FROM DATA TO PATIENT ACCESS: ENABLING SYNTHETIC CONTROL ARMS USING REAL WORLD AND SYNTHETIC DATA FOR TRIALS AND HTA DECISION-MAKING
Author(s)
Anne-Lise VATAIRE, PhD1, Jean-Louis Fraysse, DR2, Stéphanie Kervestin, PhD3, CECILE REHBY, PharmD,MSc4, Emmanuel Pham, MD, MsC5.
1Head HEOR, Sanofi, Gentilly, France, 2SILICA Botdesign, PARIS, France, 3ARIIS, PARIS, France, 4SANOFI, Gentilly, France, 5Nova in silico, Lyon, France.
1Head HEOR, Sanofi, Gentilly, France, 2SILICA Botdesign, PARIS, France, 3ARIIS, PARIS, France, 4SANOFI, Gentilly, France, 5Nova in silico, Lyon, France.
OBJECTIVES: Large-scale adoption of synthetic control arms in clinical research depends on trust from regulators, health technology assessment (HTA) bodies, clinicians, and patients. The objective of a working group was to explore how to transition these methodologies from experimental tools to routine clinical practice.
METHODS: A collaborative workshop; with academic researchers, industrials, public institutions, and patient organizations; explored the integration of alternative methodologies into routine clinical practice. It resulted in structured recommendations to facilitate the adoption of external control arms in clinical settings, in particular in situations of unmet medical need and when clinical assessment require alternative methods.
RESULTS: Three recommendations emerged. First, to reconcile the positions of regulators and industry, a clinical trial protocol incorporating three arms (treatment, real control and synthetic control) should be designed. The control arm consisting of synthetic patients, designed to validate the reliability and robustness of this virtual arm. This validation phase would allow industry to demonstrate the relevance of synthetic methods without jeopardizing trial integrity. Second, a multi-stakeholder working group could further develop and propose this methodological framework, with the objective of encouraging regulatory authorities to accept to integrate a virtual control arm in the medicine assessment, even in the event of minor statistical discrepancies between the real and virtual control arms relative to the treatment arm. Third, an independent academic trusted third party should be established to support health authorities and HTA bodies in strengthening their expertise and sharing early advice on study-design, as new methodologies are deployed. This accredited academic community would provide scientific guidance, methodological standards, and independent validation.
CONCLUSIONS: Testing multiple control arm designs is critical to identify which approaches can be sustainably adopted by health authorities. When properly validated and integrated with conventional methodologies, these tools accelerate clinical development and deliver innovations to patients faster without lowering evidentiary standards.
METHODS: A collaborative workshop; with academic researchers, industrials, public institutions, and patient organizations; explored the integration of alternative methodologies into routine clinical practice. It resulted in structured recommendations to facilitate the adoption of external control arms in clinical settings, in particular in situations of unmet medical need and when clinical assessment require alternative methods.
RESULTS: Three recommendations emerged. First, to reconcile the positions of regulators and industry, a clinical trial protocol incorporating three arms (treatment, real control and synthetic control) should be designed. The control arm consisting of synthetic patients, designed to validate the reliability and robustness of this virtual arm. This validation phase would allow industry to demonstrate the relevance of synthetic methods without jeopardizing trial integrity. Second, a multi-stakeholder working group could further develop and propose this methodological framework, with the objective of encouraging regulatory authorities to accept to integrate a virtual control arm in the medicine assessment, even in the event of minor statistical discrepancies between the real and virtual control arms relative to the treatment arm. Third, an independent academic trusted third party should be established to support health authorities and HTA bodies in strengthening their expertise and sharing early advice on study-design, as new methodologies are deployed. This accredited academic community would provide scientific guidance, methodological standards, and independent validation.
CONCLUSIONS: Testing multiple control arm designs is critical to identify which approaches can be sustainably adopted by health authorities. When properly validated and integrated with conventional methodologies, these tools accelerate clinical development and deliver innovations to patients faster without lowering evidentiary standards.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
HTA125
Topic
Health Technology Assessment, Study Approaches
Disease
No Additional Disease & Conditions/Specialized Treatment Areas