UNDERSTANDING CLINICAL DATA FOR MEDICAL DEVICES
Regardless of their classification, all medical devices require a clinical evaluation. A clinical evaluation is conducted to demonstrate safety and performance as well as the overall positive benefit-to-risk-ratio for a medical device through critical evaluation of clinical data.
Clinical data is essentially the safety and performance information that is generated from the use of a medical device. To demonstrate safety and performance of a medical device, clinical evidence must be provided. Basically, there are two possibilities to generate clinical evidence. Firstly, clinical data may be collected through clinical investigations conducted with the respective medical device. The second possibility may be the demonstration of safety and performance based on data already publicly available. This could be data published in scientific literature or data for comparable devices through the literature route. In this scenario, demonstration of comparability and/or equivalence, respectively, is required. For example, this could be based on directly comparative bench tests and/or pre-clinical studies.
If applicable, both routes of clinical investigation and clinical evaluation via literature must be used in order to prove clinical safety and performance of a medical device before a device may be placed on the market.
PMCF (Post-market clinical follow-up) studies are part of the clinical post market vigilance system and are studies which have to be conducted (in addition to any pre-market activities) after the device has been placed onto the market.
Clinical Data generated through a PMCF study may only serve to confirm safety and performance. The objectives of such a study has to be covered by the scope for which the device is already approved, e.g. with regard to intended use and indications.
Moreover, PMCF studies serve to generate data regarding complications and/or problems which may only become apparent after wide-spread or long-term use of the device.
Clinical investigation for medical devices is any systematic investigation on one or more human subjects, undertaken to evaluate the safety and/or performance of a medical device.
Clinical investigations must be carried out in accordance with EN ISO 14155 (GCP) and in accordance with local regulations. Read more about clinical investigation plans here.
CLINICAL EVALUATION REPORT
Clinical evaluation may be based upon the following databases:
- Clinical investigation or other studies of a equivalent (evidently comparable) device reported in scientific literature
- Published and/or unpublished reports on other clinical experience of either the device in question or a equivalent (evidently comparable) device
As a new medical device is not the sum of its partial equivalences to different (parts) of different established medical devices, it is essential to demonstrate the equivalency of both devices. This may be achieved through bench tests and in-vivo animal studies/pre-clinical studies. In the event that equivalence is supposed to be demonstrated through pre-clinical bench tests and/or animal studies, a scientifically sound justification is needed regarding the transferability of these data to the use of the device in humans.
According to Annex 1.I.5a of directive 90/385/EEC (AIMDD) and Annex I.I.6a of directive 93/42/EEC (MDD), demonstration of conformity with the essential requirements must include a clinical evaluation in accordance with Annex 7/Annex X of the respective directive. It is also anticipated that the guidelines of MEDDEV 2.7.1 rev. 3 - Clinical Evaluation, part of a set of guidelines relating to questions of application of EU-Directives on Medical Devices, are likely to be followed by European Union member states, even though it is legally non binding.
POST MARKET CLINICAL STUDIES
Post-market clinical follow-up studies are conducted following the CE marking of a device and are intended to answer specific questions relating to clinical safety or performance of a device when used in accordance with its approved labelling.
Post-market clinical follow-up studies may be needed as rare complications or problems may only become apparent after wide-spread or long-term use of the device. In addition, there may be limitations to the clinical data available in the pre-market phase. These include limited sample sizes, short duration of testing and heterogenous sample groups. It is important to note that data obtained from post-market clinical follow-up studies are not intended to replace the pre-market data necessary to demonstrate conformity with regulatory requirements.
The decision to conduct post-market clinical follow-up studies must be based on the identification of possible residual risks and/or the lack of clarity in long term clinical performance that may impact the benefit/risk ratio of a medical device.
Post-market clinical follow-up studies are mandatory for:
- Innovative medical device and products
- Medical devices used in high risk anatomical locations
- Medical devices affected by the emergence of new information on safety or performance
- Medical devices where the CE mark was based on the literature route/equivalence approach
MEDDEV 2.12-2 rev. 2 - Post market clinical follow up studies, is part of a set of guidelines relating to questions of application of EU-Directives on Medical Devices. It is assumed that the guidelines are being followed by European Union member states, even though it is legally non-binding.
The document reflects positions taken by representatives of interest parties in the medical devices sector and serves as a guide for manufacturers and Notified Bodies on how to carry out post-market clinical follow-up studies in order to fulfil post-market surveillance obligations according to Medical Devices Directives (MDD).
Which medical devices require a clinical evaluation?
All medical devices require a clinical evaluation regardless of their classification.
What is the purpose of the literature and the clinical investigation route?
In some cases, both routes might have to be followed to demonstrate clinical safety and performance of a medical device.
Which documents of the clinical investigation will be reviewed the notified body?
The clinical investigation plan, the letter of no objection issued by the competent authority, documents related to communication with the authority during the study (e.g. in case of deviations from the study plan), the ethics committee opinion and the signed and dated final report.
What shall an appropriate clinical evaluation report include?
Scope and context of the evaluation, clinical data including data from clinically relevant bench tests and pre-clinical studies, critical evaluation of all clinically relevant risks (under consideration of the Risk Analysis) as well as an evaluation of the overall benefit-to-risk ratio.