Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

Design and Analysis of Phase I Clinical Trials

Barry E. Storer
Biometrics
Vol. 45, No. 3 (Sep., 1989), pp. 925-937
DOI: 10.2307/2531693
Stable URL: http://www.jstor.org/stable/2531693
Page Count: 13
  • Read Online (Free)
  • Download ($14.00)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Design and Analysis of Phase I Clinical Trials
Preview not available

Abstract

The Phase I clinical trial is a study intended to estimate the so-called maximum tolerable dose (MTD) of a new drug. Although there exists more or less a standard type of design for such trials, its development has been largely ad hoc. As usually implemented, the trial design has no intrinsic property that provides a generally satisfactory basis for estimation of the MTD. In this paper, the standard design and several simple alternatives are compared with regard to the conservativeness of the design and with regard to point and interval estimation of an MTD (33rd percentile) with small sample sizes. Using a Markov chain representation, we found several designs to be nearly as conservative as the standard design in terms of the proportion of patients entered at higher dose levels. In Monte Carlo simulations, two two-stage designs are found to provide reduced bias in maximum likelihood estimation of the MTD in less than ideal dose-response settings. Of the three methods considered for determining confidence intervals-the delta method, a method based on Fieller's theorem, and a likelihood ratio method-none was able to provide both usefully narrow intervals and coverage probabilities close to nominal.

Page Thumbnails

  • Thumbnail: Page 
925
    925
  • Thumbnail: Page 
926
    926
  • Thumbnail: Page 
927
    927
  • Thumbnail: Page 
928
    928
  • Thumbnail: Page 
929
    929
  • Thumbnail: Page 
930
    930
  • Thumbnail: Page 
931
    931
  • Thumbnail: Page 
932
    932
  • Thumbnail: Page 
933
    933
  • Thumbnail: Page 
934
    934
  • Thumbnail: Page 
935
    935
  • Thumbnail: Page 
936
    936
  • Thumbnail: Page 
937
    937