Inclusion of non-inferiority analysis in superiority-based clinical trials with single-arm, two-stage Simon's design
Sampayo-Cordero, Miguel (Medica Scientia Innovation Research (MedSIR))
Miguel-Huguet, Bernat (Hospital Universitari de Bellvitge)
Pérez-García, José (QuironSalud Group)
Páez, David (Institut d'Investigació Biomèdica Sant Pau)
Guerrero-Zotano, Ángel L. (Vanderbilt University Medical Center)
Garde-Noguera, Javier (Hospital Arnau de Vilanova (Lleida, Catalunya))
Aguirre, Elena (Hospital Quirónsalud Zaragoza)
Holgado, Esther (Hospital Universitario Ramón y Cajal (Madrid))
López-Miranda, Elena (Hospital Universitario Ramón y Cajal (Madrid))
Huang, Xin (Pfizer Global Research and Development)
Malfettone, Andrea (Medica Scientia Innovation Research (MedSIR))
Llombart-Cussac, Antonio (Hospital Arnau de Vilanova (Lleida, Catalunya))
Cortés, Javier (Vall d'Hebron Institut d'Oncologia)
Universitat Autònoma de Barcelona

Fecha:	2020
Resumen:	Non-inferiority (NI) analysis is not usually considered in the early phases of clinical development. In some negative phase II trials, a post-hoc NI analysis justified additional phase III trials that were successful. However, the risk of false positive achievements was not controlled in these early phase analyses. We propose to preplan NI analyses in superiority-based Simon's two-stage designs to control type I and II error rates. Simulations have been proposed to assess the control of type I and II errors rates with this method. A total of 12,768 two-stage Simon's design trials were constructed based on different assumptions of rejection response probability, desired response probability, type I and II errors, and NI margins. P-value and type II error were calculated with stochastic ordering using Uniformly Minimum Variance Unbiased Estimator. Type I and II errors were simulated using the Monte Carlo method. The agreement between calculated and simulated values was analyzed with Bland-Altman plots. We observed the same level of agreement between calculated and simulated type I and II errors from both two-stage Simon's superiority designs and designs in which NI analysis was allowed. Different examples has been proposed to explain the utility of this method. Inclusion of NI analysis in superiority-based single-arm clinical trials may be useful for weighing additional factors such as safety, pharmacokinetics, pharmacodynamic, and biomarker data while assessing early efficacy. Implementation of this strategy can be achieved through simple adaptations to existing designs for one-arm phase II clinical trials.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Non-inferiority ; Switching to non-inferiority ; Two-stage ; Single-arm ; Phase II ; Group sequential designs
Publicado en:	Contemporary Clinical Trials Communications, Vol. 20 (november 2020) , ISSN 2451-8654

DOI: 10.1016/j.conctc.2020.100678
PMID: 33336109

9 p, 1.7 MB

El registro aparece en las colecciones:
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut de Recerca Sant Pau
Artículos > Artículos de investigación
Artículos > Artículos publicados