1、Condoms Guidance on clinical studiesPart 1: Male condoms, clinical function studies based on self-reportsBS ISO 29943-1:2017BSI Standards PublicationWB11885_BSI_StandardCovs_2013_AW.indd 1 15/05/2013 15:06 ISO 2017Condoms Guidance on clinical studies Part 1: Male condoms, clinical function studies b
2、ased on self-reportsPrservatifs Directives relatives aux tudes cliniques Partie 1: Prservatifs masculins tudes fonctionnelles cliniques bases sur des auto-dclarationsINTERNATIONAL STANDARDISO29943-1First edition2017-07Reference numberISO 29943-1:2017(E)National forewordThis British Standard is the U
3、K implementation of ISO 29943-1:2017. The UK participation in its preparation was entrusted to Technical Committee CH/157, Mechanical contraceptives.A list of organizations represented on this committee can be obtained on request to its secretary.This publication does not purport to include all the
4、necessary provisions of a contract. Users are responsible for its correct application. The British Standards Institution 2017 Published by BSI Standards Limited 2017ISBN 978 0 580 85628 0ICS 11.200Compliance with a British Standard cannot confer immunity from legal obligations. This British Standard
5、 was published under the authority of the Standards Policy and Strategy Committee on 31 July 2017.Amendments/corrigenda issued since publicationDate Text affected BRITISH STANDARDBS ISO 299431:2017 ISO 2017Condoms Guidance on clinical studies Part 1: Male condoms, clinical function studies based on
6、self-reportsPrservatifs Directives relatives aux tudes cliniques Partie 1: Prservatifs masculins tudes fonctionnelles cliniques bases sur des auto-dclarationsINTERNATIONAL STANDARDISO29943-1First edition2017-07Reference numberISO 29943-1:2017(E)BS ISO 299431:2017ISO 29943-1:2017(E)ii ISO 2017 All ri
7、ghts reservedCOPYRIGHT PROTECTED DOCUMENT ISO 2017, Published in SwitzerlandAll 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 o
8、r an intranet, without prior written permission. Permission can be requested from either ISO at the address below or ISOs member body in the country of the requester.ISO copyright officeCh. de Blandonnet 8 CP 401CH-1214 Vernier, Geneva, SwitzerlandTel. +41 22 749 01 11Fax +41 22 749 09 47copyrightis
9、o.orgwww.iso.orgBS ISO 299431:2017ISO 29943-1:2017(E)ii ISO 2017 All rights reservedCOPYRIGHT PROTECTED DOCUMENT ISO 2017, Published in SwitzerlandAll rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized otherwise in any form or by any means, electro
10、nic 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 ISOs member body in the country of the requester.ISO copyright officeCh. de Blandonnet 8 CP 401CH-1214 Vernier,
11、Geneva, SwitzerlandTel. +41 22 749 01 11Fax +41 22 749 09 47copyrightiso.orgwww.iso.orgISO 29943-1:2017(E)Foreword vIntroduction vi1 Scope . 12 Normative references 13 Terms and definitions . 14 Pilot clinical studies 25 Clinical validation investigation . 35.1 Objectives of clinical validation inve
12、stigation 35.2 Outcome measures 35.3 Study subjects 35.3.1 General 35.3.2 Enrolment of study subjects 35.4 Informed consent 55.5 Test and control condoms . 55.5.1 General 55.5.2 Test condom . 55.5.3 Control condom made from natural rubber latex . 65.5.4 Expiration date of control condom 65.5.5 Stora
13、ge conditions 65.5.6 Trial duration exceeds 1 year 65.5.7 Sampling of control condoms for bench testing . 65.6 Randomization 65.7 Allocation concealment and study masking 75.8 Use of additional lubricant . 75.9 Instructions and interactions with study couples 75.10 Interviews and data collection 85.
14、10.1 Schedule for interviews and condom distribution . 85.10.2 Enrolment interview 85.10.3 Individual condom use CRF 85.10.4 Mid-study CRF, crossover trial . 95.10.5 Compiling data from CRFs . 95.11 Data integrity . 105.11.1 General. 105.11.2 Interactive voice response systems (IVRS) 105.11.3 Mail-i
15、n and web-based data reporting 105.11.4 Web-based data collection systems and additional suggestions 115.12 Control of distribution chain 115.13 Analysis of returned condoms 125.14 Other methodological details 125.15 Statistical analysis plan . 125.15.1 General. 125.15.2 Primary study hypothesis . 1
16、35.15.3 Secondary study hypotheses 135.15.4 Study design 135.15.5 Statistical analysis 145.15.6 Additional statistical comments and concerns .145.16 Clinical study results: Review and interpretation .155.16.1 General. 155.16.2 Total clinical failure rates for control condom 155.16.3 Non-inferiority
17、155.16.4 Superiority . 155.16.5 Safety (adverse events) . 15 ISO 2017 All rights reserved iiiContents PageBS ISO 299431:2017ISO 29943-1:2017(E)5.16.6 What happens if one is unable to conclude non-inferiority? 16Annex A (informative) Formula for power calculation .17Annex B (informative) Pilot clinic
18、al investigation (sample outline) 18Annex C (informative) Time and events schedule for individual study subject (sample) .20Annex D (informative) CRF Study entry (sample) 21Annex E (informative) CRF Mid-study (sample) .24Annex F (informative) CRF Individual condom use (sample).25Annex G (informative
19、) CRF Adverse event (sample) 32Annex H (informative) Protocol for evaluation of returned used condoms .34Bibliography .41iv ISO 2017 All rights reservedBS ISO 299431:2017ISO 29943-1:2017(E)5.16.6 What happens if one is unable to conclude non-inferiority? 16Annex A (informative) Formula for power cal
20、culation .17Annex B (informative) Pilot clinical investigation (sample outline) 18Annex C (informative) Time and events schedule for individual study subject (sample) .20Annex D (informative) CRF Study entry (sample) 21Annex E (informative) CRF Mid-study (sample) .24Annex F (informative) CRF Individ
21、ual condom use (sample).25Annex G (informative) CRF Adverse event (sample) 32Annex H (informative) Protocol for evaluation of returned used condoms .34Bibliography .41iv ISO 2017 All rights reserved ISO 29943-1:2017(E)ForewordISO (the International Organization for Standardization) is a worldwide fe
22、deration 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 com
23、mittee. 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 a
24、nd 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, Pa
25、rt 2 (see 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 o
26、f the document will be in the Introduction and/or on the ISO list of patent declarations received (see 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 voluntary nature of s
27、tandards, the meaning of ISO specific terms and expressions related to conformity assessment, as well as information about ISOs adherence to the World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT) see the following URL: www .iso .org/ iso/ foreword .html.This document
28、was prepared by Technical Committee ISO/TC 157, Non-systemic contraceptives and STI barrier prophylactics.A list of all the parts of ISO 29943 can be found on the ISO website. ISO 2017 All rights reserved vBS ISO 299431:2017ISO 29943-1:2017(E)IntroductionMale condoms made from natural rubber latex (
29、NRL) have a long history of safety and effectiveness and their performance during use is well established. However, male condoms made from new materials require clinical validation to ensure that their performance during actual use is not inferior to that of NRL condoms. Such clinical validation stu
30、dies, called clinical function studies, are designed to compare the rates of acute failure event, i.e. breakage or complete slippage. Statistical analysis based on a non-inferiority comparison is employed to help ensure that the difference is not excessive.This clinical study guidance is intended to
31、 help in the design, execution, analysis and interpretation of clinical function studies conducted in accordance with requirements of the ISO 23409 for synthetic male condoms. However, it can also be used with appropriate modifications to evaluate other male condoms with additional claims for improv
32、ed efficacy or safety (see ISO 4074:2015, Clause 8). In addition to information regarding the clinical validation study, this document provides recommendations on pilot studies and statistical analysis plans. Annexes include previously used case report forms and protocols that can be modified or ada
33、pted.NOTE Based on the normative clinical requirement of relevant standards, these studies are designed to recruit participating couples who agree to use the test and control condoms for vaginal intercourse. Such studies can also collect incidental data on condom use during anal sex; however, that i
34、s not the primary objective. To satisfy study power requirements, it is critical that sufficient reports are collected on condom use during vaginal intercourse. Study sponsors typically take preventive measures, such as initial screening and consenting of study couples, and obtain agreement that stu
35、dy couples will use condoms this way.These clinical function studies are not typically designed to directly evaluate condom protection against pregnancy or sexually transmitted infections (STIs).Finally, it is important to recognize that clinical function studies of condoms are human research studie
36、s. Therefore, all persons designing, running and analysing clinical studies of new condoms should be familiar with all relevant standards for research involving human subjects, including ethical considerations. For additional information, refer to ISO 14155.vi ISO 2017 All rights reservedBS ISO 2994
37、31:2017ISO 29943-1:2017(E)IntroductionMale condoms made from natural rubber latex (NRL) have a long history of safety and effectiveness and their performance during use is well established. However, male condoms made from new materials require clinical validation to ensure that their performance dur
38、ing actual use is not inferior to that of NRL condoms. Such clinical validation studies, called clinical function studies, are designed to compare the rates of acute failure event, i.e. breakage or complete slippage. Statistical analysis based on a non-inferiority comparison is employed to help ensu
39、re that the difference is not excessive.This clinical study guidance is intended to help in the design, execution, analysis and interpretation of clinical function studies conducted in accordance with requirements of the ISO 23409 for synthetic male condoms. However, it can also be used with appropr
40、iate modifications to evaluate other male condoms with additional claims for improved efficacy or safety (see ISO 4074:2015, Clause 8). In addition to information regarding the clinical validation study, this document provides recommendations on pilot studies and statistical analysis plans. Annexes
41、include previously used case report forms and protocols that can be modified or adapted.NOTE Based on the normative clinical requirement of relevant standards, these studies are designed to recruit participating couples who agree to use the test and control condoms for vaginal intercourse. Such stud
42、ies can also collect incidental data on condom use during anal sex; however, that is not the primary objective. To satisfy study power requirements, it is critical that sufficient reports are collected on condom use during vaginal intercourse. Study sponsors typically take preventive measures, such
43、as initial screening and consenting of study couples, and obtain agreement that study couples will use condoms this way.These clinical function studies are not typically designed to directly evaluate condom protection against pregnancy or sexually transmitted infections (STIs).Finally, it is importa
44、nt to recognize that clinical function studies of condoms are human research studies. Therefore, all persons designing, running and analysing clinical studies of new condoms should be familiar with all relevant standards for research involving human subjects, including ethical considerations. For ad
45、ditional information, refer to ISO 14155.vi ISO 2017 All rights reserved Condoms Guidance on clinical studies Part 1: Male condoms, clinical function studies based on self-reports1 ScopeThis document is intended to help in the design, execution, analysis and interpretation of clinical function studi
46、es conducted in accordance with the requirements of ISO 23409 for male synthetic condoms.These clinical studies compare the performance of a new male condom to an established male condom during vaginal intercourse (not anal intercourse). In particular, these studies are designed to assess acute fail
47、ure events during use (i.e. clinical slippage and clinical breakage).This document also provides direction on the analysis of data when the study is completed, as well as interpretation of these results by manufacturers and regulatory bodies.Certain clinical trial elements are not addressed in this
48、document, including compensation, confidentiality of individuals and their records, use of local ethics committees, etc. These and many other clinical trial design issues are covered in greater detail in ISO 14155.2 Normative referencesThere are no normative references in this document.3 Terms and d
49、efinitionsFor the purposes of this document, the following terms and definitions apply.ISO and IEC maintain terminological databases for use in standardization at the following addresses: ISO Online browsing platform: available at h t t p :/ www .iso .org/ obp IEC Electropedia: available at h t t p :/ www .electropedia .org/ NOTE All of the clinical failure events defined below represents potential vaginal exposure to semen and other penile discharge. Non-clinical failure events do not ris
