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An adaptive two-arm clinical trial using early endpoints to inform decision making : design for a study of sub-acromial spacers for repair of rotator cuff tendon tears
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Parsons, Nicholas R., Stallard, Nigel, Parsons, Helen, Wells, Philip, Underwood, Martin, Mason, James and Metcalfe, Andrew J. (2019) An adaptive two-arm clinical trial using early endpoints to inform decision making : design for a study of sub-acromial spacers for repair of rotator cuff tendon tears. Trials, 20 . 694. doi:10.1186/s13063-019-3708-6 ISSN 1745-6215.
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Official URL: https://doi.org/10.1186/s13063-019-3708-6
Abstract
Background
There is widespread concern across the clinical and research communities that clinical trials, powered for patient-reported outcomes, testing new surgical procedures are often expensive and time-consuming, particularly when the new intervention is shown to be no better than the standard. Conventional (non-adaptive) randomised controlled trials (RCTs) are perceived as being particularly inefficient in this setting. Therefore, we have developed an adaptive group sequential design that allows early endpoints to inform decision making and show, through simulations and a worked example, that these designs are feasible and often preferable to conventional non-adaptive designs. The methodology is motivated by an ongoing clinical trial investigating a saline-filled balloon, inserted above the main joint of the shoulder at the end of arthroscopic debridement, for treatment of tears of rotor cuff tendons. This research question and setting is typical of many studies undertaken to assess new surgical procedures.
Methods
Test statistics are presented based on the setting of two early outcomes, and methods for estimation of sequential stopping boundaries are described. A framework for the implementation of simulations to evaluate design characteristics is also described.
Results
Simulations show that designs with one, two and three early looks are feasible and, with appropriately chosen futility stopping boundaries, have appealing design characteristics. A number of possible design options are described that have good power and a high probability of stopping for futility if there is no evidence of a treatment effect at early looks. A worked example, with code in R, provides a practical demonstration of how the design might work in a real study.
Conclusions
In summary, we show that adaptive designs are feasible and could work in practice. We describe the operating characteristics of the designs and provide guidelines for appropriate values for the stopping boundaries for the START:REACTS (Sub-acromial spacer for Tears Affecting Rotator cuff Tendons: a Randomised, Efficient, Adaptive Clinical Trial in Surgery) study.
Item Type: | Journal Article | ||||||
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Subjects: | R Medicine > R Medicine (General) R Medicine > RD Surgery |
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Clinical Trials Unit Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences > Statistics and Epidemiology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Clinical trials -- Design, Shoulder joint -- Rotator cuff -- Wounds and injuries, Tendons -- Wounds and injuries -- Treatment | ||||||
Journal or Publication Title: | Trials | ||||||
Publisher: | Biomed Central | ||||||
ISSN: | 1745-6215 | ||||||
Official Date: | 9 December 2019 | ||||||
Dates: |
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Volume: | 20 | ||||||
Article Number: | 694 | ||||||
DOI: | 10.1186/s13063-019-3708-6 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||
Date of first compliant deposit: | 4 December 2019 | ||||||
Date of first compliant Open Access: | 4 December 2019 | ||||||
RIOXX Funder/Project Grant: |
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