Noninferiority Margin (noninferiority + margin)

Distribution by Scientific Domains

Selected Abstracts

Noninferiority and equivalence designs: Issues and implications for mental health research

Carolyn J. Greene
The terms noninferiority and equivalence are often used interchangeably to refer to trials in which the primary objective is to show that a novel intervention is as effective as the standard intervention. The use of these designs is becoming increasingly relevant to mental health research. Despite the fundamental importance of these designs, they are often poorly understood, improperly applied, and subsequently misinterpreted. In this article, the authors explain noninferiority and equivalence designs and key methodological and statistical considerations. Decision points in using these designs are discussed, such as choice of control condition, determination of the noninferiority margin, and calculation of sample size and power. With increasing utilization of these designs, it is critical that researchers understand the methodological issues, advantages, disadvantages, and related challenges. [source]

Once-Daily Prolonged-Release Tacrolimus (ADVAGRAF) Versus Twice-Daily Tacrolimus (PROGRAF) in Liver Transplantation

P. Trune
The efficacy and safety of dual-therapy regimens of twice-daily tacrolimus (BID; Prograf) and once-daily tacrolimus (QD; Advagraf) administered with steroids, without antibody induction, were compared in a multicenter, 1:1-randomized, two-arm, parallel-group study in 475 primary liver transplant recipients. A double-blind, double-dummy 24-week period was followed by an open extension to 12 months posttransplant. The primary endpoint, event rate of biopsy-proven acute rejection (BPAR) at 24 weeks, was 33.7% for tacrolimus BID versus 36.3% for tacrolimus QD (Per-protocol set; p = 0.512; treatment difference 2.6%, 95% confidence interval ,7.3%, 12.4%), falling within the predefined 15% noninferiority margin. At 12 months, BPAR episodes requiring treatment were similar for tacrolimus BID and QD (28.1% and 24.7%). Twelve-month patient and graft survival was 90.8% and 85.6% for tacrolimus BID and 89.2% and 85.3% for tacrolimus QD. Adverse event (AE) profiles were similar for both tacrolimus BID and QD with comparable incidences of AEs and serious AEs. Tacrolimus QD was well tolerated with similar efficacy and safety profiles to tacrolimus BID. [source]

Sequential Tests for Noninferiority and Superiority

BIOMETRICS, Issue 1 2003
W. Brannath
Summary. The problem of simultaneous sequential tests for noninferiority and superiority of a treatment, as compared to an active control, is considered in terms of continuous hierarchical families of one-sided null hypotheses, in the framework of group sequential and adaptive two-stage designs. The crucial point is that the decision boundaries for the individual null hypotheses may vary over the parameter space. This allows one to construct designs where, e.g., a rigid stopping criterion is chosen, rejecting or accepting all individual null hypotheses simultaneously. Another possibility is to use monitoring type stopping boundaries, which leave some flexibility to the experimenter: he can decide, at the interim analysis, whether he is satisfied with the noninferiority margin achieved at this stage, or wants to go for more at the second stage. In the case where he proceeds to the second stage, he may perform midtrial design modifications (e.g., reassess the sample size). The proposed approach allows one to "spend," e.g., less of , for an early proof of noninferiority than for an early proof of superiority, and is illustrated by typical examples. [source]

Carotid artery revascularization in high surgical risk patients with the NexStent and the Filterwire EX/EZ

1-Year results in the CABERNET trial
Abstract Objective: The multicenter, single-arm CABERNET trial evaluated outcomes in high-surgical-risk patients with carotid artery stenosis treated with the NexStent® plus FilterWire EX®/EZÔ Emboli Protection System. Background: For patients at high surgical risk, carotid artery stenting (CAS) offers a less invasive alternative to carotid endarterectomy (CEA). Methods: The trial enrolled 454 high-surgical-risk patients with carotid stenosis by angiography ,50% for symptomatic patients and ,60% for asymptomatic patients. The comparator primary endpoint was the 1-year major adverse event (MAE, defined as any death, stroke, or myocardial infarction [MI]) rate. It was compared with a proportionally weighted objective performance criterion (OPC) of 12.1% representative of published CEA results in similar patients plus a prespecified noninferiority margin (delta) of 4%. A second primary endpoint was the composite rate of 30-day MAE plus late (31,365 days) ipsilateral stroke. Results: Symptoms of carotid stenosis were present in 24.2% of patients; 36.6% of patients were considered high-surgical-risk due to comorbid risk factors and 63.4% due to anatomic risk factors. The rate of 30-day MAE plus late ipsilateral stroke was 4.7% (20/438). The comparator primary endpoint of 1-year MAE was 11.6% (51/438) and was noninferior to the OPC of 12.1% (95% upper confidence interval of 14.5% versus OPC plus delta of 16.1%, P = 0.005). Late ipsilateral stroke was 0.7% and target vessel revascularization at 1 year was 2.4%. Conclusions: The CABERNET trial demonstrates that CAS with NexStent and FilterWire is noninferior to (equivalent or better than) traditional CEA at 1 year in high-surgical-risk patients based on historical controls. © 2008 Wiley-Liss, Inc. [source]