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A study design with conditional, serially assessed co‐primary endpoints: An application to a single‐arm, pilot non‐Hodgkin's lymphoma trial
Author(s) -
Mahnken Jonathan D.,
Wick Jo A.,
Gajewski Byron J.,
Mayo Matthew S.
Publication year - 2010
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20387
Subject(s) - clinical endpoint , statistics , series (stratigraphy) , mathematics , clinical trial , medicine , computer science , econometrics , biology , paleontology
Optimizing study designs is an important responsibility for applied statisticians supporting clinical trials. We describe the study design for an early‐phase non‐Hodgkin's lymphoma trial with two co‐primary endpoints; however, evaluation of the second endpoint on a subject is conditional on a positive response to the first endpoint. Thus, these dichotomous measures are collected conditionally and in series. We present the probability density function for this study design selected and derive the parameters that describe this distribution. We also derive the maximum likelihood estimates for the unknown parameters of interest to the trial investigator. We compare the theoretical operating characteristics (type I and type II error rates) to a simulation study for the motivating example. Using this report as a guide, others designing studies with similarly measured co‐primary endpoints can utilize these formulas to calculate the operating characteristics and analyze their resulting study data. Drug Dev Res 71: 395–403, 2010. © 2010 Wiley‐Liss, Inc.