Causal Inference and Causal Estimands From Target Trial Emulations Using Evidence From Real-World Observational Studies and Clinical Trials

Enhance your ability to generate real-world evidence (RWE) for regulatory, payer, and HTA decisions through causal inference methods and target trial emulation.

This course explores the use of causal principles and modeling to improve the design and analysis of observational studies and clinical trials, especially in scenarios where traditional approaches, such as the intention-to-treat (ITT) analysis, fall short—such as treatment switching. Participants will learn how to define appropriate estimands, mitigate common biases, and apply cutting-edge methods to support transparent, decision-relevant evidence generation.

Technical Topics Include:

• Causal principles & causal diagrams – Learn how to use directed acyclic graphs (DAGs) to identify and minimize bias (e.g., time-zero bias, immortal time bias)
• Target trial emulation – Design observational studies that mimic the structure of randomized trials
• Methods to adjust for baseline confounding – Including multivariate regression and propensity score techniques
• Methods for time-varying confounding:
  • G-formula
  • Marginal structural models (MSMs) with inverse probability of treatment weighting (IPTW)
  • Rank-preserving structural failure-time models using g-estimation
• Estimands for decision-making – Define and apply appropriate estimands to address clinical or policy questions in settings impacted by treatment switching
• Applied case studies in HTA:
  • Use of external control arms in single-arm trials
  • Examples of trials influenced by treatment switching
• HTA agency insights – Examine global perspectives on acceptance and barriers to implementing causal inference methods, with a focus on Asia and beyond

FACULTY MEMBERS

Uwe Siebert, MD, MPH, MSc, ScD
Professor of Public Health, Medical Decision Making and Health Technology Assessment
UMIT TIROL - University for Health Sciences and Technology
Hall in Tirol, Austria, and Harvard Chan School of Public Health
Boston, MA, USA

Nicholas Latimer, MSc, PhD
Professor of Health Economics
SCHARR, University of Sheffield
Sheffield, Derbyshire, Great Britain and Analyst
Delta Hat Limited, Powered by Petauri
Nottingham, UK

This short course is offered in-person at the ISPOR Real-World Evidence Summit 2025. Separate registration is required. Visit the ISPOR Real-World Evidence Summit 2025 Program page to register and learn more.