An Investigation of the Traditional Algorithm-Based Designs for Phase 1 Cancer Clinical Trials
- PDF / 399,396 Bytes
- 9 Pages / 504 x 719.759 pts Page_size
- 23 Downloads / 174 Views
oO91--8615/200? Cupyrlght Q Z(K)Z Drug Infomiation Association Inc.
AN INVESTIGATION OF THE TRADITIONAL ALGORITHM-BASED DESIGNS FOR PHASE 1 CANCER CLINICAL TRIALS SEUNG-HOKANG Department of Statistics. Ewha Wornans University. Seoul. Korea
CHULW. AHN Clinical Epidemiology. University o f Texas Medical School, Houston. Texas
The primat? tiirn of11phnse I cancer clinical tricrl is to determine the nriixinircm tolerated dose of (1 new drug. Although the continuo1 reussessnrent method is shown to have better operating characteristics than trditional designs. lraditional designs are still widely used in practice. Kung und Ahn ( I ) developed an algorithm to conrpute the exact distribution of the nruxitnurtr tolerated dose (MTD) in traditionill designs with dose deescnlrition and investiguted the e.rpected toxicity rute at the M T D with the algorithnr. In this paper; using the e.riict forniuliie derived by Lin nnd Shih (2). Lt’e study the e.ul,ected toxicity rate at the MTD and the e.rpected nicmber of patients with toxicity rind puiients required when the hyperbolic tcingent and the logistic functions (ire used as the icnknow~dose-toxicity cicn~es.We consider the expected tosicity rate both withoitt und with dose deescalation. No further study u m dontz before in ca.ses nhere dose level zero is chosen as the MTD. Since, in real pructice. dose levels lire lorvered f o r adjustment mid a new trial is conducted M.hen dose level ;ero is decided as the MTD, M’e d s o incorporate this dose mdjustment. Ke? Words; Dose finding studies; Algorilhrn-based design; Phase 1 cancer trials; Maximum tolerated dose; Toxicity
INTRODUCTION THE PRIMARY AIM of a phase 1 cancer clinical trial is to determine the MTD of a new drug. Unlike other phase 1 trials, phase 1 cancer clinical trials do not use healthy volunteers. Instead, the trials enroll extremely ill patients with cancer who will often be at very high risk of death in the short term under all standard therapies. some of which may have already failed. Since the benefit of a new drug is believed to increase with dose, the highest possible dose is sought. However, toxicity is also expected to increase with dose, so the aim is to find the highest possible dose without causing an unacceptable amount of toxicity in the patients; this is often called the MTD. O’Quigley et al. ( 3 ) proposed the continual reassessment method, which is a promising alternative to the traditional designs. A lot of research has been done to investigate and Reprint address: Seung-Ho Kang. PhD, Department of Statistics, Ewha Womans University. 1 1-1. Dong, SeoDaeMun-Gu. Seoul, KOREA, 120-750 (e-mail: [email protected]).
865
Downloaded from dij.sagepub.com at UCSF LIBRARY & CKM on April 30, 2015
DaeHyun-
866
Seung-Ho Knng and Chul W.Ahn
improve the performance of the continual reassessment method (4- 10).The continual reassessment method is shown to have better operating characteristics than traditional designs. However, traditional designs are still widely used in practice because of their algorit
Data Loading...
