Medical College of Wisconsin
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A group sequential test for treatment effect based on the Fine-Gray model. Biometrics 2018 09;74(3):1006-1013 PMID: 29534294 PMCID: PMC6146968

Pubmed ID

29534294

DOI

10.1111/biom.12871

Abstract

Competing risks endpoints arise when patients can fail therapy from several causes. Analyzing these outcomes allows one to assess directly the benefit of treatment on a primary cause of failure in a clinical trial setting. Regression models can be used in clinical trials to adjust for residual imbalances in patient characteristics, improving the power to detect treatment differences. But, none of the competing risks methods currently available for use in group sequential trials adjust for covariates. We propose a group sequential test for treatment effect that, because it is based on the Fine-Gray model, permits adjustment for covariates. Our derivations show that its sequence of test statistics has an asymptotic distribution with an independent increments structure, which allows standard techniques such as O'Brien-Fleming designs and error spending functions to be employed to meet type I error rate and power specifications. We demonstrate the test in a reanalysis of BMT CTN 0402, a phase III clinical trial that evaluated an experimental treatment for the prevention of adverse outcomes following blood and marrow transplant. Moreover, using a simulation study of randomized group sequential trials, we demonstrate that the proposed method preserves the type I error rate and power at their nominal levels in the presence of influential covariates.

Author List

Martens MJ, Logan BR

Author

Brent R. Logan PhD Director, Professor in the Institute for Health and Equity department at Medical College of Wisconsin




Scopus

2-s2.0-85043497709

MESH terms used to index this publication - Major topics in bold

Bone Marrow Transplantation
Clinical Trials as Topic
Computer Simulation
Endpoint Determination
Humans
Long Term Adverse Effects
Peripheral Blood Stem Cell Transplantation
Risk
Treatment Failure
Treatment Outcome
jenkins-FCD Prod-332 f92a19b0ec5e8e1eff783fac390ec127e367c2b5