Multihealth presents the first installment of its "short guide for beginners in clinical research. "Specializing in the clinical development of health products, the group emphasizes the importance of consulting external experts to better meet the expectations of the authorities.
The clinical development plan for a medical device is a strategic document that defines the steps necessary to evaluate the safety and performance of the device in a clinical environment, with a view to obtaining regulatory approval and ensuring post-market surveillance of the device.
The clinical development strategy is conceived very early in the life cycle of a medical device (MD) and involves multiple areas of expertise to best meet the needs of manufacturers, notified bodies, and reimbursement assessment authorities.
Very broadly speaking, there are two types of studies: those that demonstrate the performance and safety of the MD and therefore enable it to obtain CE marking, and post-market clinical follow-up (PMCF) studies, which involve collecting and evaluating clinical data on the use of the MD in real life. Although PMCF studies are non-interventional, their design also requires a significant amount of upstream thinking to identify the key data to be collected and to anticipate how it will best be used.
For MD manufacturers taking their first steps in clinical research, it may be strategic to surround themselves from the outset with a medical and scientific committee made up of experts such as doctors, scientists, statisticians, and clinical research professionals. These experts have in-depth knowledge of study designs, types of research, investigation plans, current regulations, and best practices.
The committee of experts is involved upstream of the project, during the planning stages, to provide the necessary insights into the scientific and clinical relevance of the objective and the feasibility of the investigation.
Define the objective and expected performance
Regardless of the investigation, the first question to ask concerns the objective of the clinical investigation.
An objective must be specific and measurable. It is customary to say that a clinical investigation answers one question and one question only. A detailed question that specifies the criterion being evaluated, the measurement tool, the timing of the measurement, and the target population.
This may involve, for example, evaluating the performance of a new medical device in reducing symptoms according to a given scale in adult patients with a specific condition after a precisely defined period of treatment.
It may also involve comparing different diagnostic methods or investigations carried out for exploratory purposes to evaluate different treatment pathways.
The MD manufacturer must ensure that the objective it has set is relevant to clinical practice and that it makes a significant contribution to the field of research. It is important to demonstrate why the clinical investigation in question is necessary and how it can impact patient care. A review of the literature is essential at this stage in order to gain a thorough understanding of:
- studies already conducted in the field of application
, or the therapeutic area of interest, - methodologies implemented,
- the results obtained and the limitations highlighted by the authors.
At this stage, the manufacturer must also be able to position itself in terms of expected performance in order to define the criteria for success. What will enable us to conclude that performance is good or that the objective has been achieved? For example, it could be a specific 10% reduction in symptoms, a 4-point improvement in the patient quality of life score, or a 25% reduction in post-surgical complications. It is on the basis of this expected difference at a specific point in the investigation that the number of patients required to meet the primary objective is assessed.
Ensure the feasibility of the planned investigation
Once the objective has been correctly formulated with the expected level of detail, the design of the proposed investigation must be tested against the reality on the ground.
This involves assessing feasibility. Several questions then arise:
- Is the number of patients envisaged realistic?
- What resources need to be mobilized?
- What are the practical constraints?
- Is the total budget in line with what has been provisioned?…
The expertise available within a medical-scientific committee enables manufacturers to optimize the design of their studies and ensure the quality of the methodology and scientific rigor expected of their clinical investigations. Support from this type of committee also facilitates the dissemination of research results, since at the end of the investigation, the experts are asked to contribute to the promotion and communication of the results and to the writing of the final investigation reports.
Use the objective recommendations of a DSMB
Duringthe clinical investigation, a second committee may be necessary or even mandatory: the DSMB (Data and Safety Monitoring Board), also known as the data and safety monitoring committee. This is an independent committee that plays a key role in monitoring and evaluating clinical investigations. Its main responsibilities include data monitoring, safety assessment, and efficacy analy
.
The DSMB is often called upon in the context of implantable medical devices during initial studies conducted to evaluate their performance.
This concerns, for example, innovations such as pacemakers or coronary stents, or new generations of joint prostheses in the field of orthopedics.
The data collected during the clinical investigation generally enable the benefit/risk ratio to be assessed. The DSMB analyzes the data on a very regular basis to detect trends, unexpected adverse effects, or safety signals corresponding to new, important information that may be related to a risk to the health or safety of patients or users of a medical device. When evidence reveals that the initially demonstrated benefit-risk assessment is no longer favorable for the patient in the study, the investigation may be called into question.
DSMBs are also important when an interim analysis is planned to decide on how to proceed with the clinical investigation.
In sequential investigations, the DSMB may also be required to assess the benefit-risk ratio after the inclusion and follow-up period of the first five patients. The conclusions reached will determine the inclusion of subsequent patients.
Based on its analyses and assessments, the DSMB makes recommendations regarding the clinical investigation. These recommendations may include continuing the study, modifying the protocol, temporarily or permanently suspending the study, or any other measures deemed necessary to protect the safety of participants and ensure data integrity.
Within a DSMB, different areas of expertise are generally required to ensure a thorough assessment of data and safety.
For this reason, these committees may include:
- clinicians with relevant clinical experience in the therapeutic area covered by the clinical study,
- safety specialists, experts in vigilance who will be able to evaluate data relating to adverse effects and serious adverse events,
- as well as statisticians, to conduct an objective analysis of the data collected during the clinical study.
The specific composition of the DSMB depends on the nature of the clinical trial, the medical device under investigation, and the applicable regulatory requirements.
Although appointed by the trial sponsor, DSMB members must be independent, i.e., they must not have any conflicts of interest or be subject to any influence of any kind. An official document, the DSMB charter, describes the tasks entrusted to this independent committee, the frequency of its members' meetings, and the milestones of the investigation that determine the analysis expected from these experts.
Identify in advance the expertise you can rely on
In conclusion, the clinical development strategy for a medical device requires support from complementary medical, scientific, regulatory, statistical, clinical, and other experts throughout the device's life cycle. Before or after CE marking, specific skills are required to meet the expectations of the authorities. Independent and impartial supervision of the study design and the data collected ensures the relevance and reliability of the results and guarantees the safety of the patients included.
It is important to be aware of these expert requirements well in advance of clinical investigations in order to identify the appropriate profiles and skills, set up the appropriate committees, and thus conduct the investigations in an optimal manner in the best interests of patients.
Frequently Asked Questions
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Are you preparing a clinical investigation for your medical device? Our experts CLINACT will assist you in setting up your medical-scientific committee, designing the methodology, and monitoring your study.
