The statistics of phase 0 trials

Larry V. Rubinstein, Seth M. Steinberg, Shivaani Kummar, Robert Kinders, Ralph E. Parchment, Anthony J. Murgo, Joseph E. Tomaszewski, James H. Doroshow

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


The PD-driven phase 0 trial is a new form, designed to be a first-in-man study, often of a new agent, conducted to assess drug effect on a molecular target, by means of a pharmacodynamic (PD) assay, in a very small number (10-15) of patients. Such a study is meant to be a proof of principle trial to determine whether the agent yields the PD effect predicted by pre-clinical studies. The dosage is meant to be pharmacologically active, but is neither toxic nor likely to yield clinical benefit. Such a trial may be used to serve as a very early test of an agent's biologic effect, allowing for early weeding out of ineffective agents, or as an early means of determining the most promising of competing analogue agents. This manuscript will present designs for such PD-driven studies that are statistically efficient and rigorous, focusing on non-comparative trials. The phase 0 trial promises to become an increasingly important tool for facilitating and speeding the development of new therapeutic agents, particularly in oncology.

Original languageEnglish (US)
Pages (from-to)1072-1076
Number of pages5
JournalStatistics in Medicine
Issue number10
StatePublished - May 10 2010
Externally publishedYes


  • First-in-man study
  • PD-driven phase 0 trial
  • Pharmacodynamic assay
  • Phase 1 clinical trial
  • Phase 2 clinical trial

ASJC Scopus subject areas

  • Epidemiology
  • Statistics and Probability


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