       Document 0692
 DOCN  M9610692
 TI    Use of historical marker data for assessing treatment effects in phase
       I/II trials when subject selection is determined by baseline marker
       level.
 DT    9601
 AU    Lin HM; Hughes MD; Department of Biostatistics, Harvard School of Public
       Health,; Boston, Massachusetts 02115, USA.
 SO    Biometrics. 1995 Sep;51(3):1053-63. Unique Identifier : AIDSLINE
       MED/96054346
 AB    Although the primary focus of Phase I clinical trials is to assess
       clinical pharmacology and possible toxicities, any information on the
       potential effect of treatment would be useful in helping to determine
       priorities between treatments for further study. We consider the
       scenario where data are routinely collected on a marker of disease
       progression on all patients attending a clinic, but the trial is
       restricted to patients who have a marker level within a defined range at
       study baseline. Using a two-step approach to estimation, the marker
       histories are used to give predictions of marker values during trial
       follow up, assuming no treatment effect and adjusted for the regression
       to the mean effect, for those subjects selected for the trial.
       Comparison between the observed responses and the predicted values then
       forms the basis for moment-based estimation and hypothesis testing for
       the treatment effect. The method is easily extended to compare summary
       measures for repeated measurements during follow up in the trial to
       predicted summary measures. An example using CD4 cell counts in an AIDS
       study is given.
 DE    Biometry  *Clinical Trials, Phase I  *Clinical Trials, Phase II
       Comparative Study  Controlled Clinical Trials/METHODS  Human  HIV
       Infections/*DRUG THERAPY  Mathematics  *Models, Statistical  *Patient
       Selection  Placebos  Randomized Controlled Trials/METHODS  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       Zidovudine/*TOXICITY/*THERAPEUTIC USE  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

