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Review
. 2023 Dec;50(6):501-506.
doi: 10.1007/s10928-023-09858-8. Epub 2023 Apr 24.

External control arms for rare diseases: building a body of supporting evidence

Artak Khachatryan  1 , Stephanie H Read  2 , Terri Madison  3
Affiliations
Review

External control arms for rare diseases: building a body of supporting evidence

Artak Khachatryan et al. J Pharmacokinet Pharmacodyn. 2023 Dec.

Erratum in

Abstract

Comparator arms in randomized clinical trials may be impractical and/or unethical to assemble in rare diseases. In the absence of comparator arms, evidence generated from external control studies has been used to support successful regulatory submissions and health technology assessments (HTA). However, conducting robust and rigorous external control arm studies is challenging and despite all efforts, residual biases may remain. As a result, regulatory and HTA agencies may request additional external control analyses so that decisions may be made based upon a body of supporting evidence.This paper introduces external control studies and provides an overview of the key methodological issues to be considered in the design of these studies. A series of case studies are presented in which evidence derived from one or more external controls was submitted to regulatory and HTA agencies to provide support for the consistency of findings.

Keywords: External control; Historical control; Rare disease; Real-world data; Real-world evidence.

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Conflict of interest statement

The authors declare no competing interests.

References

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