After an initial phase focused on identifying new methodological approaches in clinical research and developing recommendations, the joint AIS-F-CRIN initiative has entered a new phase: demonstrating their value through concrete research projects.
In this context, the National Research Agency (ANR), as the initiative’s operator—with support from the AIS and funding from France 2030—launched a call for expressions of interest (AMI) in April 2025 to select pilot projects using innovative clinical research methodologies.
The goal is to produce, within 24 months, scientific and methodological evidence to facilitate the adoption of these new approaches by the entire clinical research ecosystem and regulatory authorities.
Evaluating New Clinical Research Methodologies in Real-World Settings
Projects must demonstrate the value of methodologies that complement or serve as alternatives to randomized controlled trials, particularly when such trials are difficult to implement—for example, in rare diseases, pediatrics, or certain conditions with a small patient population.
Three main categories of approaches were targeted:
- Modeling and simulation: virtual arms, synthetic data, health data enrichment, in silico models;
- Advanced statistical methods: artificial intelligence, machine learning, innovative statistical analysis methods, validation of surrogate endpoints;
- Real-world studies: simulation of clinical trials, use of cohorts, registries, or data warehouses to strengthen the level of evidence.
Beyond scientific demonstration, this initiative must also identify the methodological, regulatory, and organizational conditions necessary for integrating these approaches into future clinical trials.
For more information: Link to the press release announcing the call for expressions of interest
The Winners
The call for proposals generated significant interest within the scientific community, with 51 letters of intent submitted. These projects cover numerous therapeutic areas: oncology, hematology, rare diseases, cardiology, immunology and allergology, and orthopedics.
Following the evaluation, 16 pilot projects were selected for total funding of more than 3 million euros, with grants of up to 250,000 euros per project. The maximum duration of each project is 24 months.
They employ a variety of methodologies, such as artificial intelligence, synthetic data, virtual control arms, in silico simulations, and real-world data:
- ETNA-DCT Project, led by Unicancer: “Methodological validation of a decentralized de-escalation trial for early-stage triple-negative breast cancer with elevated TILs (tumor-infiltrating lymphocytes).”
- NEG-CoNTRoL Project led by the Léon Bérard Center: strengthening the level of evidence for targeted trial emulations using negative controls, applied to metastatic breast cancer.
- ACCESS-RARE Project led by the Gustave Roussy Institute: innovative methodologies to evaluate immunotherapy and improve access to treatments for rare cancers, with an application to thyroid cancer.
- ADIUVO-Speed Project led by the Gustave Roussy Institute: combination of a parallel cohort and a synthetic arm in randomized trials for rare adrenal cancers.
- LOGICAN-BOOST Project led by Unicancer: accelerating patient enrollment through artificial intelligence and controlled decentralization of a clinical trial for advanced gastroesophageal cancers.
- EXCORD–SM Project led by the Institut Curie: new statistical methods for external cohorts in therapeutic trials for rare diseases, applied to uveal melanoma.
- SMART Project led by Inserm: development of synthetic arms in gastrointestinal oncology by learning from case studies of metastatic neuroendocrine cancers.
- 3AD-Design Project led by Unicancer: use of artificial data to expand controlled clinical trials in oncology and evaluate their impact and level of evidence.
- PREVLOG Project led by Angers University Hospital: reinventing preventive follow-up in pediatric oncology with LOG-after and digital twin simulations.
- SYNERGY Project led by LYSARC: creation of synthetic arms in hematology based on real-world data on lymphomas.
- INVENTS+ Project led by Inserm: simulation and modeling methods to create virtual and augmented controls in small-scale clinical trials for rare diseases.
- SILICO Project led by the IMAGINE Institute: use of in silico methods to augment data on rare diseases, with a use case in ciliopathies.
- HEART-AI3D Project led by Sorbonne University: characterization of arrhythmogenic cardiomyopathy using artificial intelligence and dynamic CT scans, for personalized risk assessment (anatomy, strain, and 3D fat).
- CAMELIA Project led by INRIA: Development of causal alternatives to meta-analysis, applied to immunology and allergology.
- TWINICAL Project led by Sorbonne University: development of mixed patient cohorts (physical and digital) for the clinical analysis of shoulder prostheses.
- DANTE Project led by the Artificial Intelligence and Cancer Cluster: use of standardized early-access data, followed by automated natural language processing, for their evaluation.
For more information: Link to the press release announcing the winners
Methodological and Regulatory Support
The selected projects now receive support from a number of national stakeholders to facilitate their implementation and assess any potential scientific or regulatory obstacles.
In particular, they are supported by:
- the French National Agency for Medicines and Health Products Safety (ANSM);
- the National Commission on Information Technology and Civil Liberties (CNIL);
- the Health Data Platform;
- methodological experts.
Scientific monitoring of the pilot cases is conducted as part of the AIS x F-CRIN mission to evaluate the level of evidence provided by these new methodologies, identify the conditions for their use and the factors for success, and contribute to their dissemination in clinical research.
The results of the projects will be presented in a summary report.
Contact
Would you like to contact the AIS x F-CRIN joint mission? Visit our contact form or feel free to send us an email at contact.fcrin@inserm.fr
