SIST EN ISO 20916:2024
(Main)In vitro diagnostic medical devices - Clinical performance studies using specimens from human subjects - Good study practice (ISO 20916:2019)
In vitro diagnostic medical devices - Clinical performance studies using specimens from human subjects - Good study practice (ISO 20916:2019)
This document defines good study practice for the planning, design, conduct, recording and reporting of clinical performance studies carried out to assess the clinical performance and safety of in vitro diagnostic (IVD) medical devices for regulatory purposes.
NOTE 1 The purpose of these studies is to assess the ability of an IVD medical device in the hands of the intended user, to yield results pertaining to a particular medical condition or physiological/pathological state, in the intended population.
The document is not intended to describe whether the technical specifications of the IVD medical device in question are adequately addressed by the clinical performance study.
This document identifies the principles that underpin clinical performance studies and specifies general requirements intended to
— ensure the conduct of the clinical performance study will lead to reliable and robust study results,
— define the responsibilities of the sponsor and principal investigator,
— assist sponsors, clinical research organization, investigators, ethics committees, regulatory authorities and other bodies involved in the conformity assessment of IVD medical devices, and
— protect the rights, safety, dignity and well-being of the subjects providing specimens for use in clinical performance studies.
Analytical performance studies are out of the scope of this document.
NOTE 2 When the collection of specimens specifically for the analytical performance study creates an additional collection risk for subjects, some of the elements of this document (particularly the annexes) can be useful for ensuring subject safety.
Clinical performance studies that are performed for reasons other than pre- and post-market regulatory purposes, such as for re-imbursement purposes, are out of the scope of this document.
NOTE 3 Some of the elements of this document can be useful for the design of such studies, including subject safety and data integrity.
This document does not include safety information for laboratory workers or other personnel collecting the study specimens.
NOTE 4 Such information is included in other publications[1][12][13].
NOTE 5 Users of this document can consider whether other standards and/or requirements also apply to the IVD medical device which is the subject of the clinical performance study, for instance, in the situation for which there is an IVD medical device and a medical device used in an integrated system (e.g. a lancet, an IVD test strip, and a glucose meter), aspects of both this document and ISO 14155 can be considered.
In-vitro-Diagnostika - Klinische Leistungsuntersuchungen an menschlichem Untersuchungsmaterial - Gute Studienpraxis (ISO 20916:2019)
Dieses Dokument legt die gute Studienpraxis für die Planung, Design, Durchführung, Aufzeichnung und Meldung klinischer Leistungsstudien fest, die durchgeführt werden, um die klinische Leistungs¬fähigkeit und Sicherheit von In vitro-Diagnostika (IVD) für Zulassungszwecke zu bewerten.
ANMERKUNG 1 Das Ziel dieser Studien ist es, die Fähigkeit eines In vitro-Diagnostikums in den Händen des bestimmungsgemäßen Anwenders zu bewerten, Ergebnisse in Bezug auf eine bestimmte gesundheitliche Verfassung oder einen physiologischen/pathologischen Zustand in der bestimmungsgemäßen Population zu liefern.
Das Dokument soll nicht beschreiben, ob die technischen Spezifikationen des betreffenden In vitro-Diagnostikums durch die klinische Leistungsstudie ausreichend abgedeckt sind.
Dieses Dokument legt die Grundsätze fest, die klinischen Leistungsstudien zugrunde liegen, und gibt allgemeine Anforderungen an, die dazu dienen
sicherzustellen, dass die Durchführung der klinischen Leistungsstudie zu zuverlässigen und soliden Studienergebnissen führen wird,
die Verantwortlichkeiten des Sponsors und Hauptprüfers festzulegen,
die Arbeit von Sponsoren, klinischen Forschungseinrichtungen, Prüfern, Ethik-Kommissionen, Regulierungsbehörden und anderen am Konformitätsbewertungsverfahren für In vitro-Diagnostika beteiligten Institutionen zu unterstützen und
die Rechte, Sicherheit, Würde und das Wohlbefinden der Prüfungsteilnehmer zu schützen, die Untersuchungsmaterial zur Verwendung in klinischen Leistungsstudien bereitstellen.
Analytische Leistungsstudien liegen außerhalb des Anwendungsbereiches dieses Dokuments.
ANMERKUNG 2 Wenn die Entnahme von Untersuchungsmaterial speziell für die analytische Leistungsstudie ein zusätzliches Entnahmerisiko für den Prüfungsteilnehmer darstellt, können einige der Elemente dieses Dokuments (insbesondere die Anhänge) nützlich sein, um die Sicherheit des Prüfungsteilnehmers sicherzustellen.
Klinische Leistungsstudien, die aus anderen Gründen als Zulassungszwecke vor und nach dem Inverkehrbringen durchgeführt werden, z. B. zu Zwecken der Erstattung, fallen nicht in den Anwendungs-bereich dieses Dokuments.
ANMERKUNG 3 Einige der Elemente dieses Dokuments können für das Design solcher Studien nützlich sein, einschließlich der Sicherheit des Prüfungsteilnehmers und der Datenintegrität.
Dieses Dokument enthält keine Sicherheitshinweise für Labormitarbeiter oder anderes Personal, das das Untersuchungsmaterial entnimmt.
ANMERKUNG 4 Diese Informationen sind in anderen Veröffentlichungen [1] [12] [13] enthalten.
ANMERKUNG 5 Anwender dieses Dokuments können in Betracht ziehen, ob andere Normen und/oder Anforderungen auch für das In vitro-Diagnostikum gelten, das Gegenstand der klinischen Leistungsstudie ist, z. B. können in dem Fall, in dem es ein In vitro-Diagnostikum und ein Medizinprodukt gibt, die in einem integrierten System verwendet werden (z. B. eine Lanzette, ein IVD Teststreifen und ein Blutzuckermessgerät), Aspekte sowohl dieses Dokuments als auch von ISO 14155 berücksichtigt werden.
Dispositifs médicaux de diagnostic in vitro - Études des performances cliniques utilisant des prélèvements de sujets humains - Bonnes pratiques d'étude (ISO 20916:2019)
Le présent document définit les bonnes pratiques pour la planification, la conception, la conduite, l'enregistrement et l'établissement du rapport d'études des performances cliniques menées en vue d'évaluer les performances cliniques et la sécurité de dispositifs médicaux de diagnostic in vitro (DIV) à des fins réglementaires.
NOTE 1 Ces études visent à évaluer la capacité d'un dispositif médical DIV, mis à disposition de l'utilisateur concerné, à produire des résultats propres à une affection particulière ou à un état physiologique/pathologique particulier, au sein de la population concernée.
Le document n'est pas destiné à décrire si les spécifications techniques du dispositif médical DIV en question sont adéquatement prises en compte ou non par l'étude des performances cliniques.
Le présent document identifie les principes étayant les études des performances cliniques et spécifie les exigences générales visant à
— assurer que la conduite de l'étude des performances cliniques donnera des résultats d'étude fiables et robustes,
— définir les responsabilités du promoteur et de l'investigateur principal,
— aider les promoteurs, les organismes de recherche clinique, les investigateurs, les comités d'éthique, les autorités réglementaires et les autres organismes impliqués dans l'évaluation de la conformité des dispositifs médicaux DIV, et
— protéger les droits, la sécurité, la dignité et le bien-être des sujets fournissant des prélèvements utilisables dans les études des performances cliniques.
Les études des performances analytiques ne font pas partie du domaine d'application du présent document.
NOTE 2 Lorsque la collecte de prélèvements spécifiques à l'étude des performances analytiques crée un risque de collecte supplémentaire pour les sujets, certains des éléments du présent document (en particulier les annexes) peuvent être utiles pour assurer la sécurité du sujet.
Les études des performances cliniques menées à des fins autres que réglementaires pré- et post-commercialisation, notamment dans le cadre d'une demande de remboursement, ne font pas partie du domaine d'application du présent document.
NOTE 3 Certains des éléments du présent document peuvent être utiles pour concevoir ces études, notamment la sécurité du sujet et l'intégrité des données.
Le présent document ne comprend pas d'informations de sécurité pour les personnels de laboratoire ou les autres personnels les prélèvements d'étude.
NOTE 4 Ces informations figurent dans d'autres publications[1][12][13].
NOTE 5 Les utilisateurs du présent document peuvent tenir compte du fait que d'autres normes et/ou exigences s'appliquent également au dispositif médical DIV qui fait l'objet de l'étude des performances cliniques ; par exemple, si un dispositif médical DIV et un dispositif médical sont utilisés dans un système intégré (par exemple, une lancette, une bandelette réactive DIV et un glucomètre), les aspects du présent document et de l'ISO 14155 peuvent être pris en considération.
Diagnostični medicinski pripomočki in vitro - Klinične študije učinkovitosti z uporabo človeških vzorcev - Dobre študijske prakse (ISO 20916:2019)
Ta dokument določa dobro študijsko prakso za načrtovanje, izvajanje, beleženje in poročanje o študijah klinične učinkovitosti, izvedenih za ocenjevanje klinične učinkovitosti in varnosti diagnostičnih medicinskih pripomočkov in vitro (IVD) za regulativne namene.
OPOMBA 1: Namen teh študij je oceniti sposobnost medicinskega pripomočka in vitro, ki ga uporablja predvideni uporabnik, da zagotovi rezultate, ki se nanašajo na posebno zdravstveno stanje ali fiziološko/patološko stanje ciljne populacije.
Dokument ni namenjen opisovanju, ali so tehnične specifikacije medicinskega pripomočka in vitro ustrezno obravnavane v študiji klinične učinkovitosti.
Ta dokument opredeljuje načela, na katerih temeljijo študije klinične učinkovitosti, in določa splošne zahteve za
– zagotavljanje, da bo izvedba študije klinične učinkovitosti dala zanesljive rezultate,
– opredelitev odgovornosti sponzorja in glavnega preiskovalca,
– pomoč sponzorjem, organizaciji za klinične raziskave, preiskovalcem, odborom za etiko, regulativnim organom in drugim organom, ki so vključeni v oceno skladnosti medicinskih pripomočkov in vitro, in
– zaščito pravic, varnosti, dostojanstva in dobrega počutja subjektov, ki zagotavljajo vzorce za uporabo v študijah klinične učinkovitosti.
Študije analitične učinkovitosti ne spadajo v področje uporabe tega dokumenta.
OPOMBA 2: Če zbiranje vzorcev posebej za študijo analitične učinkovitosti ustvarja dodatno tveganje pri zbiranju za subjekte, so lahko nekateri elementi tega dokumenta (predvsem dodatki) uporabni za zagotavljanje varnosti subjekta.
Študije klinične učinkovitosti, ki niso izvedene zaradi regulativnih namenov pred dajanjem in po dajanju na trg, na primer za namene povračila, niso zajete v področje uporabe tega dokumenta.
OPOMBA 3: Nekateri elementi tega dokumenta so lahko uporabni pri snovanju tovrstnih študij, vključno z varnostjo subjekta in celovitostjo podatkov.
Ta dokument ne vključuje informacij o varnosti za laboratorijske delavce ali drugo osebje, ki zbira vzorce za študijo.
OPOMBA 4: Te informacije so zajete v druge publikacije [1][12][13].
OPOMBA 5: Uporabniki tega dokumenta lahko preučijo, ali tudi drugi standardi in/ali zahteve veljajo za medicinski pripomoček in vitro, ki je predmet študije klinične učinkovitosti, na primer v primeru, ki vključuje medicinski pripomoček in vitro in medicinski pripomoček v integriranem sistemu (npr. lanceta, preskusni trak in vitro in merilec krvnega sladkorja), se lahko upošteva vidike iz tega dokumenta in standarda ISO 14155.
General Information
Standards Content (Sample)
SLOVENSKI STANDARD
01-maj-2024
Diagnostični medicinski pripomočki in vitro - Klinične študije učinkovitosti z
uporabo človeških vzorcev - Dobre študijske prakse (ISO 20916:2019)
In vitro diagnostic medical devices - Clinical performance studies using specimens from
human subjects - Good study practice (ISO 20916:2019)
In-vitro-Diagnostika - Klinische Leistungsuntersuchungen an menschlichem
Untersuchungsmaterial - Gute Studienpraxis (ISO 20916:2019)
Dispositifs médicaux de diagnostic in vitro - Études des performances cliniques utilisant
des prélèvements de sujets humains - Bonnes pratiques d'étude (ISO 20916:2019)
Ta slovenski standard je istoveten z: EN ISO 20916:2024
ICS:
11.100.10 Diagnostični preskusni In vitro diagnostic test
sistemi in vitro systems
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
EN ISO 20916
EUROPEAN STANDARD
NORME EUROPÉENNE
March 2024
EUROPÄISCHE NORM
ICS 11.100.10
English Version
In vitro diagnostic medical devices - Clinical performance
studies using specimens from human subjects - Good study
practice (ISO 20916:2019)
Dispositifs médicaux de diagnostic in vitro - Études des In-vitro-Diagnostika - Klinische
performances cliniques utilisant des prélèvements de Leistungsuntersuchungen an menschlichem
sujets humains - Bonnes pratiques d'étude (ISO Untersuchungsmaterial - Gute Studienpraxis (ISO
20916:2019) 20916:2019)
This European Standard was approved by CEN on 7 August 2023.
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, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway,
Poland, Portugal, Republic of North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Türkiye and
United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
CEN-CENELEC Management Centre: Rue de la Science 23, B-1040 Brussels
© 2024 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 20916:2024 E
worldwide for CEN national Members.
Contents Page
European foreword . 3
Annex ZA (informative) Relationship between this European Standard the General Safety
and Performance Requirements of Regulation (EU) 2017/746 aimed to be covered . 4
European foreword
The text of ISO 20916:2019 has been prepared by Technical Committee ISO/TC 212 "Clinical laboratory
testing and in vitro diagnostic test systems” of the International Organization for Standardization (ISO)
and has been taken over as EN ISO 20916:2024 by Technical Committee CEN/TC 140 “In vitro
diagnostic medical devices” 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 September 2024, and conflicting national standards
shall be withdrawn at the latest by March 2027.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN shall not be held responsible for identifying any or all such patent rights.
This document has been prepared under a standardization request addressed to CEN by the European
Commission. The Standing Committee of the EFTA States subsequently approves these requests for its
Member States.
For the relationship with EU Legislation, see informative Annex ZA, which is an integral part of this
document.
Any feedback and questions on this document should be directed to the users’ national standards body.
A complete listing of these bodies can be found on the CEN website.
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, France, Germany, Greece, Hungary, Iceland,
Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Republic of
North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Türkiye and the
United Kingdom.
Endorsement notice
The text of ISO 20916:2019 has been approved by CEN as EN ISO 20916:2024 without any modification.
Annex ZA
(informative)
Relationship between this European Standard the General Safety and
Performance Requirements of Regulation (EU) 2017/746 aimed to be
covered
This European standard has been prepared under M/575 to provide one voluntary means of
conforming to the General Safety and Performance Requirements of Regulation (EU) 2017/746 of
5 April 2017 concerning in vitro diagnostic medical devices [OJ L 117] and to system or process
requirements including those relating to quality management systems, risk management, post-market
surveillance systems, performance studies, clinical evidence or post-market performance follow-up.
Once this standard is cited in the Official Journal of the European Union under that Regulation,
compliance with the normative clauses of this standard given in Table ZA.1 confers, within the limits of
the scope of this standard, a presumption of conformity with the corresponding General Safety and
Performance Requirements of that Regulation, and associated EFTA Regulations.
Where a definition in this standard differs from a definition of the same term set out in Regulation
(EU) 2017/746, the differences shall be indicated in the Annex ZA. For the purpose of using this
standard in support of the requirements set out in Regulation (EU) 2017/746, the definitions set out in
this Regulation prevail.
Where the European standard is an adoption of an International Standard, the scope of this standard
can differ from the scope of the European Regulation that it supports. As the scope of the applicable
regulatory requirements differ from nation to nation and region to region, the standard can only
support European regulatory requirements to the extent of the scope of the In vitro Diagnostic
Regulation (EU) 2017/746.
NOTE 1 Where a reference from a clause of this standard to the risk management process is made, the risk
management process needs to be in compliance with Regulation (EU) 2017/746. This means that risks have to be
‘reduced as far as possible’, ‘reduced to a level as low as reasonably practicable’, ‘reduced to the lowest possible
level’, ‘reduced as far as possible and appropriate’, ‘removed or reduced as far as possible’, ‘eliminated or reduced
as far as possible’, ‘prevented’ or ‘minimized’, according to the wording of the corresponding General Safety and
Performance Requirement.
NOTE 2 The manufacturer’s policy for determining acceptable risk must be in compliance with General Safety
and Performance Requirements 1, 2, 3, 4, 5, 8, 10, 11, 13, 15, 16, 17, 18 and 19 of the Regulation.
NOTE 3 When a General Safety and Performance Requirement does not appear in Table ZA.1, it means that it is
not addressed by this European Standard.
Table ZA.1 — Correspondence between this European Standard and Annex I of
Regulation (EU) 2017/746 [OJ L 117] and to system or process requirements including those relating
to quality management systems, risk management, post-market surveillance systems, clinical
investigations, clinical evaluation or post-market clinical follow-up
Clause(s) / sub-
General Safety and
clause(s)
Performance Requirements Remarks / Notes
of Regulation (EU) 2017/746
of this EN
3 (b) C.5 Covered with respect to in vitro
diagnostic medical devices under
clinical performance study
3 (c) C.5 Covered for in vitro diagnostics medical
devices under clinical performance
study with the exemption of the
estimation and evaluation of risks
associated with and during the
“reasonably foreseeable misuse”
4 (c) C.5 Covered with respect to safety
principles and risk control measures
for devices under clinical performance
study except aspects regarding training
to users.
8 B.7 Covered with respect to the benefit-
risk evaluation performed during a
clinical performance study
9.1 (a) 5.3 (i) Covered with respect to the items listed
in 5.3 (i) that are included in the
clinical performance study.
9.1 (b) 5.3 Covered with respect to the items listed
in 5.3 (j) that are included in the
clinical performance study. Expected
values in normal and affected
populations are not covered.
9.4. (a) 5.3 c) 4), 5. 3 g), 5. 3 h) Covered with respect to the items listed
in 5.3 c) 4), 5. 3 g), 5. 3 h) that are
included in the clinical performance
study.
9.4. (b) 5.3 c) 4), 5. 3 g), 5. 3 h) Covered with respect to the items listed
in 5.3 c) 4), 5. 3 g), 5. 3 h) that are
included in the clinical performance
study.
20.2 (e) 5.12 Covered with respect to the labelling of
the in vitro diagnostics medical device
under clinical performance study.
Table ZA.2 – Correspondence between this European standard and Annex XIII of Regulation (EU)
2017/746 [OJ L 117]
Requirements of Regulation Clause(s) / sub-clause(s)
Remarks / Notes
2017/746, Annex XIII (EU) of this EN
2.2 4.1, 4.3, 4.4, 5.5.2 (b), 5.5.2 Covered with respect to ethical
(n), 5.5.3.17, 5.10 (c), 7.3.1 considerations
2.3.1 5.3, B.8.1 c) Covered with respect to the study
design, the items listed in 5.3 that
are included in the clinical
performance study and with respect
to bias minimalization
2.3.2 first and second 5.5.3 Covered with respect to the content
paragraphs of CPSP
2.3.2 (b) 5.5.3.4 Covered with respect to the sponsor
information
2.3.2 (c) 5.9 Covered with respect to study site
identification and qualification if
included in the clinical performance
study
2.3.2 (e) 5.5.3.3, 5.5.3.8 Covered with respect to the
information of the in vitro
diagnostics medical device
2.3.2 (f) 5.5.3.9, 5.7 Covered with respect to the
specimen information
2.3.2 (g) 5.5.3.6 Covered with respect to the
summary of the study; current state
of the art in diagnosis and/or
medicine is not covered.
2.3.2 (o) 5.10 Covered
2.3.3 8.2, Annex D Covered
Table ZA.3 – Correspondence between this European standard and Annex XIV of Regulation (EU)
2017/746 [OJ L 117]
Requirements of Regulation Clause(s) / sub-clause(s)
Remarks / Notes
(EU) 2017/746, Annex XIV of this EN
1.6. 5.3, 5.5.3, Annex B Covered with respect to the design
of the clinical performance study
and the content of the CPSP
1.10. 5.5.3.3 Covered except the classification of
the in vitro diagnostics medical
device
1.11. 5.5.3.6 Covered
1.12. 5.5.3.8 Covered
Requirements of Regulation Clause(s) / sub-clause(s)
Remarks / Notes
(EU) 2017/746, Annex XIV of this EN
1.13. 5.1 3rd paragraph, 6.3 Covered with respect to
qualification evidence of the
investigator and the study site
1.13. 5.9 Covered with respect to the
capability/suitability of the site
1.17. Annex C.6 Covered with respect to the list of
applied standards
2. Annex C Covered with respect to IB
2.5. Annex B.7 and C.5 Covered
2.7. Annex C.6 a) and b) Covered with respect to the list of
applied standards
3. 5.5.3 Covered with respect to the content
of the CPSP
4.2. 6.2 f), Annex E.3 Covered
4.4. 4.5, Annex A.8 2nd Covered with respect to leftover or
paragraphe, Annex E.2 c), archived specimen, compensation,
Annex F.2, Annex F.4, Annex needed translation of the document,
E.3 process for obtaining informed
consent and the provided
information and content of the
informed consent document
4.6. 5.2 Covered with respect to Risk
analysis
Chapter II 1. 7.2 c), 7.2. g) Covered with respect to sponsors
obligations to provide information
to the authorities
Chapter II 2. Annex G Covered with respect to the
categorisation of adverse events
Chapter II 4. 5.10 Covered with respect to the study
monitoring obligations, but not with
respect to the independence of the
monitor
WARNING 1 — Presumption of conformity stays valid only as long as a reference to this European
standard is maintained in the list published in the Official Journal of the European Union. Users of this
standard should consult frequently the latest list published in the Official Journal of the European
Union.
WARNING 2 — Other Union legislation may be applicable to the product(s) falling within the scope of
this standard.
INTERNATIONAL ISO
STANDARD 20916
First edition
2019-05
In vitro diagnostic medical devices —
Clinical performance studies using
specimens from human subjects —
Good study practice
Dispositifs médicaux de diagnostic in vitro — Études des
performances cliniques utilisant des prélèvements de sujets humains
— Bonnes pratiques d'étude
Reference number
ISO 20916:2019(E)
©
ISO 2019
ISO 20916:2019(E)
© ISO 2019
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ISO 20916:2019(E)
Contents Page
Foreword .v
Introduction .vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Ethical considerations .11
4.1 General .11
4.2 Improper influence or inducement .11
4.3 Responsibilities .11
4.4 Ethics committee involvement .11
4.5 Informed consent .12
5 Clinical performance study planning .12
5.1 General .12
5.2 Risk evaluation .13
5.3 Design of the clinical performance study .14
5.4 Investigator brochure.14
5.5 Clinical Performance Study Protocol (CPSP) .15
5.5.1 General.15
5.5.2 Principal investigator responsibilities .15
5.5.3 Contents of the CPSP .16
5.6 Case report forms .19
5.7 Recording of specimen information .20
5.8 Specimen accountability and integrity.20
5.9 Study site selection .20
5.9.1 Site qualification.20
5.9.2 Site assessment .20
5.9.3 Site selection .20
5.10 Monitoring plan .21
5.11 Agreements .21
5.12 Labelling .21
6 Study site initiation .21
6.1 General .21
6.2 Prerequisites .22
6.3 Training .22
6.4 Initiation of the study site .22
7 Clinical performance study conduct .23
7.1 General .23
7.2 Responsibilities of the sponsor .23
7.3 Study site monitoring .23
7.3.1 General.23
7.3.2 Routine monitoring .23
7.3.3 Monitoring reports.24
7.4 Security and confidentiality of data .25
8 Close-out of the clinical performance study .25
8.1 Close-out activities .25
8.2 Clinical performance study report .25
8.3 Document retention.27
8.4 Suspension or premature termination of the clinical performance study .27
9 Auditing .28
Annex A (normative) Additional general requirements for certain studies .29
ISO 20916:2019(E)
Annex B (normative) Clinical performance study protocol (CPSP) .32
Annex C (normative) Investigator brochure .36
Annex D (normative) Clinical performance study report .38
Annex E (normative) Communication with the ethics committee .41
Annex F (normative) Informed consent .43
Annex G (normative) Adverse event categorization .47
Annex H (informative) Good clinical performance study documentation .51
Annex I (informative) Auditing .56
Bibliography .57
iv © ISO 2019 – All rights reserved
ISO 20916:2019(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 (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 of 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 of the voluntary nature of standards, the meaning of ISO specific terms and
expressions related to conformity assessment, as well as information about ISO's adherence to the
World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT) see www .iso
.org/iso/foreword .html.
This document was prepared by Technical Committee ISO/TC 212, Clinical laboratory testing and in
vitro diagnostic test systems.
Any feedback or questions on this document should be directed to the user’s national standards body. A
complete listing of these bodies can be found at www .iso .org/members .html.
ISO 20916:2019(E)
Introduction
In vitro diagnostic (IVD) medical devices are used to conduct tests outside of the human body to provide
valuable information regarding a person’s health or physiological status. They include tests and related
devices, such as test strips and reagents, using specimens such as blood, tissue or urine, to carry out
screening, diagnosis, prognosis, predictive testing, and monitoring of conditions. IVD medical devices
are fundamentally different from other medical devices because they perform their function outside
of the body on specimens taken from the human body. Human subjects are typically not exposed to
risks with the performance testing of IVD medical devices, except for the risk associated with specimen
collection procedures or when the obtained information is used for patient management. The specimens
are obtained via normal body functions (e.g. urine) or through the use of invasive medical devices to
allow for the specimen to be obtained (e.g. biopsy). The specimens are never reintroduced into the
human body. These differences make the performance and risk characteristics of IVD medical devices
different and unique from other medical devices.
Most of the studies for IVD medical devices are performed using samples resulting from the remnants
of specimens taken for purposes of standard of care (leftover or archived). In these studies, there is no
risk for the subjects arising from either the information provided by the IVD medical device or from
the collection procedure of the specimen. However, when leftover specimens are not used, additional
requirements should be considered
— when the specimens are collected specifically for the study and the specimen collection procedures
present additional risk of direct harm for the subject (e.g. lumbar puncture or tissue biopsy, blood
collection from neonates or critically ill patients), and/or
— when the information obtained from the IVD medical devices during the study is used to make
patient management decision (i.e. interventional studies), presenting a risk of indirect harm for
the subject (e.g. false negative or false positive result leading to inappropriate patient management
decisions).
For the majority of IVD clinical performance studies, issues related to the use of vulnerable subjects
might not arise but should be considered on a case by case basis.
Considering the reliance on specimens taken from the body and the absence of direct contact of the
IVD with the patient, issues related to procedures for obtaining informed consent for IVD clinical
performance studies differ from those associated with other medical devices, especially for studies
with leftover or archived specimens. This document will provide guidance on the requirements for the
various situations described above for IVD medical devices.
This document is intended for clinical performance studies as these studies involve specimens taken
from the human body. When specimens other than leftover or archived specimens are used, there might
be additional collection risks for the subject. Also in interventional studies, there might be a risk for the
subject coming from the information provided by the result of the IVD under investigation.
This document is specific for IVD medical devices and therefore uses definitions and concepts that are
appropriate for IVD medical devices. It is a stand-alone standard for clinical performance studies for
IVD medical devices. In the situation for which there is an IVD medical device and a medical device used
in an integrated system (e.g. a lancet, an IVD test strip and a glucose meter), the respective jurisdiction’s
regulation will define it as either an IVD medical device or a medical device and subsequently, aspects
of both this document and ISO 14155 might need to be considered.
Except for these situations, this document should not be read in conjunction with ISO 14155, which
excludes IVD medical devices from its scope.
The flowchart represented in Figure 1 provides guidance on how to use this document.
vi © ISO 2019 – All rights reserved
ISO 20916:2019(E)
Figure 1 — Clinical performance study flow chart
The main body of the document, in addition to Annex G, includes minimum requirements for all studies.
No additional requirements apply for studies using leftover/archived specimens or studies with
specimen collection procedures that pose no additional risks to the subject.
However, additional requirements for interventional studies, and those studies in which the specimen
collection procedures pose a risk to subjects primarily recruited for the study, are found in Annexes A to
F. The nature of these studies warrants an increased level of stringency in the requirements for conduct
of the study. The flowchart indicates the annexes which describe the additional requirements for each
type of more complex studies. When necessary, the annexes describe differences in the requirements
for the different types of study. Additionally, informative annexes are included to provide information
on good study practice documentation (see Annex H) and auditing (see Annex I).
INTERNATIONAL STANDARD ISO 20916:2019(E)
In vitro diagnostic medical devices — Clinical performance
studies using specimens from human subjects — Good
study practice
1 Scope
This document defines good study practice for the planning, design, conduct, recording and reporting
of clinical performance studies carried out to assess the clinical performance and safety of in vitro
diagnostic (IVD) medical devices for regulatory purposes.
NOTE 1 The purpose of these studies is to assess the ability of an IVD medical device in the hands of the
intended user, to yield results pertaining to a particular medical condition or physiological/pathological state, in
the intended population.
The document is not intended to describe whether the technical specifications of the IVD medical device
in question are adequately addressed by the clinical performance study.
This document identifies the principles that underpin clinical performance studies and specifies general
requirements intended to
— ensure the conduct of the clinical performance study will lead to reliable and robust study results,
— define the responsibilities of the sponsor and principal investigator,
— assist sponsors, clinical research organization, investigators, ethics committees, regulatory
authorities and other bodies involved in the conformity assessment of IVD medical devices, and
— protect the rights, safety, dignity and well-being of the subjects providing specimens for use in
clinical performance studies.
Analytical performance studies are out of the scope of this document.
NOTE 2 When the collection of specimens specifically for the analytical performance study creates an
additional collection risk for subjects, some of the elements of this document (particularly the annexes) can be
useful for ensuring subject safety.
Clinical performance studies that are performed for reasons other than pre- and post-market regulatory
purposes, such as for re-imbursement purposes, are out of the scope of this document.
NOTE 3 Some of the elements of this document can be useful for the design of such studies, including subject
safety and data integrity.
This document does not include safety information for laboratory workers or other personnel collecting
the study specimens.
[1][12][13]
NOTE 4 Such information is included in other publications .
NOTE 5 Users of this document can consider whether other standards and/or requirements also apply to the
IVD medical device which is the subject of the clinical performance study, for instance, in the situation for which
there is an IVD medical device and a medical device used in an integrated system (e.g. a lancet, an IVD test strip,
and a glucose meter), aspects of both this document and ISO 14155 can be considered.
2 Normative references
There are no normative references in this document.
ISO 20916:2019(E)
3 Terms and definitions
For 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 https: //www .iso .org/obp
— IEC Electropedia: available at http: //www .electropedia .org/
3.1
adverse device effect
adverse event (3.2) related to the use of an IVD medical device under investigation
Note 1 to entry: This definition includes any adverse event resulting from insufficient or inadequate instructions
for use, installation, operation, or any malfunction of the IVD medical device under investigation.
Note 2 to entry: This definition includes any event resulting from use error or from intentional misuse of the IVD
medical device under investigation.
1)
[SOURCE: ISO 14155:— , 3.1, modified — Adapted for IVD medical devices.]
3.2
adverse event
AE
any untoward medical occurrence, inappropriate patient management decision, unintended disease or
injury, or untoward clinical signs in subjects, users, or other persons, with any connection to study
related activities, whether or not related to the IVD medical device under investigation
Note 1 to entry: Adverse events can be caused by, for instance, insufficient or inadequate instructions for use,
deployment, installation, operation, or any malfunction of the IVD medical device under investigation.
Note 2 to entry: This definition includes the malfunction or deterioration of a device which has not yet caused
death or serious injury, but which could lead to death or serious injury.
Note 3 to entry: This definition is not intended to be used in determining whether an event is reportable to a
regulatory authority.
Note 4 to entry: For users or other persons, this definition is restricted to events related to investigational (IVD)
medical devices.
Note 5 to entry: False negative or false positive results are not considered an adverse event unless in an
interventional study, inappropriate patient management decisions are made based on those false results.
3.3
analytical performance
ability of an IVD medical device to detect or measure a particular analyte
[SOURCE: GHTF/SG5/N6: 2012]
Note 1 to entry: Analytical performance can include analytical sensitivity (e.g. limit of detection), analytical
specificity (e.g. interference, cross-reactivity), accuracy (derived from trueness and precision), linearity, etc.
3.4
analytical performance study
study undertaken to establish or confirm the ability of an IVD medical device to detect or measure a
particular analyte
1) Under preparation. Stage at the time of publication: ISO/DIS 14155:2019.
2 © ISO 2019 – All rights reserved
ISO 20916:2019(E)
3.5
anticipated serious adverse device effect
effect which by its nature, incidence, severity or outcome has been identified in the risk analysis report
Note 1 to entry: Anticipated serious adverse device effects can also be described in the study protocol,
investigator brochure, and subject informed consent, when applicable.
3.6
archived specimen
archived sample
specimen or sample (3.42) that was collected in the past and is obtained from repositories (e.g. tissue
banks, commercial vendor collections)
[SOURCE: GHTF/SG5/N8: 2012]
3.7
audit
systematic independent examination of activities and documents related to a clinical performance study
to determine whether these activities were conducted, and the data recorded, analyzed and accurately
reported according to the clinical study performance protocol, standard operating procedures,
specified requirements
1)
[SOURCE: ISO 14155:— , 3.3, modified — Adapted for IVD medical devices.]
Note 1 to entry: Specified requirements are those described in this document and may include any other
applicable requirements such as regulatory provisions.
3.8
blinding
masking
procedure in which one or more parties to the clinical performance study are kept unaware of any
information related to the condition or physiological state, treatment, prior test results, demographics,
etc., of the individual from whom the specimen for testing was obtained in order to reduce bias
3.9
case report forms
CRFs
set of printed or electronic documents for each subject on which information to be reported to a sponsor
is recorded, as required by the clinical performance study protocol
1)
[SOURCE: ISO 14155:— , 3.6, modified — Adapted for IVD medical devices.]
3.10
clinical performance of an IVD medical device
ability of an IVD medical device to yield results that are correlated with a particular clinical condition
or physiological/pathological process/state in accordance with the intended use (clinical test purpose,
target population and intended user)
Note 1 to entry: In accordance with intended use, clinical performance can include expected values, diagnostic
sensitivity and diagnostic specificity based on the known clinical condition or physiological/pathological
process/state of the individual, and negative and positive predictive values based on the prevalence of the
disease.
[SOURCE: GHTF/SG5/N6: 2012]
3.11
clinical performance study
study undertaken to establish or confirm the clinical performance of an IVD medical device (3.10)
Note 1 to entry: Testing performed pre-market that is not designed to address clinical performance of an IVD
medical device is not considered a clinical performance study (e.g. customer feedback studies, external analytical
performance studies, research studies).
ISO 20916:2019(E)
[SOURCE: GHTF/SG5/N6: 2012]
3.12
clinical performance study protocol
CPSP
document that states the rationale, objectives, design, risk, proposed analysis, methodology, monitoring,
conduct and record-keeping of the clinical performance study (3.11)
Note 1 to entry: The CPSP need not be a single document but a series of documents related and referenced to each
other for the purpose of creating the CPSP.
[SOURCE: GHTF/SG5/N8: 2012]
3.13
clinical performance study report
CPSR
document describing the objectives design, execution, statistical analysis, results and conclusion(s) of a
clinical performance study
Note 1 to entry: Some elements of the clinical performance study report can be covered by stand-alone documents
that are references in the clinical performance study report.
Note 2 to entry: The CPSR need not be a single document but a series of documents related and referenced to each
other for the purpose of creating the CPSR.
[SOURCE: GHTF/SG5/N8: 2012]
3.14
contract research organization
person or organization contracted by the sponsor (3.49) to perform one or more of the sponsor’s clinical
performance study-related duties and functions
3.15
device accountability records
records documenting the physical location of all IVD medical devices under investigation, from
shipment of the devices to the study site until return or disposal, a
...
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