Phase 1 oncology clinical trials for related subpopulations: The power walk design

Georgene Schroeder, Jeff A Sloan, Stephen Cha, Pamela Atherton, Cristine Allmer, Charles Erlichman

Research output: Contribution to journalArticle

Abstract

Motivation/Background: This paper addresses designing a Phase 1 trial where the dose-response curve differs across patient subpopulations. We examine a design which “power walks” through clinically ineffective dose levels, accruing from either subpopulation, until dose limiting toxicity appears. The design then splits into two Phase 1 trials for each subpopulation. Methods/Results: We performed simulation studies of 10000 Phase 1 trials comparing the “power walk” design to the alternatives. The power walk design correctly estimates the maximum tolerated dose (MTD) up to 20% more often. The power walk design performs best with a steep dose-response curve, and overestimates the MTD roughly 10% of the time. Conclusions: The power walk design is appropriate to obtain MTDs for separate patient subpopulations where the initial dose is clinically ineffective or substantially below the MTD. A power walk design study involves fewer patients and achieves the correct MTD more often. The power walk design is not recommended when the initial dose level is near the MTD.

Original languageEnglish (US)
Pages (from-to)581-593
Number of pages13
JournalTherapeutic Innovation and Regulatory Science
Volume36
Issue number3
DOIs
StatePublished - 2002

Keywords

  • Dose-response curve
  • Heterogeneous subpopulations
  • Oncology
  • Phase 1 trial
  • Simulation studies

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
  • Public Health, Environmental and Occupational Health
  • Pharmacology (medical)

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