Modeling adverse event counts in phase I clinical trials of a cytotoxic agent

Clinical Trials : Journal of the Society for Clinical Trials
Daniel G MuenzJeremy M G Taylor

Abstract

Background/Aims The goal of phase I clinical trials for cytotoxic agents is to find the maximum dose with an acceptable risk of severe toxicity. The most common designs for these dose-finding trials use a binary outcome indicating whether a patient had a dose-limiting toxicity. However, a patient may experience multiple toxicities, with each toxicity assigned an ordinal severity score. The binary response is then obtained by dichotomizing a patient's richer set of data. We contribute to the growing literature on new models to exploit this richer toxicity data, with the goal of improving the efficiency in estimating the maximum tolerated dose. Methods We develop three new, related models that make use of the total number of dose-limiting and low-level toxicities a patient experiences. We use these models to estimate the probability of having at least one dose-limiting toxicity as a function of dose. In a simulation study, we evaluate how often our models select the true maximum tolerated dose, and we compare our models with the continual reassessment method, which uses binary data. Results Across a variety of simulation settings, we find that our models compare well against the continual reassessment method in terms of selecting...Continue Reading

References

Jun 15, 1995·Statistics in Medicine·S N GoodmanS Piantadosi
Nov 1, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·André RogatkoAlan Porter
May 14, 2009·Journal of the National Cancer Institute·Christophe Le TourneauLillian L Siu
Sep 30, 2010·Biostatistics·Shing M LeeYing Kuen Cheung
Feb 24, 2011·Statistics in Medicine·Emily M Van MeterDipankar Bandyopadhyay
Jan 22, 2013·Statistics in Medicine·Monia EzzalfaniMarie-Cécile Le Deley
Jun 24, 2014·Cancer Control : Journal of the Moffitt Cancer Center·Aaron R HansenLillian L Siu
Nov 20, 2014·Pharmaceutical Statistics·Yunfei Wang, Anastasia Ivanova

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Software Mentioned

R
gsl package
hyperg

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society
Peter F Thall, S-J Lee
Pharmaceutical Statistics
Yunfei Wang, Anastasia Ivanova
Clinical Trials : Journal of the Society for Clinical Trials
Nolan A WagesJohn O'Quigley
© 2022 Meta ULC. All rights reserved