The Smooth Away From Expected (SAFE) non-inferiority frontier: theory and implementation with an application to the D3 trial

Autor: Matteo Quartagno, Man Chan, Anna Turkova, Deborah Ford, Ian R. White
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Trials, Vol 24, Iss 1, Pp 1-12 (2023)
Druh dokumentu: article
ISSN: 1745-6215
DOI: 10.1186/s13063-023-07586-5
Popis: Abstract Background In a non-inferiority trial, the choice of margin depends on the expected control event risk. If the true risk differs from expected, power and interpretability of results can be affected. A non-inferiority frontier pre-specifies an appropriate non-inferiority margin for each value of control event risk. D3 is a non-inferiority trial comparing two treatment regimens in children living with HIV, designed assuming a control event risk of 12%, a non-inferiority margin of 10%, 80% power and a significance level (α) of 0.025. We consider approaches to choosing and implementing a frontier for this already funded trial, where changing the sample size substantially would be difficult. Methods In D3, we fix the non-inferiority margin at 10%, 8% and 5% for control event risks of ≥9%, 5% and 1%, respectively. We propose four frontiers which fit these fixed points, including a Smooth Away From Expected (SAFE) frontier. Analysis approaches considered are as follows: using the pre-specified significance level (α=0.025); always using a reduced significance level (to achieve α≤0.025 across control event risks); reducing significance levels only when the control event risk differs significantly from expected (control event risk
Databáze: Directory of Open Access Journals
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