Single-arm phase 3 designs: An oxymoron?

Autor: Hussein A; ECSTRRA, 1, avenue Claude Vellefaux, Paris 75010, France., Levy V; ECSTRRA, 1, avenue Claude Vellefaux, Paris 75010, France; D́epartement de Recherche Clinique, Hôpital Avicenne, Bobigny 93000, France., Chevret S; ECSTRRA, 1, avenue Claude Vellefaux, Paris 75010, France; Institut Universitaire de France, Paris 75, France. Electronic address: sylvie.chevret@u-paris.fr.
Jazyk: angličtina
Zdroj: Contemporary clinical trials [Contemp Clin Trials] 2024 Jun; Vol. 141, pp. 107506. Date of Electronic Publication: 2024 Mar 18.
DOI: 10.1016/j.cct.2024.107506
Abstrakt: Background: Since the 1950s, randomized clinical trials (RCTs) have served as the gold standard for confirming the benefits of a new drug. Accordingly, phase 3 trials, the last steps in the evaluation process for a new drug, have been recommended to all be RCTs. Nevertheless, single-arm phase 3 trials still appear to be in use.
Methods: We performed a PubMed search to identify the use of a single-arm design in phase 3 trials, excluding only non-English articles. Three categories were distinguished: past use of an RCT, of any other trial design, or no previous trial; and according to diagnosis (oncology, infection, others).
Results: A total of 176 single-arm phase 3 trials (19 oncology, 43 infections and 114 others) were identified by the search, with exponential growth since 1994, in parallel with that of RCTs. Among them, 64 (36%) were preceded by an RCT, 58 (33%) by a non-randomized trial, and 54 (31%) had no previous trial, with no main influence of the diagnosis setting. Justification of the design was reported in 30 (18%) of those trials, with ethical concerns comprising one-third of those justifications. This was similar in the 14 single-arm phase 2-3 trials, with about one-third in each group, and 17% justification of a non-comparative design.
Conclusion: The use of a single-arm phase 3 trial is heterogeneous, ranging from first trials up to confirmatory trials after a previously conducted RCT. Justification for these single-arm designs as confirmatory evidence should be more clearly reported, along with potential sources of bias.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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