SIST EN ISO 11979-7:2014
(Main)Ophthalmic implants - Intraocular lenses - Part 7: Clinical investigations (ISO 11979-7:2014)
Ophthalmic implants - Intraocular lenses - Part 7: Clinical investigations (ISO 11979-7:2014)
ISO 11979-7 specifies particular requirements for clinical investigations for posterior and anterior chamber intraocular lenses (IOLs).
Ophthalmische Implantate – Intraokularlinsen - Teil 7: Klinische Prüfungen (ISO 11979-7:2014)
Dieser Teil von ISO 11979 legt besondere Anforderungen an die klinische Prüfung von Hinterkammer- und Vorderkammer-Intraokularlinsen (IOLs) fest.
Implants ophtalmiques - Lentilles intraoculaires - Partie 7: Investigations cliniques (ISO 11979-7:2014)
L'ISO 11979-7:2014 spécifie les exigences particulières relatives aux investigations cliniques sur les lentilles intraoculaires (LIO) de chambres antérieure et postérieure.
Očesni vsadki (implantati) - Intraokularne leče - 7. del: Klinične raziskave (ISO 11979-7:2014)
Standard ISO 11979-7 določa posebne zahteve za klinične raziskave za intraokularne leče v zadnjem in sprednjem prekatu.
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 11979-7:2014
01-november-2014
1DGRPHãþD
SIST EN ISO 11979-7:2006
SIST EN ISO 11979-7:2006/A1:2012
2þHVQLYVDGNL LPSODQWDWL ,QWUDRNXODUQHOHþHGHO .OLQLþQHUD]LVNDYH ,62
Ophthalmic implants - Intraocular lenses - Part 7: Clinical investigations (ISO 11979-
7:2014)
Ophthalmische Implantate – Intraokularlinsen - Teil 7: Klinische Prüfungen (ISO 11979-
7:2014)
Implants ophtalmiques - Lentilles intraoculaires - Partie 7: Investigations cliniques (ISO
11979-7:2014)
Ta slovenski standard je istoveten z: EN ISO 11979-7:2014
ICS:
11.040.70 Oftalmološka oprema Ophthalmic equipment
SIST EN ISO 11979-7:2014 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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SIST EN ISO 11979-7:2014
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SIST EN ISO 11979-7:2014
EUROPEAN STANDARD
EN ISO 11979-7
NORME EUROPÉENNE
EUROPÄISCHE NORM
September 2014
ICS 11.040.70 Supersedes EN ISO 11979-7:2006
English Version
Ophthalmic implants - Intraocular lenses - Part 7: Clinical
investigations (ISO 11979-7:2014)
Implants ophtalmiques - Lentilles intraoculaires - Partie 7: Ophthalmische Implantate - Intraokularlinsen - Teil 7:
Investigations cliniques (ISO 11979-7:2014) Klinische Prüfungen (ISO 11979-7:2014)
This European Standard was approved by CEN on 18 July 2014.
CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this European
Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references concerning such national
standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN member.
This European Standard exists in three official versions (English, French, German). A version in any other language made by translation
under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management Centre has the same
status as the official versions.
CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and United
Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
CEN-CENELEC Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2014 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 11979-7:2014 E
worldwide for CEN national Members.
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SIST EN ISO 11979-7:2014
EN ISO 11979-7:2014 (E)
Contents Page
Foreword .3
2
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SIST EN ISO 11979-7:2014
EN ISO 11979-7:2014 (E)
Foreword
This document (EN ISO 11979-7:2014) has been prepared by Technical Committee ISO/TC 172 “Optics and
photonics” in collaboration with Technical Committee CEN/TC 170 “Ophthalmic optics” the secretariat of which
is held by DIN.
This European Standard shall be given the status of a national standard, either by publication of an identical
text or by endorsement, at the latest by March 2015, and conflicting national standards shall be withdrawn at
the latest by March 2015.
Attention is drawn to the possibility that some of the elements of this document may be the subject of patent
rights. CEN [and/or CENELEC] shall not be held responsible for identifying any or all such patent rights.
This document supersedes EN ISO 11979-7:2006.
According to the CEN-CENELEC Internal Regulations, the national standards organizations of the following
countries are bound to implement this European Standard: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech
Republic, Denmark, Estonia, Finland, Former Yugoslav Republic of Macedonia, France, Germany, Greece,
Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal,
Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the United Kingdom.
Endorsement notice
The text of ISO 11979-7:2014 has been approved by CEN as EN ISO 11979-7:2014 without any modification.
3
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SIST EN ISO 11979-7:2014
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SIST EN ISO 11979-7:2014
INTERNATIONAL ISO
STANDARD 11979-7
Third edition
2014-09-01
Ophthalmic implants — Intraocular
lenses —
Part 7:
Clinical investigations
Implants ophtalmiques — Lentilles intraoculaires —
Partie 7: Investigations cliniques
Reference number
ISO 11979-7:2014(E)
©
ISO 2014
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SIST EN ISO 11979-7:2014
ISO 11979-7:2014(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2014
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized otherwise in any form
or by any means, electronic or mechanical, including photocopying, or posting on the internet or an intranet, without prior
written permission. Permission can be requested from either ISO at the address below or ISO’s member body in the country of
the requester.
ISO copyright office
Case postale 56 • CH-1211 Geneva 20
Tel. + 41 22 749 01 11
Fax + 41 22 749 09 47
E-mail copyright@iso.org
Web www.iso.org
Published in Switzerland
ii © ISO 2014 – All rights reserved
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SIST EN ISO 11979-7:2014
ISO 11979-7:2014(E)
Contents Page
Foreword .iv
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Justification for a clinical investigation . 1
5 Ethical considerations . 1
6 General requirements . 1
6.1 General . 1
6.2 Design . 2
6.3 Characteristics . 2
6.4 Investigation duration . 4
6.5 Enrollment . 4
6.6 Bilateral implantation . 4
6.7 Surgical technique . 4
6.8 Examination and treatment of subjects. 5
6.9 Adverse events reports . 5
6.10 Inclusion and exclusion criteria . 5
Annex A (informative) Elements of a clinical investigation . 7
Annex B (informative) Evaluation of post-operative adverse event and visual acuity rates .15
Annex C (informative) Additional elements for toric IOLs .19
Annex D (informative) Additional elements for accommodating IOLs .26
Annex E (informative) Clinical tests .35
Bibliography .41
© ISO 2014 – All rights reserved iii
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SIST EN ISO 11979-7:2014
ISO 11979-7:2014(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
through ISO technical committees. Each member body interested in a subject for which a technical
committee has been established has the right to be represented on that committee. International
organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.
ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of
electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2. www.iso.org/directives
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received. www.iso.org/patents
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation on the meaning of ISO specific terms and expressions related to conformity
assessment, as well as information about ISO’s adherence to the WTO principles in the Technical Barriers
to Trade (TBT) see the following URL: Foreword - Supplementary information
The committee responsible for this document is ISO/TC 172, Optics and photonics, Subcommittee SC 7,
Ophthalmic optics and instruments.
This second edition cancels and replaces the third edition (ISO 11979-7:2006), which has been technically
revised. It also incorporates the Amendment ISO 11979-7:2006/Amd1:2012 .
ISO 11979 consists of the following parts, under the general title Ophthalmic implants — Intraocular
lenses:
— Part 1: Vocabulary
— Part 2: Optical properties and test methods
— Part 3: Mechanical properties and test methods
— Part 4: Labelling and information
— Part 5: Biocompatibility
— Part 6: Shelf-life and transport stability testing
— Part 7: Clinical investigations
— Part 8: Fundamental requirements
— Part 9: Multifocal intraocular lenses
— Part 10: Phakic intraocular lenses
iv © ISO 2014 – All rights reserved
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SIST EN ISO 11979-7:2014
INTERNATIONAL STANDARD ISO 11979-7:2014(E)
Ophthalmic implants — Intraocular lenses —
Part 7:
Clinical investigations
1 Scope
This part of ISO 11979 specifies particular requirements for clinical investigations for posterior and
anterior chamber intraocular lenses (IOLs).
2 Normative references
The following documents, in whole or in part, are normatively referenced in this document and are
indispensable for its application. For dated references, only the edition cited applies. For undated
references, the latest edition of the referenced document (including any amendments) applies.
ISO 11979-1, Ophthalmic implants — Intraocular lenses — Part 1: Vocabulary
ISO 11979-10, Ophthalmic implants — Intraocular lenses — Part 10: Phakic intraocular lenses
ISO 14155, Clinical investigation of medical devices for human subjects — Good clinical practice
ISO 14971, Medical devices — Application of risk management to medical devices
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 11979-1 and ISO 14155 apply.
4 Justification for a clinical investigation
If the need for a clinical investigation is identified, the requirements of ISO 14155 shall apply, with
additional requirements given below.
If a new IOL model is a modification of a model for which the safety and performance have been
established through clinical investigation in accordance with this part of ISO 11979 no or limited
[1]
clinical investigation is needed. ISO/TR 22979 provides guidance in determining whether or not a
modification is minor.
5 Ethical considerations
For clinical investigations of medical devices for human subjects, the requirements in ISO 14155 shall
apply.
6 General requirements
6.1 General
The requirements for a clinical investigation given in ISO 14155 shall apply, with additional requirements
given below.
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SIST EN ISO 11979-7:2014
ISO 11979-7:2014(E)
6.2 Design
6.2.1 General
A clinical investigation shall be designed to compare results to historical data on adverse events and
visual acuity rates. Annex A provides general guidance for the design of a clinical investigation. Historical
data can be found in Annex B.
6.2.2 Additional requirements for toric IOLs
For all toric IOLs, the rotational stability of a non-toric version that is mechanically and geometrically
equivalent to the toric IOL shall be demonstrated.
The following performance criteria for rotational stability shall be fulfilled: the rotation of the meridian
defined by the IOL axis indicator as measured and compared between Day 0 (the day of surgery) post-
operative examination and the form 4 examination shall be less than 10° in 90 % of the cases, less than
20° in 95 % of the cases, and less than 30° in 99 % of the cases.
Then, if necessary due to risk analysis, a clinical investigation shall be performed using the toric version
of the model.
In the event that a toric IOL clinical investigation is required due to risk analysis, the subjects that
undergo secondary surgery to correct IOL axis mark rotation shall have their clinical results prior to
the secondary surgery carried forward as the final results for that subject. In the case of examinations
scheduled to be performed later in the clinical investigation, the sponsor shall consider requiring each
of these examinations to be performed prior to the secondary surgery, if possible.
Additional elements for toric IOLs are outlined in Annex C.
6.2.3 Additional requirements for accommodating IOLs
A controlled clinical investigation of an accommodating IOL shall evaluate the additional safety and
performance concerns, specifically including the evaluation of accommodative amplitude using at least
one objective method. Guidance on clinical investigation of accommodating IOLs is outlined in Annex D.
It shall consist of two phases, with phase two beginning only after the first phase has demonstrated
that the accommodating IOL provides an average of at least 1 D of objective accommodation. The overall
study shall demonstrate that the accommodating IOL also provides 1 D of objective accommodation at
the point of stabilization.
6.3 Characteristics
The clinical investigational plan shall provide information regarding characteristics to be studied, and
instructions regarding the grading and documentation of these characteristics. Whenever possible,
objective methods shall be used, such as photographic imaging.
The following characteristics shall be considered. If additional claims are to be made, additional
corresponding characteristics shall be studied.
6.3.1 General characteristics
a) best spectacle corrected visual acuity (BSCVA);
b) subjective refraction;
c) intraocular pressure;
d) corneal status;
2 © ISO 2014 – All rights reserved
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SIST EN ISO 11979-7:2014
ISO 11979-7:2014(E)
e) signs of inflammation:
1) anterior chamber cells;
2) anterior chamber flare;
3) cystoid macular oedema;
4) hypopyon;
5) endophthalmitis;
f) pupillary block;
g) retinal detachment;
h) status of anterior and posterior capsule;
[2]
i) IOL decentration;
[2]
j) IOL tilt;
k) IOL discoloration;
l) IOL opacity.
6.3.2 Toric IOL characteristics
a) uncorrected visual acuity;
b) keratometry;
c) IOL mark axis rotation.
6.3.3 Accommodating IOL characteristics
a) uncorrected visual acuity at distance, intermediate and near;
b) visual acuity at near and intermediate with best distance correction;
c) best corrected near visual acuity;
d) additional refraction (over best distance subjective correction) required to achieve best corrected
near acuity;
e) objective accommodative amplitude;
f) contrast sensitivity;
g) subject questionnaire;
h) pupil size.
6.3.4 Additional characteristics
If justified by the risk analysis, these additional characteristics shall be considered.
a) cycloplegic refraction;
b) specular microscopy;
c) gonioscopic examination;
d) pupil size;
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SIST EN ISO 11979-7:2014
ISO 11979-7:2014(E)
e) anterior chamber depth measurement.
6.4 Investigation duration
The minimum duration of the clinical investigations shall be one year (see Annex A for visit window
tolerance) for aphakic posterior chamber IOLs which are not modifications of a model for which safety
and performance data have been established through clinical investigation.
The minimum duration of the clinical investigations shall be three years (see Annex A for visit window
tolerance) for aphakic anterior chamber IOLs which are not modifications of a model for which safety
and performance data have been established through clinical investigation.
For all toric IOLs, a six-month study of the non-toric version of the IOL shall be performed to ensure
rotational stability. Then for toric IOLs that are a modification of an IOL that has met the requirements
of all parts of ISO 11979, risk analysis may require that this rotational stability study is followed by a
clinical investigation of the actual toric IOL for six months. Toric IOLs that are not a modification of an
IOL that has met the requirements of all parts of ISO 11979 shall require a full clinical investigation of
one year duration.
The minimum study duration for accommodating IOLs through clinical investigation shall be one year
but may require up to three years based on the risk analysis.
[1]
Consult ISO/TR 22979 for guidance on investigation duration for modifications of lens models for
which safety and performance have been established through clinical investigation.
All subjects in a clinical investigation that have not been discontinued shall complete all visits of the
investigation. The clinical investigation shall be considered completed when all subjects that have been
enrolled in the investigation, including subjects whose IOL was removed or replaced, have reached the
final reporting period.
6.5 Enrollment
To minimize the risks associated with the clinical investigation of a new IOL, subject enrollment shall
occur in stages. The subject data from each stage shall be evaluated and found acceptable by the sponsor
and the coordinating investigator (and by the regulatory body, if applicable) prior to the continuation
of the clinical investigation. Guidance on phased enrollment is included in Annex A (monofocal IOL),
Annex C (toric IOL) and Annex D (accommodating IOL).
Risk analysis should be used to determine if an earlier phase than the phase 1 listed in the Annexes
above is needed to address safety issues associated with the IOL design.
6.6 Bilateral implantation
Any plans for fellow eye implantation shall be described in the clinical investigation plan. Bilateral
implantation shall not be implemented until initial safety and performance data have been collected,
evaluated and confirmed by the sponsor and coordinating investigator (and by the risk analysis, if
applicable). Only the first eye of each subject shall be included in the primary statistical analysis.
When implantation of fellow eye is permitted, the clinical investigation plan shall specify time period
between implantation of first eye and of fellow eye, based upon risk analysis.
NOTE The review of data from at least 50 eyes with six months of follow-up is recommended prior to fellow
eye implantation. Risk analysis might allow an earlier implantation in fellow eyes if sufficiently justified by
previous clinical experience.
6.7 Surgical technique
The clinical investigation plan shall contain descriptions of the surgical technique, the intraoperative
use of ophthalmic viscosurgical devices, and the use of preoperative, intraoperative and postoperative
medications. Any deviation shall be recorded on the case report forms.
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SIST EN ISO 11979-7:2014
ISO 11979-7:2014(E)
For toric IOLs, the clinical investigation plan shall specify the type and location of the incision. The
estimated effect of the incision on the corneal astigmatism shall be used in the protocol for choosing the
appropriate cylindrical power.
6.8 Examination and treatment of subjects
The reporting periods are described in Annex A.
The clinical investigation plan shall describe how subject visits and ophthalmic adverse events that
occur between standard reporting periods will be handled in the data analyses.
6.9 Adverse events reports
Serious adverse events and all adverse device effects shall be reported using a special case report
form and forwarded to the sponsor as required. All other ophthalmic adverse events shall be reported
using either the standard visit case report form or specific adverse event forms and be collected during
monitoring. Non-ophthalmic events that are non-serious are not required to be reported.
6.10 Inclusion and exclusion criteria
6.10.1 General
The following inclusion/exclusion criteria shall be considered. Additional criteria shall be included
depending on the risk analysis for the particular IOL model.
6.10.1.1 Inclusion criteria
a) adult;
b) cataract (does not apply for phakic IOL);
c) best corrected visual acuity projected to be 0,2 logMAR or lower;
d) calculated IOL power is within the range of the investigational IOL;
e) signed informed consent form.
6.10.1.2 Exclusion criteria
a) previous intraocular and corneal surgery;
b) traumatic cataract;
c) pregnancy and lactation;
d) concurrent participation in another drug or device investigation.
6.10.2 Additional criteria for toric IOL
6.10.2.1 Inclusion criteria
a) corneal cylindrical error within the range defined in the clinical investigation plan (CIP);
b) stability of the cornea has been demonstrated by keratometry;
c) expected dilated pupil size at least large enough to visualize the axis markings.
6.10.2.1.1 Additional inclusion criteria for phakic toric IOLs
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SIST EN ISO 11979-7:2014
ISO 11979-7:2014(E)
a) the inclusion criteria described in ISO 11979-10 shall be considered.
6.10.2.2 Exclusion criteria
6.10.2.2.1 Additional exclusion criteria for phakic toric IOLs
The exclusion criteria described in ISO 11979-10 shall be considered.
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SIST EN ISO 11979-7:2014
ISO 11979-7:2014(E)
Annex A
(informative)
Elements of a clinical investigation
A.1 General
The following are elements of a clinical investigation plan which can assist in collecting data for the
purpose of determining the safety and performance of IOLs.
A.2 Number of subjects
The clinical investigation includes a minimum of 300 subjects when the results are compared to the
safety and performance end points in Annex B. In the case of an investigation with a concurrent control
group, calculate the number of subjects sufficient to detect differences in the safety and performance end
points in Annex B with similar statistical power to the investigation mentioned above. Any additional
claims, beyond those for safety and performance, require calculation of a sample size for that purpose.
To take into account that some subjects are lost during the course of the clinical investigation (including
deceased subjects and subjects who have the IOL explanted), enrol about:
a) 390 subjects in the one-year investigation;
b) 500 subjects in the three-year investigation.
Significantly larger numbers of subjects are not to be enrolled in order to minimize exposure to the risks
of a new IOL.
To assist in achieving a balance in the number of subjects from each investigator, each surgeon contributes
a minimum of 20 subjects, but no more than 25 % of the subjects in the investigation.
[1]
If the risk analysis determines that a limited clinical investigation is sufficient (see ISO/TR 22979 ),
then enroll 125 subjects.
A.3 Phased enrolment
To minimize the potential risks, the clinical investigation consists of two phases:
a) phase 1: a maximum of 100 subjects are included. After at least 50 of those have reached case report
form 4, their data are evaluated. If the results are acceptable, the next phase can begin;
b) phase 2: the remainder of the subjects are included.
A.4 Reporting periods
The time frames for the reporting periods are defined below:
a) case report form 0: pre-operative/operative reporting;
b) case report form 1: 1 or 2 days post-operatively;
c) case report form 2: 7 to 14 days post-operatively;
d) case report form 3: 30 to 60 days post-operatively;
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SIST EN ISO 11979-7:2014
ISO 11979-7:2014(E)
e) case report form 4: 120 to 180 days post-operatively;
f) case report form 5: 330 to 420 days post-operatively.
g) case report form 6: 630 to 780 days post-operatively;
h) case report form 7: 990 to 1 140 days post-operatively.
The minimum sample size needs to be achieved at each of the reporting periods.
A.5 Standardization of the clinical evaluation
Define criteria for evaluation of all studied variables. Define testing conditions for all measurements.
Before commencing the investigation instruct and train all investigators to use these, in order to obtain
data that can be combined for the purpose of statistical analysis.
A.6 Data analysis
Consider the following analyses for both the first eye group and the total eye group:
a) visual acuity (VA) stratified by age;
b) VA for best-case subjects;
c) VA stratified by adverse event;
d) VA stratified by pre-operative ocular pathology;
e) VA stratified by investigator;
f) subject-by-subject analysis of reasons why subject failed to achieve 0,3 logMAR VA;
g) frequency of, and the cause of loss of 10 letters or more on an EDTRS chart (or equivalent) compared
to best post-op visual acuity;
h) frequency of cumulative adverse events stratified by age;
i) frequency of persistent adverse events stratified by age;
j) adverse event stratified by investigator;
k) IOL related adverse events (two-sided 95 % confidence interval).
A.7 Subject accountability
The general requirement for accountability of subjects is given in ISO 14155. More specific guidance for
subject accountability at each of the post-operative visits in IOL clinical investigations is provided in
Table A.1.
8 © ISO 2014 – All rights reserved
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...
SLOVENSKI STANDARD
oSIST prEN ISO 11979-7:2012
01-september-2012
2þHVQLYVDGNL LPSODQWDWL ,QWUDRNXODUQHOHþHGHO .OLQLþQHUD]LVNDYH ,62',6
Ophthalmic implants - Intraocular lenses - Part 7: Clinical investigations (ISO/DIS 11979-
7:2012)
Ophthalmische Implantate – Intraokularlinsen - Teil 7: Klinische Prüfungen (ISO/DIS
11979-7:2012)
Implants ophtalmiques - Lentilles intraoculaires - Partie 7: Investigations cliniques
(ISO/DIS 11979-7:2012)
Ta slovenski standard je istoveten z: prEN ISO 11979-7
ICS:
11.040.70 Oftalmološka oprema Ophthalmic equipment
oSIST prEN ISO 11979-7:2012 en,fr,de
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
---------------------- Page: 1 ----------------------
oSIST prEN ISO 11979-7:2012
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oSIST prEN ISO 11979-7:2012
EUROPEAN STANDARD
DRAFT
prEN ISO 11979-7
NORME EUROPÉENNE
EUROPÄISCHE NORM
June 2012
ICS 11.040.70 Will supersede EN ISO 11979-7:2006
English Version
Ophthalmic implants - Intraocular lenses - Part 7: Clinical
investigations (ISO/DIS 11979-7:2012)
Implants ophtalmiques - Lentilles intraoculaires - Partie 7: Ophthalmische Implantate - Intraokularlinsen - Teil 7:
Investigations cliniques (ISO/DIS 11979-7:2012) Klinische Prüfungen (ISO/DIS 11979-7:2012)
This draft European Standard is submitted to CEN members for parallel enquiry. It has been drawn up by the Technical Committee
CEN/TC 170.
If this draft becomes a European Standard, CEN members are bound to comply with the CEN/CENELEC Internal Regulations which
stipulate the conditions for giving this European Standard the status of a national standard without any alteration.
This draft European Standard was established by CEN in three official versions (English, French, German). A version in any other language
made by translation under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management
Centre has the same status as the official versions.
CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland,
Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and United Kingdom.
Recipients of this draft are invited to submit, with their comments, notification of any relevant patent rights of which they are aware and to
provide supporting documentation.
Warning : This document is not a European Standard. It is distributed for review and comments. It is subject to change without notice and
shall not be referred to as a European Standard.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2012 CEN All rights of exploitation in any form and by any means reserved Ref. No. prEN ISO 11979-7:2012: E
worldwide for CEN national Members.
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oSIST prEN ISO 11979-7:2012
prEN ISO 11979-7:2012 (E)
Contents Page
Foreword .3
2
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oSIST prEN ISO 11979-7:2012
prEN ISO 11979-7:2012 (E)
Foreword
This document (prEN ISO 11979-7:2012) has been prepared by Technical Committee ISO/TC 172 “Optics
and photonics” in collaboration with Technical Committee CEN/TC 170 “Ophthalmic optics” the secretariat of
which is held by DIN.
This document is currently submitted to the parallel Enquiry.
This document will supersede EN ISO 11979-7:2006.
Endorsement notice
The text of ISO/DIS 11979-7:2012 has been approved by CEN as a prEN ISO 11979-7:2012 without any
modification.
3
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oSIST prEN ISO 11979-7:2012
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oSIST prEN ISO 11979-7:2012
DRAFT INTERNATIONAL STANDARD ISO/DIS 11979-7
ISO/TC 172/SC 7 Secretariat: DIN
Voting begins on Voting terminates on
2012-06-21 2012-11-21
INTERNATIONAL ORGANIZATION FOR STANDARDIZATION МЕЖДУНАРОДНАЯ ОРГАНИЗАЦИЯ ПО СТАНДАРТИЗАЦИИ ORGANISATION INTERNATIONALE DE NORMALISATION
Ophthalmic implants — Intraocular lenses —
Part 7:
Clinical investigations
Implants ophtalmiques — Lentilles intraoculaires —
Partie 7: Investigations cliniques
[Revision of second edition (ISO 11979-7:2006)]
ICS 11.040.70
ISO/CEN PARALLEL PROCESSING
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processed under the ISO-lead mode of collaboration as defined in the Vienna Agreement.
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five-month enquiry.
Should this draft be accepted, a final draft, established on the basis of comments received, will be
submitted to a parallel two-month approval vote in ISO and formal vote in CEN.
To expedite distribution, this document is circulated as received from the committee
secretariat. ISO Central Secretariat work of editing and text composition will be undertaken at
publication stage.
Pour accélérer la distribution, le présent document est distribué tel qu'il est parvenu du
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Secrétariat central de l'ISO au stade de publication.
THIS DOCUMENT IS A DRAFT CIRCULATED FOR COMMENT AND APPROVAL. IT IS THEREFORE SUBJECT TO CHANGE AND MAY NOT BE
REFERRED TO AS AN INTERNATIONAL STANDARD UNTIL PUBLISHED AS SUCH.
IN ADDITION TO THEIR EVALUATION AS BEING ACCEPTABLE FOR INDUSTRIAL, TECHNOLOGICAL, COMMERCIAL AND USER PURPOSES,
DRAFT INTERNATIONAL STANDARDS MAY ON OCCASION HAVE TO BE CONSIDERED IN THE LIGHT OF THEIR POTENTIAL TO BECOME
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RECIPIENTS OF THIS DRAFT ARE INVITED TO SUBMIT, WITH THEIR COMMENTS, NOTIFICATION OF ANY RELEVANT PATENT RIGHTS OF WHICH
THEY ARE AWARE AND TO PROVIDE SUPPORTING DOCUMENTATION.
© International Organization for Standardization, 2012
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Copyright notice
This ISO document is a Draft International Standard and is copyright-protected by ISO. Except as permitted
under the applicable laws of the user’s country, neither this ISO draft nor any extract from it may be
reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic,
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Contents Page
Foreword . v
1 Scope . 6
2 Normative references . 6
3 Terms and definitions . 6
4 Justification for a clinical investigation . 6
5 Ethical considerations . 6
6 General requirements . 7
6.1 General . 7
6.2 Design . 7
6.2.1 General . 7
6.2.2 Additional requirements for toric IOLs . 7
6.2.3 Additional requirements for accommodating IOLs . 7
6.3 Variables . 8
6.3.1 General variables . 8
6.3.2 Toric IOL variables . 8
6.3.3 Accommodating IOL variables . 8
6.3.4 Additional variables . 9
6.4 Investigation duration . 9
6.5 Enrollment . 10
6.6 Bilateral implantation . 10
6.7 Surgical technique . 10
6.8 Examination and treatment of subjects . 10
6.9 Adverse events reports . 10
6.10 Inclusion and exclusion criteria . 10
6.10.1 General . 10
6.10.2 Additional criteria for toric IOL . 11
Annex A (informative) Elements of a clinical investigation . 12
A.1 General . 12
A.2 Number of subjects . 12
A.3 Phased enrollment . 12
A.4 Reporting periods . 13
A.5 Standardization of the clinical evaluation . 13
A.6 Data analysis . 13
A.7 Subject accountability . 14
A.8 Clinical case report forms . 15
Annex B (informative) Evaluation of post-operative adverse event and visual acuity rates . 21
B.1 General . 21
B.2 Background . 21
B.3 Adverse event and visual acuity rates . 21
B.4 Additional guidance . 23
Annex C (informative) Additional elements for toric IOLs . 25
C.1 General . 25
C.2 Rotational stability investigation of non-toric IOL . 25
C.3 Clinical investigation of toric IOLs . 26
C.3.1 Investigation design . 26
C.3.2 Outcomes . 26
C.3.3 Investigational group . 27
C.3.4 Control group . 27
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C.3.5 Investigation duration .27
C.3.6 Clinical tests .27
C.3.7 Data analyses .28
C.3.8 Statistical considerations .30
Annex D (informative) Additional elements for accommodating IOLs .32
D.1 General .32
D.2 Investigation design .32
D.3 Clinical investigation of accommodating IOLs .32
D.3.1 Outcomes .32
D.3.2 Investigation and control groups .33
D.3.3 Enrolment of subjects .33
D.3.4 Investigation duration .33
D.3.5 Data analyses .36
D.3.6 Statistical considerations .37
D.3.7 Calculation of necessary sample sizes .38
Annex E (informative) Clinical tests .40
E.1 Visual acuity – distance, intermediate and near .40
E.1.1 Luminance .40
E.1.2 Data recording procedures .40
E.2 Pupil size .41
E.3 Accommodation measurements .41
E.3.1 Subjective accommodation measurements: Defocus curves .41
E.3.2 Objective accommodation measurement methods .41
E.4 Specular microscopy .44
E.4.1 General .44
E.4.2 Collection of data .44
Bibliography .46
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oSIST prEN ISO 11979-7:2012
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Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies
(ISO member bodies). The work of preparing International Standards is normally carried out through ISO
technical committees. Each member body interested in a subject for which a technical committee has been
established has the right to be represented on that committee. International organizations, governmental and
non-governmental, in liaison with ISO, also take part in the work. ISO collaborates closely with the
International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization.
International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2.
The main task of technical committees is to prepare International Standards. Draft International Standards
adopted by the technical committees are circulated to the member bodies for voting. Publication as an
International Standard requires approval by at least 75 % of the member bodies casting a vote.
Attention is drawn to the possibility that some of the elements of this document may be the subject of patent
rights. ISO shall not be held responsible for identifying any or all such patent rights.
ISO 11979-7 was prepared by Technical Committee ISO/TC 172, Optics and photonics, Subcommittee SC 7,
and by Technical Committee CEN/TC 170, Ophthalmic optics in collaboration.
This second edition cancels and replaces the first edition (ISO 11979-7:2006, ISO 11979-7:2006/Amd1:2012),
which has been technically revised.
ISO 11979 consists of the following parts, under the general title Ophthalmic implants — Intraocular lenses:
⎯ Part 1: Vocabulary
⎯ Part 2: Optical properties and test methods
⎯ Part 3: Mechanical properties and test methods
⎯ Part 4: Labelling and information
⎯ Part 5: Biocompatibility
⎯ Part 6: Shelf-life and transport stability
⎯ Part 7: Clinical investigations
⎯ Part 8: Fundamental requirements
⎯ Part 9: Multifocal lenses
⎯ Part 10: Phakic intraocular lenses
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oSIST prEN ISO 11979-7:2012
DRAFT INTERNATIONAL STANDARD ISO/DIS 11979-7
Ophthalmic implants — Intraocular lenses — Part 7: Clinical
investigations
1 Scope
This part of ISO 11979 specifies particular requirements for clinical investigations for posterior and anterior
chamber intraocular lenses (IOLs).
2 Normative references
The following referenced documents are indispensable for the application of this document. For dated
references, only the edition cited applies. For undated references, the latest edition of the referenced
document (including any amendments) applies.
ISO 11979-1, Ophthalmic implants — Intraocular lenses — Part 1: Vocabulary
ISO 11979-10:2006, Ophthalmic implants — Intraocular lenses — Part 10: Phakic intraocular lenses
ISO 14155, Clinical investigation of medical devices for human subjects — Good clinical practices
ISO 14971, Medical devices — Application of risk management to medical devices
3 Terms and definitions
For the purposes of this document the terms and definitions given in ISO 11979-1 and ISO 14155 shall apply.
4 Justification for a clinical investigation
A clinical evaluation in accordance with ISO 14155 shall be performed together with risk analysis, in
accordance with ISO 14971.
If the need for a clinical investigation is identified, the requirements of ISO 14155 shall apply, with additional
requirements given below.
If a new IOL model is a modification of a model for which the safety and performance have been established
through clinical investigation in accordance with this part of ISO 11979 no or limited clinical investigation is
needed. ISO TR 22979 [1] provides guidance in determining if a modification is minor.
5 Ethical considerations
For clinical investigations of medical devices for human subjects, the requirements in ISO 14155 shall apply.
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6 General requirements
6.1 General
The requirements for a clinical investigation given in ISO 14155 shall apply, with additional requirements given
below.
6.2 Design
6.2.1 General
A clinical investigation shall be designed in one of two ways:
a) As an uncontrolled investigation, in which case the results are compared to historical data on adverse
events and visual acuity rates. This design is applicable only to those IOL types for which there are
historical data in Annex B.
b) As a controlled investigation, with the provision that the statistical power to detect differences in the
adverse event rates and visual acuity is similar to the uncontrolled investigation. The control lens shall be
an IOL previously approved under national regulations.
Annex A provides general guidance for the design of a clinical investigation.
6.2.2 Additional requirements for toric IOLs
For all toric IOLs, the rotational stability of a non-toric version that is mechanically and geometrically
equivalent to the toric IOL shall be demonstrated.
The following performance criteria for rotational stability shall be fulfilled:
⎯ The rotation of the meridian defined by the IOL axis indicator as measured and compared between the
Day 1 (the day after surgery) post-operative examination and the 4 to 6 month examination shall be less
than 10° in 90 % of the cases, and less than 20° in 99 % of the cases.
Then, if necessary due to national requirements, a clinical investigation shall be performed using the toric
version of the model.
The following performance criterion for clinical investigation shall be fulfilled:
⎯ The mean achieved reduction in cylinder shall be ≥ 68 % of the intended cylinder reduction.
In the event that a toric IOL clinical investigation is required due to national regulations, the subjects that
undergo secondary surgery to correct IOL mark axis rotation shall have their clinical results prior to the
secondary surgery carried forward as the final results for that subject. In the case of examinations that are
scheduled to be performed later in the clinical investigation (e.g., questionnaire), the sponsor shall consider
requiring each of these examinations to be performed prior to the secondary surgery, if possible.
Additional elements for toric IOLs are outlined in Annex C.
6.2.3 Additional requirements for accommodating IOLs
A clinical investigation of an accommodating IOL shall evaluate the additional safety and performance
concerns outlined in Annex D, specifically including the evaluation of accommodative amplitude using at least
one objective method. It shall consist of two phases, with phase two beginning only after the first phase has
demonstrated that the accommodating IOL provides an average of at least 1 D of objective accommodation.
The overall study shall demonstrate that the accommodating IOL provides statistically greater objective
accommodative amplitude compared to the control IOL.
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6.3 Variables
The following variables shall be considered. If additional claims are to be made, additional corresponding
variables shall be studied.
The clinical investigational plan should provide instructions regarding recording observations. In the event of
any lens displacement or dislocation from the intended position causing visual symptoms, the instructions
should include obtaining a photographic image if possible (or a detailed sketch) and recording as much
detailed information in the subject’s chart as possible.
6.3.1 General variables
a) best spectacle corrected visual acuity (BSCVA);
b) subjective refraction;
c) intraocular pressure;
d) corneal status;
e) anterior chamber cells;
f) anterior chamber flare;
g) cystoid macular edema;
h) hypopyon;
i) endophthalmitis;
j) pupillary block;
k) retinal detachment;
l) status of anterior and posterior capsule;
m) IOL decentration [2];
n) IOL tilt [2];
o) IOL discoloration;
p) IOL opacity.
6.3.2 Toric IOL variables
a) uncorrected visual acuity;
b) keratometry;
c) IOL mark axis rotation;
d) subject questionnaire.
6.3.3 Accommodating IOL variables
a) uncorrected visual acuity at distance, intermediate and near;
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b) visual acuity at near and intermediate with best distance correction;
c) best corrected near visual acuity;
d) add power (over best distance subjective correction) required to achieve best corrected near acuity;
e) objective accommodative amplitude;
f) contrast sensitivity;
g) subject questionnaire;
h) pupil size.
6.3.4 Additional variables
If justified by the risk analysis, these additional variables shall be considered.
a) cycloplegic refraction;
b) specular microscopy;
c) gonioscopic examination;
d) pupil size;
e) anterior chamber depth measurement.
6.4 Investigation duration
The minimum duration of the clinical investigations shall be 1 year (see Annex A for visit window tolerance) for
aphakic posterior chamber IOLs which are not modifications of a model for which safety and performance data
have been established through clinical investigation.
The minimum duration of the clinical investigations shall be 3 years (see Annex A for visit window tolerance)
for aphakic anterior chamber IOLs which are not modifications of a model for which safety and performance
data have been established through clinical investigation.
The minimum study duration for accommodating IOLs through clinical investigation shall be 1 year but may
require up to 3 years based on the risk analysis.
For all toric IOLs, a 6 month study of the non-toric version of the IOL shall be performed to insure rotational
stability. Then for toric IOLs that are a modification of an IOL that has met the requirements of all parts of
ISO 11979, national regulations may require that this rotational stability study is followed by a clinical
investigation of the actual toric IOL for 6 months. Toric IOLs that are not a modification of an IOL that has met
the requirements of all parts of ISO 11979 shall require a full clinical investigation of 1 year duration.
Consult ISO/TR 22979 for guidance on investigation duration for modifications of lens models for which safety
and performance has been established through clinical investigation.
All subjects in a clinical investigation that have not been discontinued shall complete all
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