A clinical investigation is defined by the MDR as any systematic investigation involving one or more human subjects undertaken to assess the safety and performance of a medical device, that is the ability of the device to achieve its intended purpose leading to a clinical benefit.
Do you need to perform a clinical investigation on a medical device?
The clinical investigation is not always mandatory, but must be conducted when the clinical data available from other sources (scientific literature and PMS or PMCFU) are not sufficient to prove compliance with (one or more) essential safety and performance requirements of referred to in Annex I. This general rule is subject to an exception for implantable and class III devices.
So much so that, the clinical investigation is always required for:
- Implantable and class III MD, except if:
- MD designed by modifications of a device already marketed by the same manufacturer; modified MD demonstrated by the manufacturer to be equivalent to the marketed device, as per MDR, with this demonstration endorsed by the notified body; and the clinical evaluation of the marketed device is sufficient to demonstrate conformity of modified MD with relevant safety and performance requirements.
- MD demonstrated by the manufacturer to be equivalent to a device marketed by another manufacturer, as per above, as well as providing a contract is in place between the two manufacturers (full access to the technical documentation on an ongoing basis), and the original clinical evaluation has been performed in compliance with MDR (evidence to be provided to the Notified Body).
- MD lawfully placed on the market or put into service in accordance with Directive 90/385/EEC or Directive 93/42/EEC and for which the clinical evaluation is based on sufficient clinical data and compliant.
- MD such as sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips or connectors for which the clinical evaluation is based on sufficient clinical data and is compliant
- Innovative MD
Which is the documentation required for the clinical investigation?
- Clinical Investigation Plan (CIP)
- Investigator’s Brochure (IB) or Instruction for Use (IFU) (the latter for MD with CE marking)
- Information and Informed Consent (ICF)
- Consent to data processing (GDPR)
- CRF
- Monitoring plan
- MD Declaration of Conformity
- Labelling
- Certifications Manufacturer/Sponsor
- Investigation site selection report (qualification and rationale for selection)
Collection of Clinical Experience Data
Collection of clinical experience data should include collection of data from completed clinical studies, adverse events, and corrective action related to clinical risks.
The clinical data and clinical evaluation results relating to a device should be in sufficient quality and quantity to allow a qualified assessment of the device's capacity to obtain the expected clinical benefits and safety when used as intended by the manufacturer.
As far as design is concerned, clinical studies can be divided into prospective study, retrospective study, randomized controlled trials, non-randomized controlled trials, single-arm studies, case reports, post-market clinical follow-up (PCMF) studies, etc.
The applicant is required to collect and submit the opinions from Ethics Committee (if applicable), the clinical research plan and the clinical research report.
Why not fear a clinical study?
Before starting and conducting a clinical study, careful consideration should be given to the question of why the study has been proposed and whether that study is truly necessary to answer the question(s) posed. The actual need for a study should always be addressed and demonstrated, since there are sometimes relatively simple alternatives to conducting a study.
It is fundamental that one should seek the least complex approach to answering or addressing a clearly stated clinical problem, hypothesis or question. In formulating an approach to the question to be addressed in the study and in establishing the study design to answer that question, it may be helpful to think of the approach as a balanced between sample size and depth of information.
The study design is the framework by which the study objectives will be met. The design is generally estabilished after the study objectives have been clearly elucidated.
There are several reasons why the specific study design required to address the study objectives may be either unsuitable or impossible to adopt. The design might require:
- Methods that are beyond the state of the art in the particular field of medicine involved
- Equipment that is too expensive or too difficult to obtain or operate
- Too many patients
- Efforts that are too arduous for patients to meet confortably
- Too long a period to conduct
- Too much manpower to conduct
- Any other numerous possibilities.
Thus, it may be necessary to revise the study objectives to bring them within the limitations imposed on the study design by resources, state-of-the-art considerations, or other factors.
In summary, solutions can be found for every practical, ethical, scientific and temporal problem: this is why the clinical trial should not be feared, but approached with attention, competence and logical organization.
What are the phases of a clinical investigation?
What are the Competent Authorities or Body involved?
- Central Competent Authority – Ministry of Health
- Ethics Committee (EC)
- Notified Bodies