TY - JOUR
T1 - The statistics of phase 0 trials
AU - Rubinstein, Larry V.
AU - Steinberg, Seth M.
AU - Kummar, Shivaani
AU - Kinders, Robert
AU - Parchment, Ralph E.
AU - Murgo, Anthony J.
AU - Tomaszewski, Joseph E.
AU - Doroshow, James H.
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/5/10
Y1 - 2010/5/10
N2 - 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.
AB - 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.
KW - First-in-man study
KW - PD-driven phase 0 trial
KW - Pharmacodynamic assay
KW - Phase 1 clinical trial
KW - Phase 2 clinical trial
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U2 - 10.1002/sim.3840
DO - 10.1002/sim.3840
M3 - Article
C2 - 20419759
AN - SCOPUS:77951605058
VL - 29
SP - 1072
EP - 1076
JO - Statistics in Medicine
JF - Statistics in Medicine
SN - 0277-6715
IS - 10
ER -