Clinical Evidence - Key Definitions and Concepts
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Clinical Evidence - Key Definitions and Concepts
Source: https://www.imdrf.org/documents/clinical-evidence-key-definitions-and-concepts
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FINAL DOCUMENT
International Medical Device Regulators Forum
Title: Clinical Evidence – Key Definitions and Concepts
Authoring Group: Medical Device Clinical Evaluation Working Group
Date: 10 October 2019
Elena M. Astapenko, IMDRF Chair
This document was produced by the International Medical Device Regulators Forum. There are no restrictions on the reproduction or use of this document; however, incorporation of this document, in part or in whole, into another document, or its translation into languages other than English, does not convey or represent an endorsement of any kind by the International Medical Device Regulators Forum.
Copyright © 2019 by the International Medical Device Regulators Forum
CONTENTS
Preface
1.0 Introduction 4
2.0 Scope 4
3.0 References 5
4.0 Definitions and Concepts 5
4.1 Clinical investigation 5
4.2 Clinical data 6
4.3 Clinical evaluation 6
4.4 Clinical evidence 6
Preface
The document herein was produced by the International Medical Device Regulators Forum (IMDRF), a voluntary group of medical device regulators from around the world. The document has been subject to consultation throughout its development.
There are no restrictions on the reproduction, distribution or use of this document; however, incorporation of this document, in part or in whole, into any other document, or its translation into languages other than English, does not convey or represent an endorsement of any kind by the International Medical Device Regulators Forum.
Introduction
This document supersedes an earlier version produced under the Global Harmonization Task Force (GHTF) with the same title in May, 2007(GHTF/SG5/N1R8:2007).[1]
It is anticipated that convergence of requirements for clinical evidence, including common data submissions, will lead to better understanding of medical device safety, clinical performance and/or effectiveness by all stakeholders, more efficient use of resources of the clinical community, medical device regulators and industry, and increased transparency and confidence in the global regulatory model. Ultimately, there should be more efficient, predictable and timely access to safe and effective medical technology by patients and society worldwide.
Clinical evidence and the Essential Principles of safety and performance of medical devices
The IMDRF Essential Principles of Safety and Performance of Medical Devices and IVD Medical Devices(the Essential Principles) set out the requirements relating to the safety and performance of medical devices. Of these, Essential Principles 5.1.1, 5.1.6, 5.1.7 and 5.1.9 in particular require that a medical device achieve its intended performance during use according to its labelling and that the known, and foreseeable risks, and any undesirable side-effects, are minimised and acceptable when weighed against the benefits of the intended performance.
The diversity of medical devices and the technologies on which they are based pose special challenges for manufacturers, conformity assessment bodies and regulators alike when trying to identify what should constitute evidence sufficient to demonstrate compliance with the Essential Principles. Some technologies have been available for many years and are well characterised from a safety, clinical performance and/or effectiveness viewpoint. On the other hand, many medical devices utilise new, state-of-the-art technology that has had little prior application in the treatment of humans.
Furthermore, their intended purpose and clinical application can vary widely with end results influenced by a wide range of different and differently experienced end-users.
Given the complexity of the medical devices milieu, the assessment of what is acceptable clinical evidence for the purpose of demonstrating compliance with the Essential Principles must be undertaken on a case-by-case basis. To this end, it is important to have an understanding of how medical devices are brought to market and of the role that clinical data and its evaluation plays in this process.
2.0 Scope
This document is intended to:
- introduce the concepts of clinical evaluation and clinical evidence;
- examine the relationship between clinical investigation, clinical data, clinical evaluation and clinical evidence; and
- serve as guidance to all those involved in the generation, compilation and review of clinical evidence sufficient to support the marketing of medical devices (regulatory authorities, conformity assessment bodies, manufacturers of medical devices and their associated industry groups).
The definitions and concepts contained within this document are intended to apply to the establishment and maintenance of conformity with the relevant Essential Principles for medical devices generally. Specific guidance has been developed in other documents in relation to in vitro diagnostic devices.
3.0 References
IMDRF/GHTF final documents
IMDRF GRRP WG/N47 FINAL: 2018 Essential Principles of Safety and Performance of Medical Devices and IVD Medical Devices
IMDRF Registry WG/N33FINAL:2016 Principles of International System of Registries Linked to Other Data Sources and Tools
GHTF SG1/ N78:2012 Principles of Conformity Assessment for Medical Devices
International standards
ISO 14155:2011 Clinical investigation of medical devices for human subjects — Good clinical practice
4.0 Definitions and Concepts
Clinical investigation
Definition : Any systematic investigation or study in or on one or more human subjects, undertaken to assess the safety, clinical performance and/or effectiveness of a medical device.
Explanation : This term is synonymous with ‘clinical trial’ and ‘clinical study’.
Effectiveness is the ability of a medical device to achieve clinically meaningful outcome(s) in its intended use as claimed by the manufacturer.
Clinical investigations include feasibility studies and those conducted for the purpose of gaining market approval, as well as investigations conducted following marketing approval.
Clinical data
Definition : Safety, clinical performance and/or effectiveness information that is generated from the clinical use of a medical device.
Explanation : Sources of clinical data may include:
* 1. results of pre- and post-market clinical investigation(s) of the device concerned- results of pre- and post-market clinical investigation(s) or other studies reported in the scientific literature of a comparable device
- published and/or unpublished reports on clinical experience of either the device in question or a comparable device
- other sources of clinical experience such as registries, adverse event databases and medical records.
Clinical evaluation
Definition: A set of ongoing activities that use scientifically sound methods for the assessment and analysis of clinical data to verify the safety, clinical performance and/or effectiveness of the medical device when used as intended by the manufacturer.
Explanation : This is a process undertaken by manufacturers of medical devices to help establish compliance with the relevant Essential Principles for safety and performance. The result of this process is a report, which can be reviewed by conformity assessment bodies and regulators. The report details the extent of available data and its quality, demonstrating how the clinical data satisfies compliance with the Essential Principles. Clinical evaluation is an ongoing process - information about safety, clinical performance and/or effectiveness (e.g. adverse event reports, results from any further clinical investigations, published literature etc.) should be monitored routinely by the manufacturer once the device is available on the market and the benefits and risks reassessed in light of this additional information.
The inputs for clinical evaluation are primarily clinical data in the form of clinical investigation reports, literature reports/reviews and clinical experience. The data required to establish the evidence of compliance with the Essential Principles may vary according to the characteristics of the medical device, its intended use, the claims made by the manufacturer, the existence and adequacy of warnings and other restrictions, and the extent of experience with its use. A key goal of the clinical evaluation is to establish that any risks associated with the use of the medical device are acceptable when weighed against the benefits to the patient and are compatible with a high level of protection of health and safety. The clinical evaluation will, therefore, also need to cross-reference risk management documents.
Clinical evidence
Definition : The clinical data and its evaluation pertaining to a medical device.
Explanation : Clinical evidence is an important component of the technical documentation of a medical device, which along with other design verification and validation documentation, device description, labelling, risk analysis and manufacturing information, is needed to allow a manufacturer to demonstrate conformity with the Essential Principles. It should be cross-referenced to other relevant parts of the technical documentation that impact on its interpretation.
In accordance with applicable local regulations, clinical evidence, in part or in total, may be submitted to and reviewed by conformity assessment bodies and regulatory authorities. The clinical evidence is used to support the marketing of the medical device, including any claims made about the safety, clinical performance and/or effectiveness of the device, and the labelling of the device. Figure 1 shows how the need for clinical evidence drives the processes of data generation and clinical evaluation, which produce clinical data and clinical evidence, respectively.
Clinical evidence should be reviewed and updated throughout the product life cycle by the manufacturer as new information relating to safety, clinical performance and/or effectiveness is obtained from clinical experience during marketing of the device in question and/or comparable devices.
DATA GENERATION
- Literature searching and/or
- Clinical experience and/or
- Clinical investigation
NEED FOR CLINICAL EVIDENCE
CLINICAL EVIDENCE
Clinical Evaluation Report with relevant clinical data
INCLUSION OF CLINICAL
EVIDENCE IN THE TECHNICAL DOCUMENTATION
CLINICAL EVALUATION
CLINICAL DATA
- Literature based data and/or
- Clinical experience data and/or
- Clinical investigation data
Published papers
Clinical investigation reports etc.
Figure 1 Overview of process for data generation and clinical evaluation
- This document is intended to provide an update on definitions and other terminology arising from regulatory updates in different regions. It does not update methodology such that it reflects a (best practice) life cycle approach. ↑