France 2030: call for expressions of interest to evaluate methodologies of interest in clinical research

The aim of clinical research is to evaluate the therapeutic or diagnostic value, conditions of use, possible side effects and safety of healthcare products. With the increasing availability of healthcare data, particularly real-life data, artificial intelligence and the development of personalized treatments, new clinical research methodologies are developing. Despite the interest shown in these approaches, there is still insufficient hindsight to ensure their full appropriation by the ecosystem and healthcare authorities. To enable their integration into the healthcare system, for the benefit of patients, the Agence de l'innovation en santé is carrying out various projects in partnership with the F-CRIN (French Clinical Research Infrastructure Network) infrastructure.

An initial stage of inventorying and analyzing the acceptability of new approaches to clinical research methodologies

New methodological approaches in clinical research could enable the development of healthcare products in areas where proof of efficacy is difficult to establish using conventional methods (small populations, very slowly progressing diseases, antibiotic resistance...), or accelerate their development, while providing patients with guarantees of efficacy and safety of use.

These methodological approaches to evaluation in clinical research of interest are of varying natures and encompass both new study designs and the optimization of "classic" clinical trials (external control groups on registry or cohort-type data; mechanistic models of the synthetic arm type / "in silico" trials).

As part of France 2030, which is steered under the authority of the Prime Minister by the General Secretariat for Investment (SGPI), the Innovation santé 2030 plan, its healthcare component , aims to equip France with a strategy to become Europe's leading innovative and sovereign nation in healthcare. As such, clinical research issues, including the use of new methodologies, are among the priorities identified by the Agence de l'innovation en santé, within the SGPI, in its roadmap, and are central to the various projects it has initiated.

Thus, after an initial sequence of inventory and analysis of the acceptability of these methodological approaches by the authorities, a group of experts led by the Agence de l'innovation en santé and the F-CRIN (French Clinical Research Infrastructure Network), formulated recommendations around the use of health data for clinical research purposes (link).

A call for expressions of interest aimed at demonstration

Continuing the work undertaken with the F-CRIN infrastructure, the recommendations published and the international symposium organized on June 24, 2024 in Lille, the AIS is entering an operational phase, starting with concrete cases, enabling the establishment, with regulators and evaluators, of a suitable regulatory and evaluation framework.

This operational phase will make it possible to define the level of proof as well as the terms of use and evaluation of these tools and approaches, which differ from the classic medical experimentation scheme. It is taking shape today with the launch of a call for expressions of interest aimed at "the evaluation of new clinical research methodologies"[1].

This call for expressions of interest (AMI) will enable the selection of pilot cases, i.e. research projects integrating the following technologies or tools:

• Modeling/simulation: integration of so-called virtual data (virtual arms provided for in the protocol); enrichment of health data to improve the power of a study or creation of new informative data;
• Advanced statistical tools (machine learning / artificial intelligence, innovative statistical model fitting methods, validation of surrogate criteria...);
• Implementation of real-life studies or study arms : emulation; enrichment of data sources (cohorts, registries, warehouses) to meet the methodological standards expected for the evaluation of new treatments.

Winners will be selected for their ability to meet the objective of demonstrating the value of these alternative or complementary methodological approaches to conventional development plans, with the aim of disseminating these practices and thus accelerating the development of innovative healthcare technologies.

The AMI also aims to identify possible changes to the legal framework that need to be implemented to guarantee the safety and performance of the innovations evaluated, as well as their integration into the healthcare system.

The initiative aims to select pilot cases, with data already accessible, or accessible in a short timeframe compatible with the AMI deadlines, carried out by promoters (public alone or in association with private players) that will make it possible to assess the value of these complementary or alternative modalities to the standard "randomised clinical trial" model.

The selection of pilot cases will take place in two stages:

• 1st phase: submission of a letter of intent of no more than 5 pages outlining the objectives and broad lines of the project, as well as the prospective consortium (application deadline June 24, 2025)
• 2nd phase: the leaders of projects pre-selected in the 1st phase will be invited to submit a full document of no more than 15 pages (application deadline December 2, 2025).

Selection as a pilot case focuses solely on methodological aspects: it in no way prejudges the intrinsic assessment of the technology by the health authorities. The aim is to use a panel of studies and research projects to identify common features that have led either to their acceptability, or to a refusal of validation by the regulatory authorities, and to provide useful information for health innovation promoters in France to develop their future projects appropriately.

[1] Arrêté du 18 février 2025 relatif à l'approbation du cahier des charges de l'appel à manifestation d'intérêt " Evaluation des nouveaux outils, nouveaux usages et nouvelles approches méthodologiques de recherche clinique " - Légifrance