A Review of Causal Inference for External Comparator Arm Studies

Gerd Rippin (), Nicolás Ballarini, Héctor Sanz, Joan Largent, Chantal Quinten and Francesco Pignatti
Additional contact information
Gerd Rippin: IQVIA
Nicolás Ballarini: IQVIA
Héctor Sanz: IQVIA
Joan Largent: IQVIA
Chantal Quinten: European Medicines Agency
Francesco Pignatti: European Medicines Agency

Drug Safety, 2022, vol. 45, issue 8, No 1, 815-837

Abstract: Abstract Randomized controlled trials (RCTs) are the gold standard design to establish the efficacy of new drugs and to support regulatory decision making. However, a marked increase in the submission of single-arm trials (SATs) has been observed in recent years, especially in the field of oncology due to the trend towards precision medicine contributing to the rise of new therapeutic interventions for rare diseases. SATs lack results for control patients, and information from external sources can be compiled to provide context for better interpretability of study results. External comparator arm (ECA) studies are defined as a clinical trial (most commonly a SAT) and an ECA of a comparable cohort of patients—commonly derived from real-world settings including registries, natural history studies, or medical records of routine care. This publication aims to provide a methodological overview, to sketch emergent best practice recommendations and to identify future methodological research topics. Specifically, existing scientific and regulatory guidance for ECA studies is reviewed and appropriate causal inference methods are discussed. Further topics include sample size considerations, use of estimands, handling of different data sources regarding differential baseline covariate definitions, differential endpoint measurements and timings. In addition, unique features of ECA studies are highlighted, specifically the opportunity to address bias caused by unmeasured ECA covariates, which are available in the SAT.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
http://link.springer.com/10.1007/s40264-022-01206-y Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:spr:drugsa:v:45:y:2022:i:8:d:10.1007_s40264-022-01206-y

Ordering information: This journal article can be ordered from
http://www.springer.com/adis/journal/40264

DOI: 10.1007/s40264-022-01206-y

Access Statistics for this article

Drug Safety is currently edited by Nitin Joshi

More articles in Drug Safety from Springer
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().