Skip to main content

PERSPECTIVE article

Front. Drug Saf. Regul.
Sec. Advanced Methods in Pharmacovigilance and Pharmacoepidemiology
Volume 4 - 2024 | doi: 10.3389/fdsfr.2024.1409102

External Comparator Studies and the Joint Application of the Estimand and Target Trial Emulation Frameworks

Provisionally accepted
Gerd Rippin Gerd Rippin 1*Héctor Sanz Héctor Sanz 2
  • 1 IQVIA, Frankfurt, Germany
  • 2 IQVIA (Spain), Barcelona, Catalonia, Spain

The final, formatted version of the article will be published soon.

    The Estimand Framework (EF) and the Target Trial Emulation Framework (TTEF) are two important frameworks that can inform the design and analysis of External Comparator (EC) studies. The EF helps clarifying the quantity which is aimed to be estimated (the estimand), especially regarding the handling of post-baseline intercurrent events which interfere with the existence or interpretation of endpoints. Similarly, the TTEF is instrumental for specifying key design components of a hypothetical randomized trial and identifying which of those an EC study can and cannot emulate. We offer considerations about the joint application of both frameworks by combining the 5 EF attributes treatment, population, endpoint, intercurrent events, and population-level summary with the 7 TTEF components eligibility criteria, treatment strategies, assignment procedures, follow-up period, outcomes, causal contrasts, and data analysis plan. Any overlap is identified, as well as omissions and unique contributions from both frameworks. Furthermore, specific considerations when applying these joint elements to EC studies are highlighted.

    Keywords: External Comparator studies, External Control Arm Studies, Externally Controlled Trials, Historical Control Studies, estimands, target trial emulation

    Received: 29 Mar 2024; Accepted: 07 Oct 2024.

    Copyright: © 2024 Rippin and Sanz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Gerd Rippin, IQVIA, Frankfurt, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.