Clinical Evaluation Guidance Document
All medical devices require a clinical evaluation and a clinical investigation in order to prove that the product is safe to be used by the intended users and that it achieves what the manufacturer claims the device was designed for, i.e. the device’s intended use.
This document was designed to provide guidance to manufacturers of medical devices to help them understand the requirements for clinical evaluation and investigation of their product(s) under the new EU Medical Device Regulation 2017/745.
All medical devices require a clinical evaluation and a clinical investigation in order to prove that the product is safe to be used by the intended users and that it achieves what the manufacturer claims the device was designed for, i.e. the device’s intended use.
This document was designed to provide guidance to manufacturers of medical devices to help them understand the requirements for clinical evaluation and investigation of their product(s) under the new EU Medical Device Regulation 2017/745.
Table of Contents 1.0 Introduction ................................................................................................................................................................ 3 2.0 Relationship of the clinical evaluation in regard to other process ................................................................................ 3 3.0 Definitions .................................................................................................................................................................. 4 4.0 The stages of the clinical evaluation ........................................................................................................................... 5 Step 0: Define Scope .................................................................................................................................................... 5 Step 1: Identify Data .................................................................................................................................................... 6 Scientific Literature ......................................................................................................................................................... 6 Clinical Experience........................................................................................................................................................... 6 Step 2: Assess Data ...................................................................................................................................................... 6 Quality and validity ......................................................................................................................................................... 6 Relevance ........................................................................................................................................................................ 7 Step 3: Analyse Data ................................................................................................................................................... 8 Sound Methods ............................................................................................................................................................... 8 Comprehensive Analysis.................................................................................................................................................. 9 Equivalence ..................................................................................................................................................................... 9 Step 4: Clinical Evaluation ........................................................................................................................................... 9 5.0 Clinical Investigation ................................................................................................................................................ 10 A. Introduction .......................................................................................................................................................... 10 B. Articles .................................................................................................................................................................. 10 C. Key Words ............................................................................................................................................................. 11 D. Purpose of the clinical investigation ...................................................................................................................... 11 Chapter 1 .................................................................................................................................................................. 11 1.1 General obligations of each responsible body, involved in the clinical investigation ............................................. 11 1.2 General requirements regarding clinical investigations conducted to demonstrate conformity of devices ........... 16 1.3 Informed Consent.................................................................................................................................................... 16 1.4 Emergency conditions ............................................................................................................................................. 17 1.5 Application for clinical investigation ....................................................................................................................... 18 1.6 Conduct of the clinical investigation ....................................................................................................................... 19 1.7 Substantial modifications to clinical investigations ................................................................................................. 20 1.8 End of the clinical investigations ............................................................................................................................. 20 1.9 Cases in which the clinical investigation could not be performed .......................................................................... 21 Chapter 2 .................................................................................................................................................................. 22 2.1 Application Form ..................................................................................................................................................... 22 2.2 Investigator’s Brochure ........................................................................................................................................... 23 2.3 Clinical Investigation Plan ........................................................................................................................................ 24 2.4 Clinical Investigation Report .................................................................................................................................... 27 6.0 ISO 14155 ................................................................................................................................................................. 28 6.1 Scope ................................................................................................................................................................... 28 6.2 Definitions ........................................................................................................................................................... 29 6.3 Ethical considerations .......................................................................................................................................... 29 6.4 Clinical investigation planning ............................................................................................................................. 29 6.4.1 Clinical Investigation Plan (CIP) ............................................................................................................................ 30 6.4.2 Investigator’s brochure (IB) .................................................................................................................................. 30 6.4.3 Case report forms (CRFs) ...................................................................................................................................... 30 6.5 Clinical Investigation report ................................................................................................................................. 31 Appendix A: Comparison of MDD with EU MDR in regard to clinical evaluation including clinical investigation .............. 32 Appendix B: Comparison of ISO 14155 with EU MDR in regard to clinical evaluation including clinical evaluation .......... 47 2
1.0 Introduction Clinical evaluation is the systematic process of collecting and analysing clinical data of a medical device, the clinical information is collected from the post-market surveillance (PMS) and from the post-market clinical follow-up (PMCF). This process aims to provide patients and healthcare professionals with confidence about the device which they are going to use. The clinical evaluation ensures the safety and the effectiveness of the device and meanwhile ensures that the device is going to quickly be available on the market. Furthermore, this process aims to increase the availability of innovative companies by attracting investors, estimate costs and most importantly anticipate procedures. This document aims to give guidelines to any responsible body who is involved in the clinical evaluation. Furthermore, this document is going to illustrate the relationship between the clinical evaluation and other important processes and explain the impact on them. Appendix A illustrates the difference between the EU MDR and MDD regarding clinical evaluation. 2.0 Relationship between the clinical evaluation and other processes The flowchart below illustrates the relationship between the design development phase and the post production phase. Through these two phases it is shown that the clinical evaluation is directly linked with the PMCF and hence with the PMS. Figure 1 - Relationship of the clinical evaluation in regard to other process 3
Table of Contents<br />
1.0 Introduction ................................................................................................................................................................ 3<br />
2.0 Relationship of the clinical evaluation in regard to other process ................................................................................ 3<br />
3.0 Definitions .................................................................................................................................................................. 4<br />
4.0 The stages of the clinical evaluation ........................................................................................................................... 5<br />
Step 0: Define Scope .................................................................................................................................................... 5<br />
Step 1: Identify Data .................................................................................................................................................... 6<br />
Scientific Literature ......................................................................................................................................................... 6<br />
<strong>Clinical</strong> Experience........................................................................................................................................................... 6<br />
Step 2: Assess Data ...................................................................................................................................................... 6<br />
Quality and validity ......................................................................................................................................................... 6<br />
Relevance ........................................................................................................................................................................ 7<br />
Step 3: Analyse Data ................................................................................................................................................... 8<br />
Sound Methods ............................................................................................................................................................... 8<br />
Comprehensive Analysis.................................................................................................................................................. 9<br />
Equivalence ..................................................................................................................................................................... 9<br />
Step 4: <strong>Clinical</strong> <strong>Evaluation</strong> ........................................................................................................................................... 9<br />
5.0 <strong>Clinical</strong> Investigation ................................................................................................................................................ 10<br />
A. Introduction .......................................................................................................................................................... 10<br />
B. Articles .................................................................................................................................................................. 10<br />
C. Key Words ............................................................................................................................................................. 11<br />
D. Purpose of the clinical investigation ...................................................................................................................... 11<br />
Chapter 1 .................................................................................................................................................................. 11<br />
1.1 General obligations of each responsible body, involved in the clinical investigation ............................................. 11<br />
1.2 General requirements regarding clinical investigations conducted to demonstrate conformity of devices ........... 16<br />
1.3 Informed Consent.................................................................................................................................................... 16<br />
1.4 Emergency conditions ............................................................................................................................................. 17<br />
1.5 Application for clinical investigation ....................................................................................................................... 18<br />
1.6 Conduct of the clinical investigation ....................................................................................................................... 19<br />
1.7 Substantial modifications to clinical investigations ................................................................................................. 20<br />
1.8 End of the clinical investigations ............................................................................................................................. 20<br />
1.9 Cases in which the clinical investigation could not be performed .......................................................................... 21<br />
Chapter 2 .................................................................................................................................................................. 22<br />
2.1 Application Form ..................................................................................................................................................... 22<br />
2.2 Investigator’s Brochure ........................................................................................................................................... 23<br />
2.3 <strong>Clinical</strong> Investigation Plan ........................................................................................................................................ 24<br />
2.4 <strong>Clinical</strong> Investigation Report .................................................................................................................................... 27<br />
6.0 ISO 14155 ................................................................................................................................................................. 28<br />
6.1 Scope ................................................................................................................................................................... 28<br />
6.2 Definitions ........................................................................................................................................................... 29<br />
6.3 Ethical considerations .......................................................................................................................................... 29<br />
6.4 <strong>Clinical</strong> investigation planning ............................................................................................................................. 29<br />
6.4.1 <strong>Clinical</strong> Investigation Plan (CIP) ............................................................................................................................ 30<br />
6.4.2 Investigator’s brochure (IB) .................................................................................................................................. 30<br />
6.4.3 Case report forms (CRFs) ...................................................................................................................................... 30<br />
6.5 <strong>Clinical</strong> Investigation report ................................................................................................................................. 31<br />
Appendix A: Comparison of MDD with EU MDR in regard to clinical evaluation including clinical investigation .............. 32<br />
Appendix B: Comparison of ISO 14155 with EU MDR in regard to clinical evaluation including clinical evaluation .......... 47<br />
2
Change language