Mind the gap (and close it at ISPOR Europe in Vienna): New assessment rules are testing the limits of observational evidence

Adigens Health helps pharmaceutical and rare disease companies design real-world evidence strategies built around the target trial framework: from early development planning through HTA submission. Get in touch at info@adigenshealth.com.

When the European Union began its joint clinical assessments of new medicines, it set drugmakers a demanding task. Comparative evidence must now arrive at the moment of market authorisation. In oncology, the comparators in scope frequently outpace the available randomised data.

Observational data can fill some of the gap, if handled with care. The target trial framework, set out by Miguel Hernán and James Robins in 2016, asks researchers to specify the randomised trial they would ideally run and then emulate it with real-world data. A valid design depends on knowing treatment patterns, outcome definitions, eligibility criteria and covariates in advance. Purpose-built evidence platforms can make the gathering of that knowledge structured and replicable.

Design choices also govern one of the best-known flaws in observational research: immortal time. It arises when the start of follow-up, the confirmation of eligibility and the assignment of treatment fall at different moments. Patients are then credited with survival time during which, by construction, they could not have died. In intensive care, where randomisation is often impractical, aligning time zero with the clinical decision point removes the bias at its source.

Looming over all this is artificial intelligence. Rapid advances are reshaping how healthcare data are generated, curated and analysed. That raises an open question. Will causal inference continue to rest on explicitly designed epidemiological frameworks, or will AI systems increasingly infer causal relationships directly from large datasets? The answer carries implications for transparency, reproducibility and regulatory trust.

Adigens Health will take up these questions at ISPOR Europe 2026 in Vienna. Our poster on structured evidence for JCA and target trial planning in oncology runs on Monday 9 November at 10:30 CET. That afternoon, at 13:45, Radek Wasiak chairs an issue panel on AI and causal inference with panelists including our co-founder Miguel Hernán. A poster on target trial emulation in drug-resistant ICU infections follows on Tuesday at 16:00. On Wednesday at 08:00, a workshop examines the biases that generate immortal time and how to address them in HTA submissions. It is chaired by Miguel Hernan and includes contributions from Adigens Health VP Science, Xabier Garcia de Albeniz.