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Your search keyword '"Statistical hypothesis testing"' showing total 2 results
2 results on '"Statistical hypothesis testing"'

1. A Bayesian approach to pilot-pivotal trials for bioequivalence assessment.

Author

Lv, Duo, Grayling, Michael J., Zhang, Xinyue, Zhao, Qingwei, and Zheng, Haiyan

Subjects
*STATISTICAL hypothesis testing, *SAMPLE size (Statistics), *TREATMENT effectiveness, *DATA analysis, *DECISION making
Abstract

Background: To demonstrate bioequivalence between two drug formulations, a pilot trial is often conducted prior to a pivotal trial to assess feasibility and gain preliminary information about the treatment effect. Due to the limited sample size, it is not recommended to perform significance tests at the conventional 5% level using pilot data to determine if a pivotal trial should take place. Whilst some authors suggest to relax the significance level, a Bayesian framework provides an alternative for informing the decision-making. Moreover, a Bayesian approach also readily permits possible incorporation of pilot data in priors for the parameters that underpin the pivotal trial. Methods: We consider two-sequence, two-period crossover designs that compare test (T) and reference (R) treatments. We propose a robust Bayesian hierarchical model, embedded with a scaling factor, to elicit a Go/No-Go decision using predictive probabilities. Following a Go decision, the final analysis to formally establish bioequivalence can leverage both the pilot and pivotal trial data jointly. A simulation study is performed to evaluate trial operating characteristics. Results: Compared with conventional procedures, our proposed method improves the decision-making to correctly allocate a Go decision in scenarios of bioequivalence. By choosing an appropriate threshold, the probability of correctly (incorrectly) making a No-Go (Go) decision can be ensured at a desired target level. Using both pilot and pivotal trial data in the final analysis can result in a higher chance of declaring bioequivalence. The false positive rate can be maintained in situations when T and R are not bioequivalent. Conclusions: The proposed methodology is novel and effective in different stages of bioequivalence assessment. It can greatly enhance the decision-making process in bioequivalence trials, particularly in situations with a small sample size. [ABSTRACT FROM AUTHOR]

Published
2023
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2. 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

Author

Martin Underwood, Nigel Stallard, Helen Parsons, Andrew J. Metcalfe, James Mason, Philip Wells, and Nicholas R. Parsons

Subjects
Stopping for futility, medicine.medical_specialty, Decision Making, Medicine (miscellaneous), Design characteristics, Rotator Cuff Injuries, Medicine, Humans, Pharmacology (medical), Medical physics, Rotator cuff, Research question, Statistical hypothesis testing, lcsh:R5-920, Adaptive clinical trial, Clinical Trials as Topic, business.industry, Adaptive design, Methodology, R1, Clinical trial, medicine.anatomical_structure, Early endpoints, Research Design, Group sequential, Tendon tears, lcsh:Medicine (General), business, Acromion, RD
Abstract

BackgroundThere 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.MethodsTest 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.ResultsSimulations 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.ConclusionsIn 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.Trial registrationISRCTN Registry, ISRCTN17825590. Registered on 5 March 2018.

Published
2019

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