University of Oulu

Tenhunen, O., Lasch, F., Schiel, A. and Turpeinen, M. (2020), Single‐Arm Clinical Trials as Pivotal Evidence for Cancer Drug Approval: A Retrospective Cohort Study of Centralized European Marketing Authorizations Between 2010 and 2019. Clin. Pharmacol. Ther., 108: 653-660. https://doi.org/10.1002/cpt.1965

Single‐arm clinical trials as pivotal evidence for cancer drug approval : a retrospective cohort study of centralized European marketing authorizations between 2010 and 2019

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Author: Tenhunen, Olli1,2; Lasch, Florian3; Schiel, Anja4;
Organizations: 1Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
2Finnish Medicines Agency, Helsinki, Finland
3Hannover Medical School, Hannover, Germany
4Norwegian Medicines Agency, Oslo, Norway
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe2020111189918
Language: English
Published: John Wiley & Sons, 2020
Publish Date: 2021-06-23
Description:

Abstract

The traditional drug development paradigm, consisting of sequential phases and randomized studies, has been challenged in oncology and hemato‐oncology. In the regulatory context, a number of new products have been authorized based on nonrandomized efficacy and safety data. We retrospectively analyzed the European public assessment reports for anticancer treatments authorized between 2010 and 2019 to describe the data behind such approvals. Twenty‐two initial marketing authorizations, mainly conditional, were identified. Fifty percent of the products had an orphan indication, and 77% had received previous scientific advice. Conclusions of clinical benefit were based on tumor responses, ranging between 15.8 and 88%. Our data shows that single‐arm clinical studies leading to positive regulatory outcomes share common methodological approaches and end points, mostly comparing the overall response rate with a fixed success threshold as the primary analysis. The clinical indications in these approvals are clustered in late‐line settings, hematological malignancies, and lung cancer. Our findings underline the need to reflect on the current practice, the methodological aspects, and end points in single‐arm studies, and develop specific regulatory guidance on nonrandomized and novel study designs.

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Series: Clinical pharmacology & therapeutics
ISSN: 0009-9236
ISSN-E: 1532-6535
ISSN-L: 0009-9236
Volume: 108
Issue: 3
Pages: 653 - 660
DOI: 10.1002/cpt.1965
OADOI: https://oadoi.org/10.1002/cpt.1965
Type of Publication: A1 Journal article – refereed
Field of Science: 317 Pharmacy
Subjects:
Copyright information: © 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics. This is the peer reviewed version of the following article: Tenhunen, O., Lasch, F., Schiel, A. and Turpeinen, M. (2020), Single‐Arm Clinical Trials as Pivotal Evidence for Cancer Drug Approval: A Retrospective Cohort Study of Centralized European Marketing Authorizations Between 2010 and 2019. Clin. Pharmacol. Ther., 108: 653-660, which has been published in final form at https://doi.org/10.1002/cpt.1965. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.