Reports and Publications

This report aims to explore the impact of methodological developments in clinical research relative to the gold standard, the randomized controlled trial. It draws on contributions from experts in complementary fields (medicine, statistics, law, and computer science), supplemented by work conducted during hearings, workshops (such as the Giens Workshops), or within the framework of associations such as SILICA.

This work has identified approaches that complement the double-blind randomized trial and are useful at various stages of a health product’s life cycle, from its development through its market launch and ongoing evaluation. These methods aim to maintain a high level of evidence while addressing the limitations of the traditional design, all within the broader context of the proliferation of diagnostic and therapeutic innovations (or what is presented as such). The examples presented demonstrate both the growing interest in these new approaches and the high standards required for their validation.

The sources, nature, and origin of health data have multiplied. They may stem from care provided by healthcare professionals, research protocols (including clinical trials), or directly from patients, whether they are health economics data, observational data (digitized or not), epidemiological, or any other data sources reflecting patient care. This revolution, which served as the starting point for the development of new clinical trial methodologies, is both an opportunity—providing a wealth of information on changes in health status and patient care— and a challenge, as the sheer volume and heterogeneity of these data make their use complex.

This collective reflection and the recommendations it contains constitute the first part of a comprehensive examination of evolving methodologies in clinical research.

The work of the joint AIS x F-CRIN mission is intended to provide insights into the acceptability and implementation conditions of alternative clinical trial methodologies to the traditional randomized clinical trial where gaps or a need for improvement are observed, particularly regarding the use of external data or in silico trials.

This non-exhaustive report, based on objective selection criteria for relevance, was conducted by Horiana, a consulting firm specializing in health data analysis and epidemiology, and PASS, a consulting firm focused on “Market Access, pricing, and health economics,” in collaboration with the two pilot projects of the joint mission.