![MDR and IVDR Challenges and Opportunities of the New Regulations]()
The new European MDR (Medical Device Regulation) and IVDR (In Vitro Diagnostic Regulation) emphasize the importance of clinical or performance evaluation, risk management, and risk-benefit analysis throughout the product lifecycle. Therefore, manufacturers are required to verify and confirm the compliance of their devices even after commercialization, both in terms of clinical performance and safety.
Based on the regulatory pathway to be undertaken, both for MD and IVD, it may be crucial to plan one or more clinical investigations/performance studies to confirm the claims of the product, whether it is yet to be marketed, already commercialized, or proposed for a new indication of use for a CE-marked product
The design of a clinical investigation/performance study must be defined by a study protocol written in accordance with the Declaration of Helsinki, MDCG guidelines, and applicable standards for conducting clinical studies (ISO 14155 “Clinical investigation of medical devices for human subjects — Good clinical practice” for MDs and ISO 20916 “In vitro diagnostic medical devices — Clinical performance studies using specimens from human subjects — Good study practice” for IVDs)
The success of a clinical study for any device depends on numerous factors, but a key point remains the correct identification of the target population.
The aspects to consider for its identification are:
- The claims of the experimental product
- The state of the art
- The standard therapy
- The inclusion and exclusion criteria
The first fundamental step to consider is the intended use of the device, and therefore for which therapeutic/diagnostic area it is intended.
Based on the device in question, it is necessary to understand the state of the art and the gold standard (the reference standard) for the treatment/diagnosis of the specific clinical/therapeutic condition and to understand what the minimum expectations are in terms of performance/efficacy and safety for the type of device, always protecting and prioritizing the well-being of the patient/subject involved
The information derived from bibliographic research and the opinion of the clinician involved in the study will help identify the population of interest that can benefit from the use of the experimental product.
Once the clinical, diagnostic, demographic parameters that best define the target population are identified, in light of preclinical data and results, a list of eligibility criteria will be created, i.e., inclusion and exclusion criteria, to select the subjects that can be enrolled (the sample population).
The inclusion criteria define the main characteristics of the population (e.g., type of disease, clinical parameters, age, gender). The exclusion criteria must consider the contraindications of the experimental product (e.g., if the device cannot be used under 18 years old) and serve to minimize potential risks for participants by excluding subjects at high risk of adverse events. The eligibility criteria must also prevent possible biases and exclude subjects with concomitant diseases or treatments that could interfere with data analysis and quality.
One of the most challenging aspects in defining a target population is certainly being able to select an adequate but at the same time representative population of the “real” population.
Therefore, the eligibility criteria should not be too stringent to avoid excluding potentially representative subgroups, while also excluding at-risk subjects or those who would not benefit from the device under study.
The main actors contributing to selecting an adequate study population are:
- The manufacturer
- The clinician involved in the study
- The supporting CRO
The manufacturer knows all the technical, performance, and safety aspects of the device. The clinician conducting the study knows exactly the population that can best benefit from the device and all the clinical parameters needed for the inclusion/exclusion criteria.
The CRO can support all the various steps of clinical activities. For each phase, the CRO uses specialized figures (e.g., medical writers and biostatisticians for study design and data analysis; CRAs, clinical project managers, and data managers for study management).
The success of a clinical investigation/performance study therefore depends on the study design and the identification of the target population. The convergence of various figures with different skills helps to define the best target population for any clinical study, in compliance with guidelines and ensuring the safety and well-being of patients.
