Many manufacturers ask themselves whether a clinical evaluation or clinical trial is necessary for their medical devices. The MDR requirements are quite extensive and specific. Various products previously categorized as equivalent under the MDD now belong to a different risk class and existing clinical data are often no longer accepted by notified bodies. The MDR also places greater focus on the benefit-risk ratio for patients.
What does the clinical evaluation of medical devices involve? What kind of data need to be collected? Which documents are required by the MDR? In this article, we would like to give you a clearer idea about this topic. In addition, we discuss the clinical investigation of medical devices and go into more detail about the so-called equivalence route.
The Clinical Evaluation
MDR 2017/745 requires manufacturers to demonstrate the safety and performance of their medical devices through evaluation and analysis of clinical data. The scope of this clinical evaluation depends on the risk class of the product and the corresponding data basis:
|Class I||Class IIa||Class IIb||Class III|
|Applicable data||Clinical data (before or after market access)||Clinical data or clinical investigation||Clinical investigation|
According to MDR, clinical data are scientific literature from pre-clinical, clinical, and post-market surveillance. These can be product-specific information or data on a product whose equivalence to the product under investigation has been demonstrated. In the case of class I medical devices and older medical devices (legacy devices), there are often no sufficient clinical data. Therefore, all applicable data form the basis for these products. Possible reasons for this are, for instance, the low risk or the use of less innovative technology. Latter often holds true for legacy devices.
The Clinical Evaluation Report (CER)
The outcomes of data research or the clinical trial must be recorded in form of a Clinical Evaluation Report (CER). In addition to information on safety and performance, the CER includes results on undesirable side effects and the benefit-risk ratio of the medical devices. The CER is part of the technical documentation. Thus, it is an important prerequisite for the Conformity assessment procedure by Notified Bodies. Medical devices of Class I are an exception here. For these, technical documentation including a CER is also required but must only be submitted upon request by the competent authority.
In addition to the CER, a short report on the safety and performance of the respective medical device must be created. It is uploaded to EUDAMED after validation by a Notified Body and made available to the public. Currently, the EUDAMED module (Clinical Investigation & Performance Studies) is still under development.
The Clinical Evaluation Plan (CEP) and Clinical Development Plan (CPD)
The Clinical Evaluation Plan (CEP) forms the basis and driving force for the CER. On the one hand, this plan describes the available information about the product. Among them are technical details, intended use, clinical benefit, and current state-of-art of the embedded technology. On the other hand, it defines the data collection process. Including the methodology chosen to demonstrate clinical evidence, the search strategy, and the evaluation criteria for the device’s benefit-risk ratio. More detailed information on the CEP can be found in the MDR (Annex XIV, Part A).
In the context of CEP, the MDR (Annex XIV, Part A) also refers to a Clinical Development Plan (CPD). This document does not exist separately but must be understood as a firmly integrated component of the CEP document. It describes the clinical development process of the medical device – from exploratory studies to confirmatory studies – and specifies milestones and possible acceptance criteria.
The Route of Equivalence
Manufacturers of Class III implantable devices and Class IIb active devices can consult an expert panel before conducting a clinical trial. Under certain conditions, a clinical trial must not be performed. For instance, if a predecessor product of the same manufacturer is technically, biologically, and clinically equivalent to the new medical device or if a comparable product is already being marketed by another manufacturer. The prerequisite here is that both manufacturers contractually agree on the insight into the technical documentation of a similar medical device.
Clinical investigation(s) before market access
The MDR stipulates the performance of a clinical trial for medical devices of risk classes III and IIb. Responsibility for the clinical investigation(s) lies with the sponsor. This would be the company that holds the market license for the respective medical device. The sponsor is responsible for defining the objectives of the clinical trial, selecting clinical study centers and principal investigators. Additionally, they have to obtain approval from ethics committees and competent authorities. During the entire course of the study, they are responsible for warranting compliance with regulatory requirements.
To ensure a smooth process, principal investigators, their staff, and clinical research associates are instructed at the beginning of the trial. Training topics include product information and handling, study endpoints, design, study performance, and data collection. The data collected by the trial centers must be continuously evaluated in the background. In doing so, the trial centers or authorities can be contacted as quickly as possible if problems arise, and the clinical trial can be adjusted or terminated if necessary. At the end of the study, a report is prepared with the collected clinical data, including negative results, and their critical evaluation.
The MDR also goes into more detail on the education and treatment of certain groups of people. Children, pregnant or breastfeeding women, and persons not capable of giving consent may only participate in a clinical trial if there are no comparable data from other subjects or if these cannot be collected using other research methods. If that is the case, a legal representative for incapacitated subjects and minors must be determined. The decision here is up to the individual EU Member State.
Clinical investigation(s) following market access.
Besides creating a clinical evaluation for their medical decices, manufacturers are also expected to systematically monitor their medical devices after being placed on the market. As evidence, the MDR requires the discussion of post-market surveillance activities in the CER, a Post-Market Clinical Follow-Up (PMCF) Plan, and the creation of a PMCF Evaluation Report. The aim of these documents is to obtain clinical data on the performance and safety of each medical device throughout its life cycle.
To be regulatory compliant, especially regarding innovative medical devices, such as class III devices or class IIb active devices, it is recommended to plan the clinical development and data collection after CE marking at an early stage of the product’s development process.[Disclaimer]
This information is only one possible interpretation of the regulations. They are also in a constant state of change, so the information in this article may be incomplete or out of date. The above article is expressly no legal advice. Please refer to the official documents for information before making any business decisions. (Status of information: March 2023)