EMA/2020/46/TDA, Lot 3 - ROC36 Use of causal inference methods commonly used in non-interventional studies to estimate treatment effects in clinical trials

Study identification

• EU PAS number:
  EUPAS1000000720
• Study ID:
  1000000720
• Official title and acronym:
  EMA/2020/46/TDA, Lot 3 - ROC36 Use of causal inference methods commonly used in non-interventional studies to estimate treatment effects in clinical trials
• DARWIN EU® study:
  No
• Study countries:
  Austria

  Germany

  Sweden
• Study description:
  This project evaluates the use of causal inference methods for estimating treatment effects in randomized controlled trials (RCTs) under the ICH E9(R1) estimand framework. ; In a structured review of the scientific and regulatory literature, we will identify causal inference methods used to derive estimators for different estimand strategies to handle intercurrent events such as treatment policy, hypothetical, principal stratum, composite, and while-on-treatment strategies. Estimation methods proposed in this context include inverse probability weighting, g-estimation, g-computation, and targeted minimum loss based estimation. ; Clinically relevant trial scenarios will be identified where intercurrent events such as treatment switching or use of rescue medication affect outcome interpretation. ; The literature review and scenario identification will inform a comprehensive simulation study assessing key statistical properties of the selected estimators including bias, variance, coverage probabilities, type I error rate, and power. ; A focus of the assessment will be the robustness of methods to model misspecification. Simulations will be conducted using a modular R based framework on high performance computing servers. The results of this project will support the assessment of strategies for handling intercurrent events.
• Study status:
  Ongoing

Research institutions and networks

Institutions

Medical University of Vienna

Austria

Uppsala University

University Medical Centre Göttingen (UMG)

Germany

Österreichische Agentur für Gesundheit und Ernährungssicherheit

Study timelines

Date when funding contract was signed

Actual:30/07/2025

Study start date

Actual:30/07/2025

Date of final study report

Planned:30/07/2026

Sources of funding

EMA

Regulatory

• Was the study required by a regulatory body?:
  No
• Is the study required by a Risk Management Plan (RMP)?:
  Not applicable