities – in the central 4mm of the cornea 
 
infectious corneal ulcers 
 
uveitis 
 
iritis 
 
endophthalmitis 
 
hypopyon 
 
hyphema 
 
penetration of bowman’s membrane 
 
persistent epithelial defect 
 
limbal cell damage leading to conjunctivalisation. 
 
 
 
 
 
Serious adverse events are reportable. 

 
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12.3.3. Significant Adverse Events 
 
Significant Adverse Events are those that are symptomatic and warrant 
discontinuation (temporary or permanent) of contact lens wear (excluding 
serious adverse events noted above).  They include, but are not limited to: 
 
 
Peripheral and non-infectious corneal ulcer: Inflammatory reaction of 
the cornea characterised by peripheral or mid-peripheral corneal 
infiltrate with necrosis of the anterior stroma and excavation of the 
corneal epithelium. Bowman’s layer is intact. Symptoms include 
moderate to severe pain, foreign body sensation, irritation, redness and 
tearing. 
 
 
Acute red eye: Inflammatory reaction of the cornea characterised by 
small, focal and diffuse corneal infiltration with minimal or no epithelial 
involvement. Symptoms include irritation, pain, redness, tearing, and 
photophobia. 
 
 
Infiltrative keratitis: Inflammatory reaction of the cornea characterised 
by anterior stromal infiltrates with or without epithelial involvement. 
Symptoms include mild to moderate irritation, and redness. Staining may 
be slight to moderate. 
 
 
Conjunctivitis: Inflammatory reaction of the conjunctiva characterised 
by discharge, grittiness, redness and swelling. 
 
 
Contact Lens Induced Papillary Conjunctivitis: Inflammatory reaction 
of the palpebral conjunctiva characterised by raised, swollen papillae. 
 
 
Corneal Erosion: Full thickness epithelial loss over a discrete area.    
 
 
Superior Epithelial Arcuate Lesion: Mechanical injury to the cornea 
characterised by an arc-like lesion in the periphery of the superior 
cornea. 
 
 
12.3.4. Non-Significant Adverse Events 
 
Non-significant 
Adverse 
Events 
are 
those 
that 
do 
not 
warrant 
discontinuation of contact lens wear, but may cause a reduction in wear 
time. Treatment, if needed, is usually with over the counter products. They 
include, but are not limited to: 
 
asymptomatic infiltrative keratitis 
 
blepharitis 
 
meibomitis 
 
contact dermatitis 
 
localised allergic reactions. 
 
 

 
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12.3.5. Unanticipated Adverse Device Events 
Adverse device events or serious adverse device events are considered 
“unexpected” or “unanticipated” if they do not appear listed in the device 
technical manuals to date. These events require expedited reporting. 
 
 
12.3.6. Event Severity 
Events should be rated by a study investigator according to their severity: 
Mild:  
No treatment required 
Moderate:   
Treatment required. May involve temporary interruption of 
contact lens wear. 
Severe:  
Requires referral to and treatment by an ophthalmologist. 
 
 
12.4. Reporting 
In the event of persistent irritation, redness, reduced visual acuity or any other 
unusual signs or symptoms, the participants will be advised to remove their lenses 
immediately. 
 
Non-serious and anticipated device-related adverse events and adverse events 
should be recorded as part of Good Clinical Practice. Sponsors are expected to 
maintain up-to-date tabulations and/or line listings of all adverse device events. 
 
All Serious Adverse Events should be reported to the HREC as per their reporting 
requirements. This should be followed by a more detailed written report 
commenting on potential confounding factors, results of investigations, treatment 
required and outcome.  The Sponsor(s) and the Principal Investigator should review 
the events in conjunction with the known information about the device, and make a 
determination as to whether the event is device-related or not. 
 
 
 
12.4.1. Expedited Reporting 
UNSW, via the Principal Investigator (PI) of the clinical trial is required to 
report to the Therapeutic Goods Administration (TGA) single cases of 
serious and unanticipated device related adverse events.   
 
Fatal or life-threatening unexpected adverse events – the TGA 
should be notified as soon as possible but no later than 7 calendar days 
after first knowledge by the PI that the case qualifies, followed by a 
complete report as possible within eight additional calendar days. 
 
All other serious, unexpected adverse events – TGA notification as 
soon as possible but no later than 15 calendar days after first knowledge 
by the PI that the case meets the minimum criteria for expedited 
reporting. 
 
In the case of an unexpected and serious adverse event that occurs outside 
Australia with use of the same product, the TGA and HREC should also be 

 
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notified. The time frame for this reporting should be within 72 hours of any 
significant safety issue which has arisen from an analysis of overseas 
reports or action which has been taken by another country’s regulatory 
agency. This advice must include the basis for such action. Investigators 
should also be notified, who must in turn notify the HREC. 
  
Reports should be on the ‘Medical Device Incident Report Form’ located on 
the TGA website (http://www.tga.gov.au/docs/html/forms/iris_mdir.htm) or 
similar format, and clearly marked ‘Clinical Trial Adverse Device Event’ and 
sent to: 
 
 
 
 
 
The Medical Officer 
 
 
 
Office of Devices, Blood and Tissues 
 
 
 
Therapeutic Goods Administration 
 
 
 
PO Box 100 
 
 
 
Woden  ACT  2606 
 
 
12.4.2. Foreseeable Adverse Events and Adverse Device Events 
 
Risks associated with the use of the study lenses include: 
 
• Eye discomfort (<1%) 
• Eye redness (<1%) 
• Blurry vision (<10%) 
• Headaches (<10%) 
 
 
12.4.3. Other Observations 
 
There may be other situations that may necessitate rapid communication to 
regulatory authorities. Scientific and medical judgment should be applied for 
each situation. In general, information that might materially influence the 
benefit-risk assessment of a product or that would be sufficient to consider 
changes in product administration or in the overall conduct of a clinical 
investigation represent such situations. 
 
 
12.5. Follow-up 
 
Participants who experience an adverse response will be discontinued from the 
study and followed up until the condition resolves or the participant is referred to 
another practitioner.   
 
 
 

 
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12.6. Referrals 
 
Participants will be referred to a medical expert when judged by the optometrist to 
be necessary. After hours, participants will be referred to Sydney Eye Hospital 
(Table 6). 
 
 
 
Table 6 
Title: 
Emergency Department 
Address: 
Sydney Eye Hospital 
South Block  
Number 8 Macquarie Street 
Sydney  NSW  2000 
Telephone: 
+61 2 9382 7111 
 
 
 
  
 

 
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13. STATISTICS 
 
13.1. Description 
 
Data stored in relational databases will be imported into SPSS software for 
statistical purposes. Statistical analysis will initially be reported in Excel. Data will be 
investigated for quality using range checks and frequency distribution. Underlying 
distributions of variables will be tested. Details of statistical analysis are described 
in Section 13.1.3.  
 
 
 
 
13.1.1. Number of Participants 
 
25 participants will be required to complete the study.  
 
This sample size is an estimate for this preliminary study, to determine whether 
differences in microbial contamination rates on the back surface of worn soft contact 
lenses can be detected. 
 
The results of this study will be used to inform the detection limits for microbial 
contamination rates on the back surface of worn soft contact lenses between the two 
different types of lens packaging. This will assist to determine the appropriate 
sample size required to conduct a longer-term dispensing study. 
 
 
 
13.1.2. Significance 
 
A p-value less than or equal to 5% will be considered to be statistically 
significant. 
 
 
 
 
13.1.3. Analysis 
 
Participants who complete the study treatment will be included in the 
analysis dataset. Reasons and frequency distribution of participants 
discontinued will be reported.   
 
Overall contamination rates, expressed as a binary variable, and 
contamination rates for type of organism will be compared between the worn 
contact lenses extracted from the two different types of lens packaging, as 

 
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well as between the hydrogel and silicone hydrogel lens materials extracted 
from the two different types of lens packaging.  
 
Data will be summarised as means ± standard deviations for variables 
measured on an interval scale and median ± inter-quartile range for ordinal 
variables. Statistical tests will be employed to determine significant 
differences between the worn contact lenses extracted from the two different 
types of packaging. Commonly used tests of significance at each visit may 
include paired t-tests and group t-test for parametric data and Wilcoxon sign 
rank test and rank sum test for non-parametric data. 
 
 
13.2. Criteria for Termination of the Trial 
 
The trial will be terminated upon completion of the final study visit by the last 
participant or unless any of the conditions of Section 7.4 are met. An active 
participant is one who is enrolled in the study and has not been discontinued. 
 
 
13.3. Accountability of Data 
 
 
Individual data points that are missing will be excluded from analysis involving only 
those specific variables. A participant’s complete visit data will not be excluded if 
some of the observations are missing. Inclusion of outliers in the analysis will be 
based on the magnitude of change in test statistic with and without the outliers. 
Outliers will preferably be retained unless there is significant change in test results. 
 
 
 

 
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14. DATA HANDLING AND RECORD KEEPING 
 
14.1. Source Data 
 
The Investigator/Institution is to maintain the trial documents as specified in ICH 
GCP guidelines and as required by the applicable local regulations.  The 
Investigator/Institution is to also take measures to prevent accidental or premature 
destruction of clinical trial-related documentation. 
 
Paper Case Report Forms are utilized for this clinical trial, and will be entered into 
Excel spreadsheets for importing into statistical software. For tests conducted that 
produce printed results, these should be included in the participant’s file. Source 
data includes, but is not limited to printouts, diagrams, videos, photos, and any 
other paper, electronic or digital data that is the first recording of that information, 
and these must be maintained by the Investigator in the source files for the 
participant, or if unable to file (e.g. digital images), then reference should be made 
to their location. The clinic records will maintain a record of trial participation but will 
not be considered as the source. 
 
 
14.2. Direct Access to Source Data/Documents 
 
The Investigator will conduct this clinical trial under HREC review. As necessary the 
Investigator will provide the HREC and appropriate regulatory authorities direct 
access to source data/documents for review.  
 
 
14.3. Data Management 
 
The data will be accessible to study personnel only, secured and backed up 
regularly.   
 
 
14.4. Data Archiving 
 
Electronic data will be stored in a secure off-site storage facility.  Paper records are 
archived approximately 3 months after study closeout.  The records are initially kept 
on site in a secure location, and may later be transferred to a secure off-site storage 
facility. 
 
 
 
 

 
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14.5. Retention of Essential Documents  
 
The Investigator/Institution is to retain essential documents until at least 2 years 
after the last approval of a marketing application in an ICH region and until there 
are no pending or contemplated marketing applications in an ICH region. However, 
these documents should be retained for longer if required by local regulatory 
agencies.  
 
The Investigator/Institution must also retain essential documents for 15 years as per 
TGA requirements following the completion of a clinical trial. However, essential 
documents may need to be retained longer after consideration of the following:  
product liability and the potential need to produce records at any time during, and 
possibly beyond, the life of a product in the event of a claim as a result of an 
adverse outcome associated with the use of the product. 

 
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15. QUALITY CONTROL AND QUALITY ASSURANCE  
 
15.1. Ethical Considerations 
 
This trial requires HREC approval prior to start.   
 
The Investigator is to ensure that the protocol, Participant Information Statement 
and Consent Form, available safety information, information about payment and 
compensation to participants, advertising or any clinical trial specific information 
provided to participants (including potential participants), the Investigator’s CV 
and/or evidence of appropriate qualifications and any other documentation they 
may request are submitted, reviewed and approved. Any subsequent amendments 
will be reviewed and approved by an HREC prior to implementation.  
 
The HREC must be appropriately constituted, and will perform its functions in 
accordance with the applicable local regulatory requirements (TGA and NHMRC) 
and GCP. 
 
This trial will be conducted in accordance with local guidelines and requirements 
(including those of the NHMRC and TGA, as applicable). 
 
 
15.1.1. Confidentiality 
 
Confidentiality will be maintained throughout the clinical trial by all parties 
involved in accordance with guidelines under section 95 of the Privacy Act 
1998, and guidelines approved under section 95a of the Privacy Act 1998 
(December 2001). Data will be secured against unauthorised access. 
 
Privacy and confidentiality of information about each clinical trial participant 
will be preserved in the reports and any publication of the clinical 
investigation data. 
 
 
15.1.2. Informed Consent 
 
The nature and purpose of the trial will be fully explained to each participant. 
Written informed consent must be obtained from each participant prior to 
any trial procedures being performed. 
 
The informed consent documentation to be used for the trial will include all 
the elements of informed consent per GCP, and TGA requirements as 
applicable, and will be reviewed and approved by the HREC prior to use. 
 
 

 
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15.1.3. Protocol Amendments 
 
The Investigator will review deviations to determine the need to amend the 
protocol or to terminate the investigation.  Justification for any changes will 
be provided.   
 
Protocol amendments will be submitted to the HREC for review and 
approval prior to implementation, unless the change required is to eliminate 
an immediate hazard to trial participants, or involves only administrative 
and/or logistical aspects of the trial (e.g. Change in contact numbers). 
 
 
 
15.1.4. 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 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, 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 HREC approval is received prior to the 
start of the clinical trial, that the HREC 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 HREC and 
receive 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; 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 clinical trial participants are 
provided with emergency contact details along with a procedure to follow in 
the case of an emergency, and that clinical trial 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.  Case Report Forms 
are to be signed by the Investigator, and any alterations to data are to be by 
authorised personnel, initialled and dated by same. 
 

 
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The Investigator must ensure that data be kept for the minimum time as 
specified by this protocol, investigational 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. 
 
 
 
 
 
 

 
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16. FINANCING AND INSURANCE 
 
Memorandum of Agreement can be provided on request. 
 
 
 
17. PUBLICATION POLICY 
 
 
Please refer to Memorandum of Agreement. 
 
 
 
 
 

 
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INVESTIGATOR AGREEMENT 
 
 
 
 
 
“I agree to conduct the trial outlined above according to the terms and conditions of the protocol, 
Good Clinical Practice Guidelines and with the applicable regulatory requirements.  All information 
pertaining to the trial shall be treated in a confidential manner.”   
 
 
 
 
 
 
Principal Investigator’s Signature:  
_______________________   Date:______________ 
 
 
Principal Investigator’s Printed Name: 
_______________________ 
 
 

 
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APPENDIX I 
 
DECLARATION OF HELSINKI

 
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APPENDIX I:  WORLD MEDICAL ASSOCIATION DECLARATION OF  
 
 
     HELSINKI 
Ethical Principles for Medical Research Involving Human Subjects 
 
The Declaration of Helsinki (Document 17.C) is an official policy document of the World Medical Association (WMA), the 
global representative body for physicians. 
 
Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964 and amended by the 
29th WMA General Assembly, Tokyo, Japan, October 1975 
35th WMA General Assembly, Venice, Italy, October 1983 
41st WMA General Assembly, Hong Kong, September 1989 
48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996 and the 
52nd WMA General Assembly, Edinburgh, Scotland, October 2000 
 
A. 
 
INTRODUCTION 
1.  
The World Medical Association has developed the Declaration of Helsinki as a statement of ethical principles to 
provide guidance to physicians and other participants in medical research involving human subjects. Medical 
research involving human subjects includes research on identifiable human material or identifiable data. 
2. 
It is the duty of the physician to promote and safeguard the health of the people. The physician's knowledge and 
conscience are dedicated to the fulfilment of this duty. 
3. 
The Declaration of Geneva of the World Medical Association binds the physician with the words, "The health of 
my patient will be my first consideration," and the International Code of Medical Ethics declares that, "A 
physician shall act only in the patient's interest when providing medical care which might have the effect of 
weakening the physical and mental condition of the patient."  
4. 
Medical progress is based on research which ultimately must rest in part on experimentation involving human 
subjects. 
5. 
In medical research on human subjects, considerations related to the well-being of the human subject should 
take precedence over the interests of science and society. 
6. 
The primary purpose of medical research involving human subjects is to improve prophylactic, diagnostic and 
therapeutic procedures and the understanding of the aetiology and pathogenesis of disease. Even the best 
proven prophylactic, diagnostic, and therapeutic methods must continuously be challenged through research for 
their effectiveness, efficiency, accessibility and quality.  
7. 
In current medical practice and in medical research, most prophylactic, diagnostic and therapeutic procedures 
involve risks and burdens.  
8. 
Medical research is subject to ethical standards that promote respect for all human beings and protect their 
health and rights. Some research populations are vulnerable and need special protection. The particular needs 
of the economically and medically disadvantaged must be recognized. Special attention is also required for 
those who cannot give or refuse consent for themselves, for those who may be subject to giving consent under 
duress, for those who will not benefit personally from the research and for those for whom the research is 
combined with care.  
9. 
Research Investigators should be aware of the ethical, legal and regulatory requirements for research on human 
subjects in their own countries as well as applicable international requirements. No national ethical, legal or 
regulatory requirement should be allowed to reduce or eliminate any of the protections for human subjects set 
forth in this Declaration. 
 
B. 
BASIC PRINCIPLES FOR ALL MEDICAL RESEARCH 
10.  
It is the duty of the physician in medical research to protect the life, health, privacy, and dignity of the human 
subject.  
11. 
Medical research involving human subjects must conform to generally accepted scientific principles, be based 
on a thorough knowledge of the scientific literature, other relevant sources of information, and on adequate 
laboratory and, where appropriate, animal experimentation. 
12. 
Appropriate caution must be exercised in the conduct of research which may affect the environment, and the 
welfare of animals used for research must be respected. 
13. 
The design and performance of each experimental procedure involving human subjects should be clearly 
formulated in an experimental protocol. This protocol should be submitted for consideration, comment, 
guidance, and where appropriate, approval to a specially appointed ethical review committee, which must be 
independent of the investigator, the sponsor or any other kind of undue influence. This independent committee 
should be in conformity with the laws and regulations of the country in which the research experiment is 
performed. The committee has the right to monitor ongoing trials. The researcher has the obligation to provide 
monitoring information to the committee, especially any serious adverse events. The researcher should also 
submit to the committee, for review, information regarding funding, sponsors, institutional affiliations, other 
potential conflicts of interest and incentives for subjects.  

 
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APPENDIX I:  Declaration of Helsinki (cont.) 
 
14. 
The research protocol should always contain a statement of the ethical considerations involved and should 
indicate that there is compliance with the principles enunciated in this Declaration.  
15. 
Medical research involving human subjects should be conducted only by scientifically qualified persons and 
under the supervision of a clinically competent medical person. The responsibility for the human subject must 
always rest with a medically qualified person and never rest on the subject of the research, even though the 
subject has given consent. 
16. 
Every medical research project involving human subjects should be preceded by careful assessment of 
predictable risks and burdens in comparison with foreseeable benefits to the subject or to others. This does not 
preclude the participation of healthy volunteers in medical research. The design of all studies should be publicly 
available. 
17. 
Physicians should abstain from engaging in research projects involving human subjects unless they are 
confident that the risks involved have been adequately assessed and can be satisfactorily managed. Physicians 
should cease any investigation if the risks are found to outweigh the potential benefits or if there is conclusive 
proof of positive and beneficial results. 
18. 
Medical research involving human subjects should only be conducted if the importance of the objective 
outweighs the inherent risks and burdens to the subject. This is especially important when the human subjects 
are healthy volunteers.  
19. 
Medical research is only justified if there is a reasonable likelihood that the populations in which the research is 
carried out stand to benefit from the results of the research.  
20. 
The subjects must be volunteers and informed participants in the research project. 
21. 
The right of research subjects to safeguard their integrity must always be respected. Every precaution should be 
taken to respect the privacy of the subject, the confidentiality of the patient's information and to minimize the 
impact of the study on the subject's physical and mental integrity and on the personality of the subject. 
22. 
In any research on human beings, each potential subject must be adequately informed of the aims, methods, 
sources of funding, any possible conflicts of interest, institutional affiliations of the researcher, the anticipated 
benefits and potential risks of the study and the discomfort it may entail. The subject should be informed of the 
right to abstain from participation in the study or to withdraw consent to participate at any time without reprisal. 
After ensuring that the subject has understood the information, the physician should then obtain the subject's 
freely-given informed consent, preferably in writing. If the consent cannot be obtained in writing, the non-written 
consent must be formally documented and witnessed.  
23. 
When obtaining informed consent for the research project the physician should be particularly cautious if the 
subject is in a dependent relationship with the physician or may consent under duress. In that case the informed 
consent should be obtained by a well-informed physician who is not engaged in the investigation and who is 
completely independent of this relationship.  
24. 
For a research subject who is legally incompetent, physically or mentally incapable of giving consent or is a 
legally incompetent minor, the investigator must obtain informed consent from the legally authorized 
representative in accordance with applicable law. These groups should not be included in research unless the 
research is necessary to promote the health of the population represented and this research cannot instead be 
performed on legally competent persons.  
25. 
When a subject deemed legally incompetent, such as a minor child, is able to give assent to decisions about 
participation in research, the investigator must obtain that assent in addition to the consent of the legally 
authorized representative. 
26. 
Research on individuals from whom it is not possible to obtain consent, including proxy or advance consent, 
should be done only if the physical/mental condition that prevents obtaining informed consent is a necessary 
characteristic of the research population. The specific reasons for involving research subjects with a condition 
that renders them unable to give informed consent should be stated in the experimental protocol for 
consideration and approval of the review committee. The protocol should state that consent to remain in the 
research should be obtained as soon as possible from the individual or a legally authorized surrogate. 
27. 
Both authors and publishers have ethical obligations. In publication of the results of research, the investigators 
are obliged to preserve the accuracy of the results. Negative as well as positive results should be published or 
otherwise publicly available. Sources of funding, institutional affiliations and any possible conflicts of interest 
should be declared in the publication. Reports of experimentation not in accordance with the principles laid 
down in this Declaration should not be accepted for publication.  
 
 
C. 
ADDITIONAL PRINCIPLES FOR MEDICAL RESEARCH COMBINED WITH MEDICAL CARE  
28. 
The physician may combine medical research with medical care, only to the extent that the research is justified 
by its potential prophylactic, diagnostic or therapeutic value. When medical research is combined with medical 
care, additional standards apply to protect the patients who are research subjects. 
29. 
The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best 
current prophylactic, diagnostic, and therapeutic methods. This does not exclude the use of placebo, or no 
treatment, in studies where no proven prophylactic, diagnostic or therapeutic method exists. 
 

 
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APPENDIX I:  Declaration of Helsinki (cont.) 
 
 
30. 
At the conclusion of the study, every patient entered into the study should be assured of access to the best 
proven prophylactic, diagnostic and therapeutic methods identified by the study. 
31. 
The physician should fully inform the patient which aspects of the care are related to the research. The refusal 
of a patient to participate in a study must never interfere with the patient-physician relationship. 
32. 
In the treatment of a patient, where proven prophylactic, diagnostic and therapeutic methods do not exist or 
have been ineffective, the physician, with informed consent from the patient, must be free to use unproven or 
new prophylactic, diagnostic and therapeutic measures, if in the physician's judgement it offers hope of saving 
life, re-establishing health or alleviating suffering. Where possible, these measures should be made the object of 
research, designed to evaluate their safety and efficacy. In all cases, new information should be recorded and, 
where appropriate, published. The other relevant guidelines of this Declaration should be followed. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Page 44 of 47 
 
 
 
 
 
 
 
 
 
 
 
APPENDIX II 
 
CCLRU GRADING SCALES 
 
 

 
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Page 45 of 47 
 
APPENDIX II:  CCLRU Grading Scales 
 
The CCLRU Grading Scale uses a 0-4 scale in 0.5 steps, as shown in the following table: 
 
 
 
Table 7 
Grade 
Description 
0 
Absent 
1 
 
 
  Very Slight 
2 
 
 
  Slight 
3 
 
 
  Moderate 
4 
 
 
  Severe 
 
The scale is to be used in conjunction with the colour photographs as a standard to compare the 
observed finding and grade accordingly. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Page 46 of 47 
 
 
 
 
 
 
 
 
 
 
 
APPENDIX III 
 
CIBA GRADING SCALES 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Page 47 of 47 
 
APPENDIX III:  CIBA Grading Scales 
SLIT-LAMP QUANTIFICATION CHART 
 
BIOMICROSCOPY SIGNS 
Limbal Redness 
 
0 
= 
None:  No injection 
1 
= 
Trace:  Mild segmented injection 
2 
= 
Mild:  Mild circumcorneal injection 
3 
= 
Moderate:  Marked segmented 
4 
= 
Severe:  Marked circumcorneal injection 
 
Bulbar Redness 
 
0 
= 
None:  White and clear 
1 
= 
Trace:  Regional hyperemia 
2 
= 
Mild:  Diffuse hyperemia 
3 
= 
Moderate:  Marked regional or diffuse hyperemia 
4 
= 
Severe:  Diffuse episcleral or scleral hyperemia 
 
Epithelial Staining 
 
0 
= 
None:  No staining 
1 
= 
Trace:  Regional superficial stippling and/or foreign body tracks 
2 
= 
Mild:  Regional or diffuse punctate staining and/or F.B. tracks 
3 
= 
Moderate:  Dense coalescent staining and/or abrasions 
4 
= 
Severe:  Epithelial loss, or full thickness abrasion