AcrySof IQ Toric A-Code Post-Market Clinical Study
Phase: NA
Conditions: Cataract, Astigmatism
Sponsor: Alcon Research

AcrySof IQ Toric A-code post-market clinical study 
Clinical Research Protocol 
Alcon Japan Ltd. 
Toranomon Minato-ku, Tokyo 
Protocol No. ILV814-P001
ClinicalTrials,gov NCT03350503
Ver.4.0：January 29, 2020 
Ver.5.0：June 16, 2021 

Protocol No.：ILV814-P001 
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 
Device Deficiencies 
Usage 
Implant IOL to aphakic eye. 
Examinations 
Schedule 
 
Visit 0 (Preoperative) 
 
Visit 00 (Surgery day, during surgery) 
 
Visit 00-A（Surgery day, 1 hour +/-30min after surgery） 
 
Visit 1 (Day 1-2) 
 
Visit 2 (Day 7-14) 
 
Visit 3 (Day 30-60) 
 
Visit 4 (Day 120-180) 
 
Visit 5 (Day 330-420) 
 
Visit 6 (Day 630-780) 
 
Visit 7 (Day 990-1140) 
Estimated 
Total 
Sample Size 
Required: 100 subjects (eyes), Planned: 120 subjects (eyes) 
One eligible eye will be selected as a target eye for efficacy analysis. If both eyes are eligible, the 
eye in which IOL is implanted first will be selected as a target eye. 
Anticipated 
Study Period 
October 2017 to May 2022 
Representative 
Investigator 
 
Study Sponsor Alcon Japan Ltd.:  
Creating the trial plan of clinical research and provide funding and services related to conducting 
research. 
Regulations 
This study will be conducted in accordance with the principles set forth in the Declaration of 
Helsinki, the Clinical Trials Act (Act No. 16 of April 14, 2017), the Enforcement Regulations of the 
Clinical Trials Act (No.17 of February 28, 2018), and other relevant laws, ministerial ordinances, 
ministerial notifications, etc. 
Protocol 
Effective Date 
Approval by the certified review board 
 
 
 

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TABLE OF CONTENTS 
 
1．Introduction ......................................................................................................................................................... 7 
1.1 History of development ................................................................................................................................. 7 
1.2 Information on safety or efficacy ................................................................................................................... 8 
2．STUDY OBJECTIVES ........................................................................................................................................ 8 
3．TEST ARTICLES ................................................................................................................................................ 8 
3.1 Test articles .................................................................................................................................................... 8 
3.2 Usage ............................................................................................................................................................. 8 
3.3 Instructions on package and labeling ............................................................................................................. 8 
3.4 Storage and management ............................................................................................................................... 8 
4．SUBJECTS .......................................................................................................................................................... 8 
4.1 Estimated total sample size ............................................................................................................................ 8 
4.2 Inclusion criteria ............................................................................................................................................ 9 
4.3 Exclusion criteria ........................................................................................................................................... 9 
5．STUDY DESIGN .............................................................................................................................................. 10 
6．STUDY PROCEDURE ......................................................................................................................................11 
6.1 Study outline .................................................................................................................................................11 
6.2 Method of subject selection ..........................................................................................................................11 
6.3 Examination schedule. ................................................................................................................................. 12 
6.4 Examinations procedure .............................................................................................................................. 13 
6.5 Study period (Plan) ...................................................................................................................................... 16 
7．CONCOMITANT THERAPY ........................................................................................................................... 16 
8．DISCONTINUED SUBJECTS ......................................................................................................................... 17 
8.1 Discontinued subjects .................................................................................................................................. 17 
8.2 Discontinuation of the entire study .............................................................................................................. 17 
9．Statistical Analysis ............................................................................................................................................. 18 
9.1 Evaluability .................................................................................................................................................. 18 
9.2 Datasets ........................................................................................................................................................ 18 
9.3 Demographic factors and baseline characteristics ....................................................................................... 18 
9.4 Effectiveness analysis .................................................................................................................................. 18 
9.5 Missing data imputation .............................................................................................................................. 22 
9.6 Safety analysis ............................................................................................................................................. 22 
9.7 Interim analysis ............................................................................................................................................ 22 
9.8 Sample size justification .............................................................................................................................. 22 
9.9 Revision of statistical analysis plan ............................................................................................................. 22 
10．ADVERSE EVENTS, DISEASE OR THE LIKE, AND DEVICE DEFICIENCIES, etc. .............................. 22 
10.1 General information ..................................................................................................................................... 22 
10.2 Assessment of AE ........................................................................................................................................ 24 

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10.3 Assessment of disease or the like ................................................................................................................ 25 
10.4 Follow-up of subjects / subjects with AEs ................................................................................................... 25 
10.5 Actions for disease or the like and device deficiency .................................................................................. 25 
10.6 Procedure for reporting to the study sponsor ............................................................................................... 26 
10.7 Report of disease or the like to the certified review board and the Minister of Health, Labour and Welfare...26 
10.8 Other measures to be taken .......................................................................................................................... 28 
10.9 Pregnancy of subjects .................................................................................................................................. 28 
10.10 Information provision of safety information .............................................................................................. 28 
11．ETHICS ........................................................................................................................................................... 28 
11.1 Certified review board ................................................................................................................................. 28 
11.2 Ethical consideration ................................................................................................................................... 29 
11.3 Protection of subjects’ privacy ..................................................................................................................... 29 
11.4 Specifications to secure safety of study subjects ......................................................................................... 29 
11.5 Compensation for health hazards ................................................................................................................. 29 
11.6 Payment to subjects ..................................................................................................................................... 29 
12．PROTOCOL etc. AMENDMENTS ................................................................................................................. 30 
13．CONSIDERATIONS FOR DOCUMENTATION AND COMPLETION OF CASE REPORT FORM .......... 30 
14．MONITORING ................................................................................................................................................ 30 
15．RETENTION OF THE RECORDS ................................................................................................................. 30 
16．CONFIDENTIALITY AND PUBLICATION OF STUDY ............................................................................ 31 
17．DIRECT ACCESS TO SOURCE DATA AND DOCUMENTS ...................................................................... 31 
18．QUALITY CONTROL AND QUALITY ASSURANCE OF THE STUDY ................................................... 31 
19．OBLIGATIONS OF INVESTIGATORS ......................................................................................................... 32 
20．INFORMED CONSENT ................................................................................................................................. 36 
21．PROVIDE SERVICES RELATED To CONDUCTING RESEARCH ............................................................ 39 
22．CONFLICT OF INTEREST ............................................................................................................................ 39 
23．REFERENCES ................................................................................................................................................ 39 
 
 

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1．Introduction 
1.1 
History of development 
In Japan, in 1985, the intraocular lenses (IOLs) of five companies were approved by the Ministry of Health, 
Labour and Welfare (MHLW). After IOLs began to be covered by health insurance in 1992, IOL usage has spread 
rapidly1. Subsequently, a range of foldable IOLs was developed2, and through advances in small incision techniques 
and their increased use, early recovery of visual acuity, early ambulation, and early rehabilitation became possible. 
In addition, a series of reconstructive lens surgeries that accompany the insertion of IOLs, have made it an almost 
complete surgical procedure3. 
In recent years, the cataract surgery is not merely an operation to restore visual acuity, and the needs of refractive 
cataract surgery, such as not requiring to wear glasses after surgery, is increasing. Miyake et al. reported that 15.4% 
of patients with cataract surgery had more than 1.5 D of corneal astigmatism4. Since this astigmatism cannot be 
corrected only with the monofocal IOL, a Toric IOL is applied to treat them.  
Toric IOLs were first implanted in humans in 19945. Alcon Japan received Regulatory approval of AcrySof Toric 
IOL in Japan in 2009 and it currently sells the models that can correct corneal astigmatism from 1.03 D to 4.11 D. 
One of the important features required for Toric IOL is the rotational stability. Since the astigmatic correction 
effect of Toric IOL decreases by 3.3% per degree of IOL rotation5, it is necessary to carry out a surgery to reposition 
the IOL axis in the case that a large rotation occurs after the surgery. 
In Japan, a manufacturing improvement of the AcrySof family of lenses has been implemented in 2017 (A-code) 
 
 
 this study (ILV814-P001) will be 
implemented to clinically confirm the rotational stability of AcrySof IQ toric A-code. 
This study was conducted in accordance with ICH Harmonized Tripartite Guidelines for Good Clinical Practice 
or Ministerial Ordinance Regarding Good Clinical Practice Principles for Medical Devices (2005, Ministry of 
Health, Labour and Welfare Ordinance No.36) and Ethical Guidelines for Clinical Studies (2014, Ministry of 
Education, Culture, Sports, Science and Technology and Ministry of Health, Labour and Welfare Notification No.3), 
in principle. 
With the enforcement of the Clinical Trials Act, this study was to be conducted under the Clinical Trials Act. 
After completion of the transition to Clinical Trials Act on February 21, 2019, this study will be conducted in 
accordance with the principles set forth in the Declaration of Helsinki, the Clinical Trials Act (Act No. 16 of April 
14, 2017), the Enforcement Regulations of the Clinical Trials Act (No.17 of February 28, 2018), and other relevant 
laws, ministerial ordinances, ministerial notifications, etc. 
                                                   
1 Shinichi Ito. Medical insurance and intraocular lenses. Journal of the Eye, 20: 615-620, 2003. 
2 Ken Hayashi. New foldable intraocular lenses. Japanese Journal of Cataract and Refractive Surgery, 16: 453-
458, 2002. 
3 Kimiya Shimizu. Revaluation of cataract surgery. Journal of the Eye, 16(9): 1185-1189, 1999. 
4 Toshiyuki Miyake. Corneal astigmatism before cataract surgery. Journal of Japanese Ophthalmological Society, 
115: 447-453, 2011. 
5 Kimiya Shimizu, et al. Toric intraocular lenses correcting astigmatism while controlling axis shift. J Cataract 
Refract Surg., 29: 523-526, 1994. 

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4.2 
Inclusion criteria 
1) Adults, 20 years of age or older at the time of informed consent, of either gender or any race, diagnosed with 
cataracts with planned cataract removal by phacoemulsification. 
2) Able to comprehend and willing to sign informed consent and complete all required postoperative follow-up 
procedures. 
3) Calculated lens power within the available range. 
4) Eyes for which the implantation of SN6AT3, SN6AT4 or SN6AT5 IOLs is recommended by the Alcon online 
Toric IOL calculator. 
5) Potential postoperative Best Corrected Distance visual acuity (BCDVA) of 0.7 decimal or better in study eye 
based on Investigator expert medical opinion.  
NOTE: Subjects with any pathology that could reduce visual potential should not be enrolled in this study. 
6) Clear intraocular media other than cataract in study eye 
7) Eyes whose predicted postoperative refraction is emmetropia. 
 
[Rationale for inclusion criteria] 
1), 3), 4): To confirm eligible for Toric IOL 
2): Required for Medical Device GCP 
5), 6): Conditions to minimize the potential non-IOL confounding factors which may affect the primary 
efficacy endpoint. 
7): To avoid effect of post-operative uncorrected visual acuity. 
 
4.3 
Exclusion criteria 
Exclusion criteria (Prior to surgery) 
1) Clinically significant corneal abnormalities per the Investigator’s expert medical opinion. 
2) Previous corneal transplant. 
3) Previous refractive surgery or planned refractive surgery procedures throughout the entire duration of the 
subject participation in the clinical study (including, but not limited to LASIK, astigmatic keratotomy and 
limbal relaxing incisions) 
4) History of or current retinal conditions or predisposition to retinal conditions, including previous history of or 
a predisposition to retinal detachment or presence of diabetic retinopathy that the Investigator determines that 
could confound outcomes (NOTE: Including but not limited to background diabetic retinopathy, diabetic 
macular edema or proliferative diabetic retinopathy, macular degeneration) 
5) Amblyopia 
6) Rubella, congenital, traumatic, atopic or complicated cataracts 
7) Any recurrent severe anterior or posterior segment inflammation of any etiology, and /or history of any disease 
producing an intraocular inflammatory reaction 
8) Iris neovascularization 
9) Glaucoma (uncontrolled with medication) or ocular hypertension 

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10) Optic nerve atrophy 
11) Subjects with diagnosed degenerative eye disorders 
12) Pregnancy current or planned during the course of the study 
13) Any subject currently participating in another investigational drug or device study that may confound the 
results of this investigation 
14) Subjects who may reasonably be expected to require an ocular surgical treatment at any time during the study 
(other than Nd:YAG capsulotomy) 
15) Situations where the need for a large capsulotomy can be anticipated by the Investigator’s expert medical 
opinion (e.g., diabetics, retinal detachment in the fellow eye, peripheral retinal pathology, etc.) 
16) Subjects who are expected to require retinal laser treatment 
17) Patient with the poor mydriasis and who is expected that it cannot confirm Toric mark even if they were dilated 
18) Patient with corneal irregular astigmatism 
19) Disqualified by the investigator or the sub investigator because of systemic or ophthalmic diseases. 
 
[Rationale for exclusion criteria (prior to surgery)] 
14), 15), 17): Factors potentially affecting primary and exploratory efficacy endpoint. 
Others: General safety considerations. 
 
Exclusion criteria (During surgery) 
1) Eyes with any other additional procedures during the cataract surgery and IOL implant due to intraoperative 
complications that required further intervention (including but not limited to posterior capture rupture, vitreous 
loss, zonular dehiscence that may make the IOL implant less stable, etc.) 
2) Significant anterior chamber bleeding 
3) Uncontrolled intraocular pressure 
4) Unrecognized (pre-existing but discovered during surgery) ocular conditions or complications in which the IOL 
stability could be compromised, including zonular weakness. 
5) Bag-sulcus, sulcus-sulcus or unknown placement of the haptics. 
6) Any capsulorhexis other than continuous curvilinear capsulorhexis (e.g., no anterior radial inconsistencies in 
the capsulorhexis such as anterior capsular tears or any areas of ‘can-opener’ capsulotomy). 
 
[Rationale for exclusion criteria (during surgery)] 
Factors potentially affecting primary and exploratory efficacy endpoint. 
 
5．STUDY DESIGN 
Prospective, single arm, multicenter study 
 

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6．STUDY PROCEDURE 
6.1 
Study outline 
The outline of this study is shown in Figure 6-1. The subject who has corneal astigmatism and was judged by 
Alcon Toric IOL calculator to be eligible implantation of SN6AT3, SN6AT4, SN6AT5 and will be implanted 
recommended IOL model will be enrolled. The subjects are examined from pre-operative visit to 3 years post-
operatively. One hundred and twenty subject will be enrolled. 
 
 
Figure 6-1 Study Outline 
 
 
 
6.2 
Method of subject selection 
Subjects selection and subject identification code assignment are follows. 
1） After an explanation of the study details is given to a prospective subject, his/her consent to participate in the 
study will be obtained. 
2） The subject identification code will be assigned to a subject whose consent is obtained.  
3） The investigator will assess the eligibility of the subject through examinations and observations needed to 
assess the eligibility based on the inclusion and exclusion criteria. 
4） One eligible eye will be selected as a target eye for efficacy analysis. If both eyes are eligible, the eye in which 
eye will be implanted IOL first will be selected as a target eye. 
 
 
 
 
 
 
 
 
 
 
Post-ope. examination
Cataract surgery and Study IOL
implantation
Pre-op. examination, 
Inclusion/exclusion criteria
Informed consent

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6.3 
Examination schedule. 
Overview of the study procedure is presented in Table 6-1. The examination/observation period is from 
preoperative to 990-1140 days after surgery. 
 
 
 
 
Table 6-1  Overview of Study Procedures 
 
Nominal Time ± Visit Window Limits 
 
Visit 0 
Visit 00 
Visit 00-A 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Procedure/ 
Assessment 
Pre-
operative 
Surgery day, 
during 
surgery 
Surgery day, 
1 +/-0.5 hour 
after surgery 
Day 1-2 
Day 7-14 
Day 30-60 
Day 120-
180 
Day 330-
420 
Day 630-
780 
Day 990-
1140 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
X 
 
 
 
 
 
 
 
 
Manifest refraction 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
Uncorrected distance 
visual acuity 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
Best corrected 
distance visual acuity 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
Corneal keratometory 
(K1, K2, Ax) 
X 
 
 
 
 
 
 
 
 
 
Corneal topography 
X 
 
 
 
 
 
 
 
 
 
Toric calculator 
X 
 
 
 
 
 
 
 
 
 
Axial length 
X 
 
 
 
 
 
 
 
 
 
Anterior chamber 
depth 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Surgical records 
 
X 
 
 
 
 
 
 
 
 
Toric mark axis 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
SSNG densitometry1 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Glistening grade 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Slit examination 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
PCO 
 
 
 
X 
X 
X 
X 
X 
X 
X 
YAG laser for PCO 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
Device Deficiency 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
1 Evaluate by Pentacam or Pentacam HR 
 
 
 
 
 
 

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6.4 
Examinations procedure 
1） Visit 0 (Pre-operative) 
After an explanation of the study details is given to a prospective subject, his/her consent to participate in the 
study will be obtained. The subject identification code will be assigned to a subject whose consent is obtained. The 
investigator will assess the eligibility of the subject and select the target eye. The registration form for the subject 
will be sent to the sponsor. 
 
After the subject consents to participate in the study, the following examinations are performed. When a routine 
clinical assessment is performed before obtaining informed consent, data from these assessments may be used as 
study data. 
 
・ Subject demographics 
Gender, age (at the day of consented), medical history of eye, ophthalmic surgical history and eye complications 
 
・ Manifest refraction 
Record the spherical and cylindrical refraction and axis at the time of BCVA measurement with the visual acuity 
test chart. 
 
・ Visual acuity (Uncorrected distance visual acuity, Best corrected distance visual acuity) 
Measure the visual acuity under photopic lighting condition by decimal visual acuity chart. 
 
・ Keratometry (K1, K2, Axis) 
Measure the corneal curvature by auto keraometer. Measurement is less than 0.25 D step. 
 
・ Corneal topography 
Measure the corneal irregular astigmatism by corneal topography or any other measurement instrument. Confirm 
the subject doesn’t have corneal irregular astigmatism. 
 
・ Target refraction 
Record the target refraction which was expected by IOL power calculation. 
 
・ Toric calculator 
Record the IOL model, Toric IOL target axis, calculate formula, corneal refraction power, axial length, anterior 
chamber depth(ACD), anticipated residual astigmatism (D, degree) by Alcon online toric IOL calculator. 
 
・ Axial length 
Measure the axial length by optical measurement method. 
 

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・ Anterior chamber depth (ACD) 
Measure the anterior chamber depth (distance between corneal endothelial and anterior surface of crystalline 
lens capsular) using by optical measurement method. 
 
・ Slit lamp examination 
Confirm the presence or absence of adverse events. If any adverse event is present, record data on the event in 
the Adverse Event Case Report Form (CRF) according to Section 10 “Adverse Events and Device Deficiencies, 
etc.” of the protocol. 
 
・ Adverse events 
Collect the information of the adverse events (whole body) occurred after the subject consents. 
 
2） Visit 00 (Surgery day, during surgery) 
・ Exclusion criteria 
Confirm the exclusion criteria of during surgery. 
 
・ Information of IOL model 
Record the implanted IOL model and IOL power (D). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
・ Adverse events (whole body) and device deficiencies 

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Collect the information of the adverse events (whole body) and device deficiencies. 
 
3） Visit 00-A (post-operative 1 +/- 0.5 hours) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
4） Visit 1, 2, 3, 4, 5, 6, 7 (Post-operative) 
・ Manifest refraction 
Record the spherical and cylindrical refraction and axis at the time of BCVA measurement with the visual acuity 
test chart. 
 
・ Visual acuity (Uncorrected distance visual acuity, Best corrected distance visual acuity) 
Measure the visual acuity under photopic lighting condition by decimal visual acuity chart. 
 
 
 
 
 
 
 
 
 
 
 
 

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・ Surface light scattering densitometry 
Measure the anterior surface light scattering densitometry by using Pentacam or Pentacam HR. 
 
 
 
 
・ Slit lamp examination 
Assess the grade of glistening6 according to Protocol Supplemental Attachment C, evaluate PCO and exam 
other abnormality. If needed, exam under mydriatic condition. 
 
 
 
・ Nd: YAG laser for posterior capsulotomy 
Record the operation date of Nd: YAG laser for PCO. 
 
. 
 
・ Adverse events (whole body) and device deficiencies 
Collect the information of the adverse events (whole body) and device deficiencies. 
 
6.5 
Study period (Plan) 
October 2017 to May 2022 
 
7．CONCOMITANT THERAPY 
No prohibited therapy. 
 
                                                   
6 Akira Miyata. Glistening particles on the implanted acrylic intraocular lens. Japanese Journal of Clinical 
Ophthalmology, 51(4): 729-732, 1997. 

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8．DISCONTINUED SUBJECTS 
8.1 
Discontinued subjects 
Subjects are discontinued the study in the following cases: 
1) Upon onset of adverse events which make study continuation difficult. 
2) Upon cancellation of consent to the study by the subject. 
3) Upon request of the subject to discontinue the study. 
4) Hospital referral or move of the subject during the study, making it difficult to continue the study. 
5) If the investigators judge it necessary to discontinue the study. 
 
Upon discontinuation of the study, if the investigators decided the examination or observation is necessary, the 
examination or observation should be carried out as far as possible under the subject’s consent, and reason of 
discontinuation is entered in the case report form. In case which continuation of the study is difficult because of 
discontinued visit of the subject to the clinic, the subject is followed as possible over telephone, by mail or other 
appropriate means and the reason for discontinued visit, survival/death of the subject, presence/absence of adverse 
events, etc., are entered in the case report form. 
 
8.2 
Discontinuation of the entire study 
If discontinuation of the entire study has become inevitable for reasons of reports on serious safety information, 
problems pertaining to the quality of the test articles, and so on, the notice shall be given as follows. 
1) In case that the representative investigator determined discontinuation of the study 
The representative investigator shall immediately notify the principal investigator(s) and the sponsor of the 
discontinuation of the study and its reasons. The representative investigator shall also report these information to 
the administrator of the investigational site to which the representative investigator belongs, and the certified review 
board. The principal investigator(s) shall report the discontinuation of the study and its reasons to the administrator 
of the investigational site to which he/she belongs, and immediately inform the subjects who participant in the study 
of them and take appropriate actions such as changing to appropriate treatment. 
 
2) In case that the sponsor determined discontinuation of the study 
The sponsor shall immediately notify the representative investigator of discontinuation of the study and its 
reasons and discuss discontinuation of the study with the representative investigator. The representative investigator 
shall notify the principal investigator(s) of these information. The representative investigator shall also report it to 
the administrator of the investigational site to which the representative investigator belongs, and the certified review 
board. The principal investigator(s) shall report the discontinuation of the study and its reasons to the administrator 
of the investigational site to which he/she belongs, and immediately inform the subjects who participant in the study 
of them and take appropriate actions such as changing to appropriate treatment. 
 

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9．Statistical Analysis 
9.1 
Evaluability 
Subject evaluability based on pre-specified deviations and their impact on analysis sets will be determined prior 
to locking the database. 
 
9.2 
Datasets 
Datasets used for effectiveness and safety analysis are as follows. 
(1) Safety Analysis Set 
The pre-treatment safety analysis set will include all subjects who consented to participate in the study. The 
pre-treatment safety analysis set will be the set that will be used to summarize occurrence of adverse experiences 
prior to exposure to the test article. The treatment-emergent safety analysis set will include all eyes with attempted 
implantation with the test article (successful or aborted after contact with the eye).  
 
(2) All-Implanted Analysis Set (AAS) 
All-Implanted Analysis Set (AAS) will include all eyes with successful test article implantation. 
 
(3) Best-Case Analysis Set (BAS) 
Best-Case Analysis Set (BAS) will include all eyes with successful test article implantation that had  
 
at least 1 postoperative visit, 
 
no major protocol violation. 
 
The pre-treatment safety analysis set will be used to summarize occurrence of adverse experiences prior to 
exposure to the test article. The treatment-emergent safety analysis set will be used for safety analysis after 
implantation of test article.  
 
  The AAS and BAS will be used for primary effectiveness analysis in the study, with priority given to AAS 
results.  The AAS will be used for exploratory analysis in the study. 
 
9.3 
Demographic factors and baseline characteristics 
For all datasets (Safety Analysis Set, AAS, BAS), demographic factors (sex, age, axis length, planned IOL angle, 
pre-operative astigmatism, IOL model, pre-operative astigmatism volume), descriptive statistics will be provided.  
For sex, age (<60, 60-69, 70-79, ≥ 80), axial length (<22, 22-26.9, 27≤ mm), planned IOL angle (0-45° or 135-180°, 
46-136°), pre-operative astigmatism (with-the rule, against-the rule, oblique), IOL model (SN6AT3, SN6AT4, 
SN6AT5), the N and percentage will be provided.  For age, axis length and pre-operative astigmatism volume, 
arithmetic mean, standard deviation, N, median, min and max) will be provided. 
 
9.4 
Effectiveness analysis 
The objective of this study is to describe safety and effectiveness for patients who are implanted with AcrySof 
IQ Toric (A-code). The one eye will be selected as the target eye for effectiveness analysis. The first implanted eye 

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9.5 
Missing data imputation 
No missing data imputation will be conducted. 
 
9.6 
Safety analysis 
A patient listing of adverse experiences prior to exposure to the test article will be provided. Safety variables after 
exposure to the test article are as follows. Each safety variable will be summarized descriptively.  Descriptive 
statistics (mean, standard deviation, N, median, min and max) will be provided for actual value and change from 
appropriate baseline at each visit for continuous variables.  For categorical variables, N and percent will be 
provided for each category.  
・ Glistening grade (0,1,2,3) 
・ YAG laser treatment rate for post capsular opacification 
・ Adverse events 
・ Device deficiencies 
 
9.7 
Interim analysis  
 
 The primary analysis will be conducted after all 
subjects complete Visit 4. The final analysis will be conducted after all subjects complete Visit 7 (Day 990-1140). 
Interim analyses are not intended to stop the study early.  
 
 
 
9.8 
Sample size justification 
According to ISO standards*, at least 100 subjects should be enrolled to investigate IOL rotation.  The 120 
subjects will be enrolled assuming that dropout rate is around 16%.  
* ISO 11979-7:2014(E), 6.2.2 Additional requirements for toric IOLs 
 
9.9 
Revision of statistical analysis plan 
The statistical analysis plan will be prepared before the data base lock. If the statistical analysis plan is necessary 
to be revised, it will be get approved by the certified review board and the revision will be explained in the CSR of 
this study.  
 
10．ADVERSE EVENTS, DISEASE OR THE LIKE, AND DEVICE DEFICIENCIES, etc.  
10.1 General information 
The definitions of the terms are described below. 
 
Adverse Event (AE): 
Any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal 
laboratory findings) in subjects after signed informed consent, users or other persons, whether or not related to the 

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23 
 
investigational medical device (test article). For subjects, this definition includes events related to the test article or 
the procedures involved. For users or other persons, this definition is restricted to events related to the test article. 
 
Serious Adverse Event (SAE): 
AE that led to any of the following, or that needed treatment not to lead to the following results: 
・ 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 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. 
D) A congenital anomaly/birth defect 
E) A medically important event or reaction 
 
Non-serious AE: 
AE that does not meet the criteria for a serious AE. 
 
Adverse Device Effect (ADE): 
AE related to the use of an investigational medical device (test 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. 
 
Serious Adverse Device Effect: 
ADE that has resulted in any of the consequences characteristic of a SAE. 
 
Disease or the Like: 
Among AEs, any disease, disability, death or infection which is suspected of being due to the conduct of the 
study, as well as an abnormal laboratory data and symptoms. 
 

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Infection: 
A suspicion of concomitant of the pathogens from biological raw materials or biological materials into biological 
products. In addition, it shall be also reported as an infection when the viral marker such as HBV, HCV, HIV, etc. 
shows positive. 
 
Device Deficiency: 
Inadequacy of a medical device with respect to its identity, quality, durability, reliability, safety, or performance. 
 
Safety Information: 
Information about quality, efficacy and safety for medical device and information which is needed for appropriate 
use, including: 
・ Use error 
・ Abnormal Use 
・ Product tampering 
・ Product counterfeiting 
・ Product theft 
 
10.2 Assessment of AE 
Report of AE and Causality Assessment: 
All AEs which occurred after the subject consents to participate in the study (related and unrelated to the medical 
device) will be documented on the AE CRF. 
For every AE in the study, the investigator must assess the causality (Related or Not Related to the medical 
device). 
 
Intensity Assessment of AE: 
For every AE, the investigator must assess the intensity (severity). Events should be classified as mild, moderate, 
or severe. These classifications should be based on the following definitions: 
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. 
 
Outcome: 
The outcome shall be assessed as either recovered/resolved, recovering/resolving, not recovered/not resolved, 
recovered/resolved with sequelae, death or unknown.  
 
 

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10.3 Assessment of disease or the like 
Severity Assessment: 
Refer to 10.1 the definition of SAE. 
 
Predictability assessment： 
For every disease or the like, the investigator must assess the predictability as either ”predictable” or 
“unpredictable”. If it is not listed in the following documents, etc., and the investigator judge that it cannot be 
predicted, it shall be "unpredictable”.  
1) 
The clinical research protocol or the explanation document 
2) 
The latest package insert for the test articles 
3) 
The precautions on the container or package of the test articles, or the interview form of the test articles, etc. 
 
10.4 Follow-up of subjects / subjects with AEs 
In the event of acknowledging any adverse events, the investigators should immediately take appropriate actions 
irrespective of the presence or absence of causal relationship with the test article. And the investigators will make a 
follow-up of the adverse event if it is possible. When the subject needs medical treatment, the investigators should 
inform the subject of the matter.  
For subjects who are experiencing ongoing unresolved adverse events at the time of their study completion or 
early discontinuation from the study, it is recommended that the investigator schedule an appropriate follow-up visit 
in order to determine the outcome of the event. 
 
10.5 Actions for disease or the like and device deficiency 
10.5.1 Record and report of disease or the like and device deficiency  
When the principal investigator or the sub-investigator recognizes an occurrence of a disease or the like or a 
device deficiency, he/she shall take necessary measures against the subject and prepare the CRF after documenting 
the occurrences etc. to the patient records. If the sub-investigator recognizes an occurrence of a disease or the like 
or a device deficiency, he/she shall report its details to the principal investigator.  
 
10.5.2 Report of serious disease or the like and device deficiency that may cause serious disease or the 
like 
1) Principal investigator 
When the principal investigator recognizes an occurrence of a serious disease or the like or a device deficiency 
that may cause serious disease or the like among occurrences of disease or the like which is suspected of being due 
to the conduct of the study, he/she shall report it to the administrator of the investigational site to which the principal 
investigator belongs. The principal investigator shall also report it to the representative investigator. 
 
2) Sub-investigator, etc. 
When the sub-investigator, etc. recognizes an occurrence of a serious disease or the like or a device deficiency 

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that may cause serious disease or the like, he/she shall report it to the principal investigator (or the representative 
investigator if it was occurred at the study site to which the representative investigator belongs.)  
 
3) Representative investigator 
When the representative investigator obtains an information of a serious disease or the like or a device deficiency 
that may cause serious disease or the like, he/she shall report it to the administrator of the investigational site to 
which he/she belongs, and the certified review board in accordance with the procedure described in 10.7. The 
representative investigator shall also provide the information to the other principal investigator(s).  
 
10.6 Procedure for reporting to the study sponsor 
The investigator will report the SAE, serious disease or the like, or device deficiency which may cause a serious 
disease or the like to the sponsor within 24 hours after confirming the event or acknowledging the possibility of 
occurrence of the event. 
In addition, after obtaining the detailed information on SAE, serious disease or the like, or device deficiency 
which may cause a serious disease or the like, the investigator will prepare a report and promptly submit it to the 
sponsor and the administrator of the investigational site. 
 
If the sponsor receives the report of “death or a life-threatening ADE, disease or the like (device deficiency)” or 
“serious and unexpected ADE, disease or the like (device deficiency) other than death or a life-threatening event” 
from the investigator, the sponsor shall give full consideration to promptly notify the information in writing to the 
representative investigator, the administrators of all investigational sites and all the principal investigators.  
 
10.7 Report of disease or the like to the certified review board and the Minister of Health, Labour and 
Welfare 
10.7.1 Reporting period of disease or the like and device deficiency  
When the representative investigator obtain an information of the following disease or the like and device 
deficiency, he/she shall report it to the administrator of the investigational site and also report it to the certified 
review board which is written in the clinical research protocol within each reporting period using Clinical Trials Act 
Form. The order of reporting to the administrator of the investigational site and to the certified review board may 
be changed. The representative investigator shall provide the information to the manufacturer. The representative 
investigator shall report the information as the first report within the reporting period as far as he/she obtained, even 
if the information such as a cause of occurrence of disease or the like is not clear. Afterwards, when the 
representative investigator obtain more information, he/she shall report the information immediately as the 

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following report. The report to the Minister of Health, Labour and Welfare shall be made at the periodic report. 
 
The reporting period for Specified Clinical Trials using a medical device that has been already approved or   
a medical device within indication 
Disease or the like  
Expecting infection  
Infection  
Unpredictable 
Predictable 
Unpredictable 
Predictable 
(1) Death  
15 days  
15 days 
15 days 
15 days 
(2) In-patient hospitalization or 
prolonged hospitalization  
15 days 
30 days 
15 days 
15 days 
(3) A life-threatening illness or 
injury 
15 days 
30 days 
15 days 
15 days 
(4) Any potentially sight-
threatening event or 
permanent impairment to a 
body structure or a body 
function 
15 days 
30 days 
15 days 
15 days 
(5) A congenital anomaly/birth 
defect 
15 days 
30 days 
15 days 
15 days 
(6) A medically important event 
or reaction 
15 days 
30 days 
15 days 
15 days 
(7) Other disease or the like: 
every year (within 2 months 
of the end of the period) 
Periodic 
report 
Periodic 
report 
15 days 
Periodic 
report 
 
Report period of device deficiency 
Device deficiencies that may cause disease or the like (1)-(6): within 30 days  
Other device deficiencies: unnecessary to report  
 
10.7.2 Periodic report  
1) Report to the certified review board 
Regarding disease or the like which is suspected of being due to the conduct of the study and applies to the 
periodic report, the representative investigator shall report the information to the administrator of the 
investigational site and report to the certified review board using the format of Clinical Trials Act at the periodic 
report. Periodic report shall be made every year from the date of publication of the trial plan in the Registry of 
Clinical Trials (jRCT), the database maintained by the MHLW.  
 
2) Report to the Minister of Health, Labour and Welfare 
The representative investigator shall make the periodic report to the Minister of Health, Labour and Welfare 
using the format of Clinical Trials Act.  
 
10.7.3 Action to opinions of the certified review board 
When the certified review board states opinions to the representative investigator, the representative investigator 
shall respect such opinions and take necessary measures. The representative investigator shall report the opinions 

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of the certified review board to the administrator of the investigational site to which he/she belongs. If a specific 
action is required based on the opinions of the certified review board, the requirement shall be also reported. The 
representative investigator shall provide the information with other principal investigator(s). When the principal 
investigator obtain the information from the representative investigator, he/she shall report it to the administrator of 
the investigational site to which he/she belongs to, and also share the information with the sub-investigator(s).  
 
10.8 Other measures to be taken  
When AE, disease or the like, or device deficiency etc. was occurred, the principal investigator shall determine 
the following and take an action in accordance with the clinical research protocol. If the principal investigator makes 
the following 2) or 3) decisions, he/she shall inform the representative investigator of it. The representative 
investigator shall take necessary measures if he/she obtained information from other principal investigator or if the 
representative investigator made the following 2) or 3) decisions. 
1) Discontinuation of the study in each subjects 
2) Discontinuation or completion of the study 
3) Revision of the explanation document or consent document 
 
10.9 Pregnancy of subjects  
Women who is planning to become pregnant during this study period or women who are pregnant at the time of 
study entry are excluded from participation. 
 
10.10 Information provision of safety information 
When the safety information is identified, the investigator will provide the necessary information to the sponsor.  
 
11．ETHICS 
11.1 Certified review board  
Prior to the study initiation, the representative investigator asks the certified review board to inspect and evaluate 
the planned study from the ethical, scientific and medical points of view with an ultimate goal of protecting the 
human rights and welfare of the subjects, as to the acceptability of implementing the study, appropriateness of the 
contents of the protocol, case report form, questionnaire and informed consent document, and other matters related 
to the study. 
 
 
  
 
 
 
 

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11.2 Ethical consideration  
The study is implemented after a contract on implementation of the study is concluded between the sponsor and 
each study site following inspection and authorization of the study by the certified review board. 
If deemed necessary to ensure safe implementation of the study, the protocol of this study may be revised in 
accordance with the provisions set forth in “Section 12. PROTOCOL AMENDMENTS”. 
This study will be conducted in accordance with the principles set forth in the Declaration of 
Helsinki, the Clinical Trials Act (Act No. 16 of April 14, 2017), the Enforcement Regulations of the 
Clinical Trials Act (No.17 of February 28, 2018), and other relevant laws, ministerial ordinances, 
ministerial notifications, etc.  
 
11.3 Protection of subjects’ privacy 
To protect the privacy of individual subjects, only identification codes is used to represent the subjects whose 
data are used in case reports, etc., so that leakage of the identifiable individual information about the subjects can 
be prevented. 
 
11.4 Specifications to secure safety of study subjects 
1) Actions to take for AEs 
In the event of acknowledging any AEs, the investigator or the subinvestigator should promptly take appropriate 
actions irrespective of the presence or absence of causal relationship with the test article. 
 
2) Supply of new information 
In the case of obtaining safety-related new and significant information related to the clinical study, the sponsor 
should supply the information in writing to all the principal investigators and the heads of all study sites and take 
necessary actions. 
 
3) Avoiding emergent risks 
In the event of deviating from the clinical research protocol to avoid the emergent risk and secure safety of the 
study subject or because of other unavoidable clinical reasons, the investigator will retain the record and submit the 
documentation and reason of the protocol deviation to the administrator of the investigational site, the representative 
investigator, and the study sponsor. 
 
11.5 Compensation for health hazards 
If any subject has sustained health hazards arising from this study, best healthcare is provided to that subject. The 
Sponsor needs to be covered by insurance for liability arising from clinical trial. 
 
11.6 Payment to subjects 
 the sponsor pays an amount of money, 
predetermined through negotiation with each participating medical institution, to each subject. This payment 

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is not intended to force any subject to remain in the study. Explains the cost to reduce such burden as 
transportation expenses 
 
12．PROTOCOL etc. AMENDMENTS  
When the protocol, etc. are revised, the sponsor and the investigator will exchange an agreement in writing. The 
representative investigator will hear the opinion and obtain approval of the protocol amendments from the certified 
review board which is described in the clinical clinical research protocol. And then, the principal investigator will 
obtain approval of the protocol amendments from the administrator of the investigational site based on the results 
of the review. 
 
13．CONSIDERATIONS FOR DOCUMENTATION AND COMPLETION OF CASE REPORT 
FORM 
The investigator will complete the CRF by himself or herself based on source data in accordance with the protocol 
and the preparation procedure of the CRF. After preparation of the CRF, the investigator will sign or name and seal 
and date it, and submit it to the sponsor through the monitor. 
 
14．MONITORING 
The monitoring will be entrusted to the sponsor under the responsibility of the principal investigator and 
conducted under the supervision of the principal investigator. The Sponsor will designate a monitor to conduct the 
appropriate site visits at the appropriate intervals. The clinical investigation will be monitored to ensure the 
following items. The monitor will report the monitoring results to the Monitoring manager and the principal 
investigator. The principal investigator who received the report will notify the representative investigator of the 
contents of the report, if necessary. The representative investigator who received the notification will share the 
information of the notification to the other principal investigators. 
1) The rights and well-being of the subjects are protected. 
2) The reported data are accurate, complete, and verifiable from the source documents. 
3) The study is conducted in compliance with the current approved protocol (and amendment[s], if applicable), 
with the Clinical Trials Act (Act No. 16 of April 14, 2017), the Enforcement Regulations of the Clinical Trials 
Act (No.17 of February 28, 2018), and other relevant laws, ministerial ordinances, ministerial notifications, 
etc. 
 
15．RETENTION OF THE RECORDS 
The principal investigators shall preserve the protocol, source documents, informed consent forms agreed, 
informed consent form and other records that must be preserved in accordance with the Clinical Trials Act (Act 
No. 16 of April 14, 2017), the Enforcement Regulations of the Clinical Trials Act (No.17 of February 28, 2018), 
and other relevant laws, ministerial ordinances, ministerial notifications, etc. Above documents excluding medical 
records should be retained five years after the date of completion of the study. The storage period of clinical 
record depend on Medical Practitioners Act and other related regulations. 
At the end of the retention period, documents should be anonymized and disposed of in an appropriate manner. 

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16．CONFIDENTIALITY AND PUBLICATION OF STUDY 
All information related to this clinical study including the protocol and the clinical study results are the property 
of the sponsor, and the investigator and all other medical staff engaged in the clinical study must keep such 
information confidential. 
The sponsor can submit the results of this clinical study to the health authority and use the results as “Information 
on Proper Use” of the product. The representative investigator will register the summary of the study to jRCT before 
conducting the study, and will properly update it based on the revision of the trial plan or the study progression. 
When publishing the results of this clinical study in the congresses or medical journals etc., the investigators and 
all other medical staff engaged in the clinical study must obtain prior approval from the sponsor. The sponsor can 
confirm the contents of presentation before publication. After completion of the study, the sponsor and the 
investigators will report the results of the study after taking necessary steps for protecting the right and benefits of 
the subjects, related persons, sponsor, investigators, and so on. 
 
17．DIRECT ACCESS TO SOURCE DATA AND DOCUMENTS 
The investigator and the study site must make source data available to the sponsor or the regulatory authority at 
their request. Such direct access to source data will be performed so that the sponsor or the regulatory authority may 
confirm whether the clinical study is conducted in accordance with the protocol and whether data of the CRF are 
indicated accurately. 
With reference to [Assessment of AE] and [Comment of the investigator, etc.], there are no source data and they 
are information directly indicated on the CRF. 
The source data is all materials or documents that will become the basis of the data which is recorded in the CRF 
as results of the study. The source data in this study shall be patient records (including worksheets), informed consent 
forms agreed, informed consent form and other records, the photographic imaging data and the results of the central 
evaluation. The CRF shall be a source data if the description such as investigator’s opinion is written directly in the 
CRF.  
 
18．QUALITY CONTROL AND QUALITY ASSURANCE OF THE STUDY 
The quality control will be entrusted to the sponsor under the responsibility of the principal investigator. The 
sponsor will carry out the quality control in compliance with the sponsor’s standard operational procedures (SOP) 
for a clinical research under the supervision of the principal investigator. 
The quality assurance will be entrusted to the sponsor under the responsibility of the principal investigator. The 
sponsor will carry out the quality assurance in compliance with the sponsor’s SOP for the audit and the audit 
procedure of this study under the supervision of the principal investigator. 
The auditor will evaluate that the study is properly conducted according to the protocol, SOP of the department 
in charge of clinical research design/planning/implementation (Medical Affairs, Clinical Development, Clinical 
Biometrics), the Clinical Trials Act (Act No. 16 of April 14, 2017), the Enforcement Regulations of the Clinical 
Trials Act (No.17 of February 28, 2018), and other relevant laws, ministerial ordinances, ministerial notifications, 
etc. The auditor will report the audit results in accordance with the audit procedure of this study. 

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19．OBLIGATIONS OF INVESTIGATORS 
19.1 Obligations of principal investigators 
Agreement on and compliance with clinical research protocol(s) 
Prior to reaching an agreement with the sponsor on the clinical research protocol(s) and CRFs, the principal 
investigator(s) shall confer with the sponsor on the basis of the clinical research protocol(s), CRF, and other required 
materials and information submitted by the sponsor, and shall give full consideration to the ethical and scientific 
suitability of conducting the study. The same shall apply if the clinical research protocol(s) or CRF are revised. 
The principal investigator shall reach agreement with sponsor on the content of the clinical research protocol(s) 
and CRFs, and as evidence of agreement to comply with the clinical research protocol(s), the principal investigator 
and sponsor shall date and affix their signatures or personal seals to a trial contract or alternative document. The 
same shall apply if the clinical research protocol(s) or CRFs are revised, or if, due to a directive of the administrator 
of the investigational site based on the opinion the certified review board, the clinical research protocol(s) or CRF 
is corrected. 
 
Selection of study subjects 
In the selection of trial subjects, the principal investigator and sub-investigators shall, from the standpoint of 
human rights and on the basis of the standards for selection and exclusion set forth in the clinical research protocol(s), 
carefully consider whether to request participation in the study, taking into consideration such factors as the subject’s 
general state of health, symptoms, age, sex, capacity to consent, dependency on investigator, etc., and participation 
in other trials. 
 
Obtaining consent of subjects 
The principal investigator and sub-investigators shall obtain consent for the subject to participate in the trial from 
the subject or legally acceptable representative thereof, in accordance with Clinical Trials Act. 
 
Medical treatment of subjects 
The principal investigator shall have the responsibility for all decisions on medical treatment relating to the study. 
The administrator of the investigational site and the principal investigator shall ensure that the subject is provided 
with adequate medical treatment for all study-related AEs that constitute clinical problems during and after the 
subject’s participation in the study. Further, when the principal investigator or sub-investigator becomes aware of 
the need for medical treatment of an AE, he/she shall so inform the subject. 
The principal investigator or the sub-investigators shall confirm whether the subject has an another primary care 
physician or not, and with the subject's consent, inform the primary care physician of the subject’s participation in 
the study. 
If a subject desires to withdraw or withdraws participation during the study, the subject is not obliged to clarify 
the reason for withdrawal, but the principal investigator or sub-investigators shall make appropriate efforts, based 
on full respect for the rights of the subject, to determine the reason. After this study, the investigator shall provide 
the best treatment for the subjects using the result of this study. 

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Submission of documents to the certified review board 
Before and during the study period, the principal investigator shall keep current those documents that are subject 
to review by the certified review board and are to be submitted by the principal investigator. If these documents are 
augmented, updates or revised, all must be submitted promptly to the representative investigator. 
 
Permission from the administrator of the investigational site 
The principal investigator should start the clinical research after the certified review board has approved the 
conduct of the study or approved the conduct study, subject to any modification, and after obtaining the permission 
of the administrator of the investigational site based on the approval from the certified review board and confirming 
publication of such medical institution site in the jRCT. 
 
Use, etc., of the investigational product(s) 
The principal investigator shall ensure that the investigational product(s) are used only in accordance with 
methods that comply with the approved clinical research protocol(s). 
 
Compliance with clinical research protocol(s) 
The principal investigator or sub-investigators shall not undertake any deviation from or modification of study 
trial protocol(s) without prior written agreement between the principal investigator and the sponsor and written 
approval based on prior inspection by the certified review board. This is not, however, applicable in the case of 
changes related solely to cases that are medically unavoidable in order to avoid imminent danger to the subject, or 
in the case of management matters (e.g., a change in telephone number). 
 
Management of the deviations 
Deviation is defined as a condition in which the study is non-compliance from the ministerial ordinance or clinical 
research protocol pertaining to the conduct of the Specified Clinical Trials. Deviations, regardless of the reason, 
shall be managed as follows. The principal investigator or sub-investigator must record all deviations from the 
clinical research protocol, regardless of the reason. 
1) 
When the principal investigator finds a deviation, he/she shall promptly report it to the administrator of the 
investigational site and notify the representative investigator.  
2) 
If a significant deviation is identified that may affect the human rights, safety of subjects, the progress of the 
clinical research and the reliability of the results (e.g., non-compliance with inclusion/exclusion criteria, 
termination criteria, etc.), the principal investigator shall promptly request the representative investigator to 
hear the opinion of the certified review board listed in the protocol. 
Significant deviations do not include failure to comply with the protocol for unavoidable medical reasons, 
such as to avoid immediate danger to the subjects. 
3) 
When the sub-investigator becomes aware of a deviation, he/she shall promptly report it to the principal 
investigator. 
 

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Recording and reporting the CRF 
The principal investigator or sub-investigators shall prepare CRFs in accordance with the clinical research 
protocol(s), affix thereto his or her signature or personal seal, and submit them to the sponsor. The principal 
investigator shall retain copies of the CRFs submitted. 
The principal investigator shall inspect CRFs prepared by sub-investigators prior to their submission to the 
sponsor, and upon confirming that there is no problem, affix thereto his or her signature or personal seal. The 
principal investigator shall also inspect modifications or revisions to CRFs undertaken by sub-investigators, and 
confirm that there is no problem. 
The principal investigator shall ensure that the data in the CRFs and all other documents submitted to the sponsor 
are accurate, complete, legible, and submitted in a timely manner, and that a subject identification code is used for 
identifying subjects. 
Data in the CRFs that are based on original materials shall not conflict with the original materials. When there is 
any discrepancy with the original, the principal investigator shall prepare a record explaining the reason therefore, 
submit it to the sponsor, and retain a copy. 
In modifying or correcting CRFs, the principal investigator or sub-investigators shall follow the manual provided 
by the sponsor. If there is any modification or correction whatever in a CRF, it must be dated and the signature or 
personal seal affixed. An explanation of the change must be provided if the change is critical. Further the 
modification or correcting shall not be such as to render the initial writing unclear (i.e., an audit trail shall be 
maintained). 
The principal investigator should submit records of modification and correction of the CRFs to the sponsor and 
retain a photocopy of each record. 
 
19.2 Obligations of representative investigator 
Reporting of the significant deviations 
When the representative investigator recognize the significant deviation that may affect the human rights and 
safety of subjects, the progress of the research, and the reliability of the results (e.g., non-compliance with 
inclusion/exclusion criteria, termination criteria, etc.), he/she shall promptly hear the opinion of the certified review 
board listed in the protocol. 
Significant deviations do not include failure to comply with the protocol for unavoidable medical reasons, such 
as to avoid immediate danger to the subjects.  
 
The periodical reports to the certified review board 
The representative investigator shall report the status of the progress of the Specified Clinical Trials to the 
administrator of the investigational site every year from the date of submission of the Trial Plan to the Minister of 
Health, Labour and Welfare, and within two months after the expiration of the period. In addition, the representative 
investigator should make periodic reports to the certified review board listed in the research protocol. The following 
items shall be reported on the status of progress/implementation; 
 
Number of subjects  

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 
Occurrence of disease or the like and its progress 
 
Occurrence of deviations and subsequent actions 
 
Evaluation of safety and scientific validity 
 
Matters concerning the involvement of manufacturers described in the conflict of interest management 
standards 
 
The periodical reports to the Minister of Health, Labour and Welfare 
The representative investigator shall report the status of the progress of the Specified Clinical Trials with the 
following matters to the Minister of Health, Labour and Welfare within one month from the date on which the 
certified review board listed in the trial plan stated opinion; 
 
Name of the certified review board described in the Trial Plan 
 
Adequacy of continuation of this research judged by the certified review board 
 
Number of subjects 
 
Occurrence of the disease or the like and its progress 
 
Occurrence of deviations and subsequent actions 
 
Evaluation of safety and scientific validity 
 
Matters concerning the involvement of manufacturers described in COI management standards 
 
Discontinuation of clinical research / Reporting of the study completion 
When discontinuing the entire clinical research, the representative investigator should state the reason for the 
termination in the discontinuation notice (Clinical Trials Act format) and submit it to the certified review board 
within 10 days from the discontinuation date. At the same time, a notification form for discontinuation of the 
Specified Clinical Trials (Ministerial Ordinance Form) must be entered and notified to the Minister of Health, Labor 
and Welfare. 
The representative investigator shall provide information with the principal investigator and, if necessary, hear 
the opinion of the certified review board regarding the timing and the method of completion of the study due to the 
subject's measures. Even if representative investigator submit a discontinuation notice, he/she shall continue to 
report disease or the like and periodic reports, etc. until the research is completed. If the trial plan needs to be 
changed, the change shall be notified. 
In the case where the representative investigator submits a notification of discontinuation and completes the 
measures of the subject, he/she shall prepare a CSR within 1 year from the date of study discontinuation or the end 
of the period for collecting data related to all evaluation items, whichever is later. The representative investigator 
shall submit the CSR to the certified review board. In addition, the representative investigator shall also submit the 
CSR to both the administrator of the investigational site and the Minister of Health, Labor and Welfare. 
 
Publication of research results and completion report  
The representative investigator shall prepare the primary outcome report within a year from the date of the end 
of the collection period of the primary endpoint data, and hear the opinion of the certified review board using the 

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review request form for change (Clinical Trials Act format).After approval, the report should be registered in the 
jRCT and reported to the administrator of the investigational site. And the representative investigator shall submit 
the notification for changes in trial plan (Ministerial Ordinance Form)  to the Minister of Health, Labor and Welfare. 
The representative investigator shall prepare a CSR and a summary of CSR (Clinical Trials Act Exhibit Form) 
within a year of the completion from the date of the end of all data collection periods, and shall hear the opinion of 
the certified review board after preparation of a termination notice (Clinical Trials Act form). The representative 
investigator shall register the summary of CSR in the jRCT within one month of approval from the certified review 
board, and shall report it to the administrator of the investigational site and submit the summary of CSR along with 
the clinical research protocol and statistical analysis plan to the Minister of Health, Labor and Welfare. 
The representative investigator shall provide information about the above to each principal investigators, and 
the principal investigators shall report it to the administrators of the investigational sites. 
 
Retention of the records 
The principal investigator shall refer to "15. RETENTION OF THE RECORDS" and storage the relevant 
materials appropriately.  
 
Others 
The representative investigator should report to the certified review board and the Minister of Health, Labour and 
Welfare as necessary and appropriate, including applications for changes and reports as stipulated in “Report of 
disease or the like to the certified review board and the Minister of Health, Labour and Welfare”. 
 
20．INFORMED CONSENT 
Time to obtain consent 
The principal investigator or sub-investigator will obtain written consent by the study subject prior to the 
commencement of the study. 
 
Methods for explaining to trial subjects 
The principal investigator (or sub-investigator) will give explanations to study subjects. Study collaborators can 
give supplemental explanations. 
The explanations should be given based on the explanation/consent document using terms which are the most 
easy to understand (non-technical terms). Questions made by trial subjects should be answered appropriately in the 
way the study subjects can understand. 
 
Methods for obtaining consent 
(1) 
The principal investigator (or sub-investigator) who has given explanations will sign and date the consent 
document. 
(2) 
If any study collaborator has given supplemental explanations, the study collaborator will also sign and date 
the consent document. (Study collaborators are not allowed to solely give all necessary explanations to study 

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37 
 
subjects.) 
(3) 
Supply the study subject with the consent document and explanation document describing aforementioned 
necessary information and take sufficient time for the study subject to decide whether or not he/she should 
participate in the clinical study. 
(4) 
Before obtaining consent, take sufficient time for the study subject to sufficiently review the consent items 
and ask any questions. Answer the questions in a convincing manner. 
(5) 
Obtain the study subject's spontaneous written consent to participate in the clinical study. 
(6) 
After obtaining the consent document signed and dated by the study subject, the principal investigator (or 
sub-investigator) will enter the date of consent in the CRF and in the medical record. All consent documents 
must be retained. 
(7) 
Supply the study subject with the copy (duplicate for the study subject) of the consent document and the 
explanation document before the study subject participates in the clinical study. 
(8) 
If the explanation document or consent document is subject to revision during the participation of the study 
subject, follow the above procedures and re-obtain consent. 
 
Items mentioned for the written informed consent form and explanatory documents 
The items mentioned for the written informed consent form and explanatory documents are in accordance with 
“Clinical Study Protocol (version 3.0)” because the informed consent has been already obtained from all of the 
study subjects in this study. 
(1) 
The fact that the clinical study involves research. 
(2) 
The purpose of the study. 
(3) 
The name and title of the principal investigator or sub-investigator, and how he/she can be contacted. 
(4) 
The study method (including the aspects of the trial that are experimental, subject’s inclusion/exclusion 
criteria, and when the study is randomized, the probability of randomization for each treatment). 
(5) 
The expected clinical benefits, and the foreseeable risks or inconveniences to the subjects. (If any benefits 
for the subject will not be expected, it must be informed to the subject.) 
(6) 
When the persons to be enrolled as study subjects are patients, the availability of other medical treatments 
for their condition, and the potential major benefits and risks of such treatments as are available. 
(7) 
The expected duration of the subjects’ participation in the study. 
(8) 
That participation in the study is voluntary; that the study subject can refuse to participate in the study or can 
withdraw from the study at any time and that the subjects will not be disadvantaged or lose any benefit to 
which they are entitled if they refuse to enroll in the trial or if they withdraw from the trial after enrolling. 
(9) 
Handling of investigational products in case of withdrawing from the clinical study.  
(10) That the study monitor, auditor, Institutional Review Board (IRB), and regulatory authorities are allowed to 
examine the source data, that the confidentiality of the study subjects will be protected when those data are 
examined by those persons; and that the subjects authorize the perusal of those data by those persons by 
sealing and/or signing the written consent form. 
(11) That the subjects’ confidentiality will be protected even when the results of the clinical study are published. 

Protocol No.：ILV814-P001 
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38 
 
(12) The person in the study site whom the subjects should contact for further information about the study or their 
rights, or if they develop a health problem associated with the study. 
(13) The compensation and medical treatment the study subjects can receive should they develop a health problem 
associated with the study. 
(14) The number of subjects expected to be enrolled in the study (including discrete variable). 
(15) That if information is received that may affect the will of the subjects regarding the subjects’ ongoing 
participation in the study, that information will be passed on promptly to the subjects. 
(16) The circumstances under which or the reasons subjects will be withdrawn from the study. 
(17) The specifics about any expense the study subjects will have to pay. 
(18) The specifics about any cash or the like that will be paid to the study subjects (including the arrangement for 
calculating the sum to be paid). 
(19) Responsibilities of the study subjects. 
(20) Information about IRB. 
(21) The name of the study and the fact that the head of medical institute approved the conduct of the study 
(22) The procedure of disclosure of information 
(23) The fact that the documents related to protocol and procedure of the study are available, as far as there is no 
interruption regarding protection of personal information and originality of the study, depending on the 
request from subject etc. Also procedure of its access. 
(24) Handling of personal information (including the procedure of anonymity, if applicable). 
(25) The procedure of storing and disposal of the information. 
(26) Conflict of interest of the investigator, medical institution etc. regarding the study, including funding source, 
personal income and so on. 
(27) If there is a possibility that the sample or information of subjects might be used in future study or provided 
to other research institution, the fact and assumed contents when informed consent is obtained. 
 
Revision of informed consent form and explanatory documents 
If the principal investigator acknowledges the necessity of revising the explanatory document used for obtaining 
consent, in the case of the obtainment of the information which may affect the study subject's intention to 
continuously participate in the clinical study or in other cases, the principal investigator shall immediately report it 
to the representative investigator. The representative investigator inform the other principal investigator of it 
immediately. The principal investigator shall revise the explanatory document as needed (refer to “12. PROTOCOL 
AMENDMENTS”). The representative investigator will hear the opinion and obtain approval of the revision of 
explanatory document from the certified review board which is described in the clinical clinical research protocol. 
And then, the principal investigator will obtain approval of the revision of explanatory document from the 
administrator of the investigational site based on the results of the review. 
 
 

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39 
 
21．PROVIDE SERVICES RELATED To CONDUCTING RESEARCH 
In this clinical research, Alcon Japan provides the following services. The following services will be entrusted to 
Alcon Japan under the responsibility of the principal investigator and conducted supervised by the representative 
investigator. 
Details of the services to be provided: Creating a protocol, data management, monitoring, statistics, analysis,  
audit, creating reports, registration and updating of jRCT etc. 
 
22．CONFLICT OF INTEREST 
Alcon Japan Ltd. is the sponsor of this clinical study. Alcon Japan Ltd. and the administrator of the investigational 
site will sign a contract for the clinical study. Financial cost of the study will be sponsored by Alcon Japan Ltd. in 
accordance with the contract. 
Regarding cost of the central evaluation, Alcon Japan Ltd. 
 will sign a contract for 
collaborative research about the central evaluation. Financial cost of the central evaluation will be sponsored by 
Alcon Japan Ltd. in accordance with the contract. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23．REFERENCES 
1） Shinichi Ito. Medical insurance and intraocular lenses. Journal of the Eye, 20: 615-620, 2003. 
2） Ken Hayashi. New foldable intraocular lenses. Japanese Journal of Cataract and Refractive Surgery, 16: 453-
458, 2002. 
3） Kimiya Shimizu. Revaluation of cataract surgery. Journal of the Eye, 16(9): 1185-1189, 1999. 
4） Toshiyuki Miyake. Corneal astigmatism before cataract surgery. Journal of Japanese Ophthalmological Society, 
115: 447-453, 2011. 
5） Kimiya Shimizu, et al. Toric intraocular lenses correcting astigmatism while controlling axis shift. J Cataract 
Refract Surg., 29: 523-526, 1994. 
 

 
40 
 

 
 
 
 
 
 
 
 
 
AcrySof IQ Toric A-code Post Market Clinical Study 
 
 
 
 
Clinical Research Protocol  
Supplemental Attachment 
 
 
 
A 
Clinical Trial System, Participating Facilities and Principal Investigators 
B 
Package Insert: Alcon® AcrySof® IQ Toric Single-Piece IOL 
C 
Grading Scales for Glistening 
 
 
 
 
F 
Creation and Storage of Records Relating to the Provision of Samples 
and Information 
 
 
Alcon Japan Ltd. 
Toranomon Minato-ku, Tokyo 
 
 
 
 
 
Protocol No.：ILV814-P001 
Ver.4.0: January 5, 2021 
Ver.5.0: March 22, 2021 

 
1 
 
Supplemental Attachment A: 
Clinical Trial System, Participating Facilities and Principal Investigators 
 
1．CLINICAL TRIAL SYSTEM 
1.1 
Sponsor 
Alcon Japan Ltd. Representative: Richard Kozloski, CEO 
1-23-1 Toranomon, Minato-ku, Tokyo, 105-6333, Japan 
TEL: 03-6899-5061/FAX: 03-6257-3650 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 

 
2 
 
 
 
  
 
 
  
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
3 
 
Supplemental Attachment B: Package Insert 
 

 
4 
 
 

 
5 
 
 

 
6 
 
Supplemental Attachment C: Grading Scales for Glistening 
 
Frequency of the glistening in optic segment of IOL shall be observed by slit-lamp and assessed using following 
scales. 
 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
No glistening 
Mild 
(50/mm3) 
Moderate 
(100/mm3) 
Severe 
(200/mm3) 
 
 
 
 
 
Reference: Akira Miyata. Glistening particles on the implanted acrylic intraocular lens. Japanese Journal of Clinical 
Ophthalmology, 51(4): 729-732, 1997. 
 
 
 
 

 
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