A Bilateral Dispensing Comparison of Biofinity Toric and Ultra for Astigmatism
Phase: NA
Conditions: Astigmatism
Sponsor: CooperVision, Inc.

1 
EX-MKTG-91 PIAN0-2 Protocol_14feb2018.docx 
 
® £2 u 
 
 
 
 
 
  
 
 
UNIVERSITY  OF WATERLOO 
FACULTY OF SCIENCE 
School of Optometry & Vision Science 
 
Centre for Ocular Research & Education (CORE) 
 
School of Optometry & V1s1on SCience IUn1vers1ty of Waterloo. 200 un,vers1ty Avenue West I Waterloo. ON. Canada N2L 3Gl 
+1 (519) 888-47421 CORE uwaterloo.ca 
 
 
 
 
Protocol 
 
 
 
A BILATERAL DISPENSING COMPARISON 
OF BIOFINITY TORIC AND ULTRA FOR 
ASTIGMATISM (PIAN0-2 ) 
 
Sponsor Company 
Sponsor Study number: 
 
 
 
 
 
 
 
Document Type: 
Clinical Site: 
 
CooperVision, Inc. 
EX-MKTG-91 
 
 
 
 
 
 
Study protocol 
CORE, University of Waterloo 
 
This protocol remains the exclusive property of the CORE until it is commissioned by the sponsors , 
 
Reviewed and approved, name & signature 
Date 
ddlmmmf 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 

EX-MKTG-91 PIANO-2 Protocol_14feb2018.docx 
1 
 
 
 
Centre for Ocular Research & Education (CORE), 
 
School of Optometry & Vision Science | University of Waterloo, 200 University Avenue West | Waterloo, ON, Canada N2L 3G1 
 
+1 (519) 888-4742 | CORE.uwaterloo.ca 
 
 
 
 
Protocol 
 
 
 
A BILATERAL DISPENSING COMPARISON 
OF BIOFINITY TORIC AND ULTRA FOR 
ASTIGMATISM (PIANO-2) 
 
Sponsor Company 
CooperVision, Inc. 
Sponsor Study number: 
EX-MKTG-91 
 
 
 
 
 
 
 
 
 
 
 
 
Document Type: 
Study protocol 
Clinical Site: 
CORE, University of Waterloo 
 
This protocol remains the exclusive property of the CORE until it is commissioned by the sponsors. 
 
Reviewed and approved, name & signature 
Date 
dd/mmm/yyyy 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 

EX-MKTG-91 PIANO-2 Protocol_14feb2018.docx 
2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table of contents 
1 
Introduction .......................................................................................................................... 8 
2 
Objectives ............................................................................................................................ 8 
3 
Hypothesis ........................................................................................................................... 8 
4 
Materials and methods ......................................................................................................... 8 
4.1 
Study design  ................................................................................................................ 8 
4.1.1 
Overall design  ....................................................................................................... 8 
4.1.2 
Randomization  ...................................................................................................... 9 
4.1.3 
Masking  ................................................................................................................. 9 
4.2 
Statement of compliance  ............................................................................................ 10 
4.3 
Ethics review  .............................................................................................................. 10 
4.4 
Clinical Trial Registration  ............................................................................................ 10 
4.5 
Informed Consent  ....................................................................................................... 10 
4.6 
Study population  ......................................................................................................... 10 
4.6.1 
Number of participants  ........................................................................................ 10 
4.6.2 
Inclusion and exclusion criteria  ............................................................................ 11 
4.6.3 
Repeated screenings  ........................................................................................... 12 
4.7 
Study materials  ........................................................................................................... 12 
4.7.1 
Lenses  ................................................................................................................ 12 
4.7.2 
Contact Lens care system  ................................................................................... 13 
4.7.3 
Rewetting drops  .................................................................................................. 13 
4.7.4 
Contact lens dispensing  ...................................................................................... 13 
4.7.5 
Ordering consumables  ........................................................................................ 13 
4.7.6 
Disposing of consumables  ................................................................................... 13 
4.7.7 
Product accountability  ......................................................................................... 14 
4.8 
Scheduled and unscheduled visits  .............................................................................. 14 
4.8.1 
Study visits  .......................................................................................................... 14 
4.8.2 
Screening  ............................................................................................................ 15 

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4.8.3 
Dispensing lens pair #1  ....................................................................................... 16 
4.8.4 
1-month follow-up of pair #1  ................................................................................ 18 
4.8.5 
Dispensing lens pair #2  ....................................................................................... 19 
4.8.6 
1-month follow-up of pair #2 & Study exit  ............................................................. 20 
4.8.7 
Unscheduled visits  .............................................................................................. 22 
4.9 
Summary of Study procedures  ................................................................................... 22 
 
 
 
 
  
 
 
5 
Monitoring protocol adherence  .......................................................................................... 24 
6 
Potential Risks and Benefits to Human participants  .......................................................... 24 
7 
Adverse events  ................................................................................................................. 25 
7.1 
Adverse Event Definitions  ........................................................................................... 25 
7.2 
Normal or adaptive symptoms  .................................................................................... 27 
7.3 
Procedures for Adverse Events  .................................................................................. 27 
7.4 
Reporting Adverse Events  .......................................................................................... 28 
8 
Discontinuation from the study  .......................................................................................... 28 
9 
Device Malfunctions  .......................................................................................................... 29 
10 Study completion and remuneration  .................................................................................. 30 
11 Statistical analysis and data management  ........................................................................ 30 
11.1 
Sample size calculation  ........................................................................................... 30 
11.2 
Statistical analysis  ................................................................................................... 30 
12 Data Quality Assurance  .................................................................................................... 31 
12.1 
Study monitoring  ..................................................................................................... 31 
12.2 
Sponsor Responsibilities  ......................................................................................... 32 
12.3 
Investigator Responsibilities  .................................................................................... 32 
12.4 
Record keeping  ....................................................................................................... 32 
12.5 
Retention of study records and data  ........................................................................ 33 
12.6 
Data entry / Data management  ............................................................................... 33 
13 Protocol training  ................................................................................................................ 33 

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14 Study monitoring  ............................................................................................................... 33 
15 Study management  ........................................................................................................... 34 
15.1 
Protocol deviations  .................................................................................................. 34 
15.1.1 Major protocol deviations  ..................................................................................... 34 
15.1.2 Minor protocol deviations  ..................................................................................... 34 
15.1.3 Reporting and documenting protcol deviations  .................................................... 35 
15.2 
Premature termination of the study  ......................................................................... 35 
15.3 
Study participant records  ........................................................................................ 35 
15.4 
Retention of study records and data  ........................................................................ 36 
16 Confidentiality  ................................................................................................................... 36 
17 Publication  ........................................................................................................................ 36 
18 Study Costs  ...................................................................................................................... 36 
19 Report  ............................................................................................................................... 36 
 
  
 
 

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Confidentiality 
This is a private document and the property of the Centre for Ocular Research & Education 
(CORE). It is therefore confidential to the recipient and must not be quoted from or distributed 
beyond the company to which it is sent without the express written permission of the Director 
(or her/his designate) of the Centre for Ocular Research & Education. Release of information 
from this document is governed by the research agreement on file. 
Disclaimer 
This study will be conducted for research purposes only and is not intended to be used to support safety 
and efficacy in a regulatory submission. 

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1 
INTRODUCTION 
CooperVision is evaluating the subjective acceptance of BiofinityToric (CooperVision) in 
comparison with Ultra for Astigmatism (Bausch & Lomb), when each lens is worn on a daily wear 
basis over one (1) month in a randomized bilateral, cross-over, dispensing study. 
2 
OBJECTIVES 
 
 
The objective of the study is to evaluate the subjective acceptance of Biofinity Toric test lens 
when worn on a daily wear modality over 1 month. 
 
The primary study measures are: 
 
• 
Comfort subjective ratings (0-10 scale) and lens preference with respect to comfort (5- 
step Likert) 
 
• 
Dryness subjective ratings (0-10 scale) and lens preference with respect to dryness (5- 
step Likert) 
 
The secondary study measures are: 
 
 
Handling subjective ratings (0-10 scale) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 
HYPOTHESIS 
 
The study hypothesis is that Biofinity Toric (BT) ‘test lens’ will have equal or better subjective 
acceptance by wearers than the ‘control lens’, Ultra for Astigmatism (UT). 
 
4 
MATERI ALS AND METHODS 
 
4.1 STUDY DESIGN 
 
4.1.1 OVERALL DESIGN 

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4.2 STATEMENT OF COMPLIANCE 
 
This protocol document has been developed in accordance with the following: 
 
• 
ISO 14155 Clinical Investigation of Medical Devices for Human Subjects, Parts 1 & 2 
 
• 
ICH Harmonized Tripartite Guideline for Good Clinical Practice 
 
• 
The University of Waterloo’s Guidelines for Research with Human Participants 
 
• 
Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans, 2nd 
Edition. http://www.pre.ethics.gc.ca/eng/policy-politique/initiatives/tcps2-eptc2/Default/ 
• 
Declaration of Helsinki 
 
 
4.3 ETHICS REVIEW 
 
This study will be conducted in accordance with Institutional Review Board regulations (U.S. 
21CFR Part 56.103) or applicable IEC regulations. Copies of all IRB/IEC correspondence with 
the investigator/sponsor will be kept on file. 
 
This protocol will be submitted to and reviewed through the Office of Research Ethics (ORE) at 
the University of Waterloo, Canada. Notification of ethics clearance of the application is required 
prior to the commencement of the study. The conduct of this study will be given clearance by the 
Clinical Research Ethics Committee at the University of Waterloo, Canada. 
 
4.4 CLINICAL TRIAL REGISTRATION 
 
This study will be registered in the clinical trials registry (https://clinicaltrials.gov/) by the study 
sponsor. 
 
4.5 INFORMED CONSENT 
 
Informed consent shall be obtained in writing from all participants prior to their enrolment in the 
study (Appendix 1), and before any procedure specific to the clinical investigation is carried out. 
 
4.6 STUDY POPULATION 
 
4.6.1 NUMBER OF PARTICIPANTS 
 
Up to 30 participants will be dispensed / randomized with study products, with a target of 26 
completing the study. Participants will be recruited using CORE records and advertising 
approved by the UW Office of Research Ethics (Appendices 2, 3a, and 3b). Each participant will 
be given a unique study specific ID number. Additionally, all participants must meet all the study 
inclusion and none of the exclusion criteria listed below. 

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4.6.2 INCLUSION AND EXCLUSION CRITERIA 
 
A person is eligible for inclusion in the study if he/she: 
 
1. Is at least 17 years of age and has full legal capacity to volunteer; 
 
2. Has had a self-reported oculo-visual examination in the last two years. 
 
3. Has read and signed an information consent letter; 
 
4. Is willing and able to follow instructions and maintain the appointment schedule; 
 
5. Is an adapted soft contact lens wearer, who currently wears contact lenses for a  
minimum 3 days/week and 8 hours/day AND who anticipates no difficulty wearing CLs for 
6 days/week, 10 hours /day. 
 
6. Is willing to wear contact lens in both eyes for the duration of the study; 
 
7. Has a minimum astigmatism of - 0.75, determined by refraction; 
 
8. Can be fit with the two study contact lens types in the powers available; 
 
9. Has a distance visual acuity of 0.20 logMAR (approx 20/30) or better, determined by 
refraction; 
 
10. Can achieve a distance visual acuity of 0.20 logMAR (approx 20/30) or better in each eye 
with the study contact lenses. 
 
11. Has clear corneas and no active* ocular disease; 
A person will be excluded from the study if he/she: 
1. Is participating in any concurrent clinical trial; 
 
2. Has any known active* ocular disease and/or infection; 
 
3. Has a systemic condition that in the opinion of the investigator may affect a study 
measure; 
 
4. Is using any systemic or topical medications that in the opinion of the investigator 
may affect a study measure; 
 
5. Has known sensitivity to fluorescein dye or products to be used in the study; 
 
6. Appears to have any active* ocular pathology, ocular anomaly or severe insufficiency 
of lacrimal secretion (severe dry eye) that would affect the wearing of contact lenses; 
 
7. Is pregnant, lactating or planning a pregnancy at the time of enrolment (by verbal 
confirmation at the screening visit); 

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Visit 1 
V1 (V1-R1,& V1-R2 for re- 
screening if required) 
Screening, baseline & fit of both study 
lens (day 0) 
Visit 2 
V2 
Dispense lens pair #1 (day 0) 
Visit 3 
V3 
1-month follow-up of pair #1 (30±3 days 
after dispense of pair #1) 
Visit 4 
V4 
Dispense lens pair #2 
Visit 5 
V5 
1-month follow-up of pair #2 (30±3 days 
after dispense of pair #2) 
Exit 
Visit 
any 
Study exit 
 
 
 
4.8.2 SCREENING 
 
All participants who sign the informed consent letter will be assigned a study ID number. The 
investigator will determine participant eligibility using the inclusion and exclusion criteria. 
Ineligible participants will be discontinued from the study. The procedures to be performed are 
outlined below: 
 
The participant is expected to attend the screening / baseline visit not wearing their habitual 
contact lens products, instead wearing their spectacles. 
 
The participant will be required to read and sign an Informed Consent Form (Appendix 1) prior to 
enrollment. When the participant has signed the consent form, the participant will be considered 
to be enrolled in the study. 
 
Participant demographics and medical history (age, sex, medical conditions, medications, 
allergies) 
 
Contact lens history (habitual lens information and wearing habits) 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The investigator will confirm that the participant meets the eligibility specifications set out in the 
inclusion criteria and exclusion criteria and is eligible to continue in the study. 

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Trial fitting of both study lenses will be done: 
 
▪ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
▪ 
The contact lenses will be provided to participants in a manner which does not 
unmask the participant, as described in Section 4.7.4. 
 
▪ 
The lenses will be inserted by the participant. 
 
 
 
 
 
 
 
 
 
   
 
  
  
 
 
 
 
 
 
 
 
 
 
 
▪ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4.8.3 DISPENSING LENS PAIR #1 
 
The participant will be assigned a randomization ID and the first pair (lens pair #1) of contact 
lenses (either test or control lens) will be selected according to the randomization table. 
 
Lens pair #1 will be provided to participants in a manner which does not unmask the participant 
or investigator, as described in Section 4.7.4. 
 
The lenses will be inserted by the participant. 
 
The contact lenses will be allowed to settle for 10 minutes. 
 
The participant will be asked to give subjective 
 ratings (Appendix 9) for: 
 
a) Comfort at insertion (0-10 scale) 
 
 
 
 
 
 
 
 
c) 
 
 
 
 
 
 
d) Ease of insertion (0-10 scale) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
   
 
 

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• 
Participant will be provided with the contact lens care solution, lens case, and lens care 
instruction. 
 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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4.8.4 1-MONTH FOLLOW -UP OF PAIR #1 
 
Participants will be asked to wear lenses for at least 4 hours prior to the visit appointment. 
Participants who attend without lenses in-situ (wearing lenses) for at least four hours will be 
rescheduled (unless they report problems when wearing the lenses). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• 
The participant will be asked to score their subjective responses by reflecting on a typical 
day during the previous week of lens wear, 
 
  
 
 
 
 
 
 
 includes the following: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
o 
 
 
 
 
 
o Overall comfort (0-10 scale) 
o Overall dryness (0-10 scale) 
o Ease of insertion (0-10 scale) 
o Ease of removal (0-10 scale) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
   
 
 
 
 
 
 
 
   
 
   
 
 
 
 
 
 
 
 
 
 

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The lenses will be removed. Lens disposal procedures are detailed in Section 4.7.6. 
 
 
 
 
 
 
4.8.5 DISPENSING LENS PAIR #2 
 
The participant will be assigned the second pair (lens pair #2) of contact lenses (either test or 
control lens) will be selected according to the randomization table. 
 
Lens pair #2 will be provided to participants in a manner which does not unmask the participant 
or investigator, as described in Section 4.7.4. 
 
The lenses will be inserted by the participant. 
 
The contact lenses will be allowed to settle for 10 minutes. 
 
The participant will be asked to give subjective 
 ratings (Appendix 9) for: 
 
g) Comfort at insertion (0-10 scale) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
j) 
Ease of insertion (0-10 scale) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
   
 
 
 
 
 
 
 
 
 
 
 

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▪ 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
• 
Participant will be provided with more contact lens care solution, new lens case, and lens 
care verbal re-instruction. 
 
• 
The participant will be reminded to bring back 
 
 
 
 
 the 
remaining lens care solution and lens case to the next visit, 1-month visit of lens pair #2. 
 
 
 
4.8.6 1-MONTH FOLLOW -UP OF PAIR #2 & STUDY EXIT 

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Participants will be asked to wear lenses for at least 4 hours prior to the visit appointment. 
Participants who attend without lenses in-situ (wearing lenses) for at least four hours will be 
rescheduled (unless they report problems when wearing the lenses). 
 
• 
 
 
 
 
 
 
 
 
 
 
 
 
. 
 
• 
The participant will be asked to score their subjective responses and indicate any 
preference between the two lens types by reflecting on a typical day during the previous 
week of lens wear, as detailed in the subjective ratings form 
 
 and includes 
the following: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
▪ 
Overall comfort (0-10 scale) 
 
▪ 
Overall dryness (0-10 scale) 
 
▪ 
Ease of insertion (0-10 scale) 
 
▪ 
Ease of removal (0-10 scale) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
▪ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
   
 
 
 
 
 
 
 
   
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

EX-MKTG-91 PIANO-2 Protocol_14feb2018.docx 
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5 
MONITORING PROTOCOL ADHERENCE 
 
Adherence to study visit windows, lens wearing schedule, and time windows around other data 
collection points (i.e. subjective ratings) will be monitored internally by CORE. Deviations from 
the windows described in the protocol will be reported in the study report. Major protocol 
deviations will be reported to the Sponsor and the University of Waterloo’s Office of Research 
Ethics (ORE) within 7 days of becoming aware of them (as per ORE’s guidelines). 
 
6 
POTENTI AL RISKS AND BENEFITS TO HUM AN PARTICIPANTS 
 
This is a minimal risk study because of the use of marketed products and standard optometric 
assessments. 
 
Contact lenses in this study will be worn on a daily wear basis. Complications that may occur 
during the wearing of contact lenses include discomfort, dryness, aching or itching eyes, 
excessive tearing, discharge, hyperemia and variable or blurred vision. More serious risks may 
include photophobia, iritis, corneal edema or eye infection. Although contact lens-related 
infections are very infrequent, the possibility does exist. The incidence of infection due to day- 
wear soft lenses is 0.035%. Almost always an infection will occur only in one eye. This risk is 
assumed by 35-million Americans who currently wear contact lenses. 
 
When contact lenses are worn on a daily wear basis there is a small risk of an adverse event 
compared to not wearing contact lenses. When contact lenses are worn on an extended wear 
basis, there is a significantly increased risk of an adverse reaction compared with wearing 
contact lenses on a daily wear basis. 
 
Additionally, it is possible that participants may experience temporary discomfort associated with 
the study procedures /products/devices/eye drops (sodium fluorescein) including: burning and 
stinging, blurred vision, sandiness or grittiness, light sensitivity, dryness, itching, crusty eyes and 
foreign body sensation. 

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Routine clinical procedures including auto-refraction, auto-keratometry, visual acuity, anterior 
ocular health assessment, and contact lens fitting will be used. In addition, high magnification 
imaging (including video and still images) of the lens fit may be made using 35 mm or digital 
cameras. 
 
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 contact lens products. In addition, participants will receive an examination of the front part  
of their eyes and may have the opportunity to try a different type of soft contact lenses at no cost 
to them. 
 
This study may help the study sponsor to better understand the performance of the products 
being used in this study. 
 
7 
ADVERSE EVENTS 
 
7.1 ADVERSE EVENT DEFINITIONS 
 
An ‘adverse event’ refers to any undesirable clinical occurrence in a participant, whether it is 
considered to be device-related or not. Adverse events (AE) may be classified as ‘unanticipated 
adverse device effects,’ ‘serious adverse events,’ ‘significant adverse events,’ or ‘non-significant 
adverse events,’ as defined below. 
 
A number of conditions may result in temporary discontinuation until resolution. These include 
corneal infiltrates, corneal staining, limbal injection, bulbar injection or bulbar and tarsal 
conjunctival abnormalities. 
 
See SOP012_v01 for a description of adverse events, including management and reporting 
(Appendix 26). 

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28 
 
professional and/or recorded as being under appropriate health care as per investigator’s 
discretion. A written report will be completed indicating the subsequent treatment and resolution 
of the condition. 
 
7.4 REPORTING ADVERSE EVENTS 
 
All potential Serious and Unanticipated Adverse Device Effects that are related or possibly 
related to participant’s participation will be reported to the Principal Investigator and the sponsor 
within 24 hours of the investigator becoming aware of the event. The Investigator will report 
Serious Adverse Events to the ORE within 24 hours of the investigator becoming aware of the 
event and as per ORE requirements (by fax, mail/delivery, phone, or email). All fatal or life 
threatening events will be reported immediately to the ORE. 
Significant and Non-Significant Adverse Events will be reported to the sponsor as soon as 
possible, but no later than 5 working days after the occurrence. The Investigator will report the 
event to the ORE as per ORE requirements (by fax, mail/delivery, phone, or email). 
Sponsor contact details are: 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8 
DISCONTINUATION FROM THE STUDY 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 A participant’s study participation 
may be discontinued at any time if, in the opinion of the sponsor or the investigator it is in the 
best interest of the participant. All discontinuations will be fully documented on the appropriate 
study forms and the Discontinuation Form will be completed. The following is a list of possible 
reasons for discontinuation from the study: 
 
• 
Screening failure: Participants will be discontinued if they do not meet the inclusion and 
exclusion criteria outlined in section 4.6.2. 
• 
Unacceptable performance with products to be used in study: Participants may be 
discontinued if they are unable to achieve acceptable comfort and /or vision with the 
study products. 
• 
Positive slit lamp finding: Participants may be temporarily or permanently discontinued 
from the study depending on the severity of the condition and on the judgement of the 
investigator. 

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• 
Adverse event: If a participant experiences an adverse event during the study they may 
be discontinued based on the clinical judgement of the investigator. 
• 
Symptoms: If the participant has persistent symptoms they may be discontinued based 
on the clinical judgement of the investigator. 
• 
Disinterest, relocation or illness: The participant may choose to discontinue due to 
reasons within or beyond their control. 
• 
Violation of protocol or non-compliance: The participant will be discontinued if they are 
unable or unwilling to follow the protocol specified visit schedules and/or study 
procedures. 
• 
Instillation of topical ocular medication: The participant will be discontinued if they elect to 
use a topical ocular medication during the study unless that topical ocular medication is 
prescribed for a limited duration (less than two weeks) to treat a transient condition; in 
this case the participant may remain an active participant (at the discretion of the 
investigator) after stopping topical ocular medication following resolution of the ocular 
condition). 
• 
Lost to follow-up: The participant will be discontinued if they cannot be contacted and do 
not return for a final exit visit, and if the investigator has made a reasonable effort to 
contact the participant for a final study visit. 
• 
Premature termination of the study by the sponsor, CORE or the Office of Research 
Ethics at the University of Waterloo. 
 
A discontinuation form (Appendix 12) will be completed, which requires the signatures of both 
the participant and the investigator except where the participant is lost to follow-up in which case 
only the signature of the investigator is required. 
 
9 
DEVICE M ALFUNCTIONS 
 
A device malfunction means the failure of the device to meet its performance specification or 
otherwise perform as intended. Any defective lens that is likely to cause or contribute to a 
Serious Adverse Event should be reported to the Principal Investigator and the sponsor within 
24 hours of the investigator becoming aware of the malfunction. The ORE would also be notified 
within 24 hours of any device malfunction that may contribute to a Serious Adverse Event. 
 
Other defective lenses should be reported to the Sponsor as soon as possible (usually in weekly 
study updates to the Sponsor). 
 
This clinical study will also ascertain satisfaction or preference with subjective attributes such as 
comfort, vision, or lens handling. Responses to these subjective questionnaires will not be 
considered as complaints or device malfunctions. 

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10 STUDY COMPLETION AND REMUNERATION 
 
At the last scheduled protocol visit a study completion form (Appendix 13) will be completed, 
which requires the signatures of both the participant and the investigator. The participants will 
also be provided with a letter of appreciation (Appendix 15). 
 
Once their involvement in the study is complete, participants will be informed about receiving 
feedback following study completion in the Letter of Appreciation (Appendix15). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
11 STATISTICAL AN ALYSIS AND DATA M ANAGEMENT 
 
11.1 SAMPLE SIZE CALCULATION 
 
Sample size was calculated using the mean comfort rating data from the previous pilot PIANO 
study (EX-MKTG-83). The data from the PIANO-2 will be pooled with data from the pilot PIANO 
study, therefore anyone who participated in the pilot study will be excluded from participating in 
the PIANO-2 study. 
 
A total sample size of 44 is recommended to provide a minimum power of 90 with an alpha of 
 
0.05 in a two-tailed t-test to detect a difference of 1 comfort unit (scale of 0-10). Based on the 
results from the pilot study (i.e. PIANO Study) the sample size needed for PIANO-2 will be 
aimed at 26 to complete (i.e. total of 44 minus the 18 completed participants from the pilot 
study). Therefore, it is recommended that at least 30 subjects are dispensed in the PIANO-2 
study, with a target of 26 to complete. 
 
11.2 STATISTICAL ANALYSIS 
 
All data will be analyzed by CORE at the University of Waterloo. Data analysis will be conducted 
using Statistica, SPSS or SAS. Descriptive statistics will be provided on information regarding 
baseline variables (age, gender, refractive error distribution, etc.). Analysis of variables will be 
conducted separately on each eye, and data will not be pooled. For assessments conducted for 
each eye separately, the right eye will be used for analysis if there is no difference between 
eyes. If a general difference is found (e.g. for paired t-test / Wilcoxon matched pairs) between 
OD and OS, a comment will be provided. 
 
A Binomial test will be used to analyze the results for the count data of subjective preferences. 
The number of “no preference” will be evenly distributed to the two options on the basis they 
would be equally likely to choose either. 

EX-MKTG-91 PIANO-2 Protocol_14feb2018.docx 
32 
 
completed and whether there have been any unscheduled visits, discontinuations, significant or 
serious adverse events or major protocol deviations. These updates will be provided weekly. 
 
Prior to final data lock, a close-out visit/discussion may be warranted to check for accuracy and 
completeness of records. The sponsor or sponsor’s representatives will be authorized to gain 
access to the source documentation for the purposes of monitoring and auditing the study. 
 
12.2 SPONSOR RESPONSIBILITIES 
 
The Sponsor has the ultimate responsibility for monitoring. The Sponsor is to supply and keep 
an up-to-date signed protocol and protocol amendments, and provide devices which are the 
subject of the clinical investigation. 
 
The sponsor should ensure: appropriate information is provided to the Investigators to conduct 
the study; 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 study documentation as required by the regulatory authorities and to 
ensure the Investigator is aware of their record keeping responsibilities. 
 
12.3 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 study, be familiar with the 
protocol and agree to adhere to it, support monitoring and auditing activities, communicate with 
the Sponsor regarding any study issues or need for protocol modifications, make the necessary 
arrangements to ensure proper conduct and completion of the study, and ensure the protection 
and welfare of the participant, including arranging any emergency treatment as needed. 
 
The Investigator must ensure written ORE approval is received prior to the start of the study, that 
the ORE and Sponsor is kept informed of the study progress, including adverse events and 
deviations as required by them, and that any changes to the protocol are notified to the ORE 
and review written approval prior to implementation. 
 
12.4 RECORD KEEPING 

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Detailed records of all study visits will be made using the Case Report Forms (CRFs). All data 
recorded on forms will be in ink. Any corrections to the forms will be initialed and dated at the 
time they are modified. 
 
12.5 RETENTION OF STUDY RECORDS AND DATA 
 
Following study completion, data will be available in electronic and/or paper format for audit, 
sponsor use, or subsequent analysis. The original clinical raw data (including completed CRFs 
and Informed Consent forms) will be retained according to guidelines set forth in the general 
work agreement with the site. The Sponsor will be notified and consulted if ever the files are to 
be destroyed. Copies of raw data will be forwarded to the sponsor at completion of the final 
report. 
 
Records and data from this study will be retained for a minimum of 25 years. 
 
12.6 DATA ENTRY / DATA MANAGEMENT 
 
Data will be entered into an electronic spreadsheet. Study staff will only be able to modify the 
data file via password entry. The investigators will be responsible for the data integrity, and 
complete data entry for each visit in the CRFs and other relevant forms. The investigator will 
review the take home questionnaires with the participant. At the completion of the study the 
investigator will send the data collected to the study sponsor within approximately 5 business 
days after the study report is finalized. 
 
Data analysis will not be conducted on comments which have been recorded in the source 
documents. Only pre-defined comments will be entered into the study database. Only relevant 
and applicable comments will be included in the final report as deemed necessary by the lead 
investigator. 
 
13 PROTOCOL TRAINING 
 
All study personnel will be required to complete training prior to their involvement in the study. 
Records of training will be kept at CORE. 
 
14 STUDY MONITORING 
 
Status reports will be provided to the study sponsor by email on a regular basis. 
 
Status reports will include: 
 
• 
The number of participants screened, enrolled, and randomized (i.e. assigned a study ID 
number), discontinued and completed. 
• 
Details of protocol deviations. 

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• 
Reports of unintended events. 
 
Study monitoring visits may be conducted throughout the study and will be scheduled by the 
study sponsor in conjunction with the lead investigator. In addition study records may be 
inspected at CORE by the sponsor, the sponsor's designate, the Office of Research Ethics at  
the University of Waterloo, and by regulatory authorities in Canada and the United States, 
namely Health Canada and the United States Food and Drug Administration (FDA); however, no 
records containing identifiable/personal information will be permitted to leave the custody of 
CORE. 
 
15 STUDY M ANAGEMENT 
 
15.1 PROTOCOL DEVIATIONS 
 
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. 
 
15.1.1 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 University of 
Waterloo’s Office of Research Ethics (ORE): 
 
• 
Changes in procedures initiated to eliminate immediate risks/hazards to participants; 
 
• 
Enrollment of participants outside the protocol inclusion/exclusion criteria whether agreed 
to or not by the sponsor; 
 
• 
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; 
 
• 
Information consent documentation violations: no documentation of informed consent; 
incorrect version of, or incomplete, informed consent documentation used. 
 
15.1.2 MINOR PROTOCOL DEVIATIONS 
 
Protocol deviations caused by or which originate with research participants are considered 
minor, and normally are not reported to the ORE nor to the Sponsor (other than within the study 
report) unless these result in increased risk to the participant(s) or potentially affect data 

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integrity. The following are examples of protocol deviations that are considered minor and do not 
require reporting to the ORE: 
 
• 
Logistical or administrative aspects of the study (e.g., study participant missed 
appointment, change in appointment date); 
 
• 
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). 
 
15.1.3 REPORTING AND DOCUMENTING PROTCOL DEVIATIONS 
 
Major protocol deviations which require changes to the research protocol or informed consent 
process/document or other corrective actions to protect the safety, welfare, or rights of 
participants or others must be reported to the Sponsor and to the ORE within 7 days (as per 
guidelines of the ORE), using the Protocol Deviation Report Form 107 (PDRF). Information from 
the PDRF is provided to the Clinical Research Ethics Committee (CREC) at the next monthly 
meeting. 
 
All protocol deviations (major and minor) occurring during the study will be documented and 
included in the final report. 
 
15.2 PREMATURE TERMINATION OF THE STUDY 
 
The sponsor, CORE or the Office of Research Ethics at the University of Waterloo may 
terminate the study at any time for any reason. 
 
15.3 STUDY PARTICIPANT RECORDS 
 
Study participant records will be completed to comply with GCP guidelines. Records will contain: 
 
• 
Unique study acronym and/or code; 
 
• 
Participant ID; 
 
• 
Date enrolled; 
 
• 
Confirmation by investigator that participant met eligibility criteria; 
 
• 
Confirmation that participant received a signed and dated copy of informed consent; 
 
• 
Exit date; 
 
• 
Investigator’s signature confirming each participant’s study exit. 

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