title: Theoretical and practical application of traditional and accelerated titration Phase I clinical trial designs: the Wayne State University experience.
abstract: The traditional and accelerated titration (AT) designs are two frequently utilized Phase I clinical trial designs. Although each design has theoretical advantages and disadvantages, a summary of the practical application of these theories has not been reported. We report our center's experience in evaluating novel agents using both types of Phase I trial designs over a 13-year period. Results from nine Phase I clinical trials of multiple cytotoxic agents conducted at Wayne State University/Karmanos Cancer Institute in Detroit, MI, and published from 1995-2005 were analyzed for this report. Parameters analyzed included the number of patients, the number of dose levels, the total time to completion of the study, and adverse events. The mean number of patients treated on four Phase I trials using the traditional Phase I trial design was 34 compared to a mean of 23.8 patients treated on five Phase I trials using the AT schema. The mean number of dose levels in patients treated using the traditional Phase I trial design was 8.8 (range 7-11) compared to a mean of 10.6 (range 7-15) dose levels using the AT design. The mean length of study time (25-26 months) was similar in both trial designs. The theoretical advantages and disadvantages of both Phase I trial designs did not readily emerge in their actual application in clinical trials conducted at our institution.
authors.affiliation: Division of Hematology and Oncology, Wayne State University, Karmanos Cancer Institute, Detroit, Michigan 48201, USA. heathe@karmanos.org
authors.forename: Elisabeth I
authors.initials: EI
authors.lastname: Heath
authors.forename: Patricia M
authors.initials: PM
authors.lastname: LoRusso
authors.forename: S Percy
authors.initials: SP
authors.lastname: Ivy
authors.forename: Larry
authors.initials: L
authors.lastname: Rubinstein
authors.forename: Michaele C
authors.initials: MC
authors.lastname: Christian
authors.forename: Lance K
authors.initials: LK
authors.lastname: Heilbrun
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic / Q000379:methods* / Q000592:standards; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008824:Michigan; D008875:Middle Aged; D012107:Research Design; D014495:Universities; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents