A Joint AIS x F-CRIN Mission

The purpose of clinical research is to evaluate the therapeutic or diagnostic value, conditions of use, potential side effects, and safety of health products. With the increasing availability of health data—particularly real-world data—along with AI and the development of personalized treatments, new clinical research methodologies are emerging. These new methodologies could help accelerate the development of health products for the benefit of patients in areas where evidence of efficacy is difficult to demonstrate (rare or ultra-rare diseases, diseases with very slow progression, antibiotic resistance, etc.) and in a context where health products and technologies are becoming increasingly personalized (genetic or molecular abnormalities, etc.). However, despite the growing interest in these approaches, there is still insufficient historical perspective to ensure their full adoption by the healthcare ecosystem and health authorities.

To facilitate their integration, the AIS and F-CRIN have been tasked with conducting work aimed at promoting the adoption of these new methodological approaches in clinical research. 

This initiative thus helps enhance France’s appeal as a hub for clinical research and is part of the momentum behind the France 2030 plan, which aims to equip France with a strategy to become the leading innovative and sovereign European nation in healthcare by promoting the use of real-world data, new clinical trial methodologies, and digital innovations.

The mission brings together a group of 31 experts from complementary disciplines: methodologists, clinician-researchers, representatives from public research organizations, hospitals, the healthcare industry, the Health Data Hub, and other stakeholders in the innovation ecosystem.

Three subgroups have been established:

• Group 1: "Accelerate development and strengthen the level of evidence in the early stages of evaluation for market authorization and reimbursement"
• Group 2: "Measuring performance under real-world conditions, both early on and over the long term"
• Group 3: "Data Management: Level of Data Structuring, Quality, and Validity"

Together, they are working to develop operational recommendations to facilitate the use of new methodological approaches in clinical trials, drawing on concrete use cases and feedback.

The research focuses in particular on three major categories of innovative methodological approaches:

• the optimization of clinical trial designs (platform trials, combination trials, etc.);
• integration of external information, including real-world data, digital health data, or Bayesian approaches;
• extrapolation of the benefit-risk ratio from registries, cohorts, external control groups, or mechanistic models (“in silico,” synthetic arms, etc.).

The objective is to clarify how these approaches should be used, their areas of application, the criteria for acceptability, and the situations in which they provide real added value.

The mission’s work is carried out in several phases, with deliverables due at various milestones, enabling the production of recommendations that can be directly implemented by sponsors, investigators, and other stakeholders in clinical research:

• Status report and analysis of practical cases: identification of the successes and limitations of innovative approaches already used in trials that have led to marketing authorization or reimbursement. This work has already been published.
• International Symposium: On June 24, 2024, in Lille, representatives from French, European, and U.S. regulatory agencies (ANSM, HAS, EMA, FDA) gathered for the first international symposium on new methodologies in clinical research. This major event helped establish a collective and safe approach to their use.
• Development of recommendations: definition of use cases, acceptability criteria, and recommendations for use. This work has also been published.
• Monitoring of pilot projects: support for projects selected through the call for expressions of interest issued by the ANR and funded by France 2030, in order to demonstrate, under real-world conditions, the relevance and value of these new methodologies. This operational phase, based on concrete cases, will make it possible to establish, in collaboration with regulators and evaluators, an appropriate regulatory and evaluation framework, as well as to define the level of evidence and the procedures for using and evaluating these tools and approaches, which differ from the traditional medical trial model. This is being implemented through the launch of a call for expressions of interest aimed at “the evaluation of new clinical research methodologies” in 2026, which resulted in the selection, funding, and support of 16 successful applicants.

The work is being conducted in consultation with French regulatory authorities, notably the HAS and the ANSM, in order to promote the acceptance of the recommendations and their integration into practice, and to avoid duplicating discussions that have already taken place or are currently underway.

The mission is also part of a broader European effort through its participation in the ACT EU and EIT Health initiatives, thereby contributing to international discussions on the evolution of clinical evaluation methodologies.