THE MEDICAL DEVICE COORDINATION GROUP RELEASED A NEW GUIDANCE DOCUMENT REGARDING general principles of clinical evidence for In Vitro Diagnostic medical devices (IVDs) (mdcg 2022-2)
This document outlines the general principles of clinical evidence and provides guidance on the continuous process of performance evaluation for in vitro diagnostic medical devices (hereafter referred to as IVDs), as set out in Regulation (EU) 2017/746 – In Vitro Diagnostic Medical Device Regulation (IVDR).
In this guidance is described the approach by which collection, generation and documentation of supporting data for an IVD may be conducted prior to the placing on the market or putting into service. As the performance evaluation will be updated throughout the life cycle of an IVD.
Definition of IVD according to Regulation (EU) 2017/746 – In Vitro Diagnostic Medical Device Regulation (IVDR).
IVD: any medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, piece of equipment, software or system, whether used alone or in combination, intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body, solely or principally for the purpose of providing information on one or more of the following:
- a) concerning a physiological or pathological process or state;
- b) concerning congenital physical or mental impairments;
- c) concerning the predisposition to a medical condition or a disease;
- d) to determine the safety and compatibility with potential recipients;
- e) to predict treatment response or reactions;
- f) to define or monitoring therapeutic measures.
Specimen receptacles shall also be deemed to be in vitro diagnostic medical devices.
As accessories for an IVD fall under the scope of the IVDR, this document also provides guidance on these devices.
Prior to placing an IVD on the market or putting it into service, the manufacturer must demonstrate compliance with all applicable requirements of the IVDR, in accordance with the appropriate conformity assessment procedure(s). Therefore, the manufacturer must demonstrate that the IVD achieves its intended purpose in accordance with the claimed performance over the lifetime of the device.
The IVDR outlines that evidence for an IVD’s conformity is established by demonstrating and substantiating the scientific validity, analytical performance and clinical performance. Furthermore, the IVDR underlines that the necessary clinical evidence should be based on a sufficient amount and quality of data in order to allow a qualified assessment of whether the IVD is safe, performant and achieves the intended clinical benefit(s), when used as intended.
General principles of Clinical Evidence:
Clinical evidence for IVDs is established through the collection of data as a result of a performance evaluation. Performance evaluation covers the assessment and analysis of data to establish and verify the scientific validity, analytical performance and, where applicable, clinical performance of an IVD. Each indication and claimed clinical benefit specified in the intended purpose should be assessed and have the appropriate supporting clinical evidence.
Performance Evaluation is a structured, transparent, iterative and continuous process which is part of the quality management system and is conducted throughout the life cycle of an IVD. The general performance evaluation principles are laid down in Article 56 and Annex XIII, Part A, 1 of the IVDR and can be summarised as follows:
- Planning (Performance Evaluation Plan, PEP);
- Data establishment;
- Analysis, conclusions and documentation (Performance Evaluation Report, PER);
- Continuous monitoring and updates (Periodic <safety Update Report, PSUR; Post Market Performance Follow-up, PMPF).
The performance evaluation of an IVD must consider the benefit-risk ratio in light of the state-of-the-art. The three essential pillars of performance evaluation can be summarised as:
- Scientific validity: the extent to which the analyte, or marker to be determined by the IVD is associated with the targeted physiological state or clinical condition.
- Analytical performance: demonstration of the IVD’s ability to correctly detect or measure a particular analyte.
- Clinical performance: demonstration of an IVD’s ability to yield results that are correlated with a particular clinical condition or a physiological/pathological process or state in accordance with the target population and intended user.
The risk management system should be carefully aligned with and reflected in the performance evaluation process of the IVD, considering the clinical risks to be addressed as part of the performance evaluation, performance studies, and post-market performance follow-up(s). Due to their nature, in the majority of cases, deficiencies of IVDs do not directly lead to physical injury or damage to the health of people. If any, these devices may lead to indirect harm, rather than direct harm.