Treatment comparisons based on two-dimensional safety and efficacy alternatives in oncology trials

Biometrics
Peter F Thall, S C Cheng

Abstract

In addition to their desired anticancer effects, most cancer treatments may also cause transient toxicity, permanent organ damage, or death. A critical question in comparing an experimental treatment to a standard is how much increase in an adverse event rate is an acceptable trade-off for achieving a targeted improvement in efficacy, or vice versa. We consider settings where one may characterize patient outcome as a bivariate (efficacy, safety) variable and quantify treatment effect as a corresponding two-dimensional parameter. A set of target parameters, each representing a clinically meaningful improvement over the standard, are elicited from the physician. Each target is a two-dimensional generalization of the usual one-dimensional shift parameter. We define the alternative hypothesis in the two-dimensional effect space as the convex hull of the sets of parameters that are at least as desirable as each target point. The rejection region is obtained by shifting the alternative toward (0,0) to achieve a given type I error, with sample size computed to achieve a given power at the targets. The method is illustrated by application to two cancer chemotherapy trials.

References


❮ Previous
Next ❯

Citations

Mar 29, 2001·Statistics in Medicine·P F Thall, S C Cheng
Apr 23, 2009·Journal of Biopharmaceutical Statistics·Linda Z SunKamlesh Patel
Jul 12, 2008·Journal of Statistical Planning and Inference·Peter F Thall
Mar 11, 2003·Statistics in Medicine·Alexia LetierceJean Maccario
Mar 18, 2006·Biometrics·Peter F ThallElizabeth J Shpall
Jan 31, 2007·Statistics in Medicine·Shengyan Hong, Yanping Wang
Oct 12, 2005·Statistics in Medicine·Shenghua K Fan, You-Gan Wang
Jun 17, 2014·Journal of Peptide Science : an Official Publication of the European Peptide Society·Stesha C JosephDavid Sabatino
Oct 3, 2014·Statistics in Medicine·S BersimisT Papaioannou
Jun 28, 2016·Thrombosis and Haemostasis·John M KittelsonUNKNOWN Antithrombotic Trials Leadership and Steering (ATLAS) Group
Oct 31, 2003·Journal of Biopharmaceutical Statistics·Susan Todd
May 2, 2018·Therapeutic Innovation & Regulatory Science·Richard C ZinkQi Jiang
Sep 12, 2019·Pharmaceutical Statistics·Michelle DeVeauxDaniel Zelterman
Feb 11, 2005·Journal of Biopharmaceutical Statistics·Pascale Tubert-BitterAndrew Kramar
Oct 3, 2002·Statistical Methods in Medical Research·Peter F Thall
Aug 22, 2015·Statistical Methods in Medical Research·Yuanyuan Jiang, Jin Xu
Oct 14, 2020·Statistics in Medicine·Junxiao HuJohn M Kittelson

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.