A Prospective, Randomized, Controlled, Multi-Center Clinical Study of the ACRYSOF® IQ Extended Depth of Focus (EDF) IOL
Phase: NA
Conditions: Cataract
Sponsor: Alcon Research

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a Novartis company
Short Title
A Clinical Study of the ACRYSOF® IQ EDF IOL
Long Title
A Prospective, Randomized, Controlled, Multi-Center Clinical Study of the 
ACRYSOF® IQ Extended Depth of Focus (EDF) IOL
Protocol Number: 
ILI875-C001
Study Phase:
Sponsor Name & Address:
Not applicable
Alcon Research, Ltd. and its affiliates (“Alcon”)
6201 South Freeway
Fort Worth, Texas  76134-2099
Test Product:
ACRYSOF IQ Extended Depth of Focus IOL
US IND#/ IDE#/ EudraCT:
Investigator Agreement:
Not applicable
I have read the clinical study described, herein, 
recognize its confidentiality. I agree to conduct this 
study in accordance with the ethical principles contained 
within the Declaration of Helsinki, and the described 
study in compliance with the protocol, Good Clinical 
Practices (GCP), ISO 14155, and all applicable 
regulatory requirements. Additionally, I will comply 
with all procedures for data recording and reporting, will 
permit monitoring, auditing, and inspection of my 
research center, and will retain all records until notified 
by the Study Sponsor.
Principal Investigator
Name
Address
Signature
     Date
Property of Alcon Laboratories
Confidential
May not be used, divulged, published, or otherwise disclosed without the consent of 
Alcon Laboratories
 
 
  
  
  
  
 
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4.0; Most-Recent; Effective; CURRENT
TDOC-0050634
Protocol - Clinical
23-May-2018
/ NCT03010254

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TABLE OF CONTENTS
TABLE OF CONTENTS.......................................................................................................2
List of Tables .........................................................................................................................5
List of Figures........................................................................................................................5
1
GLOSSARY OF TERMS...................................................................................6
2
ABBREVIATIONS ............................................................................................9
3
PROTOCOL SUMMARY................................................................................11
4
PROTOCOL AMENDMENTS ........................................................................19
4.1
Amendment 1 (Version 2.0) .........................................................................19
4.2
Amendment 2 (Version 3.0) .........................................................................20
4.3
Amendment 3 (Version 4.0) .........................................................................22
5
SCHEDULE OF PROCEDURES AND ASSESSMENTS ..............................24
6
INTRODUCTION............................................................................................26
6.1
Rationale and Background ...........................................................................26
6.2
Purpose of the Study ....................................................................................27
6.3
Risks and Benefits........................................................................................27
6.3.1
Known and Potential Risks ......................................................................27
6.3.2
Potential Benefits .....................................................................................28
7
STUDY OBJECTIVES ....................................................................................29
7.1
Primary Objective ........................................................................................29
7.1.1
Primary Effectiveness Assessment...........................................................29
7.2
Secondary Objectives...................................................................................29
7.2.1
Secondary Effectiveness Assessments .....................................................29
7.4
Primary Safety Objective .............................................................................30
7.4.1
Primary Safety Assessment ......................................................................30
8
INVESTIGATIONAL PLAN...........................................................................31
8.1
Study Design ................................................................................................31
8.2
Rationale for Study Design ..........................................................................32
8.3
Rationale for Choice of Control Article .......................................................33
 
 
  
  
  
  
 
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8.4
Data Monitoring Committee ........................................................................33
9
SUBJECT POPULATION................................................................................33
9.1
Inclusion Criteria..........................................................................................34
9.2
Exclusion Criteria.........................................................................................34
9.3
Reasons for Discontinuation (During Surgery)............................................35
9.4
Rescreening of Subjects ...............................................................................36
10
TREATMENT ..................................................................................................36
10.1
Other Medical Device Specified for Use during the Study..........................40
10.2
Treatment Assignment / Randomization ......................................................40
10.3
Accountability Procedures ...........................................................................41
10.4
Treatment Masking.......................................................................................41
10.5
Changes to Concomitant Treatments or Procedures ....................................42
11
STUDY PROCEDURES AND ASSESSMENTS BY VISIT ..........................43
11.1
Screening/Preoperative Visit (Visit 0)..........................................................43
11.2
Operative Visits (Visit 00/00A)....................................................................45
11.3
1-Day Postoperative Visit (Visit 1/1A) ........................................................46
11.4
1-Week Postoperative Visit (Visit 2/2A)......................................................47
11.5
1-Month Postoperative Visit (Visit 3A)........................................................47
11.6
3-Month Postoperative Visit (Visit 4A)........................................................48
11.7
6-Month Postoperative Visit (Visit 5A)........................................................50
11.8
Schedule of Procedures and Assessments for Discontinued Subjects..........52
11.9
Informed Consent and Screening .................................................................54
11.10
Unscheduled Visits.......................................................................................54
11.11
Discontinued Subjects..................................................................................55
11.11.1
Screen Failures .........................................................................................55
11.11.2
Discontinuations.......................................................................................55
11.12
Clinical Study Termination ..........................................................................56
11.13
Aborted Implantation ...................................................................................56
11.13.1
First Eye Implant......................................................................................57
11.13.2
Second Eye Implant..................................................................................57
12
DEVICE DEFICIENCIES AND ADVERSE EVENTS...................................58
12.1
General Information .....................................................................................58
12.2
Serious Adverse Events (SAEs) ...................................................................59
 
 
  
  
  
  
 
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12.3
Specific Events Relevant to this Protocol ....................................................60
12.3.1
Cumulative Serious Adverse Events ........................................................60
12.3.2
Persistent Serious Adverse Events ...........................................................60
12.3.3
Device Deficiencies..................................................................................61
12.4
Monitoring for Adverse Events....................................................................61
12.5
Procedures for Recording and Reporting.....................................................62
12.5.1
Intensity and Causality Assessments........................................................63
12.5.1.1
Intensity (Severity) ...............................................................................63
12.5.1.2
Causality...............................................................................................63
12.6
Return Product Analysis...............................................................................64
12.7
Unmasking of the Study Treatment..............................................................64
12.8
Follow-Up of Subjects with Adverse Events ...............................................64
12.9
Pregnancy in the Clinical Study...................................................................65
13
ANALYSIS PLAN ...........................................................................................65
13.1
Subject Evaluability .....................................................................................65
13.2
Analysis Data Sets........................................................................................65
13.3
Demographics and Baseline Characteristics ................................................66
13.4
Effectiveness Analyses.................................................................................66
13.4.1
Analysis of Primary Effectiveness Endpoint............................................66
13.4.1.1
Statistical Hypotheses...........................................................................66
13.4.1.2
Analysis Methods .................................................................................66
13.4.2
Analysis of Secondary Effectiveness Endpoints......................................67
13.4.2.1
Statistical Hypotheses...........................................................................67
13.4.2.2
Analysis Methods .................................................................................68
70
13.5
Handling of Missing Data ............................................................................70
13.6
Multiplicity...................................................................................................70
13.7
Safety Analysis.............................................................................................71
13.8
Health Economics ........................................................................................73
13.9
Interim Analyses...........................................................................................73
13.10
Non-inferiority Margin.................................................................................73
13.11
Sample Size Justification .............................................................................73
14
DATA HANDLING AND ADMINISTRATIVE REQUIREMENTS..............74
 
 
  
  
  
  
 
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14.1
Subject Confidentiality.................................................................................74
14.2
Completion of Source Documents and Case Report Forms.........................75
14.3
Data Review and Clarifications....................................................................76
14.4
Sponsor and Monitoring Responsibilities ....................................................76
14.5
Regulatory Documentation and Records Retention.....................................77
14.6
Quality Assurance and Quality Control .......................................................77
15
ETHICS ............................................................................................................78
16
REFERENCES.................................................................................................80
List of Tables
Table 10–1
Test Article...................................................................................................36
Table 10–2
Control Article .............................................................................................38
Table 10–3
Delivery System...........................................................................................40
Table 10-4
Unmasked Individuals .................................................................................42
Table 11–1
Contact Lens Discontinuation Prior to Preoperative Visit...........................43
List of Figures
Figure 8–1
Study Design................................................................................................32
Figure 12–1
Categorization of All Adverse Events..........................................................58
Figure 12-2
Categorization of All Serious Adverse Events.............................................59
 
 
  
  
  
  
 
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1
GLOSSARY OF TERMS
ACRYSOF IQ Extended 
Depth of Focus (EDF) 
IOL (Model DFT015)
Throughout this document, this investigational product (IP)
will also be referred to as ACRYSOF IQ EDF IOL, Model 
DFT015 and test article.
ACRYSOF IQ 
Monofocal IOL (Model 
SN60WF)
Throughout this document, this IP will also be referred to as
ACRYSOF IQ Monofocal IOL, Model SN60WF and control 
article.
Adverse Device Effect 
(ADE)
Adverse event related to the use of an investigational 
medical device (test article) or control article.  Note: This 
definition includes adverse events resulting from insufficient 
or inadequate instructions for use, deployment, implantation, 
installation, or operation; any malfunction; and use error or 
intentional misuse of the test article or control article.
Adverse Event (AE)
Any untoward medical occurrence, unintended disease or 
injury, or untoward clinical signs (including abnormal 
laboratory findings) in subjects, users or other persons, 
whether or not related to the investigational medical device
(test article).  Note: For subjects, this definition includes 
events related to the test article, the control article, or the 
procedures involved. For users or other persons, this 
definition is restricted to events related to the test article.
Anticipated Serious 
Adverse Device Effect 
(ASADE)
Serious adverse device effect which by its nature, incidence, 
severity or outcome has been identified in the risk 
management file.
Device Deficiency
Inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety, or performance. Note: 
This definition includes malfunctions, use errors, and 
inadequate labeling.
Enrolled Subject
Any subject who signs an informed consent form (ICF) for 
participation in the study.
Interventional Study
A study in which prospective subject assignment is decided 
by a protocol and use of the product is linked to the decision 
to include the subject in the study. Interventions include, but 
are not restricted to, drugs, cells and other biological 
products, surgical procedures, radiologic procedures, 
devices, behavioral treatments, process-of-care changes, and 
preventive care. Additional diagnostic or monitoring 
procedures are applied and methods other than
epidemiological methods are being used for analysis of the 
data.
 
 
  
  
  
  
 
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Malfunction
Failure of a medical device to perform in accordance with its 
intended purpose when used in accordance with the 
instructions for use or clinical investigation plan.
Nonserious Adverse 
Event
Adverse event that does not meet the criteria for a serious 
adverse event.
Pre-screened Subject
Chart review completed on potential subjects by study site 
for inclusion/exclusion criteria that do not require study 
specific testing. This is based on routine clinical testing 
and/or cataract evaluation.
Randomization Subject
Any subject who is assigned a randomized treatment.
Screened Subject
Any subject who is considered for the study and may or may 
not have signed an informed consent form (ICF).
Serious Adverse Device 
Effect (SADE)
Adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event.
Serious Adverse Event 
(SAE)
Adverse event that led to any of the following: 

Death.

A serious deterioration in health that either resulted in:
a) a life-threatening illness or injury.
Note: Life-threatening means that the individual was 
at immediate risk of death from the event as it 
occurred, ie, it does not include an event which 
hypothetically might have caused death had it 
occurred in a more severe form.
b) any potentially sight-threatening event or permanent 
impairment to a body structure or a body function.
c) in-patient hospitalization or prolonged
hospitalization.
Note: Planned hospitalization for a pre-existing 
condition, without serious deterioration in health, is 
not considered a serious adverse event. In general, 
hospitalization signifies that the individual remained 
at the hospital or emergency ward for observation 
and/or treatment (usually involving an overnight 
stay) that would not have been appropriate in the 
physician’s office or an out-patient setting. 
Complications that occur during hospitalization are 
adverse events.  If a complication prolongs 
hospitalization or fulfills any other serious criteria, 
the event is serious. When in doubt as to whether 
“hospitalization” occurred, the event should be 
considered serious.
 
 
  
  
  
  
 
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d) a medical or surgical intervention to prevent a) or b), 
or any ocular secondary surgical intervention 
excluding posterior capsulotomy.
e) any indirect harm as a consequence of incorrect 
diagnostic test results when used within 
manufacturer’s instructions for use.

Fetal distress, fetal death, or a congenital abnormality or 
birth defect.
Refer to Section 12 for additional SAEs.
Unanticipated Serious 
Adverse Device Effect 
(USADE)
Serious adverse device effect which by its nature, incidence, 
severity or outcome has not been identified in the risk 
management file.
Use Error
Act or omission of an act that results in a different medical 
device response than intended by manufacturer or expected 
by user. 
Note: This definition includes slips, lapses, and mistakes. An 
unexpected physiological response of the subject does not in 
itself constitute a use error.
 
 
  
  
  
  
 
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2
ABBREVIATIONS
Abbreviation
Definition
AAS
All-implanted analysis set
ADE
Adverse device effect
AE
Adverse event
ARMD
Age-related macular degeneration
ASADE
Anticipated serious adverse device effect
BAS
Best-case analysis set
BCDVA
Best corrected distance visual acuity
CI
Coordinating Investigator
D
Diopter
DCIVA
Distance corrected intermediate visual acuity
DCNVA
Distance corrected near visual acuity
DEP
Deviations and Evaluability Plan
DoH
Declaration of Helsinki
DFU
Directions for use
eCRF
Electronic case report form
EDC
Electronic data capture
EDF
Extended depth of focus
EU
European Union
FLACS
Femtosecond laser-assisted cataract surgery
GCP
Good Clinical Practice
GPCMS
Global Product Complaint System 
HA
Health Authority
IA
Interim analysis
IB
Investigator brochure
ICF
Informed consent form
ICH
International Conference on Harmonization
IEC
Independent ethics committee
IOL
Intraocular lens
IP
Investigational product
IRB
Institutional review board
IRT
Interactive response technology
ISO
International Organization for Standardization
LASIK
Laser-assisted in situ keratomileusis
LRI
Limbal relaxing incision
MOP
Manual of procedures
OD
Right eye
OS
Left eye
OVD
Ophthalmic viscosurgical devices
 
 
  
  
  
  
 
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SADE
Serious adverse device effect
SAE
Serious adverse event
SD
Standard deviation
SOP
Standard operating procedures
SPE
Safety performance endpoint
SSI
Secondary surgical intervention
TPS
Trapezoidal phase shift
UNSV
Unscheduled visit
US
United States
USADE
Unanticipated serious adverse device effect
VA
Visual acuity
YAG
Yttrium aluminum garnet
 
 
  
  
  
  
 
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3
PROTOCOL SUMMARY
Investigation Type
Device
Study Type
Interventional 
Investigational 
Product

ACRYSOF IQ Extended Depth of Focus (EDF)
Intraocular Lens (IOL) (Model DFT015)

ACRYSOF IQ Monofocal IOL (Model SN60WF)
Purpose and 
Rationale
The purpose of the study is to demonstrate the safety and 
performance of the ACRYSOF IQ EDF IOL at Month 3/Visit 4A 
(70-100 day post 2nd eye implantation). After all subjects 
complete Month 3 (Visit 4A), the study database will be locked to 
conduct planned analyses. Results from these analyses will be 
used in a clinical study report for submission. The study will be 
continued until all subjects complete Month 6 (Visit 5A), at which 
time the study database will be locked to report longer term safety 
and performance results.
Primary Objective 

To demonstrate that ACRYSOF IQ EDF IOL is superior 
to ACRYSOF IQ Monofocal IOL in mean monocular 
photopic distance-corrected intermediate visual acuity
(DCIVA) (at 66 cm from spectacle plane) at 
Month 3/Visit 4A.
Endpoint(s) and 
assessments 
related to Primary 
Objective(s)

Monocular photopic DCIVA (logMAR) at 66 cm
Secondary 
Objectives 

To demonstrate that ACRYSOF IQ EDF IOL is non-
inferior to ACRYSOF IQ Monofocal IOL in mean 
monocular photopic best corrected distance visual acuity 
at Month 3/Visit 4A.

To demonstrate that ACRYSOF IQ EDF IOL is 
superior to ACRYSOF IQ Monofocal IOL in mean 
monocular photopic distance corrected near visual 
acuity (DCNVA) (at 40 cm from spectacle plane) at 
Month 3/Visit 4A.
 
 
  
  
  
  
 
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
To demonstrate that mean monocular defocus curve for 
ACRYSOF IQ EDF IOL has a range of defocus at least 
0.50 D greater negative range than ACRYSOF IQ 
Monofocal IOL at 0.20 logMAR (20/32 line) at Month 
3/Visit 4A.

To demonstrate that ACRYSOF IQ EDF IOL is non-
inferior to ACRYSOF IQ Monofocal IOL in mean 
monocular mesopic contrast sensitivity with and without 
glare at Month 6/Visit 5A respectively.

To demonstrate that ACRYSOF IQ EDF IOL is superior 
to ACRYSOF IQ Monofocal IOL in proportion of subjects 
who respond “Never” to Q1 and Q3 of the spectacle use 
questionnaire at Month 6/Visit 5A respectively.
Endpoint(s) and 
Assessments 
Related to 
Secondary 
Objective(s)

Monocular photopic BCDVA (logMAR) at 4 m

Monocular photopic DCNVA (logMAR) 40 cm

Monocular photopic distance-corrected depth of focus 
assessed by the mean defocus curve

Monocular mesopic contrast sensitivity at 12 cycles per 
degree with and without glare respectively

Proportion of subjects who respond “Never” to Q1 and Q3 
of the spectacle use questionnaire respectively
Primary Safety 
Objective
To demonstrate that the adverse event rates of ACRYSOF IQ 
EDF IOL are not worse than Safety Performance Endpoint (SPE) 
rates as defined in IS EN ISO 11979-7:2014 at Month 3/Visit 4A.
Assessments
related to Primary 
Safety Objective

Adverse event rates of ACRYSOF IQ EDF IOL
Study Design
Prospective, randomized, parallel group, multi-center study; 
assessor and subject masked; total duration of a subject’s 
participation is approximately 7.5 months.
Subject Population
Adults (22 years and older) with cataract in both eyes requiring 
surgery with implantation of a monofocal IOL.
Key Inclusion 
Criteria

Planned cataract removal by routine small incision 
surgery.
 
 
  
  
  
  
 
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(See Section 9.1 for 
a complete list of 
inclusion criteria)

Calculated IOL power is within the clinical study supply 
range (18.0-25.0 D in 0.5 D steps).

Preoperative regular astigmatism of less than 1.0 D.
Key Exclusion
Criteria
(See Section 9.2 for 
a complete list of 
inclusion criteria)

Pregnancy or lactation current or planned during the 
course of the study.

History of anterior segment (corneal, anterior chamber, 
sulcus) or posterior segment (uveal, vitreo-retinal) 
pathology including retinal vascular occlusive disease, 
retinal detachment or peripheral retinal laser 
photocoagulation, ARMD, glaucoma (uncontrolled or 
controlled with medication) or ocular hypertension, 
diabetic retinopathy, retinitis pigmentosa and any optic 
nerve pathology.

Any current anterior or posterior segment inflammation of 
any etiology, and/or history of any disease producing an 
intraocular inflammatory reaction.

Clinically significant corneal pathology (epithelial, 
stromal, and/or endothelial) which would adversely affect 
the visual outcome based on Investigator expert medical 
opinion.

Clinically significant severe dry eye that would affect 
study measurements based on Investigator expert medical 
opinion

History of previous intraocular or corneal (refractive or 
trauma related) surgery.

Current or history of amblyopia or monofixation 
syndrome.

Any other ocular or systemic co-morbidity that, based on 
Investigator expert medical opinion, may confound the
results of this study or prohibit the completion of the study
assessments or increase the risk for the subject.
 
 
  
  
  
  
 
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
Subjects with conditions that increase the risk of zonular
rupture during cataract extraction procedure that may 
affect the postoperative centration or tilt of the IOL.

Any other planned ocular surgical procedures including
but not limited to limbal relaxing incision 
(LRI)/Astigmatic Keratotomy and laser-assisted in situ 
keratomileusis (LASIK).

Patients who desire monovision correction.
Data Analysis and 
Sample Size 
Justification
The primary analysis set for effectiveness analyses will be the 
All-Implanted Analysis Set (AAS). AAS includes all randomized 
eyes with successful IOL implantation.
 
 
The statistical hypothesis in support of the primary effectiveness 
objective is: 

ACRYSOF IQ EDF IOL is superior to ACRYSOF IQ 
Monofocal IOL with respect to mean monocular photopic 
DCIVA (66 cm from spectacle plane) at Month 3/Visit 4A 
(70-100 day post 2nd eye implantation) for the first 
implanted eye.  
 
The statistical hypothesis in support of the secondary 
effectiveness objectives are:

ACRYSOF IQ EDF IOL is non-inferior to ACRYSOF IQ 
Monofocal IOL with respect to mean monocular photopic 
BCDVA (4m) at Month 3/Visit 4A (70-100 day post 2nd
eye implantation) for the first implanted eye.  
 
The non-
inferiority margin will be 0.10 logMAR.
 
 
  
  
  
  
 
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
ACRYSOF IQ EDF IOL is superior to ACRYSOF IQ
Monofocal IOL with respect to mean monocular photopic 
DCNVA (40 cm from spectacle plane) at Month 3 / Visit 
4A (70-100 day post-operative) for the first implanted eye.  

ACRYSOF IQ EDF IOL is non-inferior to ACRYSOF IQ 
Monofocal IOL in mean mesopic contrast sensitivity with 
and without glare at Month 6 / Visit 5A (120-180 day post 
2nd eye implantation) for the first implanted eye
respectively. 
 
The non-inferiority margin will be -0.15 log 
unit.

ACRYSOF IQ EDF IOL is superior to ACRYSOF IQ 
Monofocal IOL with respect to proportion of subjects who 
respond “Never” to Q1 and Q3 of the spectacle use 
questionnaire at Month 6 / Visit 5A (120-180 day post 2nd
eye implantation) respectively.
Analysis of primary effectiveness endpoints will be based on a 
two-sample t-test. The difference in means (ACRYSOF IQ EDF
IOL minus ACRYSOF IQ Monofocal IOL) and the associated
95% (two-sided) confidence interval will be obtained.
Analysis of first secondary effectiveness endpoint will be based on
a two-sample t-test. The difference in means (ACRYSOF IQ EDF
IOL minus ACRYSOF IQ Monofocal IOL) and the associated
one-sided 97.5% upper confidence limit will be obtained.
Analysis of second secondary effectiveness endpoint will be 
based on a two-sample t-test. The difference in means 
(ACRYSOF IQ EDF IOL minus ACRYSOF IQ Monofocal 
IOL) and the associated 95% (two-sided) confidence interval 
will be obtained.
For the third secondary effectiveness objective (depth of 
focus), the line plot of the average visual acuity at each defocus 
level (ie, defocus curve) will be used to estimate the negative 
lens induced depth of focus at 0.20 logMAR. The difference in 
 
 
  
  
  
  
 
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depth of focus between ACRYSOF IQ EDF IOL and 
ACRYSOF IQ Monofocal IOL will be presented.
Analysis of fourth secondary effectiveness endpoint will be 
based on a two-sample t-test. The difference in means 
(ACRYSOF IQ EDF IOL minus ACRYSOF IQ Monofocal 
IOL) and the associated one-sided 97.5% lower confidence 
limit will be obtained.
For the fifth secondary effectiveness endpoint, a two-sided 
95% confidence interval for the difference in proportions 
(ACRYSOF IQ EDF IOL minus ACRYSOF IQ Monofocal 
IOL) will be calculated using the Miettinen-Nurminen method 
(1985), and ACRYSOF IQ EDF IOL will be determined to be 
superior to ACRYSOF IQ Monofocal IOL if the lower 
boundary of the confidence interval is greater than zero. This is 
equivalent to using a type I error rate of 2.5%, 1-sided.
Descriptive statistics (mean, median, standard deviation, 
number of subjects/eyes, minimum, maximum, and (two-sided) 
95% confidence interval) will be provided for effectiveness 
endpoints, separately for each eye (for monocular measures).
Overall type I error will be maintained at 0.05 level for the 
Month 3/Visit 4A (70-100 day post 2nd eye implantation) 
analyses using sequential testing approach summarized in the 
figure below.
The following primary and secondary effectiveness analyses will 
be performed on the Month 6/Visit 5A (120-180 day post 2nd eye 
implantation) data using the sequential testing approach 
summarized in the figure below if the primary and both secondary 
null hypotheses are rejected for the Month 3/Visit 4A (70-100 day 
post 2nd eye implantation) analysis.
 
 
  
  
  
  
 
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The Safety Analysis Set will include all eyes with attempted IOL 
implantation (successful or aborted after contact with the eye).
Descriptive summaries (counts and percentages) for specific AEs
will be presented by IOL group. The one-sided exact 95% lower 
confidence limit of incidence rates (proportion of eyes with events) 
observed for each IOL group will be compared to the cumulative and 
persistent adverse event SPE rates. In addition to SPE rates predefined 
in IS EN ISO 11979 7, the rate of adverse events that may be 
specifically related to ACRYSOF IQ EDF IOL design features; and 
any other significant events will be provided. These rates will be 
accompanied by two-sided exact 95% confidence intervals.
Sample Size Justification:
Effectiveness
The proposed sample size (N = 234; 130 Bilateral EDF IOL and 
104 Bilateral Monofocal IOL) provides >99% power for the 
superiority hypothesis test on mean monocular DCIVA (66 cm) 
when tested at the 0.025 level of significance (one-sided). This 
assessment assumes:

Difference in DCIVA (66 cm) [logMAR]: Mean (SD) =
-0.12 (0.18)
The proposed sample size provides 81% power for the non-
inferiority hypothesis with respect to mean monocular 
BCDVA (4 m) when tested at the 0.025 level of significance (one-
sided) with a non-inferiority margin of 0.10 logMAR assuming:
 
 
  
  
  
  
 
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
Difference in BCDVA (4 m) [logMAR]: Mean (SD) =
0.04 (0.16) 
The proposed sample size provides >99% power for the 
superiority hypothesis test on mean monocular DCNVA (40 cm) 
when tested at the 0.025 level of significance (one-sided). This 
assessment assumes:

Difference in DCNVA (40 cm) [logMAR]: Mean (SD) = 
-0.12 (0.18)
The proposed sample size provides 74% power for the non-
inferiority hypothesis with respect to mean monocular mesopic 
contrast sensitivity value when tested at the 0.025 level of 
significance (one-sided) with a non-inferiority margin of -0.15 log 
unit assuming:

Difference in contrast sensitivity [log unit]: Mean (SD) = -
0.02 (0.38) 
The expected sample size (N = 131) provides 84% power, with 
α=0.025, 1-sided, to detect a difference of 25% in proportion of 
subjects who respond “Never” to Q1 and Q3 of the spectacles use 
questionnaire respectively, assuming a 50% response rate in the 
ACRYSOF IQ EDF IOL group.
Approximately 260 subjects will be randomized to achieve 234 
subjects who complete the study. It is expected that approximately 
131 subjects will respond to spectacle use questionnaire in this 
study.
Adverse Events
For any event where zero incidence is observed in130 operative
eyes with ACRYSOF IQ EDF IOL, the one-sided exact 95% 
upper confidence limit is less than 2.3%. Thus, with 95%
confidence the true adverse event rate is less than 2.3%.
 
 
  
  
  
  
 
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Key Words for 
Posting in Registries
Prospective, multi-center, randomized, parallel group, 
controlled, assessor and subject masked study; being conducted 
in approximately 4 countries outside the US.
4
PROTOCOL AMENDMENTS
Modification of the protocol is prohibited without prior written agreement in the form of a 
protocol amendment. All amendments must be created by the Study Sponsor and must be 
approved by an Independent Ethics Committee (IEC)/ Institutional Review Board (IRB)
prior to implementation except when required to mitigate immediate safety risks or when 
the changes involve only logistical or administrative revisions. 
 
 
 
 
 
 
  
 
 
  
 
 
  
 
 
 
 
 
 
  
  
  
  
 
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
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
  
 
 
 
 
 
 
 
  
  
  
  
 
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5
SCHEDULE OF PROCEDURES AND ASSESSMENTS
Visit
Visit 0
Pre-
Op
Visit 00 
OP1
Visit 
1
Visit 
2
Visit 
00A: 
OP2
Visit 
1A
Visit 
2A
Visit 
3A
Visit 
4A3
Visit 
5A3
Early 
Exit
Eye
Both
Eyes
1st
Eye
1st
Eye
1st
Eye
2nd
Eye
2nd
Eye
2nd
Eye
Both 
Eyes
Both 
Eyes
Both 
Eyes
Day Number
Day
-28-0
Surgery
Day 
1-2
Day 
7-14
Surgery
Day 
1-2
Day
7-14
Day 
30-60
Day
70-
100
Day 
120-
180
N/A
Informed Consent 
X
Demographics
X
Medical History
X
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
Inclusion/Exclusion
X
X
X
Urine Pregnancy Test4
X
X
Spectacle Use Questionnaire
X
X
Distance VA at 4 m

 

Photopic corrected 
X
X
X
X
X
X5
X
Intermediate VA at 66 cm


Photopic Distance 
Corrected
X
X
X5
Near VA at 40 cm


Photopic Distance 
Corrected
X
X5
Defocus Curve (4 m)
X5
X5
Contrast Sensitivity

Mesopic without Glare
X
X5

Mesopic with Glare
X
X5
 
 
Target Residual Refractive Error6
X
X
X
X
X
X
X
X
X
X
X
X
X
X
 
 
  
  
  
  
 
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Visit
Visit 0
Pre-
Op
Visit 00 
OP1
Visit 
1
Visit 
2
Visit 
00A: 
OP2
Visit 
1A
Visit 
2A
Visit 
3A
Visit 
4A3
Visit 
5A3
Early 
Exit
Eye
Both
Eyes
1st
Eye
1st
Eye
1st
Eye
2nd
Eye
2nd
Eye
2nd
Eye
Both 
Eyes
Both 
Eyes
Both 
Eyes
Day Number
Day
-28-0
Surgery
Day 
1-2
Day 
7-14
Surgery
Day 
1-2
Day
7-14
Day 
30-60
Day
70-
100
Day 
120-
180
N/A
Operative Eye
X
X
Incision Location7
X
X
Final Incision Size7
X
X
 
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
Secondary Surgical Interventions
X
X
X
X
X
X
X
X
X
X
Device Deficiencies
X
X
X
X
X
X
X
X
X
X
1 Visit 00 (1st eye surgery) must occur within 28 calendar days from Pre-Operative Visit (Visit 0).
2 Visit 00A (2nd eye surgery) must occur after a minimum of 7 calendar days and a maximum of 28 
calendar days after Visit 00 (1st eye surgery).
3If necessary Visits 4A and 5A may be completed over 2 days within a two week period. All visits 
must be completed within the specified visit window.
4In women of child bearing potential only.
5 Monocular (bilaterally) 
6 Data is reported in EDC at the surgical visit, but may be collected at a previous visit.
7 Captured in source. Not collected in EDC. 
 
 
  
  
  
  
 
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6
INTRODUCTION
6.1
Rationale and Background
Depth of focus is the amount of focal plane displacement behind a lens that does not 
degrade the image quality of a distant object. The distance between the nearest and farthest 
objects in a scene that appear acceptably sharp depends upon the eye’s depth of focus. 
Larger depth of focus allows sharp images of closer objects. A young, healthy human eye 
provides large depth of focus due to the large range of accommodation of the crystalline 
lens, however, the amplitude of depth of focus or accommodation gradually declines with 
age. For most people, accommodation is completely lost in the mid-fifties. While subjects
implanted with a monofocal IOL have good distance vision, quality of vision at 
intermediate and near is often insufficient to support activities of daily living. Specifically, 
intermediate vision has become increasingly significant to subjects because of daily tasks 
related to computers, mobile devices and other technologic advances. 
Premium IOL solutions, such as multifocal IOLs, provide functional intermediate vision, 
but can also result in complaints of visual disturbance. In view of this, there exists a 
medical need to provide functional vision at intermediate distances, while maintaining 
good distance vision and a visual disturbance profile similar to that of a monofocal IOL. 
The ACRYSOF IQ EDF IOL was developed to provide an extended depth of focus at 
intermediate distance (approximately 66 cm) while maintaining distance visual acuity (VA) 
and a safety profile similar to that of the ACRYSOF IQ Monofocal IOL Model SN60WF. 
Extended depth of focus is achieved on the anterior surface through Trapezoidal Phase 
Shift (TPS) technology (TDOC-0016353, Optical Design of Toric Extended Depth of Field 
IOL). The TPS structure consists of two radial steps in an aspheric central zone that 
smoothly connects to an outer annular zone. The curvature of the outer annular zone is 
identical to anterior surface of the non-toric, base design for the ACRYSOF IQ Toric IOL 
which compensates the 0.2 micron spherical aberration from the cornea. The TPS structure 
widens the depth of focus by creating interfering wavefronts from the tops and bottoms of 
the two steps. The combination of the central TPS zone and the outer annular zone 
transfers enough distance contrast under photopic conditions to provide a continuous range 
of vision. The ACRYSOF IQ EDF IOL provides an additional benefit by not using 
diffractive structures that typically induce visual disturbances. The EDF behavior is pupil 
dynamic; under mesopic conditions when the pupil size increases, the extended depth of 
focus is reduced and the performance of the ACRYSOF IQ EDF IOL is similar to a 
monofocal IOL.
 
 
  
  
  
  
 
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6.2
Purpose of the Study
The ACRYSOF IQ EDF IOL was developed to provide an extended depth of focus at 
intermediate distance (approximately 66 cm) while maintaining distance VA and a safety 
profile similar to that of the ACRYSOF IQ Monofocal IOL Model SN60WF. The purpose 
of the study is to demonstrate the safety and performance of the ACRYSOF IQ EDF IOL at 
Month 3/Visit 4A. After all subjects complete Month 3/Visit 4A, the study database will be 
locked to conduct planned analyses. Results from these analyses will be used in a clinical 
study report for submission. The study will be continued until all subjects complete Month 
6/Visit 5A, at which time the study database will be locked to report longer term safety and 
performance results. 
6.3
Risks and Benefits
6.3.1
Known and Potential Risks
Complications may occur on the surgery day or throughout the postoperative period. As 
with any type of intraocular surgery, there is a possibility of complications due to 
anesthesia, drug reactions, and surgical problems. The surgical procedure can exacerbate a 
pre-existing ocular condition. Possible problems during surgery include corneal endothelial 
touch, detached Descemet’s membrane, iris damage, iris prolapse, iris trauma, iris 
incarceration, zonular rupture, vitreous loss, capsulorhexis tear, capsular rupture, 
uncontrollable intraocular pressure (IOP), hyphema, and retinal damage. An IOP increase 
may occur from the surgical procedure, residual viscoelastic in the eye, or a steroid 
response to postoperative medications.
Additionally, potential postoperative adverse events include but are not limited to corneal 
stromal edema, cystoid macular edema, endophthalmitis, hypopyon, iritis, lens dislocation, 
membrane formation on the IOL, pupillary block, retinal detachment, cyclitic membrane, 
transient or persistent glaucoma, retinal tear, vitritis, iris touch, pupil ovalization, posterior 
synechiae, ocular inflammation, ocular discomfort or pain, inflammation, decreased vision, 
decreased contrast sensitivity, decreased color perception, visual disturbances, and corneal 
endothelial cell loss.
An IOL replacement or explantation may be appropriate in some cases of significant
residual refractive error, ocular infection, subject dissatisfaction, or visual disturbances 
(eg, glare, halos, starbursts, hazy vision, blurred vision, double vision, visual distortions, 
and color distortions, etc.). In most/majority of cases, spectacles or contact lenses may be 
prescribed to resolve residual refractive error. Other secondary surgical interventions 
include, but are not limited to: IOL repositioning, refractive laser treatment, paracentesis, 
 
 
  
  
  
  
 
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vitreous aspirations, and iridectomy or laser iridotomy for pupillary block, wound leak 
repair, and retinal detachment repair.
There may also be unknown risks with the use of the ACRYSOF IQ EDF IOL. Any
foreseen risk to subjects in this clinical study will be minimized by compliance with the 
eligibility criteria, study procedures, and clinical monitoring.
Based on the above, the risk of unanticipated adverse device effects with use of this IOL is 
considered to be low and the benefits of receiving the IOL should outweigh the risks for 
subjects that qualify for implantation in this study.
Refer to the Investigator’s Brochure (IB) and Directions for Use (DFU) for additional 
information on the IOLs being used in this study.
6.3.2
Potential Benefits
The EDF design extends the depth of focus of a monofocal IOL to +1.5 D by introducing a 
two-step phase shift to the incoming wavefront through Alcon’s proprietary technology, 
TPS. The EDF IOL provides benefits to the subject by: 

Extending the range of functional vision to intermediate distances (approximately 
66 cm) while

Maintaining the distance VA and safety profile similar to ACRYSOF IQ monofocal 
IOL (SN60WF) and

Providing improved near vision in comparison to a monofocal IOL

Eliminating the visual disturbances commonly associated with diffractive IOLs
The ACRYSOF IQ EDF IOL incorporates the TPS principle in the IOL optic and is 
designed to increase the subjective depth of focus and provide improved functional vision 
at intermediate distances. The anterior aspheric surface of the ACRYSOF IQ EDF IOL is 
designed with negative spherical aberration to compensate for the positive spherical 
aberration of the normal cornea. The magnitude of asphericity of the ACRYSOF IQ EDF 
IOL (Model DFT015) is identical to the CE Marked, Health Authority (HA)-approved (in 
applicable countries) and commercially available ACRYSOF IQ Monofocal IOL (Model 
SN60WF).
 
 
  
  
  
  
 
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7
STUDY OBJECTIVES
7.1
Primary Objective

To demonstrate that ACRYSOF IQ EDF IOL is superior to ACRYSOF IQ 
Monofocal IOL in mean monocular photopic DCIVA (at 66 cm from spectacle 
plane) at Month 3/Visit 4A (70-100 day post 2nd eye implantation).
7.1.1
Primary Effectiveness Assessment

Monocular photopic DCIVA (logMAR) at 66 cm
7.2
Secondary Objectives

To demonstrate that ACRYSOF IQ EDF IOL is non-inferior to ACRYSOF IQ 
Monofocal IOL in mean monocular photopic BCDVA (at 4 m) at Month 3/Visit 
4A.

To demonstrate that ACRYSOF IQ EDF IOL is superior to ACRYSOF IQ 
Monofocal IOL in mean monocular photopic DCNVA (at 40 cm from spectacle 
plane) at Month 3/Visit 4A.

To demonstrate that mean monocular defocus curve for ACRYSOF IQ EDF IOL 
has a range of defocus at least 0.50 D greater negative range than ACRYSOF IQ 
Monofocal IOL at 0.20 logMAR (20/32 line) at Month 3/Visit 4A.

To demonstrate that ACRYSOF IQ EDF IOL is non-inferior to ACRYSOF IQ 
Monofocal IOL in mean mesopic contrast sensitivity with and without glare at 
Month 6/Visit 5A respectively.

To demonstrate that ACRYSOF IQ EDF IOL is superior to ACRYSOF IQ 
Monofocal IOL with respect to proportion of subjects who respond “Never” to Q1
and Q3 of the spectacle use questionnaire at Month 6/Visit 5A respectively.
7.2.1
Secondary Effectiveness Assessments

Monocular photopic BCDVA (logMAR) at 4 m

Monocular photopic DCNVA (logMAR) at 40 cm

Monocular photopic distance corrected depth of focus from defocus curve 
assessment
 
 
  
  
  
  
 
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
Monocular mesopic contrast sensitivity at 12 cycles per degree with and without 
glare respectively

Proportion of subjects who respond “Never” to Q1 and Q3 of the spectacle use 
questionnaire respectively
 
7.4
Primary Safety Objective
To demonstrate that the adverse event rates of ACRYSOF IQ EDF IOL are not worse than 
SPE rates as defined in IS EN ISO 11979-7:2014 at Month 3/Visit 4A.
7.4.1
Primary Safety Assessment

AE rates of ACRYSOF IQ EDF IOL
 
 
  
  
  
  
 
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8
INVESTIGATIONAL PLAN
8.1
Study Design
This is a prospective, multi-center, randomized, parallel group, controlled, assessor and 
subject masked study. Both eyes of a subject must require cataract surgery to qualify for 
enrollment into this study. Subjects will be randomly assigned in a 5:4 ratio to receive 
either Model DFT015 (test article) or Model SN60WF (control article) in both eyes. The 
first surgical eye is defined as the eye with the worse BCDVA. If the BCDVA is the same 
in both eyes, identify the right eye (OD) as the first surgical eye. The second eye implant 
must occur within 28 days of the first eye implant.
A total of 10 scheduled visits are planned including the Screening/Visit 0 and two 
Operative Visits/Visit 00 and Visit 00A. Postoperative visits must occur at the following 
intervals: Day 1-2, Day 7-14 (after each surgery), Day 30-60, Day 70-100 and Day 120-
180 (after 2nd eye surgery). See Figure 8-1 Study Design.
 
 
  
  
  
  
 
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NOTE: Months 3 and 6 (Visits 4A and 5A) may be completed over 2 days within a two 
week period. All visits must be completed within the specified visit window.
Primary endpoint data will be collected at the Month 3/ Visit 4A (70-100 day post 2nd eye 
implantation). An interim database lock will be conducted when all subjects have 
completed this visit. All subjects will continue to be followed until Month 6/Visit 5A (120-
180 day post 2nd eye implantation) for further characterization of the performance and 
safety profile of the ACRYSOF IQ EDF IOL (Model DFT015).
Figure 8–1
Study Design
8.2
Rationale for Study Design
The test article for this study is the ACRYSOF IQ EDF IOL. This IOL is a modification of 
the CE Marked, HA-approved (in applicable countries) and commercially available 
ACRYSOF IQ Monofocal IOL which is well established in the literature and is also the 
industry standard of care. This study will aim to assess all parameters of interest including 
performance and safety at Month 3/Visit 4A. Since there is no clinical experience with the 
ACRYSOF IQ EDF IOL, all subjects will be followed up to Month 6/Visit 5A for further 
safety assessments. 
 
 
  
  
  
  
 
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All subjects and site assessors will be masked to subject treatment assignment until the end 
of the study. Subjects will be randomized to the test or control arm. The primary and 
secondary analyses will be conducted on monocular first eye implanted outcomes. 
 
 
8.3
Rationale for Choice of Control Article
The control article for this study is the CE Marked, HA-approved (in applicable countries) 
and commercially available ACRYSOF IQ Monofocal IOL (Model SN60WF). Currently, 
this IOL represents the industry standard of care for subjects who develop cataract and 
require cataract surgery with a monofocal IOL implantation. Model SN60WF has been 
well studied in previous Alcon clinical trials and the safety and effectiveness of this IOL 
have been well established. The control article has the same physical properties and is 
composed of the same material as the test article, ACRYSOF IQ EDF IOL (Model 
DFT015). The only difference between these two IOLs is the presence of the TPS optics in 
the test article, which is designed to provide improved functional vision at intermediate 
distances.  
Based on optical bench testing and simulation of the test article, the contrast sensitivity
under mesopic conditions is expected to be comparable to the control article. Therefore, 
Model SN60WF is scientifically the most appropriate control article for this study.
8.4
Data Monitoring Committee
Not Applicable.
9
SUBJECT POPULATION
The study population consists of male and female subjects 22 years of age and older with a 
diagnosis of cataract in both eyes requiring surgery with implantation of a monofocal IOL 
in the capsular bag. It is aimed to randomize approximately 260 subjects in approximately 
16 centers globally, with a target of approximately 16 subjects randomized per site. Site 
specific targets may be adjusted based on individual site capabilities.  Enrollment 
projections are as follows:

260 subjects to be randomized (10% discontinuation rate is expected)

234 subjects to successfully complete the final study visit (Visit 5A)
o
130 subjects in the Model DFT015 arm
 
 
  
  
  
  
 
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o
104 subjects in the Model SN60WF arm
Check all entry criteria at Screening/Visit 0 and at both surgical visits (Visit 00, Visit 
00A). If a subject is excluded post randomization and prior to 1st eye surgery (IOL does 
not come in contact with the eye), the subject should be discontinued from participation in 
the study. Refer to Section 11.11 Discontinued Subjects for further details.
9.1
Inclusion Criteria
Subjects eligible for inclusion in this study must fulfill all of the following criteria in both 
eyes (where applicable):
1. Subject must be able to understand and sign an IEC/ IRB approved ICF.
2. Willing and able to attend all scheduled study visits as required per protocol.
3. Adults (22 years or older at the time of enrollment in the study) diagnosed with 
cataract in both eyes.
4. Planned cataract removal by routine small incision surgery.
5. Calculated IOL power is within the clinical study supply range (18.0-25.0 D in 
0.5 D steps).
6. Preoperative regular astigmatism of less than 1.0 D, measure by automated 
keratometry in both eyes.
9.2
Exclusion Criteria
Subjects fulfilling any of the following criteria in either eye (where applicable) are not 
eligible for inclusion in this study:
1. Pregnancy or lactation current or planned during the course of the study.
2. History of anterior segment (corneal, anterior chamber, sulcus) or posterior 
segment (uveal, vitreo-retinal) pathology including retinal vascular occlusive 
disease, retinal detachment or peripheral retinal laser photocoagulation, age-related 
macular degeneration (ARMD), glaucoma (uncontrolled or controlled with 
medication), ocular hypertension, diabetic retinopathy, retinitis pigmentosa and any 
optic nerve pathology.
 
 
  
  
  
  
 
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3. Any current anterior or posterior segment inflammation of any etiology, and /or 
history of any disease producing an intraocular inflammatory reaction.
4. Clinically significant corneal pathology (epithelial, stromal, and/or endothelial)
which would adversely affect the visual outcome based on Investigator expert 
medical opinion. These ocular pathologies include but are not limited to old
significant corneal scars (including Salzman’s nodular degeneration), active or
inactive keratitis with compromise of the refractive capability of the cornea, 
keratoconjunctivitis sicca with compromise of visual function, active keratouveitis,
endothelial dystrophy (Fuch’s and non-guttate), etc.
5. Clinically significant severe dry eye that would affect study measurements based 
on Investigator expert medical opinion.
6. History of previous intraocular or corneal (refractive or trauma related) surgery.
7. Current or history of amblyopia or monofixation syndrome.
8. Any subject currently participating in another investigational drug or device study 
that may confound the results of this investigation.
9. Any other ocular or systemic co-morbidity that, based on Investigator expert 
medical opinion, may confound the results of this study or prohibit the completion 
of the study assessments or increase the risk for the subject.
10. Subjects with conditions that increase the risk of zonular rupture during cataract 
extraction procedure that may affect the postoperative centration or tilt of the IOL.
11. Any other planned ocular surgical procedures including but not limited to limbal 
relaxing incision (LRI)/Astigmatic Keratotomy and laser-assisted in situ 
keratomileusis (LASIK).
12. Patients who desire monovision correction.
13. Patients participating in the UK who are aviators falling under Civil Aviation 
Authority (CAA) regulation. 
9.3
Reasons for Discontinuation (During Surgery)
14. Surgical complications including but not limited to loss of zonular integrity/zonular
weakness, zonular rupture, anterior or posterior capsule rupture, any evidence of
 
 
  
  
  
  
 
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fluid misdirection during the cataract procedure with progressive shallowing of the
anterior chamber, uncontrollable IOP, etc.
15. Mechanical or surgical manipulation of the pupil.
16. Excessive iris mobility.
17. Inability to place the IOL in the capsular bag due to surgical complications.
If the implantation was aborted and the IOL did not touch the eye (1st eye), then the 
subject is required to discontinue from the study and standard of care for IOL implantation 
is followed. If the implantation was aborted and the IOL did touch the eye (1st eye), then 
the subject is encouraged to attend all follow-up study visits for safety evaluation on this 
eye only. Refer to Manual of Procedures (MOP) Section 5.3 for further detail. 
9.4
Rescreening of Subjects
Rescreening of subjects is not allowed in this study.
10
TREATMENT
Throughout the clinical study, the Investigator is responsible for the accounting of all IP 
and must ensure that the clinical study product is used in accordance with the 
manufacturer’s DFU and the Investigator’s Brochure.
NOTE: Femtosecond laser-assisted cataract surgery (FLACS) is permitted for 
Investigators that currently use this procedure as part of their standard of care for cataract 
surgery, however it is NOT required. May ONLY be used for the following:

Primary and sideport incisions

Capsulorhexis

Lens fragmentation
Table 10–1
Test Article
Test Product
ACRYSOF IQ EDF IOL (Model DFT015)
Manufacturer
Alcon
Indication for use
This IOL is intended for primary implantation in the capsular bag in 
the posterior chamber for the visual correction of aphakia secondary 
to removal of a cataractous lens in adult patients. The lens is intended 
 
 
  
  
  
  
 
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to provide distance vision and a continuous range of functional vision 
between distance and intermediate.
Intended Purpose in 
the current study
This IOL is intended for primary implantation in the capsular bag in 
the posterior chamber for the visual correction of aphakia secondary 
to removal of a cataractous lens in adult patients. The lens is intended 
to provide distance vision and a continuous range of functional vision 
between distance and intermediate.
Product description 
and parameters 
available for this 
study
Optic Type - Biconvex Aspheric Optic
Optics Material – Ultraviolet and blue light filtering Acrylate/ 
Methacrylate Copolymer
Optic Powers: 18.0 to 25.0 D in 0.5 D steps
Index of Refraction: 1.55
Haptic Configuration: STABLEFORCE® Haptics
Haptic Material: Ultraviolet and blue light filtering Acrylate/ 
Methacrylate Copolymer (Boettner and Wolter, 1962)
Optic Diameter (mm): 6.0
Overall Length (mm): 13.0
Haptic Angle: 0°
Formulation
N/A
Usage
IOLs are implantable medical devices and are intended for long-term 
use over the lifetime of the pseudophakic subject.
Number/Amount of
Product to be 
Provided to the 
Subject
Following randomization each subject will be bilaterally implanted 
with the control or test article.
Packaging 
description
Each IOL will be individually packaged and will have a unique serial 
number. The IOL package will contain the following items:

The IOL

A subject registration card (Lens Implant Card)

A subject identification card

Adhesive labels containing the IOL information and unique 
serial number
 
 
  
  
  
  
 
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
A package insert containing directions for use
Labeling description
Packaged in a standard Alcon IOL carton. The carton is labeled with 
the following information: name of the lens, model number, overall 
diameter, optic diameter, diopter power, serial number, name of the 
manufacture, storage condition, expiration date, sterile, and single 
use. Each package is also labeled “Exclusively for Clinical 
Investigations” and “Caution – Investigational device. Limited by 
Federal (or United States) law to investigational use”.
NOTE: In countries where applicable, an additional label will be 
added noting “Investigational Device” and “To Be Used by Qualified 
Investigators Only” (text in English and translation as appropriate).
Storage conditions
The IP must be stored in a safe, secure location with limited access 
separated from general stock. Transportation of product from one 
address to another must be documented and a Transportation Log (or 
similar documentation) utilized for appropriate accountability.
Additional 
information
In order to implant IOLs in study subjects, the surgeons participating 
in the study must be licensed ophthalmologists with cataract surgery 
experience and trained on the protocol.
More information on the test article can be found in the IB (0138) and 
DFU for ACRYSOF IQ EDF IOL (Model DFT015).
Supply
A designated amount of IOLs will be supplied to the site by the 
Sponsor.
Table 10–2
Control Article
Control Product
ACRYSOF IQ Monofocal IOL (Model SN60WF)
Manufacturer
Alcon
Indication for use
The ACRYSOF® IQ posterior chamber intraocular lens is indicated 
for the replacement of the human lens to achieve visual correction of 
aphakia in adult patients following cataract surgery. This lens is 
intended for placement in the capsular bag.
 
 
  
  
  
  
 
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Intended Purpose in 
the current study
This lens is indicated for the replacement of the human lens to achieve 
visual correction of aphakia in adult patients following cataract 
surgery. This lens is intended for placement in the capsular bag.
Product description 
and parameters 
available for this 
study
Optic Type: Biconvex Aspheric Optic
Optics Material: Ultraviolet and blue light filtering Acrylate/ 
Methacrylate Copolymer
Optic Powers: 18.0-25.0 D in 0.5 D steps
Index of Refraction - 1.55
Haptic Configuration - STABLEFORCE® Haptics
Haptic Material: Ultraviolet and blue light filtering Acrylate/ 
Methacrylate Copolymer (Boettner and Wolter, 1962)
Optic Diameter (mm) – 6.0
Overall Length (mm) – 13.0
Haptic Angle - 0°
Formulation
N/A
Usage
IOLs are implantable medical devices and are intended for long-term 
use over the lifetime of the pseudophakic subject.
Number/Amount of
Product to be 
Provided to the 
Subject
Following randomization each subject will be bilaterally implanted 
with the control or test article.
Packaging 
description
Each IOL will be individually packaged and will have a unique serial 
number. The IOL package will contain the following items:

The IOL

A subject registration card ( Lens Implant Card)

A subject identification card

Adhesive labels containing the IOL information and unique 
serial number

A package insert containing directions for use
Labeling description
This lens is marketed in the countries conducting this clinical study. In 
countries where applicable, an additional label will be added to the 
marketed product noting, “Investigational Device” and “To Be Used 
 
 
  
  
  
  
 
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by Qualified Investigators Only” or alternate country required text 
(text in English and translation as appropriate).
Storage conditions
IP must be stored in a safe, secure location with limited access 
separated from general stock. Transportation of product from one 
address to another must be documented and a Transportation Log (or 
similar documentation) utilized for appropriate accountability.
Additional 
information
In order to implant IOLs in study subjects, the surgeons participating 
in the study must be licensed ophthalmologists with cataract surgery 
experience and trained on the protocol. 
More information on the control article can be found in the DFU for 
ACRYSOF IQ Monofocal IOL (Model SN60WF).
Supply
A designated amount of IOLs will be supplied to the site by the 
Sponsor.
10.1
Other Medical Device Specified for Use during the Study
Table 10–3
Delivery System
Delivery System
Qualified Diopter Range
ACRYSOF IQ EDF IOL
(Model DFT015)
ACRYSOF IQ Monofocal
IOL
(Model SN60WF)
MONARCH® II/III C Cartridge with:

MONARCH II (green) handpiece

MONARCH III (blue) handpiece
18.0 – 25.0 D
18.0 – 25.0 D
MONARCH III D Cartridge only with:

MONARCH III (blue) handpiece
18.0 – 25.0 D
18.0 – 25.0 D
10.2
Treatment Assignment / Randomization
Subjects will be randomized in a 5:4 ratio to receive either ACRYSOF IQ EDF IOL or 
ACRYSOF IQ Monofocal IOL respectively.
Only after signing the informed consent form (ICF), a subject will be assigned a subject 
number by the electronic data capture (EDC) system. 
 
 
  
  
  
  
 
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The Investigator, or delegate, at Operative Visit / Visit 00 will initiate randomization in 
EDC after confirming that the subject meets all the eligibility criteria and confirming the 
subject is eligible for randomization. Randomization must be completed no more than two 
business days prior to the first operative visit, unless there is a valid reason to randomize 
earlier. After randomization is initiated, all eligible subjects will be randomized to one of 
two treatment arms.
10.3
Accountability Procedures
Upon receipt of IP, the Investigator or delegate must conduct an inventory of all IOLs by 
serial number, complete study specific confirmation of receipt procedures, and retain any 
required documentation in the Investigator’s clinical study records. Throughout the study, 
the Investigator or delegate must maintain records of IP use for each subject. This record 
must be made available to the study monitor for the purposes of verifying the accounting 
of IP supplies. Any discrepancies and/or deficiencies between the observed disposition and 
the written account must be recorded along with an explanation.  All IP sent to the 
Investigator must be accounted for by Study Sponsor personnel, and in no case be used in 
an unauthorized manner.

If possible, return to the Study Sponsor investigational and control products 
associated with a device deficiency. Refer to Section 12 of this protocol for 
additional information on the reporting of device deficiencies and to the MOP for 
information on return of study products associated with these events.
The Investigator is responsible for proper disposition of all unused IPs at the conclusion of 
the study, according to the instructions provided by the Sponsor.
10.4
Treatment Masking
The assessor and subject will be masked in this study. Subjects will be masked to their 
treatment assignment for the entire duration of the study. Site personnel performing the 
 and all VA testing, which will include BCDVA, 
 DCIVA, 
, DCNVA, 
 defocus curve testing and contrast sensitivity, will remain 
masked with regard to treatment assignment until after the final database lock (Visit 5A). 
Alcon and site personnel will not reveal the treatment assignment to study subjects at any 
time during the study. 
After the subject is implanted with the appropriate lens, a generic implant card is provided 
to the subject that will not reveal their treatment assignment. The treatment assignment 
 
 
  
  
  
  
 
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will only be revealed to the study subject after the final database lock and when 
investigative sites are notified by the Study Sponsor.
This level of masking will be maintained throughout the conduct of the study. Unmasking 
will occur only after all planned study data have been validated, and the database locked.  
Unmasking will also occur at the time of the interim database lock, with treatment related 
information being revealed only to designated personnel.
Masked study personnel must avoid seeking information that may compromise masking.
Unmasked study personnel must not disseminate information that is potentially unmasking 
to any masked personnel. A list of unmasked individuals can be found in Table 10-4 below. 
Table 10-4
Unmasked Individuals
Unmasked Individual
Extent of Unmasking
Rationale
Investigator
Unmasked to IP treatment
assignment
Investigator will be implanting 
the IOL and will have knowledge 
of the treatment assigned to 
study subjects
Site Personnel (not 
completing assessments 
noted Section 10.4)
Unmasked to IP treatment 
assignment
Site personnel involved with 
operative visits and data entry 
into EDC
Monitor
Unmasked to IP treatment 
assignment
Monitor will complete IP 
accountability and monitoring 
responsibilities
10.5
Changes to Concomitant Treatments or Procedures
After the subject is enrolled (signed an ICF) into the study, the Investigator must instruct 
the subject to notify the study site about:

Any new medications 

Alterations in dose or dose schedules for current medications, 

Any medical procedure or hospitalization that occurred or is planned

Any non-drug therapies (including physical therapy and blood transfusions). 
 
 
  
  
  
  
 
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The Investigator must document this information in the subject’s case history source 
documents.
11
STUDY PROCEDURES AND ASSESSMENTS BY VISIT
The following section outlines the assessments to be performed in this clinical study. 
Assessments are described in detail in the ILI875-C001 MOP, and are outlined in tabular 
format in Section 5 of this protocol. 
AEs, SAEs including secondary surgical interventions (SSIs) and device deficiencies are 
assessed and reported at all scheduled and unscheduled visits (UNSVs) for each subject, 
beginning at the time the informed consent is obtained.
NOTE: SAEs including SSIs must be entered into EDC within 24 hours of the 
Investigator’s knowledge. Refer to Section 12 for further details.
Subjects who currently wear contact lenses must discontinue their use to ensure corneal 
stability prior to the preoperative visit measurements as noted in Table 11-1. 
Table 11–1
Contact Lens Discontinuation Prior to Preoperative Visit
Type of Contact Lens
Minimum Time to Stop Wearing
before Pre-Op Visit
Hard or rigid gas permeable lenses
3 weeks
Daily wear soft lenses –Toric/Spherical
2 weeks
Soft extended-wear lenses
2 weeks
11.1
Screening/Preoperative Visit (Visit 0)
Visit 0: -28-0 Days Prior to Visit 00, Bilateral Visit
Below is a list of study procedures to be done at Visit 0. It is recommended that procedures 
are performed in the order described below unless otherwise stated. All assessments must 
be documented in the source documentation and electronic case report form (eCRF), if 
applicable.
Data from the Investigator’s previous routine clinical evaluation (eg, slit lamp exam) may 
be used, if the data 1) meet the requirements of this protocol and MOP, and 2) were 
collected within the -28 to 0 day preoperative time period.
1. Review study specific inclusion/exclusion criteria (eg, age, previous ocular history) 
to ensure that a potential subject meets all qualifications for participation in the 
study.
 
 
  
  
  
  
 
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2. For a potential subject meeting all entry criteria via pre-screening, invite him/her to 
participate in the study, and carry out the informed consent process if he/she is
interested. Refer to Section 11.9 Informed Consent Procedures.
3. Collect subject demographic, medical history information, and concomitant 
medication use. 
4. Perform a urine pregnancy test, IF the subject is a woman of childbearing potential.
 
]
.
8. Measure and record 
and BCDVA under photopic conditions at 4 m. [Both 
Eyes, Bilateral]
12. Record any AEs. Refer to Section 12 for further details.
13. Evaluate subject against all entry criteria. If subject fails criteria, screen fail the 
subject.
14. Document the target residual refractive error based on the IOL calculation power. 
[Both Eyes, Bilateral]
NOTE: This assessment may be done at any time after required biometry has been 
collected.
15. Identify the surgical eye for this study (determined by preoperative BCDVA).
16. Proceed with scheduling the surgery.
 
 
  
  
  
  
 
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11.2
Operative Visits (Visit 00/00A)
Visit 00: Day 0, Monocular 1st Eye
Visit 00A: 7-28 Days Post 1st Implantation, Monocular 2nd Eye
Below is a list of study procedures to be completed at Visit 00 and Visit 00A. It is 
recommended that procedures are performed in the order described below unless otherwise 
stated. Activities involving multiple delegated staff members may be performed in parallel. 
All assessment must be documented in source documentation and eCRF (if applicable).
NOTE: The Visit 00A window may overlap with other study visit windows (eg, Visit 2). In 
this case, both visits may be conducted on the same day at the discretion of the 
Investigator.
NOTE: It will be permitted to have two study-trained surgeons at each site perform IOL 
implantations. However, the same surgeon must complete both the left (OS) and right 
(OD) IOL implants on a subject.
1. In preparation for the operative visit, randomize the subject. It is recommended that 
subjects are contacted prior to randomization to 1) confirm willingness to continue 
trial participation, and 2) confirm scheduled surgical date and time.
2. Prior to treatment, review inclusion/exclusion criteria and ensure the subject has 
been properly consented for participation in the study.
3. Document any changes to ocular and non-ocular concomitant medications.
4. Record operative eye.
5. Prepare subject for surgery in accordance to site specific operating procedures. 
[Operative Eye Only, Monocular]
6. Perform surgery and implantation with the randomized IOL. [Operative Eye Only, 
Monocular]
7. At completion of IOL implantation measure and record incision size. [Operative 
Eye Only, Monocular]
8. Record incision location. [Operative Eye Only, Monocular]
 
 
  
  
  
  
 
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11. Record any adverse events including SSIs. Refer to Section 12 for further detail.
12. Record any device deficiencies. Refer to Section 12 for further detail.
11.3
1-Day Postoperative Visit (Visit 1/1A)
Visit 1: 1-2 Day Post 1st Eye Implantation, Monocular 1st Eye
Visit 1A: 1-2 Days Post 2nd Eye Implantation, Monocular 2nd Eye
Below is a list of study procedures to be completed at Visit 1 and Visit 1A. It is 
recommended that procedures are performed in the order described below unless otherwise 
stated. All assessments must be documented in source documentation and eCRF (if 
applicable).
1. Record changes in medical/ocular history and ocular and non-ocular concomitant 
medications.
2.
 
 
 
 
7. Record any adverse events including SSIs. Refer to Section 12 for further detail.
 
 
  
  
  
  
 
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8. Record any device deficiencies. Refer to Section 12 for further detail.
11.4
1-Week Postoperative Visit (Visit 2/2A)
Visit 2: 7-14 Days Post 1st Eye Implantation, Monocular 1st Eye
Visit 2A: 7-14 Days Post 2nd Eye Implantation, Monocular 1st Eye
Below is a list of study procedures to be completed at Visit 2 and Visit 2A. It is 
recommended that procedures are performed in the order described below unless otherwise 
stated. All assessments must be documented in source documentation and eCRF (if 
applicable).
1. Record changes in medical/ocular history and ocular and non-ocular concomitant 
medications.
Measure and record 
and BCDVA under photopic conditions at 4 m. 
[Operative Eye Only, Monocular]
 
 
 
8. Record any adverse events including SSIs. Refer to Section 12 for further detail.
9. Record any device deficiencies. Refer to Section 12 for further detail.
11.5
1-Month Postoperative Visit (Visit 3A)
Visit 3A: 30-60 Days Post 2nd Eye Implantation, Bilateral
 
 
  
  
  
  
 
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Below is a list of study procedures to be completed at Visit 3A. It is recommended that 
procedures are performed in the order described below unless otherwise stated. All 
assessments must be documented in source documentation and eCRF (if applicable).
1. Record changes in medical/ocular history and ocular and non-ocular concomitant 
medications.
.
3. Measure and record monocular
 and BCDVA under photopic conditions at 
4 m. [Both Eyes, Bilateral]
4. Measure and record monocular
and DCIVA under photopic conditions at 
66 cm. [Both Eyes, Bilateral]
 
 
 
 
10. Record any adverse events including SSIs. Refer to Section 12 for further detail.
11. Record any device deficiencies. Refer to Section 12 for further detail.
11.6
3-Month Postoperative Visit (Visit 4A)
Visit 4A: 70-100 Days Post 2nd Eye Implantation, Bilateral
Below is a list of study procedures to be completed at Visit 4A. All assessments must be 
documented in source documentation and eCRF (if applicable). It is recommended that 
procedures are performed in the order described below unless otherwise stated. If a subject 
appears fatigued, or requests a break from testing, provide a rest. If the visit is conducted 
 
 
  
  
  
  
 
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over multiple sessions or days, seek advice from Alcon staff regarding best practices.  For 
example:

Conducting primary and secondary outcome assessments day 1; and

Conducting distance, intermediate and near VA testing in an early session and 
defocus testing in a later session on day 1.
1. Record changes in medical/ocular history and ocular and non-ocular concomitant 
medications.
2. Measure photopic pupil size. [Both Eyes, Bilateral]
3.
.
4. Measure and record monocular
 and BCDVA under photopic conditions 
at  4 m. [Both Eyes, Bilateral]
5. Perform monocular defocus curve testing. [Both Eyes, Bilateral]
7. Measure and record monocular
and DCIVA under photopic conditions at 
66 cm. [Both Eyes, Bilateral]
8. Measure and record monocular
 and DCNVA under photopic conditions at 
40 cm. [Both Eyes, Bilateral]
 
 
 
 
 
 
  
  
  
  
 
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17. Record any adverse events including SSIs. Refer to Section 12 for further detail.
18. Record any device deficiencies. Refer to Section 12 for further detail.
11.7
6-Month Postoperative Visit (Visit 5A)
Visit 5A: 120-180 Days Post 2nd Eye Implantation, Bilateral with Binocular Testing
Below is a list of study procedures to be completed at Visit 5A. All assessments must be 
documented in source documentation and eCRF (if applicable). It is recommended that 
procedures are performed in the order described below unless otherwise stated. If a subject 
appears fatigued, or requests a break from testing, provide a rest. If the visit is conducted 
over multiple sessions or days, seek advice from Alcon staff regarding best practices. For 
example:

Conducting primary and secondary outcome assessments day 1; and

Conducting distance, intermediate and near VA testing in an early session and 
defocus testing in a later session on day 1.
1. Provide questionnaires (
 Spectacle Use) to the subject for 
completion. The questionnaires should be completed by the subject prior to 
administration of any other assessment.
2. Record changes in medical/ocular history and ocular and non-ocular concomitant 
medications.
3.
 
 
  
  
  
  
 
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4. Perform manifest refraction. [Both Eyes, Bilateral]
 
5. Measure and record monocular
 and BCDVA under photopic conditions at 
4 m. [Both Eyes, Bilateral]
 
7. Perform monocular defocus curve testing. [Both Eyes, Bilateral]
9. Measure and record monocular
and DCIVA under photopic conditions at 
66 cm. [Both Eyes, Bilateral]
 
11. Measure and record monocular
 and DCNVA under photopic conditions at 
40 cm. [Both Eyes, Bilateral]
 
13. Perform monocular mesopic without glare contrast sensitivity testing. [Both Eyes, 
Bilateral]
 
15. Perform monocular mesopic with glare contrast sensitivity testing. [Both Eyes, 
Bilateral]
 
17. Perform monocular photopic without glare contrast sensitivity testing. [Both Eyes, 
Bilateral]
 
 
  
  
  
  
 
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25. Record any adverse events including SSIs. Refer to Section 12 for further detail.
26. Record any device deficiencies. Refer to Section 12 for further detail.
11.8
Schedule of Procedures and Assessments for Discontinued 
Subjects
Subjects that discontinue from the study, it is recommended to complete the assessments 
noted in the table in Section 5 for an Early Exit Visit. 
1. Provide questionnaires (Quality of Vision and Spectacle Use) to the subject for 
completion. The questionnaires should be completed by the subject prior to 
administration of any other assessment.
2. Document any changes to medical/ocular history and ocular and non-ocular 
concomitant medications.
.
 
 
  
  
  
  
 
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4. Measure and record 
and BCDVA.
 
 
 
9. Record any adverse events including SSIs. Refer to Section 12 for further detail.
10. Record any device deficiencies. Refer to Section 12 for further detail.
 
 
  
  
  
  
 
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11.9
Informed Consent and Screening
The subject must sign the ICF BEFORE any study specific procedures or assessments can 
be performed. 
The Investigator must explain the purpose and nature of the study, and have the subject 
read, sign, and date the IEC/IRB approved ICF. Additionally, have the individual obtaining 
consent from the subject sign and date the ICF.
The Investigator must provide a copy of the signed document to the subject and place the 
original signed document in the subject’s chart, or provide documentation as required by 
local regulations.
11.10
Unscheduled Visits
An UNSV is defined as follows:

Ocular examination that is not standard of care and is not required by the protocol

Examination conducted by the study staff

New findings, or a change to a previous finding was discovered
An UNSV may or may not result in the capture of an AE. Likewise an AE may be captured 
without the report of an UNSV (eg, AE identified subsequent to study eye examination by 
non-study personnel).
The assessments captured at the UNSV are dictated by the Investigator per their medical 
judgment. The following assessments are recommended: 
1. Document any changes to medical/ocular history and ocular and non-ocular 
concomitant medications.
.
3. Measure and record 
and BCDVA.
 
 
 
  
  
  
  
 
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NOTE: Assessments are not limited to the above list.
The Investigator may perform additional procedures for proper diagnosis and treatment of 
the subject. The Investigator must document this information in the subject’s case history 
source documents.
If during an UNSV the subject is discontinuing from the study, then the Investigator must 
conduct Early Exit/Exit procedures according to Section 5, Schedule of Study Procedures 
and Assessments.
11.11
Discontinued Subjects
11.11.1
Screen Failures
Subjects who discontinue from the study prior to the randomization will be categorized as 
screen failures.
The Investigator may replace a subject who fails study Screening/Visit 0, but the subject 
number must not be re-used. The Investigator must document the reason for screen 
failure in the subject’s case history source documents and enter the subject in EDC.
11.11.2
Discontinuations
Discontinued subjects are individuals who have signed an ICF and who voluntarily 
withdraw or are withdrawn from the study by the Investigator post randomization. Subjects 
may discontinue from the study at any time for any reason. Subjects may also be 
discontinued at any time if, in the opinion of the Investigator, continued study participation 
poses a risk to their health. The Investigator must document the reason for study 
discontinuation in the subject’s case history source documents and complete the exit form 
in EDC.
NOTE: Subjects that meet Exclusion Criteria at the time of surgery (refer to Section 9.3) 
must be captured as discontinuations.
For subjects discontinuing from the study, the Investigator should complete Early Exit 
procedures  according to Section 5 SCHEDULE OF STUDY PROCEDURES AND 
ASSESSMENTS, if the subject is willing and able, and if in the opinion of the Investigator 
 
 
  
  
  
  
 
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it is safe for the subject to do so. To ensure the safety of all subjects who discontinue early, 
Investigators must assess each subject and, if necessary, advise them of any therapies 
and/or medical procedures that may be needed to maintain their health.
Discontinued subjects will not be replaced; subject numbers of discontinued subjects must 
not be re-used.
11.12
Clinical Study Termination
The Study Sponsor reserves the right to close the investigational site or terminate the study 
in its entirety at any time, for reasonable cause.
If the clinical study is prematurely terminated or suspended by the Study Sponsor: 
The Study Sponsor must:

Immediately notify the Investigator(s) and subsequently provide instructions 
for study termination.  

Inform the Investigator and the regulatory authorities of the 
termination/suspension and the reason(s) for the termination/suspension. 
The Investigator must:

Promptly notify the IEC/IRB of the termination or suspension and of the 
reasons. 

Provide subjects with recommendations for post-study treatment options as 
needed.
The Investigator may terminate the site’s participation in the study for reasonable cause.  
11.13
Aborted Implantation 
If the IOL implantation is attempted and aborted, due to Device Deficiency, then a Device 
Deficiency form must be completed and the IOL must be returned to the Study Sponsor in 
appropriate safe packaging supplied by the Study Sponsor. Specific guidance with regards 
to aborted implantation is detailed below.
In the sections below, the IOL touching the eye is defined as the time point when any IP
first touches the eye.
NOTE: No more than two attempts to be made to implant the control or test article.
 
 
  
  
  
  
 
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11.13.1
First Eye Implant

IF the first attempt to implant the control or test article was aborted THEN a 
second attempt is permitted (regardless if the IOL touches the eye or not).

IF the second attempt to implant the control or test article was aborted and the IOL 
did not touch the eye on either attempt THEN subject must be discontinued from 
the study.

IF the second attempt to implant the control or test article was aborted and an IOL 
did touch the eye on either attempt THEN
o
This eye must be followed for all study visits for safety evaluation only
o
The test or control article must NOT be implanted
11.13.2
Second Eye Implant 

IF the first attempt to implant the control or test article was aborted THEN a 
second attempt is permitted (regardless if the IOL touches the eye or not).

IF the second attempt to implant the control or test article was aborted and an IOL 
did not touch the eye on either attempt THEN
o
Subject must not be implanted with the control or test article
o
Standard of care followed for the second eye IOL implantation
o
The first eye will be followed for all study visits

IF the second attempt to implant the control or test article was aborted and an IOL 
did touch the eye on either attempt THEN
o
The control or test article must NOT be implanted in the second eye
o
The second eye must be followed for all study visits for safety evaluation 
only
o
The first eye will also be followed for all study visits
o
Standard of care followed for IOL implantation of the second eye
 
 
  
  
  
  
 
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12
DEVICE DEFICIENCIES AND ADVERSE EVENTS
12.1
General Information
An adverse event (AE) is any untoward medical occurrence, unintended disease or injury, 
or untoward clinical signs (including abnormal laboratory findings) in subjects, users, or 
other persons, whether or not related to the investigational medical device (test article). 
Refer to the Glossary of Terms and figures for categories of AEs and SAEs.
Figure 12–1
Categorization of All Adverse Events
 
 
  
  
  
  
 
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Figure 12-2
Categorization of All Serious Adverse Events
12.2
Serious Adverse Events (SAEs)
A serious adverse event is an AE that led to any of the following: 

Death.

A serious deterioration in the health of the subject that either resulted in:
a) a life-threatening illness or injury. 
NOTE: Life-threatening means that the individual was at immediate risk of 
death from the event as it occurred, ie, it does not include an event which 
hypothetically might have caused death had it occurred in a more severe form.
b) any potentially sight-threatening event or permanent impairment to a body 
structure or a body function. 
c) in-patient hospitalization or prolonged hospitalization. 
NOTE: Planned hospitalization for a pre-existing condition, without serious 
deterioration in health, is not considered a SAE. In general, hospitalization 
signifies that the individual remained at the hospital or emergency ward for 
observation and/or treatment (usually involving an overnight stay) that would 
not have been appropriate in the physician's office or an out-patient setting. 
Complications that occur during hospitalization are AEs. If a complication 
 
 
  
  
  
  
 
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prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred, the event 
should be considered serious.
d) a medical or surgical intervention to prevent a) or b) or any ocular secondary 
surgical intervention (excluding PC).
e) any indirect harm as a consequence of incorrect diagnostic test results when 
used within manufacturer’s instructions for use. 

Fetal distress, fetal death, or a congenital abnormality or birth defect.
12.3
Specific Events Relevant to this Protocol
In addition to reporting all AEs (serious and non-serious) meeting the definitions, the PI
must report any occurrence of the following as an SAE:
12.3.1
Cumulative Serious Adverse Events

Cystoid macular edema

Hypopyon

Endophthalmitis

Lens dislocation from posterior chamber

Pupillary block

Retinal detachment

Secondary surgical intervention (excluding PC)
12.3.2
Persistent Serious Adverse Events

Corneal stromal edema

Cystoid macular edema

Iritis

Raised IOP requiring treatment
This list is consistent with the categories provided in I.S. EN ISO 11979-7:2014. A 
persistent AE is an AE that is present at the conclusion of a clinical investigation per 
I.S. EN ISO 11979-1. Any other potentially sight-threatening event may also be considered 
 
 
  
  
  
  
 
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serious based on the judgment of the Investigator and must be reported appropriately as 
delineated in Section 12.6.
12.3.3
Device Deficiencies
A device deficiency may or may not be associated with subject harm (ie, ADE or SADE); 
however, not all ADEs or SADEs are due to a device deficiency. The Investigator should 
determine the applicable category for the identified or suspect device deficiency and report 
any subject harm separately. Examples of device deficiencies include the following:

Failure to meet product specifications (eg, incorrect IOL power)

IOL defect

Broken IOL optic

Broken IOL haptic

Scratched IOL optic

Unsealed device packaging

Suspect product contamination 

Lack of effectiveness
12.4
Monitoring for Adverse Events
At each visit, after the subject has had the opportunity to spontaneously mention any 
problems, the Investigator should inquire about AEs by asking the standard questions such 
as:

“Have you had any health problems since your last study visit?”

“Have there been any changes in the medicines you take since your last study 
visit?”
Changes in any protocol-specific ocular or systemic parameter evaluated during the study 
are to be reviewed by the Investigator. In addition, the subject’s responses to any 
questionnaire utilized during the study are to be reviewed by the Investigator. Any 
untoward (unfavorable and unintended) change in a protocol-specific parameter or 
questionnaire response that is clinically relevant, in the opinion of the Investigator, is to be 
reported as an AE. These clinically relevant changes will be reported regardless of 
causality. 
 
 
  
  
  
  
 
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12.5
Procedures for Recording and Reporting
AEs are collected from the time of informed consent. Any pre-existing medical conditions 
or signs/symptoms present in a subject prior to the start of the study (ie, before ICF is 
signed) are not considered AEs in the study and should be recorded in the Medical History 
section of the eCRF.
In addition, aqueous cells and flare, corneal edema, raised IOP and superficial punctate 
keratitis are examples of early post-operative findings that are typically observed following 
ocular surgery. These are not considered AEs if they can be reasonably expected to resolve 
within a week and not result in any untoward long term visual outcome impact. 
For each recorded event, the ADEs and SAEs documentation must include: date of 
occurrence, severity, treatment (if applicable), outcome, and assessments of the seriousness 
and causality. In addition, the Investigator must document all device deficiencies reported 
or observed with test and control articles on the Device Deficiency eCRF. The site must 
submit all available information on ADEs, SAEs, and device deficiencies to the Study 
Sponsor immediately as follows:

ADEs or SAEs are documented on the Adverse Device Effect and Serious Adverse 
Event eCRF within 24 hours of the Investigator’s or site’s awareness. 

Device deficiencies are documented on the Device Deficiency eCRF within 24 
hours of the Investigator’s or site’s awareness. Please include a printed copy of 
the completed Device Deficiency eCRF with product returns. 

Additional relevant information after initial reporting is to be entered into the 
eCRF as soon as the data become available. 

Document any changes to concomitant medications on the appropriate eCRFs.

All relevant documentation such as Discharge Summary, Autopsy Report, 
Certificate of Death etc, should be faxed to the Study Sponsor at 1-817-302-1927.
NOTE: Should the EDC system become non-operational, the site must complete the    
appropriate paper Adverse Device Effect and Serious Adverse Event Form or Device 
Deficiency Form. The completed form is faxed to the Study Sponsor at 1-817-302-
1927 within 24 hours of the Investigator’s or site’s awareness; however, the reported 
information must be entered into the EDC system once it becomes operational.
 
 
  
  
  
  
 
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Study Sponsor representatives and their contact information are provided in the 
Manual of Procedures that accompanies this protocol.
Further, depending upon the nature of the AE or device deficiency being reported, the 
Study Sponsor may request copies of applicable portions of the subject’s medical records. 
The Investigator must also report all AEs and device deficiencies that could have led to a 
SADE according to the requirements of regulatory authorities or IEC/IRB.
12.5.1
Intensity and Causality Assessments
Where appropriate, the Investigator must assess the intensity (severity) of the AE as mild, 
moderate, or severe based on medical judgment with consideration of any subjective 
symptom(s), as defined below:
12.5.1.1
Intensity (Severity)
Mild
An AE is mild if the subject is aware of but can easily tolerate the sign or 
symptom.
Moderate
An AE is moderate if the sign or symptom results in discomfort significant 
enough to cause interference with the subject’s usual activities.
Severe
An AE is severe if the sign or symptom is incapacitating and results in the 
subject’s inability to work or engage in their usual activities.
12.5.1.2
Causality
For every AE in the study, the Investigator must assess the causality (Related or Not 
Related to the medical device or test procedure). An assessment of causality will also be 
performed by a Study Sponsor physician utilizing the same definitions, as shown below:
Related
An AE classified as related may be either definitely related or possibly 
related where a direct cause and effect relationship with the medical device 
or test procedure has not been demonstrated, but there is a reasonable 
possibility that the AE was caused by the medical device or test procedure.
Not Related
An AE classified as not related may either be definitely unrelated or simply 
unlikely to be related (ie, there are other more likely causes for the AE).
 
 
  
  
  
  
 
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12.6
Return Product Analysis
Study Sponsor representatives and their contact information are provided in the MOP that 
accompanies this protocol.
Alcon Products associated with device deficiencies and/or product related AEs should be
returned and must include the Complaint # which will be provided by the Study Sponsor 
after the case is entered in the Study Sponsor’s Global Product Complaint System 
(GPCMS).
12.7
Unmasking of the Study Treatment
Masked information on the identity of the assigned medical device should not be disclosed 
during the study. If the treatment code needs to be broken in the interest of subject safety, 
the Investigator is encouraged to contact an appropriate Study Sponsor representative prior 
to unmasking the information if there is sufficient time. Dependent upon the individual 
circumstances (ie, medical emergency), the code may be broken prior to contact with the 
Study Sponsor. The Study Sponsor must be informed in all cases in which the code was 
broken and of the circumstances involved. Additionally, the Study Sponsor may be 
required to unmask the information in order to fulfill expedited regulatory reporting 
requirements.
12.8
Follow-Up of Subjects with Adverse Events
The Investigator is responsible for adequate and safe medical care of subjects during the 
study and for ensuring that appropriate medical care and relevant follow-up procedures are 
maintained after the study. 
The Investigator must provide the Study Sponsor with any new safety information (which 
includes new AEs and changes to previously reported AEs) that may affect the safety 
evaluation of the device. For AEs that are unresolved/ ongoing at time of subject exit from 
study, any additional information received at follow-up should be documented in the 
eCRFs up to study completion (ie, database lock). 
Any additional data from these follow-up procedures performed up to 6 months after subject 
discontinuation or exit must be documented and available upon the Study Sponsor’s request.
All complaints received after this time period will be considered and processed as 
spontaneous (following the post-market vigilance procedures) and should be communicated 
to the medical device’s manufacturer as per local requirements.
 
 
  
  
  
  
 
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The Investigator should also report complaints on non-Alcon products directly to the 
manufacturer as per the manufacturer’s instructions or local regulatory requirements.
12.9
Pregnancy in the Clinical Study 
Pregnancy is not reportable as an AE; however, complications may be reportable and will 
be decided on a case-by-case basis. An Alcon form will be utilized to capture all 
pregnancy-related information until birth of the child.
13
ANALYSIS PLAN
The primary time point of interest is Month 3/Visit 4A except mesopic contrast sensitivity 
and spectacle use questionnaire. After all subjects complete Month 3/Visit 4A, the study 
database will be locked to conduct planned analyses. Results from these analyses will be 
used in a clinical study report for submission.  The study will be continued until all 
subjects complete Month 6/Visit 5A (120-180 days post 2nd eye implantation), at which 
time the study database will be locked to report longer term safety and performance 
results.
13.1
Subject Evaluability
The final subject evaluability will be determined using the Deviations and Evaluability 
Plan (DEP) prior to breaking the code for masked treatment assignment and locking the 
database.
13.2
Analysis Data Sets
The primary analysis set for effectiveness analyses will be the all-implanted analysis set 
(AAS). AAS includes all randomized eyes with successful IOL implantation. 
 
The Safety Analysis Set will include all eyes with attempted IOL implantation (successful 
or aborted after contact with the eye).
 
 
  
  
  
  
 
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13.3
Demographics and Baseline Characteristics
Summary statistics will be provided for demographic and baseline characteristics by IOL
group. Number and percentage will be presented for categorical variables and descriptive 
statistics including mean, SD, minimum and maximum will be presented for continuous 
variables.
13.4
Effectiveness Analyses
A total of three hypothesis tests will be conducted to address the primary and secondary 
effectiveness objectives of the study. Overall Type I error will be maintained at the 0.05 
level using a sequential testing approach.
13.4.1
Analysis of Primary Effectiveness Endpoint
The primary endpoint is monocular photopic DCIVA at 66 cm.
13.4.1.1
Statistical Hypotheses
The null and alternative hypotheses for the primary analysis are:
H0: µDFT015VA ≥ µSN60WFVA
HA: µDFT015VA < µSN60WFVA
where µDFT015VA, µSN60WFVA, refer to the mean monocular photopic DCIVA at 66 cm for the 
test and control lenses, respectively, in the first implanted eye.
 
13.4.1.2
Analysis Methods
For the primary effectiveness analysis, treatment group comparison for photopic DCIVA
will be made and the primary objective will be demonstrated if (one-sided) P < 0.025 from 
a two-sample t-test.
Data poolability will be analyzed by testing a treatment by site interaction effect: first, the 
interaction effect between treatment and site will be tested using an alpha of 0.15; second, 
if the interaction effect is found significant, the final analysis model should include site as 
a random effect.
Descriptive statistics (mean, median, SD, number of eyes, minimum, maximum and [two-
sided] 95% confidence interval) will also be provided for monocular photopic DCIVA, 
separately for each eye.
 
 
  
  
  
  
 
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13.4.2
Analysis of Secondary Effectiveness Endpoints
The secondary effectiveness endpoints are

monocular BCDVA at 4 m

monocular DCNVA at 40 cm

monocular depth of focus assessed by the mean defocus curve

monocular mesopic contrast sensitivity at 12 cycles per degree with and without 
glare respectively

proportion of subjects who respond “Never” to Q1 and Q3 of the spectacle use 
questionnaire respectively
13.4.2.1
Statistical Hypotheses
The null and alternative hypotheses for the first secondary analysis are:
H0: µDFT015VA - µSN60WFVA ≥ ∆
HA: µDFT015VA - µSN60WFVA < ∆
where ∆ refers to the non-inferiority margin, set at 0.10 logMAR, and µDFT015VA and 
µSN60WFVA, refer to the mean monocular BCDVA at 4 m for the test and control lenses, 
respectively, in the first implanted eye.
The null and alternative hypotheses for the second secondary analysis are:
H0: µDFT015VA ≥ µSN60WFVA
HA: µDFT015VA < µSN60WFVA
where µDFT015VA and µSN60WFVA refer to the mean monocular photopic DCNVA at 40 cm for 
the test and control lenses, respectively, in the first implanted eye.
 
The null and alternative hypotheses for the fourth secondary analysis are:
H0: µDFT015CS - µSN60WFCS ≤∆
HA: µDFT015CS - µSN60WFCS > ∆
 
 
  
  
  
  
 
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where ∆ refers to the non-inferiority margin set at -0.15 log unit, and µDFT015CS and
µSN60WFCS refer to the mean monocular mesopic contrast sensitivity score (log unit) for the 
test and control lenses, respectively, in the first implanted eye. 
 
The null and alternative hypotheses for the fifth secondary analysis are:
H0: πDFT015 ≤πSN60WF
HA: πDFT015 > πSN60WF
where πDFT015 and πSN60WF refer to the proportion of subjects who responded “Never” for 
the test and control lenses.
13.4.2.2
Analysis Methods
The statistical model associated with the above hypotheses for the first secondary 
effectiveness analysis will be tested by generating a one-sided 97.5% upper confidence 
limit based on the difference in means (ACRYSOF IQ EDF IOL – ACRYSOF IQ 
Monofocal IOL) using a two-sample t-test. The upper bound of the one-sided 97.5%
confidence limit will be compared to the margin, 0.10 logMAR. If the upper bound is less 
than the margin, the null hypothesis will be rejected and it will be concluded that 
ACRYSOF IQ EDF IOL is non-inferior to ACRYSOF IQ Monofocal IOL for BCDVA at 4 
m. 
Descriptive statistics (mean, median, SD, number of eyes, minimum, maximum and (two-
sided) 95% confidence interval) will also be provided for monocular BCDVA at 4 m, 
separately for each eye.
For the second secondary effectiveness analysis, treatment group comparison for photopic 
DCNVA will be made and the objective will be demonstrated if (one-sided) P < 0.025 from 
a two-sample t-test.
Descriptive statistics (mean, median, SD, number of eyes, minimum, maximum and (two-
sided) 95% confidence interval) will also be provided for monocular DCNVA at 40 cm, 
separately for each eye.
For the third secondary effectiveness analysis (depth of focus), the line plot of the average 
VA at each defocus level (ie, defocus curve) will be used to estimate the negative lens
induced depth of focus at 0.20 logMAR. The difference in depth of focus between 
ACRYSOF IQ EDF IOL and ACRYSOF IQ Monofocal IOL will be presented.
 
 
  
  
  
  
 
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The hypotheses for the fourth secondary effectiveness analysis will be tested by generating 
a one-sided 97.5% lower confidence limit based on the difference in means (ACRYSOF IQ 
EDF IOL – ACRYSOF IQ Monofocal IOL) using a two-sample t-test. The lower bound of 
the one-sided 97.5% confidence limit will be compared to the margin, -0.15 log unit. If the 
lower bound is greater than the margin, the null hypothesis will be rejected and it will be 
concluded that ACRYSOF IQ EDF IOL is non-inferior to ACRYSOF IQ Monofocal IOL 
for monocular mesopic contrast sensitivity. Monocular mesopic contrast sensitivity without 
glare at 12 cycles per degree will best tested followed by monocular mesopic contrast 
sensitivity with glare at 12 cycles per degree.
For the fifth secondary effectiveness endpoint, a two-sided 95% confidence interval for the 
difference in proportions (ACRYSOF IQ EDF IOL – ACRYSOF IQ Monofocal IOL) will 
be calculated using the Miettinen-Nurminen method (1985), and ACRYSOF IQ EDF IOL 
will be determined to be superior to ACRYSOF IQ Monofocal IOL if the lower boundary 
of the confidence interval is greater than zero. This is equivalent to using a type I error rate 
of 2.5%, 1-sided. Response to Q3 of spectacle use questionnaire will best tested followed 
by response to Q1 of spectacle use questionnaire.
 
 
  
  
  
  
 
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13.5
Handling of Missing Data
The following sensitivity analyses will be conducted to address missing values for the 
primary endpoint. 
1.
Multiple imputation (such as fully conditional specification) method will be 
used to impute and estimate the treatment effect. 
2.
The sensitivity of inferences to departures from the MAR assumption will 
be examined using the pattern-mixture model approach (such as control-
based pattern imputation). 
The details will be described in the Statistical Analysis Plan.
13.6
Multiplicity
Overall type I error will be maintained at 0.05 level for the Month 3/Visit 4A (70-100 day 
post 2nd eye implantation) analyses using the sequential testing approach summarized in 
the figure below. 
 
 
  
  
  
  
 
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The following primary and secondary effectiveness analyses will be performed on the 
Month 6/Visit 5A (120-180 day post 2nd eye implantation) data using the sequential testing 
approach summarized in the figure below if the primary and both secondary null 
hypotheses are rejected for the Month 3/Visit 4A (70-100 day post 2nd eye implantation) 
analysis.
13.7
Safety Analysis
Adverse Events and Device Deficiencies
Descriptive summaries (counts and percentages) for specific AEs will be presented by IOL 
group. The one-sided exact 95% lower confidence limit of incidence rates (proportion of 
eyes with events) observed for each IOL group will be compared to the cumulative and 
persistent adverse event SPE rates. In addition to SPE rates predefined in 
IS EN ISO 11979-7, the rate of adverse events that may be specifically related to 
ACRYSOF IQ EDF IOL design features; and any other significant events will be provided. 
These rates will be accompanied by two-sided exact 95% confidence intervals.
The number and percentage of all adverse events will be tabulated with a breakdown by 
IOL group and implanted eye. A listing of all adverse events will also be provided.
The number and percentage of all device deficiencies will be tabulated with a breakdown 
by IOL group and implanted eye. A listing of all device deficiencies will also be provided.
 
 
  
  
  
  
 
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Mesopic and photopic contrast sensitivity (with and without glare)
Descriptive statistics (mean, median, SD, number of subjects, minimum, maximum, and 
95% confidence intervals) will be provided for
 monocular 
distance 
contrast sensitivity by IOL group.
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
  
 
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13.8
Health Economics
Not Applicable.
13.9
Interim Analyses
Not Applicable.
13.10
Non-inferiority Margin
The non-inferiority margin used for the first secondary objective analysis will be 0.10 
logMAR which equals 1 line in logMAR VA. The non-inferiority margin used for the 
fourth secondary objective analysis will be -0.15 log unit.
13.11
Sample Size Justification
Effectiveness
The proposed sample size (N = 234; 130 Bilateral ACRYSOF IQ EDF IOL and 104 
Bilateral ACRYSOF IQ Monofocal IOL) provides >99% power for the superiority 
hypothesis test on mean monocular DCIVA (66 cm) when tested at the 0.025 level of 
significance (one-sided) assuming the difference in means is -0.12 logMAR (SD = 0.18).
The proposed sample size (N = 234; 130 Bilateral ACRYSOF IQ EDF IOL and 104 
Bilateral ACRYSOF IQ Monofocal IOL) provides 81% power for the non-inferiority 
 
 
  
  
  
  
 
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hypothesis with respect to mean monocular BCDVA (4 m) when tested at the 0.025 level 
of significance (one-sided) with a non-inferiority margin of 0.10 logMAR assuming the 
difference in means is 0.04 logMAR (SD = 0.16).
The proposed sample size (N = 234; 130 Bilateral ACRYSOF IQ EDF IOL and 104 
Bilateral ACRYSOF IQ Monofocal IOL) provides >99% power for the superiority 
hypothesis test on mean monocular DCNVA (40 cm) when tested at the 0.025 level of 
significance (one-sided) assuming the difference in means is -0.12 logMAR (SD = 0.18).
The proposed sample size (N = 234; 130 Bilateral ACRYSOF IQ EDF IOL and 104 
Bilateral ACRYSOF IQ Monofocal IOL) provides 74% power for the non-inferiority 
hypothesis with respect to mean monocular mesopic contrast sensitivity value when tested 
at the 0.025 level of significance (one-sided) with a non-inferiority margin of -0.15 log unit 
assuming the difference in mean is -0.02 log unit (SD = 0.38).
The expected sample size (N = 131) will provide 84% power, with α=0.025, 1-sided, to 
detect a difference of 25% in proportion of subjects who respond “Never” to Q1 and Q3 of 
the spectacles use questionnaire respectively, assuming a 50% rate in the ACRYSOF IQ 
EDF IOL group.
Approximately 260 subjects will be randomized to achieve 234 subjects who complete the 
study. It is expected that approximately 131 subjects will respond to spectacle use 
questionnaire in this study.
Adverse Events
For any event where zero incidences is observed in 130 operative eyes with ACRYSOF IQ 
EDF IOL, the upper limit of the 95% 1-sided exact binomial confidence interval is less 
than 2.3%. Thus, with 95% confidence the true adverse event rate is less than 2.3%.
14
DATA HANDLING AND ADMINISTRATIVE 
REQUIREMENTS
14.1
Subject Confidentiality
The Investigator must ensure that the subject’s anonymity is maintained throughout the 
course of the study. In particular, the Investigator must keep an enrollment log with 
confidential identifying information that corresponds to the subject numbers and initials of 
each study participant. At the end of the clinical study, the Study Sponsor will collect a 
copy of the enrollment log without any identifying subject information. All documents 
 
 
  
  
  
  
 
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submitted to the Study Sponsor will identify the subjects exclusively by number and 
demographic information. No other personally identifying information will be transmitted 
to the Study Sponsor.
The Study Sponsor may release anonymized study data to external researchers for 
purposes of future research directly related to the study objectives, or future research that 
is beyond the scope of the current study objectives. The ICF explains this to study subjects. 
Anonymization means that all identifiable information will be removed from the dataset 
and all links to the subjects in the study will be removed. Anonymization of the data will 
maintain confidentiality of the subjects who participate in the study so that they cannot be 
identified by external researchers. The anonymized data set will contain records from all of 
the subjects in the current study, but the anonymization process might change the data set 
in some ways, so external researchers will be informed that they might not be able to 
duplicate some of the results from this study.  
External researchers who request permission to use anonymized data from studies for a 
new medicine or new indication of a medicine (studies for approved medicinal products, 
small molecule generics, and devices are excluded) must be approved by a central 
independent review panel that will adjudicate the scientific request and the competency of 
the external researcher(s), as well as determine the applicability to current standard 
operating procedures (SOPs). If approved, a data sharing agreement will be executed 
between the Study Sponsor and the external researcher(s), committing to a specified 
analysis and publication timeline. Anonymized data will be released to external researchers 
only after European Union (EU) and/or United States (US) submission of the 
investigational drug/biologic for the study indication.  The Study Sponsor will not be able 
to influence the analyses that are performed by external researchers using the data from 
this study once the anonymized data are released.  
14.2
Completion of Source Documents and Case Report Forms
The nature and location of all source documents will be identified to ensure that original 
data required to complete the eCRFs exist and are accessible for verification by the site 
monitor, and all discrepancies must be appropriately documented via the query resolution 
process. Study monitors are appointed by the Study Sponsor and are independent of study 
site staff.  
If electronic records are maintained, the method of verification must be determined in
advance of starting the study. At a minimum, source documents include the following 
information for each subject:
 
 
  
  
  
  
 
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
Subject identification (name, sex, race/ethnicity)

Documentation of subject eligibility

Date of informed consent

Dates of visits

Documentation that protocol specific procedures were performed

Results of study parameters, as required by the protocol

IP accountability records

Documentation of AEs and other safety parameters (if applicable)

Records regarding medical histories and the use of concomitant therapies prior to 
and during the study

Date of study completion and reason for early discontinuation, if applicable
It is required that the author of an entry in the source documents be identifiable. Direct 
access to source documentation (medical records) must be allowed for the purpose of 
verifying that the data recorded on the eCRF are consistent with the original source data.
Only designated individuals at the site will complete the eCRFs. The eCRFs must be 
completed at regular intervals following the clinical study visit schedule. It is expected that 
all data reported have corresponding entries in the source documents. The Investigator is 
responsible for reviewing and certifying that the eCRFs are accurate and complete. The 
only subject identifiers recorded on the eCRFs will be subject number, and subject 
demographic information. 
14.3
Data Review and Clarifications
A targeted review of eCRF data to the subject’s source data will be completed by the site 
monitor to ensure completeness and accuracy. After the eCRFs have been completed, 
additional data clarifications and/or additions may be needed as a result of the data 
cleaning process. Data clarifications are documented and are part of each subject’s eCRF. 
14.4
Sponsor and Monitoring Responsibilities
The Study Sponsor will designate a monitor to conduct the appropriate site visits at the 
appropriate intervals. The clinical investigation will be monitored to ensure that the rights 
and well-being of the subjects are protected, the reported data are accurate, complete, and 
verifiable from the source documents, and the study is conducted in compliance with the 
current approved protocol (and amendments[s], if applicable), with current GCP, and with 
applicable regulatory requirements.
 
 
  
  
  
  
 
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All sites must have a site initiation. Prior to screening subjects or performing the informed 
consent process on any subject, the site must receive a Site Activation Notification from an 
appropriate Study Sponsor representative.  Monitoring will be conducted periodically 
while the clinical study is ongoing. Monitoring methods may include site visits, telephone, 
written and fax correspondence. Close-out visits will take place after the last visit of the 
last subject or after database lock.
A Coordinating Investigator (CI) may be identified by the Study Sponsor. In cases where a 
CI is required, the Study Sponsor will select the CI based upon their experience, 
qualifications, active study participation, and their willingness and availability to take on 
this role. The CI will be bound by confidentiality obligations described in a separate 
confidentiality agreement between the CI and the Study Sponsor.
14.5
Regulatory Documentation and Records Retention
The Investigator is required to maintain up-to-date, complete regulatory documentation as 
indicated by the Study Sponsor and the Investigator’s files will be reviewed as part of the 
ongoing study monitoring. Financial information is not subject to regulatory inspection 
and is to be kept separately. 
Additionally, the Investigator must keep study records and source documents until the 
Study Sponsor provides written approval for their destruction. If the Investigator retires, 
relocates, or for any other reason withdraws from responsibility of keeping the study 
records, then the Study Sponsor must be notified and suitable arrangements made for 
retention of study records and source documents needed to comply with national and 
international regulations (generally 2 years after discontinuing clinical development or 
after the last marketing approval).
14.6
Quality Assurance and Quality Control
The Study Sponsor will secure agreement from all involved parties to ensure direct access 
to all study related sites, source data and documents, and reports for the purpose of 
monitoring and auditing by the Study Sponsor, and inspection by domestic and foreign 
regulatory authorities. Quality control will be applied to each stage of data handling to 
ensure that all data are reliable and have been processed correctly. Agreements made by 
the Study Sponsor with the Investigator/Institution and any other parties involved in the 
clinical study will be provided in writing as part of the protocol or as a separate agreement.
 
 
  
  
  
  
 
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15
ETHICS
This clinical study must be conducted in accordance with the ethical principles contained 
within:

The Declaration of Helsinki (DoH), and in compliance with the International 
Conference on Harmonization (ICH) E6 GCP Consolidated Guideline

ISO 14155:2011 Clinical investigation of medical devices for human subjects –
Good clinical practice

SOPs of the Study Sponsor and contract research organizations participating in the 
conduct of the clinical study and all other applicable regulations. 
The Investigator and all clinical study staff must conduct the clinical study in compliance 
with the protocol. The Investigator must ensure that all personnel involved in the conduct 
of the study are qualified to perform their assigned responsibilities through relevant 
education, training, and experience.
Before clinical study initiation, this protocol, the ICF, any other written information given 
to subjects, and any advertisements planned for subject recruitment must be approved by 
an IEC/IRB. The Investigator must provide documentation of the IEC/IRB approval to the 
Study Sponsor. The approval must be dated and must identify the applicable protocol, 
amendments (if any), ICF, all applicable recruiting materials, written information for 
subject, and subject compensation programs. The IEC/IRB must be provided with a copy 
of the any periodic safety updates, and all other information as required by local regulation 
and/or the IEC/IRB. At the end of the study, the Investigator must notify the IEC/IRB 
about the study’s completion. The IEC/IRB also must be notified if the study is terminated 
prematurely. Finally, the Investigator must report to the IEC/IRB on the progress of the 
study at intervals stipulated by the IEC/IRB.
Voluntary informed consent must be obtained from every subject prior to the initiation of 
any screening or other study-related procedures. The Investigator must have a defined 
process for obtaining consent. Specifically, the Investigator, or delegate, must explain the 
clinical study to each potential subject and the subject must indicate voluntary consent by 
signing and dating the approved ICF. The subject must be provided an opportunity to ask 
questions of the Investigator, and if required by local regulation, other qualified personnel. 
The Investigator must provide the subject with a copy of the consent form written in a 
language the subject understands. The consent document must meet all applicable local 
laws and provide subjects with information regarding the purpose, procedures, 
requirements, and restrictions of the study, along with any known risks and potential 
 
 
  
  
  
  
 
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benefits associated with the IP, the available compensation, and the established provisions 
for maintaining confidentiality of personal, protected health information. Subjects will be 
told about the voluntary nature of participation in the study and must be provided with 
contact information for the appropriate individuals should questions or concerns arise 
during the study. The subject also must be told that their records may be accessed by 
appropriate authorities and Sponsor-designated personnel. The Investigator must keep the 
original, signed copy of the consent and must provide a duplicate copy to each subject 
according to local regulations. 
The Study Sponsor assures that the key design elements of this protocol will be registered 
in www.clinicaltrials.gov as required by current regulations and, if applicable, other public 
databases as required by local country regulations.  In addition, results of this study will be 
made publicly available in www.clinicaltrials.gov regardless of outcome as required by 
current regulations and, if applicable, in other public databases as required by local country 
regulations.  
Amendments may necessitate that the informed consent and other study-related material be 
revised. If the consent form is revised, all subjects currently enrolled in the study must sign 
the approved, revised informed consent, as required by the IEC/IRB. 
 
 
  
  
  
  
 
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16
REFERENCES
Boettner  EA, Wolter JR. Transmission of the ocular media. Invest Ophthalmol. 
1962;1:776-83.
Clinical investigation of medical devices for human subjects - Good clinical practice, ISO 
14155 (2011).
Ophthalmic implants – Intraocular lenses – Part 7: Clinical investigations, ISO 11979-7 
(2014).
Miettinen OS and Nurminen M. (1985). Comparative analysis of two rates. Statistics in 
Medicine, 4:213-226.
TDOC- 0016353, Optical Design of Toric Extended Depth of Field IOL.
 
 
  
  
  
  
 
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Date/Time 
(mm/dd/yyyy GMT):
Signed by:
Justification:
 
 
  
  
  
  
 
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