Clinical investigation of medical devices for human subjects – Good clinical practice (ISO 14155:2011)
Abstract
ISO 14155:2011 addresses good clinical practice for the design, conduct, recording and reporting of clinical investigations carried out in human subjects to assess the safety or performance of medical devices for regulatory purposes.
The principles set forth in ISO 14155:2011 also apply to all other clinical investigations and should be followed as far as possible, depending on the nature of the clinical investigation and the requirements of national regulations.
ISO 14155:2011 specifies general requirements intended to protect the rights, safety and well-being of human subjects, ensure the scientific conduct of the clinical investigation and the credibility of the results, define the responsibilities of the sponsor and principal investigator, and assist sponsors, investigators, ethics committees, regulatory authorities and other bodies involved in the conformity assessment of medical devices.
ISO 14155:2011 does not apply to in vitro diagnostic medical devices.
DIN EN ISO 14155:2012-01 (E)
Clinical investigation of medical devices for human subjects – Good clinical practice
(ISO 14155:2011 + Cor. 1:2011)
Contents Page
Foreword ………………………………………………………………………………………………………………………………………. 4
1 Scope …………………………………………………………………………………………………………………………….. 5
2 Normative references …………………………………………………………………………………………………….. 5
3 Terms and definitions …………………………………………………………………………………………………….. 6
4 Ethical considerations ………………………………………………………………………………………………….. 11
4.1 General ………………………………………………………………………………………………………………………… 11
4.2 Improper influence or inducement ………………………………………………………………………………… 12
4.3 Compensation and additional health care ……………………………………………………………………… 12
4.4 Responsibilities ……………………………………………………………………………………………………………. 12
4.5 Communication with the ethics committee (EC) ……………………………………………………………. 12
4.5.1 General ………………………………………………………………………………………………………………………… 12
4.5.2 Initial EC submission ……………………………………………………………………………………………………. 12
4.5.3 Information to be obtained from the EC ………………………………………………………………………… 13
4.5.4 Continuing communication with the EC ………………………………………………………………………… 13
4.5.5 Continuing information to be obtained from the EC ………………………………………………………. 13
4.6 Vulnerable populations ………………………………………………………………………………………………… 13
4.7 Informed consent …………………………………………………………………………………………………………. 14
4.7.1 General ………………………………………………………………………………………………………………………… 14
4.7.2 Process of obtaining informed consent ………………………………………………………………………… 14
4.7.3 Special circumstances for informed consent ………………………………………………………………… 14
4.7.4 Information to be provided to the subject ……………………………………………………………………… 15
4.7.5 Informed consent signature ………………………………………………………………………………………….. 17
4.7.6 New information …………………………………………………………………………………………………………… 17
5 Clinical investigation planning ……………………………………………………………………………………… 18
5.1 General ………………………………………………………………………………………………………………………… 18
5.2 Risk evaluation …………………………………………………………………………………………………………….. 18
5.3 Justification for the design of the clinical investigation …………………………………………………. 18
5.4 Clinical investigation plan (CIP) ……………………………………………………………………………………. 18
5.5 Investigator’s brochure (IB) ………………………………………………………………………………………….. 19
5.6 Case report forms (CRFs) …………………………………………………………………………………………….. 19
5.7 Monitoring plan ……………………………………………………………………………………………………………. 19
5.8 Investigation site selection …………………………………………………………………………………………… 19
5.9 Agreement(s) ……………………………………………………………………………………………………………….. 19
5.10 Labelling ………………………………………………………………………………………………………………………. 19
5.11 Data monitoring committee (DMC) ………………………………………………………………………………… 20
6 Clinical investigation conduct ………………………………………………………………………………………. 20
6.1 General ………………………………………………………………………………………………………………………… 20
6.2 Investigation site initiation ……………………………………………………………………………………………. 20
6.3 Investigation site monitoring ………………………………………………………………………………………… 20
6.4 Adverse events and device deficiencies ……………………………………………………………………….. 20
6.4.1 Adverse events …………………………………………………………………………………………………………….. 20
6.4.2 Device deficiencies ………………………………………………………………………………………………………. 20
6.5 Clinical investigation documents and documentation ……………………………………………………. 21
6.5.1 Amendments ………………………………………………………………………………………………………………… 21
6.5.2 Subject identification log ……………………………………………………………………………………………… 21
6.5.3 Source documents ………………………………………………………………………………………………………. 21
6.6 Additional members of the investigation site team ……………………………………………………….. 21
6.7 Subject privacy and confidentiality of data …………………………………………………………………… 21
6.8 Document and data control ………………………………………………………………………………………….. 22
6.8.1 Traceability of documents and data ……………………………………………………………………………… 22
6.8.2 Recording of data ………………………………………………………………………………………………………… 22
6.8.3 Electronic clinical data systems …………………………………………………………………………………… 22
6.9 Investigational device accountability ……………………………………………………………………………. 23
6.10 Accounting for subjects ………………………………………………………………………………………………. 23
6.11 Auditing ………………………………………………………………………………………………………………………. 23
7 Suspension, termination and close-out of the clinical investigation ………………………………. 24
7.1 Suspension or premature termination of the clinical investigation ………………………………… 24
7.1.1 Procedure for suspension or premature termination …………………………………………………….. 24
7.1.2 Procedure for resuming the clinical investigation after temporary suspension ……………… 25
7.2 Routine close-out ………………………………………………………………………………………………………… 25
7.3 Clinical investigation report …………………………………………………………………………………………. 25
7.4 Document retention ……………………………………………………………………………………………………… 26
8 Responsibilities of the sponsor ……………………………………………………………………………………. 26
8.1 Clinical quality assurance and quality control ………………………………………………………………. 26
8.2 Clinical investigation planning and conduct …………………………………………………………………. 27
8.2.1 Selection of clinical personnel ……………………………………………………………………………………… 27
8.2.2 Preparation of documents and materials ………………………………………………………………………. 27
8.2.3 Conduct of clinical investigation ………………………………………………………………………………….. 28
8.2.4 Monitoring …………………………………………………………………………………………………………………… 28
8.2.5 Safety evaluation and reporting ……………………………………………………………………………………. 31
8.2.6 Clinical investigation close-out …………………………………………………………………………………….. 31
8.3 Outsourcing of duties and functions …………………………………………………………………………….. 32
8.4 Communication with regulatory authorities ………………………………………………………………….. 32
9 Responsibilities of the principal investigator ………………………………………………………………… 32
9.1 General ……………………………………………………………………………………………………………………….. 32
9.2 Qualification of the principal investigator …………………………………………………………………….. 32
9.3 Qualification of investigation site …………………………………………………………………………………. 33
9.4 Communication with the EC …………………………………………………………………………………………. 33
9.5 Informed consent process ……………………………………………………………………………………………. 33
9.6 Compliance with the CIP ………………………………………………………………………………………………. 33
9.7 Medical care of subjects ………………………………………………………………………………………………. 34
9.8 Safety reporting …………………………………………………………………………………………………………… 35
Annex A (normative) Clinical investigation plan (CIP) …………………………………………………………………… 36
Annex B (normative) Investigator’s brochure (IB) …………………………………………………………………………. 43
Annex C (informative) Case report forms (CRFs) …………………………………………………………………………. 45
Annex D (informative) Clinical investigation report ………………………………………………………………………. 47
Annex E (informative) Essential clinical investigation documents ………………………………………………… 52
Annex F (informative) Adverse event categorization …………………………………………………………………….. 59
Bibliography ……………………………………………………………………………………………………………………………….. 62
Annex ZA (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on Medical Devices ……………………………………….. 63
Annex ZB (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 90/385/EEC on Active Implantable Medical Devices ………… 65