Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/36193
Title: Using an interim analysis based exclusively on an early outcome in a randomized clinical trial with a long-term clinical endpoint
Authors: Barrado, Leandro Garcia
BURZYKOWSKI, Tomasz 
LEGRAND, Catherine 
BUYSE, Marc 
Issue Date: 2022
Publisher: WILEY
Source: PHARMACEUTICAL STATISTICS, 21 (1), p. 209-219
Abstract: In RCTs with an interest in a long-term efficacy endpoint, the follow-up time necessary to observe the endpoint may be substantial. In order to reduce the expected duration of such trials, early-outcome data may be collected to enrich an interim analysis aimed at stopping the trial early for efficacy. We propose to extend such a design with an additional interim analysis using solely early-outcome data in order to expedite the evaluation of treatment's efficacy. We evaluate the potential gain in operating characteristics (power, expected trial duration, and expected sample size) when introducing such an early interim analysis, in function of the properties of the early outcome as a surrogate for the long-term endpoint. In the context of a longitudinal age-related macular degeneration (ARMD) ophthalmology trial, results show potentially substantial gains in both the expected trial duration and the expected sample size. A prerequisite, though, is that the treatment effect on the early outcome has to be strongly correlated with the treatment effect on the long-term endpoint, that is, that the early outcome is a validated surrogate for the long-term endpoint.
Notes: Barrado, LG (corresponding author), Int Drug Dev Inst IDDI, Ave Prov 30, B-1340 Louvain, Belgium.
leandro.garciabarrado@iddi.be
Keywords: efficacy stopping;group-sequential design;interim analysis;randomized clinical trial;surrogate endpoint
Document URI: http://hdl.handle.net/1942/36193
ISSN: 1539-1604
e-ISSN: 1539-1612
DOI: 10.1002/pst.2165
ISI #: WOS:000694628500001
Rights: 2021 John Wiley & Sons Ltd.1
Category: A1
Type: Journal Contribution
Validations: ecoom 2022
Appears in Collections:Research publications

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