NIH Workshop:
Research Needs for the Design and Analysis
Of Surrogate Endpoints in Clinical Trials



AGENDA - DAY 1

Tuesday, December 1, 1998
8:00 a.m. - 5:15 p.m.


6:00 - 8:00 a.m. Breakfast
8:00 - 8:05 a.m. Welcoming Remarks
8:05 - 8:30 a.m.
  1. Overview of Workshop Goals and ObjectivesóVictor DeGruttola, Harvard School of Public Health (25 minutes)
    1. Clinical Perspectives-David Feigal, FDA, CBER
    2. Goals for Statistical Formulation-Victor DeGruttola; Mitchell Gail, NCI
8:30 - 10:00 a.m.
  1. Review of Important Validation Studies in Selected Disease Areas With a Focus on Methodologic Originality
    The purpose of this section is to address statistical formulations that are used in a variety of diseases and clinical conditions. It is not intended to be a thorough review of all surrogate endpoints. The discussion will specifically address the objectives of the conference.
  1. Cancer-Moderator: Mitchell Gail (90 minutes)
    1. Prevention
      Surrogate Endpoints: How Comprehensive Do They Need To Be?- Ross Prentice, Fred Hutchinson Cancer Research Center (20 minutes)
      Limitations of Surrogate Endpoints in Cancer Prevention Research? - Arthur Schatzkin, NCI (20 minutes)
      Discussant: Raymond Carroll, Texas A&M University (10 minutes)
    1. Treatment
      Using Surrogates To Select Treatments for Further Study- Richard Simon, NCI (20 minutes)
      Discussant: John Crowley, Fred Hutchinson Cancer Research Center (10 minutes)
10:00 - 10:15 a.m. Break
10:15 a.m. - 12:15 p.m.
  1. Mental Health and Alcoholism-Moderator: Scott Zeger, Johns Hopkins University School of Public Health (120 minutes)
    1. Treatment
      Schizophrenia Clinical Trials?- Peter Diggle, Lancaster University, UK (40 minutes)
      Discussant: Scott Zeger (10 minutes)
    1. Prevention
      Prevention Models for Alcoholism?- Bengt Muthen, UCLA (40 minutes)
      Discussant: William Eaton, Johns Hopkins University School of Public Health (10 minutes)
    1. Open Discussion (20 minutes)
12:15 - 1:15 p.m. Lunch
1:15 - 3:00 p.m.
  1. Cardiovascular Diseases-Moderators: Lawrence Friedman, NHLBI; David DeMets, University of Wisconsin-Madison; Janet Wittes, Statistics Collaborative (105 minutes)
    1. Treatment
      Coronary Flow as a Surrogate Endpoint in Phase II Studies of Myocardial Infarction?- Keaven Anderson, Centocor (25 minutes)
      Discussant: Robert Califf, Duke Clinical Research Institute, Duke University (15 minutes)
    1. Prevention
      Equal Risk for Equal Measures? Cardiovascular Disease, Blood Pressure, and Lipids- Barry Davis, University of Texas School of Public Health (25 minutes)
      Discussant: Jeffrey Cutler, NHLBI (15 minutes)
    1. Open Discussion (20 minutes)
3:00 - 3:15 p.m. Break
3:15 - 5:15 p.m.
  1. Infectious Diseases-Moderators: Victor DeGruttola; Susan Ellenberg, FDA, CBER (120 minutes)
    1. Treatment
      Evaluation of Surrogate Endpoints in HIV Clinical Trials?- Michael Hughes, Harvard School of Public Health (30 minutes)
      Discussant: Ron Brookmeyer, Johns Hopkins University School of Public Health (15 minutes)
    1. Prevention
      Vaccine Correlates of Immunity?- Robert Kohberger, Wyeth-Lederle Vaccines (30 minutes) Discussants: Lawrence Moulton, Johns Hopkins University School of Public Health; Janet Wittes (25 minutes)
    1. Open Discussion (20 minutes)
6:00 - 7:00 p.m. Social Gathering - Reception Area of Bolger Center
5:15 - 8:00 p.m. Evening Meal


AGENDA - DAY 2

Wednesday, December 2, 1998
8:30 a.m. - 4:00 p.m.


6:00 - 8:00 a.m. Breakfast
8:30 - 10:00 a.m.
  1. Case Study-Moderator: Gregory Downing, OD, NIH
    (90 minutes)

    The case study will present the research approaches that have been used to develop evidence in support of using a biomarker as a substitute for a clinical endpoint in colorectal adenocarcinoma chemotherapy trials. This discussion will describe the specific analyses that have been performed and the practical consequences of acceptance of tumor shrinkage or regression as a surrogate endpoint.

    While it is recognized that the path to achieving the evidence to support or refute the use of a surrogate endpoint is case specific, the goal of this session is to provide suggestions for the design of systems to conduct ongoing evaluations of the appropriateness of relying on a surrogate endpoint.

    Tumor Shrinkage or Regression as a Surrogate Endpoint for Chemotherapy Trials: Medical Background?-Pascal Piedbois, H?pital Henri Mondor, Cr?teil, France (10 minutes)

    Tumor Response as a Surrogate?-Marc Buyse, International Institute for Drug Development, Brussels, Belgium (20 minutes)

    Progression-Free Survival as a Surrogate?-Geert Molenberghs, Limburgs Universitair Centrum, Diepenbeek, Belgium (20 minutes) Discussants: Thomas Fleming, University of Washington (10 minutes); Mitchell Gail, NCI (10 minutes)

    Open discussion (20 minutes)
10:00 - 10:15 a.m. Break
10:15 - 12:30 p.m.
  1. Role of Complex Pathophysiologic Modeling in Selection of Surrogate EndpointsóModerator: Victor DeGruttola
    (135 minutes)
    This section seeks to examine whether information from models of disease pathogenesis can provide clues to the selection of appropriate surrogate endpoints to evaluate in clinical trials. One goal of this session is to develop strategies to encourage disease modelers to collaborate with statisticians on these issues.

    1. Modeling of the Pathogenesis of HIV and HCV and the Selection of Surrogate Endpoints - Alan Perelson, Los Alamos National Laboratory; Marie Davidian, North Carolina State University (45 minutes)

      Open discussion (15 minutes)


    2. Diabetes Models Based on the DCCT: Research and Health Policy Implications - Richard Eastman, NIDDK
      Risk of Microvascular Complications of Type I Diabetes Mellitus as a Function of Glycemic Exposure (HbA1C) in the Diabetes Control and Complications Trial - John Lachin, George Washington University (45 minutes)

      Open discussion (30 minutes)
12:30 - 1:30 p.m. Lunch
1:30 - 4:00 p.m.
  1. Preliminary Summary and ConclusionsóVictor DeGruttola and the Planning Committee

    Workshop organizers report on the recommendations from each session. Comments and suggestions from the participants will be solicited and will serve as the basis for the draft workshop report.



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NIH Workshop: Research Needs for the Design and
Analysis of Surrogate Endpoints in Clinical Trials