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Thirteenth annual meeting of the society for clinical trials
Final Program Thirteenth Annual Meeting of the Society for Clinical Trials May 10-13, 1992 Adam's Mark, Philadelphia, Pennsylvania
PROGRAM SUNDAY, MAY 10, 1992
7:30 AM - 2:00 PM
Registration for Pre-Conference Workshops
9:00 AM - 5:00 PM
Pre-Conference Workshops Pre-Conference I Design and Analysis of Longitudinal Clinical Trials
Grand Ballroom Foyer
Constitutional
Ballroom
Longitudinal designs are now widely used in clinical research to assess the effects of treatment on changes in physiologic or clinical measures of health status over time. This workshop will describe modern methods for the design and analysis of longitudinal clinical trials, with an emphasis on the issues that arise in randomized clinical trials with longitudinal designs. The workshop will discuss: • • • • •
design of longitudinal clinical trials choice of outcome measure modeling the mean and covariance structure sample size calculations data analysis, including models for handling attrition and missing data
Software for the analysis of longitudinal data, including REML program for growth curve analysis, the GEE program developed by Liang and Zeger, and BMD P5V, will be discussed. These presentations will make extensive use of examples from recent clinical trials research.
Speakers: Nan M, Laird James H. Ware
356 0197-2456/92/$5.00
Controlled Clinical Trials 13:356-376 0992) © Elsevier Science Publishing Co., Inc. 1992 655 Avenue of the Americas, New York, New York 10010
357
Final Program SUNDAY, MAY 10, 1992 (Continued) Pra-Conforence II Ancillary Studies In Clinical Trials: A Workshop for Clinical Trial Coordinstora
Salon A & B
This workshop will address issues related to the development of ancillary studies in clinical trials which would be of importance to nursing science. The objectives of the workshop include: (1) the identification of questions of relevance to nursing science which could be addressed in ancillary studies; (2) identification of the concerns of clinical trial investigators in the consideration of ancillary studies; (3) review of the approval process; (4) identification of funding opportunities; and (5) design issues in the development of ancillary studies. The format will include a combination of lecture and discussion. Clinical trial coordinators attending need have no previous experience with ancillary studies.
Speakers: Jacqueline Dunbar-Jacob Susan Thomas Pra-Conference III
Salon E & F
Survival Analysls-A Non-Technical Workshop on Statistical Aspects In the Planning end Analysis of Survival Studies The treatment or prevention of chronic diseases often involves evaluation of a "time-to-event" end point. The analysis of such end points, call generically "survival analysis," requries specialized statistical methods. This workshop will provide a nontechnical review of key aspects of the design, monitoring and analysis of clinical trials with time-to-event end points. Topics to be covered include end point selection, estimation of survival distributions, planning sample sizes, statistical significance tests of treatment effects, regression analysis for survival data, sequential monitoring of survival trials, competing risks and evaluating surrogate end points. Ample time will be provided for discussion and questions. The presentations will be non-technical and will emphasize case studies. Speakers: Frank E. Harrell, Jr. G. Gordon Lan Richard Simon 12:00 PM - 5:00 PM
Board of Directors Meeting
President's Ballroom
4:00 PM - 8:00 PM
Registration
Grand Ballroom Foyer
7:00 PM - 10:00 PM
Evening Social Reception
Salon A, B, & C
MONDAY, MAY 11, 1992
7:30 AM - 5:00 PM
Registration
Grand Ballroom Foyer
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Final Program MONDAY, MAY 11, 1992 (Continued)
8:30
AM
-
Exhibit Program
5:00 PM
8:30 AM - 8:45 AM
Welcome Genell L. Knatterud, President Society for Clinical Trials
8:45 AM - 10:15 AM
Plenary Session I Sharing Clinical Trials Data
Exhibit Center Grand C & D
Clinical trials typically generate substantial quantities of high quality data on the clinical course of a disease. Considering the high costs of performing a clinical trial, it is appropriate to maximize the usefulness of the effort through widely sharing the resulting database. These data may constitute unique research resources which would be invaluable to other scientists exploring related questions. In addition, the sharing of these data may lead to improvement of such methodologic techniques as study design, outcome measurement and analytic approach, and help identify reliable surrogate endpoints and prognostic indicators. Traditionally, investigators tend to be very possessive of the data collected in their studies, and often rightly so. Premature release of study data may al!ow others to "scoop" the main study results or perform a number of ancillary analyses before the original investigators have their opportunity to fully explore their data. Speakers in this session will discuss the benefits of and concerns about sharing data from ongoing and completed clinical trials. Issues such as NIH policy regarding sharing research data, possible conditions placed on data release, the timing and extent of data release, the work involved in study data documentation, and possible mechanisms for data dissemination, will be addressed. Chairperson: Peter Gilbert, National Institutes of Health Stephen Fienberg, York University Toronto Genell Knatterud, Maryland Medical Research institute George Williams, Merck, Sharp & Dohme Research Laboratories David Amato, Harvard School of Public Health 10:15 AM - 10:45 AM
Break
Exhibit Center
10:30 AM - 4:00 PM
Poster S e u l o n I (Poster Prlmatlme 10:30- 11:30 AM)
Exhibit Center
P01
Strategies for Educating and Training Clinicians to Conduct Community-Based Research: A Report from the Community Programs for Clinical Research on AIDS; Geraldine Maiatico, National Institutes of Health
P02
The Use of Computer-Assisted Instruction (CAI) for Protocol Training; Sharon Rolnick, University of Minnesota
P03
Features of Manuals of Procedures for Multicenter Randomized Clinical Trials; Claudia Moy, The Johns Hopkins University
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Final Program MONDAY, MAY 11, 1992 (Continued) 10:30 AM - 4:00 PM
Poster Session I (continued) (Poster PrlmeUme - 10:30 - 11:30 AM)
Exhibit Center
P04
Performance Evaluation of Centers Participating in a Multicenter Clinical Trials Group: A Model Developed for the Community Programs for Clinical Research on AIDS (CPCRA); Michael Hedderman, National Institutes of Allergy and Infectious Diseases
P05
Performance Evaluation in Multicenter Clinical Trials: Development of a Model by the AIDS Clinical Trials Group (ACTG); Linda Rosendorf, National Institutes of Allergy and Infectious Diseases
P06
Monitoring Investigator Compliance; Tamara Odom-Maryon, City of Hope National Medical Center
P07
CAST Coordinator Survey; Joyce Kellen, University of Calgary
P08
Determinants of Clinical Center Staff Size: Ophthalmologists and Ophthalmic Photographers Certified in a Large Multi-Center Trial; Lee McCaffrey, The Johns Hopkins University
P09
Facilitating Investigator Recruitment; Laurie Halloran, PAREXEL International Corporation
P10
Fiscal Administration of Clinics by Coordinating Centers: A Survey of Multi-Center Eye Trials; Charlotte Gerczak, The Johns Hopkins University
P11
Collaboration Between Universities and the Pharmaceutical Industry - A European Perspective; lan Ford, Glasgow University
P12
The Development of a National Perinatal Clinical Trials Network in Canada: The First Step; Mary Hannah, University of Toronto
P13
Evaluation of the Impact of Legal Regulations on the Quality of Trials in Spain; Femando Garcia-Lopez, The Johns Hopkins University
P14
Chiropractic and Pharmaceutical Treatment for Muscle Tension Headaches: A Randomized Clinical Trial; Patrick Boline, Northwestern College of Chiropractic
P15
Simplifying Large Trials: An Example from the Community Programs for Clinical Research on AIDS; John Matts, University of Minnesota
P16
Organization, Goals, and Logistical Challenges of the Community Programs for Clinical Research on AIDS; Marcia Carlyn, National Institutes of Health
P17
Are Science and Seeding Trials" Compatible?; Jean-Pierre Boissel, Unit(~ de Pharmacologie Clinique
360
Final Program MONDAY, MAY 11, 1992 (Continued)
10:30 AM - 4:00 PM
Poster Session I (continued) (Poster Prlmetlme - 10:30 - 11:30 AM)
Exhibit Center
P18
Cooperative Clinical Trials in Health Services Research in the Department of Veterans Affairs; William Henderson, VA Hospital
P19
Blocked Randomized Assignment of Treatments to Patients in Clinical Trials Using SAS (Statistical Analysis System); Maria Deloria, National Institutes of Health
P20
The Analysis of a Single-Patient Efficacy Trial of an Investigational Antiepileptic Drug; J. Todd Sahlroot; National Institutes of Health
P21
Methodological and Ethical Issues in a Series of Exploratory Multiple Crossover Double-Blind Studies in Individual Patients with Dementia to Assess the Efficacy and Safety of CGS 5649B; Tim Standish, McMaster University
P22
Low Dose Oral Anticoagulation and Cardiac Valvular Replacement: Application of the Eligibility Oriented Randomization Scheme; Nadine Bossard, Unit6 de Pharmacologie Clinique
P23
An Application of an Extended Greco-Latin Square Design to Study Gender and Race Bias; Sue Marcus, University of Pennsylvania
P24
A Controlled Clinical Trial in Ophthalmology: Formal Randomization May Not be Ethical; Margaret Ballantyne, Queen's University
P25
Conducting Clinical Trials with Database Controls; James Murphy, University of Colorado Medical School
P26
Social Security Number - - An Appropriate Algorithm for Randomization in a Community Hospital Setting?; Dawn Blackhurst, The Greenville Hospital System
P27
Assessing Quality of Life in Clinical Trials; Robert Hoop, Marion Merrell Dow Inc.
P28
Simplified Assessment of Lab Parameters in Clinical Trials - Basic Considerations; Maria Grazia Pochobradsky, Helsinn SA
P29
A Sample Size Formula for Case-Control Studies with an Independent Variable that is Continuous; Bruce Thompson, Maryland Medical Research Institute
P30
Statistical Considerations in Monitoring the Systolic Hypertension in the Elderly Program; Barry Davis, The University of Texas School of Public Health
P31
Sample Size Determination Using an Interim Analysis; David Bristol, Schering-Plough Corporation
P32
Bayesian Decision-Theoretic Clinical Trials: Monte Carlo Comparison with Classical Group Sequential Methods; Roger Lewis, Harbor-UCLA Medical Center
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Final Program MONDAY, MAY 11, 1992 (Continued)
10:30 AM - 4:00 PM
Poeter Session I (continued) (Poster Prlmetime - 10:30 - 11:30 AM)
Exhibit Center
P33
Computer Models for Editing Study Data; Susan Karabelas, Maryland Medical Research Institute
P34
The Development of Data Collection Tools to Assist in Protocol Management; Collette Houston, Memorial Sloan-Kettering Cancer Center
P35
Parent: A Strategy for Automation of Data Management Tasks in Clinical Trials and Registries; Jeffrey Martin, University of Pittsburgh
P36
Computer-Assisted Clinic Monitoring: The COMS Experience; Kelly Manos, The Johns Hopkins University
P37
Data Entry Manual for a Clinical Trial; Scott Corely, University of Washington
P38
An Inventoried Editing System: Efficient Maintenance of High Standards in Data Quality; Sharon Lawlor, University of Pittsburgh
P39
NHLBI Growth and Health Study Remote Clinical Data Systems: 5 Years Later; Ellis Clarke, Maryland Medical Research Institute
P40
Use of a Relational Database to Track Correspondence Regarding Requested Corrections to Case Data Records; Patrick McGrath, University of Missouri
P41
Databases - A Relational Design: The Pros and Cons; Paul Wainwright, University of Birmingham
P42
Selecting A RDBMS for a Multi-Disciplinary Clinical Research Database; Danny Wu, Memorial Sloan-Kettering Cancer Center
P43
Confidence Intervals for the Difference of Two Survival Probabilities: A Comparative Study; Young Jack Lee, National Institutes of Health
P44
Graphical Methods for Visualizing the Timing of Follow-up in Clinical Studies; Martin Lesser, North Shore University Hospital Cornell
P45
Graphical Display of Kaplan-Meier Plots; Mark Van Natta, The Johns Hopkins University
P46
Cox Regression Analyses Using SAS/PHREG; Michele Donithan, The Johns Hopkins University
P47
Selection of Covadates in the Cox Model: Simulations; Franca Barton, Maryland Medical Research Institute
362
Final Program MONDAY, MAY 11, 1992 (Continued) 10:30 AM - 4:00 PM
Poster Session I (continued) (Poster Prlmetlme - 10:30 - 11:30 AM)
10:45 AM - 11:30 AM
Poster Discussion Topic: Meta-Analysis Discussant: Curt Furberg
Exhibit Center
P48
Randomized Clinical Trials on Medical Treatment of Glaucoma: Are they Appropriate to Guide Clinical Practice?; Luca Rossetti, Instituto di Ricerche Farmacologiche "Mario Negri"
P49
Publication of Randomized Clinical Trials in Vision Research Submitted as Abstracts to the National Ophthalmology Meetings; Roberta Scherer, University of Maryland
P50
A Comparison of Statistical Methods of Pooling Randomized Control Trials (RCTs): An Assessment of 45+ Meta-Analyses (M-As); Joseph Lau, VA Medical Center, Boston
P51
Advantages and Limitations of Meta-Analytic Regressions of Clinical Trials Data; Jesse Berlin, University of Pennsylvania
P52
Meta-Analysis or Quantitative Overview - Is There any Difference?; Lesley Stewart, MRC Cancer Trials Office
P53
Meta-Analysis of Randomized Controlled Trials of the Benefits of Screening Women Ages 40-49; Kenneth Chu, National Cancer institute
Contributed Paper Session I (four [4] simultaneous sessions)
11:00 AM - 12:00 PM
Session IA: Statistical Methods for Special Designs in Clinical Trials Salon A & B Chairperson: Dennis Dixon 11:00 AM
01
Bayesian Guidelines for Phase II Clinical Trial Design and Analysis; Peter Thall, M.D. Anderson Cancer Center
11:20 AM
02
A Likelihood-Based Graphical Method for Meta-Analysis; Steven Goodman, The Johns Hopkins University
11:40 AM
03
An Illustrative Statistical Analysis of Cutoff-Based Randomized Clinical Trials; Joseph Cappelleri, Harvard School of Public Health
Session IB: Analysis of Surrogate End Points Chairperson: Lawrence Hauptman
Salon E & F
11:00 AM
04
Predictive Value of Repeated Measurements of CD4 Lymphocyte Counts on Progression to AIDS; Florent Boutitie, London School of Hygiene and Tropical Medicine
11:20 AM
05
Design Issues for Studies Based on UItrasonographic Measurement of the Carotid Artery IntimaI-Medial Thickness; Mark Espeland, Bowman Gray School of Medicine
11:40 AM
06
Evaluation of Coronary Arteriography Changes as a Surrogate Endpoint for Atherosclerotic Cardiac Events; John Matts, University of Minnesota
363
Final Program MONDAY, MAY 11, 1992 (Continued) Contributed Paper Session I (continued) (four [4] simultaneous sessions) Session IC: Early Stopping Chairperson: William Blackwelder
Constitution Ballroom
11:00 AM
07
Estimation in Clinical Trials that Stop Early; Maria Mori Brooks, University of Washington
11:20 AM
08
One-Sided Test for Clinical Trials with Group Sequential Design that Allow Early Acceptance of Negative Result; Benny Zee, Queen's University
11:40 AM
09
When Should Randomization to Untreated Control Groups Stop?; Thomas Chalmers, Harvard School of Public Health
Session ID: Student Scholarship Chairperson: Theodore Karrison
Salon C & D
11:00 AM
10
Cost Utility Analysis of Maintenance Treatment for Recurrent Depression; Nancy Paul, Carnegie Mellon University
11:20 AM
11
The Analysis of Incomplete Data in the Three-Period TwoTreatment Crossover Design for Clinical Trials; Barbra Richardson, UCLA
11:40 AM
12
Prognostic Indices: Who Needs Them?; Janet Dunn, University of Birmingham Exhibit Center
12:00 PM - 1:30 PM
Lunch
1:30 PM - 3:00 PM
Workshop I ConatltuUon Ballroom Data Management Symposium Approaches for managing data collected in clinical trials have changed rapidly over the past decade as computer technology has advanced. For those involved in data coordinating centers for clinical trials there is little published to help in planning or managing data centers. Two companion workshops will address current methods and technologies employed by a variety of coordinating centers in various settings.
Organization and function of a clinical trials coordinating center Herman Mitchell, New England Research Institute; Brent Blumenstein, Bonnie Hermanson, Kenneth James. This paper will lead off the discussion by providing an overview of the structure(s) of data coordinating centers and a description of their functions. Guidelines for planning a data coordinating center for various types of studies will b discussed.
Approaches to data management Eleanor McFadden, Eastern Cooperative Ontology Group; Anna Bagniewska, Fran LoPresti In this presentation, the options for data base management designs will be discussed with the relative merits of various models and systems. Requirements for adequate software and hardware will be discussed and techniques for specific data management requirements such as encoding of adverse reactions and diseases will be described.
364
Final Program 1:30 PM - 3:00 PM
Workshop I (continued) Data Management Symposium
Constitution Ballroom
Support for the development of these workshops and the ensuing manuscripts is being provided by the Johns Hopkins Center for Clinical Trials.
Chairpersons: Ruth McBride, University of Washington Steve Singer, Dedicated Response
Workshop II Adjusting the Treatment Comparison for Covarlate Imbalance
Salon C & D
In randomized clinical trials, we usually collect a large amount of information at baseline about the patients. These data can comprise patient characteristics, clinical observations, and biochemical, radiographic or pathologic test results. Some of the variables mays36have been found previously to relate to prognosis but the evidence for the prognostic importance of each variable may vary from definite to possible to weak to non-existent. Although on average, randomization will balance treatment groups with respect to these variables, any individual trial will have a degree of imbalance, and in some the imbalance may be substantial. Various statistical strategies have been proposed for dealing with covariate imbalances in the analysis and these range from reliance on the unconditional randomization distribution (no adjustment) to inclusion of all "apparently" important covariates in a statistical model. Speakers will present their own approaches to this problem, followed by criticism and discussion lead by formal discussants.
Chairperson: Laurence Freedman, National Cancer Institute Lincoln Moses, Stanford University John Tukey, Princeton University
Discussant: Paul Meier, University of Chicago Workshop III Adverse Experiences with Investlgatlonal Drugs
Salon E & F
Clinical trials of investigational drugs are primarily aimed at assessing whether the drug under study, compared with either a placebo or the current standard treatment, is efficacious in the treatment of a specific disorder. Equally important, however, is determination of the test drug's safety profile which would, at the end of the trial, allow one to conclude whether the test drug does more good than harm. These safety data are most commonly labelled as adverse experiences or events, side-effects, or adverse reactions. However, in most clinical trials the tendency to place our emphasis on operational issues relating to the "collection" and "processing" of this information without due attention to some of the conceptual issues relating to the reporting of adverse experience. These issues, if considered appropriately at the start of a trial, could indirectly affect the resolution of potential problems during the collection and processing stages. This workshop will address a number of conceptual issues including:
365
Final Program MONDAY, MAY 11, 1992 (Continued)
1:30 PM - 3:00 PM
Workshop III (continued) Adverse Experiences with InvseUgstlonal Drugs
Salon E & F
• should we, and if yes, how do we, distinguish between any newly reported signs/symptoms and adverse experiences • appropriateness of causal assessment • what constitutes an ~episode" in the context of adverse experiences and does this differ from a "report" • which study efficacy outcome events should be reported as adverse experiences • the need to meet the requirements of different regulatory authorities in an international collaborative trial • how regulatory authorities and safety monitoring committees interact with respect to serious adverse experiences during the course of a trial • the delegation of responsibility for monitoring safety to an external safety committee Chairperson: Robin Roberts, McMaster University Bruce Davidson, Wyeth-Ayerst Research Andreas Laupacis, University of Ottawa Robert Temple, Food and Drug Administration 3:00 PM - 3:30 PM
Break
3:30 PM - 5:00 PM
Plenary Saselon II
Exhibit Center Salon C & D
Cost Conslderstlons In Clinical Trials Randomized clinical trials are expensive to design and to carry out. Costs are associated with the individual participants in the trials, the investigators, the clinical centers, the various staffs, the central laboratories, and the data coordinating center. The literature on clinical trials includes a number of papers on the ultimate economic benefit of a trial to the population at large. Little has been written, however, on methods for designing trials with a view toward minimizing costs. The aim of this session is to open a discussion on methods for formal incorporation of economic considerations into the design of randomized clinical trials. The session will deal with two specific aspects of using cost considerations to help design clinical trials. First, in the context of community-based randomized trials in AIDS, the session will discuss various approaches to structuring the trials with the view toward efficient designs. The methods have potential applicability to diseases other than AIDS. The second topic will be a proposal to use formal cost functions to aid in the design of trials. By analogy with methods in common use in the design of sample surveys, a cost function can be constructed that will allow a design to minimize cost for fixed precision or to maximize precision for fixed cost. Examples of the use of such a function will be presented. Chairperson: Peter Peduzzi, VA Cooperative Study Program Group James Neaton, University of Minnesota Sonja McKinlay, New England Research Institute Inc. Joel Verter, Henry Ford Hospital
366
Final Program MONDAY, MAY 11, 1992 (Continued) 5:15 PM
Business Mectlng
Salon C & D
TUESDAY, MAY 12, 1992
7:30 AM - 5:00 PM
Registration
8:00 AM - 5:00 PM
Exhibit Program
8:30 AM - 10:00 AM
Plenary Session III
Grand Ballroom Exhibit Center Salon C & D
The Role of the Government, Industry, and Academia In the Conduct of Large-Scale Clinical Trials There are two major sources for funding large-scale clinical trials: government agencies and the pharmaceutical industry. Those who fund clinical trials accomplish the collection and analysis of the data derived from the trials by one of three methods: in-house; through contractual relationships with free-standing academic coordinating centers; or in collaborative partnership among government, the pharmaceutical industry and academic coordinating centers. As the costs and complexities of clinical trials increase, the pressure for collaboration is increasing. However, the interests of each group may differ at each stage of conducting a trial: in the initial planning of the trial (including framing the hypotheses to be tested), in selecting the rules by which the data are collected and analyzed in the oversight of the trial as it progresses, and in the final assembly and reporting of the data, both to the FDA and to the general public. The speakers in this session will present their individual viewpoints, representing federal funding sources, the pharmaceutical companies' perspective, and the position of the academic coordinating center. The speakers will describe their past experience with shared clinical trials, giving insight into past performance and future promise of the collaboration. Chalrperaon: Daniel Deykin, Veterans Administration Cooperative Studies Program Edward Scolnick, Merck, Sharp & Dohme Laboratories Michael Gent, Hamilton Civic Hospital Research Centre 10:00 AM - 10:30 AM
Break
Exhibit Center
10:00 AM - 4:00 PM
Poster Session II (Poster Primstime 10:15 - 11:30 AM)
Exhibit Center
P54
Clinical Trial Enrollers Versus Nonenrollers: Recruitment and Enrollment Assessment in Clinical Trials (REACT) Project; Larry Gorkin, Institute for Behavioral Medicine
367
Final Program TUESDAY, MAY 12, 1992 (Continued) 10:00 AM - 4:00 PM
Poster S e s s i o n II ( c o n t i n u e d ) ( P o s t e r P r l m e t l m e - 10:15 - 11:30 A M )
Exhibit C e n t e r
P55
The Use of Focus Groups in the Design of Cholesterol Education Intervention Programs; Rebecca Masters, The Johns Hopkins University School of Medicine
P56
Non-Ulcer Dyspepsia and the Randomized Multiple Cross-Over Model; Kornelia HOschen, SmithKline Beecham Pharma Munich
P57
Problems in Assessing Left Ventricular Function in Clinical Trials; Sylvie Ahn, University of Louvain
P58
Termination Issues in Long-Term Clinical Trial Research; Judith Jensen, St. Louis University Medical Center
P59
Long Term Adherence in Patients Who Fail the Initial Prerandomization Adherence Screen. The Studies of Left Ventricular Dysfunction Experience; Milena Henzlova, University of Alabama
P60
Predicting Noncompliance Among HIV Positive Asymptomatic Individuals in a Randomized Controlled Clinical Trial; Richard Berzon, Burroughs Wellcome Company
P61
Methodological Issues in Screening for Relapse in Early Breast Cancer; Roldano Fossati, Istituto di Ricerche Farmacologiche =Mario Negri"
P62
Population Screening for Randomization into Large Scale Cholesterol Reduction Clinical Trials; John Norrie, University of Glasgow
P63
Developing a Prognostic Index for Stomach Cancer; Janet Dunn, University of Birmingham
P64
Regression to the Mean in Clinical Trials with Entry Based on Counting Events; Robert McMahon, Maryland Medical Research Institute
P65
The Paradox of Rapid Accrual; Michael Palmer, National Cancer Institute of Canada
P66
A Predictive Model of Inclusion Rates in a Very Large Scale Clinical Trial with General Practitioners; Yves Alamercery, Societe R.C.T.s
P67
A Deming Approach to Recruiting: The National Institute of Neurological Disorders and Stroke (NINDS) t-PA Stroke Trial Experience; Barbara Tilley, Henry Ford Health Sciences Center
P68
Recruitment Experience in the Home Intravenous Antibiotic Trial; Frances Mather, Tulane University
P69
Lessons for Coordinating Center Management from a Centralized, Computer-Assisted Randomization System; Townes Coates, The Johns Hopkins University
P70
A Software for Registration and Stratified Randomization in MulUcenter Clinical Trials: The Experience of the European Lung Cancer Working Party; Marianne Paesmans, Institut Jules Bordet
368
Final Program TUESDAY, MAY 12, 1992 (Continued)
10:00 AM - 4:00 PM
Poster Session II (continued) (Poster Prlmetlme - 10:15 - 11:30 AM)
Exhibit Center
P71
Quality Assurance & Multicenter Clinical Trials; Beverly Koski, Queen's University
P72
Standardization Description of Dose-Ranging Trial Protocols; Jean-Pierre Boissel, Unit~ de Pharmacologie Clinique
P73
Continuing Review of Trials by Local Ethics Boards: A Reminder System for Keeping Participating Centres on Track; Nancy Paul, Queen's University
P74
Impact of a Randomized Trial on Transfusion Practice in Orthopedic Surgery; Lenore Dickson, McMaster University
P75
Health Care Directives in the Elderly and Health Care Utilization; Bonnie Rush, McMaster University & Geriatric Research Group
P76
Are there Gender-Related Differences Among Attitudes of Patients in Heart Failure Trials?; Glenda Blackburn, University of Alabama Medical Center
P77
Retrospective Psychometric Reports are Poor Estimates of Treatment Success; Jocelyne Feine, Universite de Montreal
P78
Variation in Resource Center Workload and Productivity Over a 13-Year Period; Barbara Hawkins, The Johns Hopkins University
P79
Registry of Resource Centers for Multicenter Clinical Studies; Nancy Fink, The Johns Hopkins University
P80
A Comparison of Three Database Packages, SIR, Paradox and DBaselV with Respect to Their Ability to Perform Data Management Tasks; Julie Weston, University of Toronto
P81
Difficulties in the Data Management of Recurrent and Transient Events in Prospective Randomized Clinical Trials: Example from a Randomized Trial Comparing Two Different Brachytherapy Dose Rates in Gynaecological Cancer; Jeannine Bouzy, Institute Gustave Roussy
P82
Common Toxicity Criteria: The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) Experience; Nancy Wainman, National Cancer Institute of Canada
P83
The Measurement of Visual Analogue Scale Data Is Not a Burden; Michael Palmer, Queen's University
P84
Development of a Composite Index for Noncompliance Patients in Clinical Trials; Marisa De Rosa, CINECA - Inter University Computing Center
P85
A Coding System for Medication Use Based on the American Hospital Formulary Service; June Pierce, Bowman Gray School of Medicine
369
Final Program TUESDAY, MAY 12, 1992 (Continued) Poster Session II (continued) (Poster Prlmstime - 10:15 - 11:30 AM)
10:00 AM - 4:00 PM
Exhibit Center
P86
Online With WHO: Electronic Medication Coding; Kathleen Gallinger, PAREXEL International Corporation
P87
Comparison Between Two Drug Titration Systems Developed for the POST CABG Studies Clinical Trial; Evelyn Mirenzi, Maryland Medical Research Institute
P88
Subject File Checklists to Facilitate Clinical Trial Close-Out Activities; Rita Pelusio, University of Rochester
P89
Techniques for Editing Longitudinal Growth Data; Bruce Barton, Maryland Medical Research Institute
P90
Pursuing High Quality Data Through Structured Form Design; Nancy Remaley, University of Pittsburgh
P91
Computer Generated Drug Distribution and Accountability for a Clinical Trial; Patrick McGrath, University of Missouri
P92
Using SAS to Monitor Tdal Supplies - Experience Gained in a Multicenter Trial; Caroline Gould, Bard Limited
P93
Simulation Study Comparing Cumulative Mean Change with Slope Estimate Summaries: Application to a Comparative Trial of Venlafaxine, Imipramine and Placebo; A. Richard Entsuah; WyethAyerst Research
P94
Analysis of Risk Factors for Conditions Defined by Extremes of a Distribution; Bruce Barton, Maryland Medical Research Institute
P95
Conventions for Handling Missing Data; Linda Ward, University of Birmingham
P96
Rank Statistics for Analysis of a Clinical Trial with Multiple Events Per Patient: The Multicentar Study of Hydroxyurea in Sickle Cell Anemia (MSH); Robert McMahon, Maryland Medical Research Institute
P97
Problems in Drawing Conclusions in Barrier Contraceptive Clinical Tdals with Compliance Problems; Inder Sharma, Family Health Intamational
P98
Comparing Trials for the Treatment of Myelomatosis; Janet Dunn, University of Birmingham
P99
Documentation and Analysis of Adverse Event Data in Clinical Tdals: The German Chronic Myeloid Leukemia Study Experience; Joerg Hasford, Biometric Center for Therapeutic Studies
370
Final Program TUESDAY, MAY 12, 1992 (Continued)
10:30 AM - 12:30 PM
Contributed Paper Session II (four [4] simultaneous sessions)
session IIA: Logistic Regression and Survival Analysis Chairperson: Mohan Beltangady
Salon A & B
10:30 AM
13
Clinical Use of Logistic Regression Models to Predict Treatment Efficacy in the Presence of Treatment-Covariate Interaction; Thomas Moritz, VA Medical Center, Hines
10:50 AM
14
Patient Compliance as an Explanatory Variable in the Aspirin Myocardial Infarction Study; David Zurakowski, University of Chicago
11:10 AM
15
Modelling the Time-Varying Course of Compliance in a Clinical Trial; Robert Glynn, Harvard Medical School
11:30 AM
16
Nonparametric Survival Regression Trees and Application to Three Radiation Therapy Oncology Group (RTOG) Malignant Glioma Trials; Charles Scott, Radiation Therapy Oncology Group
11:50 AM
17
Observational Analyses with Time Dependency and Missing Values in the Thrombolysis in Myocardial Infarction (TIMI) II Clinical Trial; Michael Terrin, Maryland Medical Research Institute
12:10 PM
18
Parametric Approaches to Quality Adjusted Survival Analysis; Bernard Cole, Dana-Farber Cancer Institute seselon liB: Data Management Issues In Drug Toxicity and Drug Dispensation Chairperson: Michael Hamrell
Salon E & F
10:30 AM
19
Lessons Learned and Pitfalls to be Avoided in the Design of Study Drug Titration Systems; Norma Lynn Fox, Maryland Medical Research Institute
10:50 AM
20
Adverse Medical Events in Clinical Trials: Reporting and Evaluation; Philip Day, VA Medical Center, Albuquerque
11:10 AM
21
Bar-Coding in Validating Investigational Drug Packaging; Mark Jones, VA Medical Center, Albuquerque
11:30 AM
22
Toxicity Grading Systems; Hilary Franklin, The Netherlands Cancer Institute
11:50 AM
23
ARGO: An On-Line Prescription Monitoring System; Marisa DeRosa, CINECA Session IIC: Phase I - II Designs Chairperson: Judith Feinberg
10:30 AM
24
Salon C & D
Design and Implementation of the NHLBI and the VA Cooperative Studies Program Collaborative Study, "Trial to Evaluate the Effect of Digitalis on Mortality in Heart Failure"; William Williford, VA Medical Center, Perry Point
371
Final Program TUESDAY, MAY 12, 1992 (Continued) Contributed Paper Session II (continued) (four [4] simultaneous sessions)
10:30 AM - 12:30 PM
10:50 AM
25
Design of the Veterans Administration Cooperative Study of Active Immunotherapy of HIV Infection; Peter Peduzzi, VA Medical Center, West Haven
11:10 AM
26
Mean Daytime Diastolic Blood Pressure as an Entry Criterion in a Parallel Factorial Design Study to Assess the Antihypertensive Efficacy of Nebivolol (NEB) Alone or in Combination with Hydrochlorothiazide; Jean Lefebvre, Centre Hospitalier de I'Universite Laval
11:30 AM
27
A Phase II Elimination Procedure of Treatments for a Serious Illness; Christopher Palmer, University of Cambridge
11:50 AM
28
Preliminary Safety and Activity Evaluation of New Agents for the Treatment of HIV-1 Infection: Recommended Guidelines for Trial Design; Daniel Stein, National Institute of Allergy and Infectious Diseases
12:10 PM
29
Randomized, Three-Step Trial Design for Phase 1 Study of Chemopreventive Agents; Paul Carbone, Wisconsin Comprehensive Cancer Center
Session liD: Classification for Design Analysis Chairperson: Joseph Pater
Constitution Ballroom
10:30 AM
30
Assessing Disease-Specific Causes of Death in a Trial of AllCause Mortality; Jan Markowitz, The Johns Hopkins University
10:50 AM
31
A Questionnaire to Measure Morbidity in Patients Receiving Radiation Therapy for Head and Neck Cancer; Peter Skingley, McMaster University
11:10 AM
32
Improving the Classification of Stage: A Potential Problem for Comparative Studies; Linda Ward, Cancer Research Campaign Trials Unit
11:30 AM
33
Classification of Protocol Deviations in a Complex Study; Claudia Moy, The Johns Hopkins University
11:50 AM
34
Eligible-Non-Randomized Patients: Their Impact on Generalizability; Deborah Marcellus, McMaster University
12:10 PM
35
Effect of Selective Decontamination of the Digestive Tract (SDD) Upon Mortality; Luca Brazzi, Instituto di Ricerche Farmacologiche 'Mario Negri"
12:30 PM - 2:00 PM
Lunch
Exhibit Center
372
Final Program TUESDAY, MAY 12, 1992 (Continued) 2:00 PM - 3:30 PM
Three Simultaneous Workshops Workshop IV Constitution Ballroom Data Management Symposium (Continued) The second of two companion workshops on data management will focus on current methodologies in data collection, quality assurance, reporting and archiving.
Data collection and transcription Jim Hosking, University of North Carolina; Lance Bailey, Barbara Hawkins, Marvin Newhouse Data collection, the measurement and recording of data, is perhaps the most crucial stage in the overall data management process. This paper will describe current methodologies in forms design, data entry, data coding and transfer of data. Data quality assurance and monitoring Jennifer Gassman, Cleveland Clinic; Duke Owen This presentation will examine quality control strategies for the study database. It will discuss decisions related to which items to check, where to check them, how to handle discrepant data and reporting data quality.
Study reporting, archlvlng and cloeeout Ruth McBride, University of Washington; Steve Singer, John Matts What should be included in monitoring and other reports requires careful consideration as does the format of presentation. The first part of this talk will discuss design and production of various types of reports from clinical trials. At the termination of a clinical trial, the focus of the coordinating center shifts to issues related to close-out. This period will be the final opportunity to make sure that data are as complete and accurate as possible. During this period the database and other materials will need to be finally archived. The second part of this presentation will discuss issues and methodologies related to close-out and archiving. 2:00 PM - 3:30 PM
Workshop V Issues In PhsrmacoklneUcs and Phsrmacodynamlca In Clinical Trials
Salon C & D
Pharmacokinetics (PK) refers to the time-course of drugs and their metabolites in various tissues of the body. Pharmacodynamics (PD) refers to the relationship between drug levels and the pharmacologic effects of drugs. The planning, design, analysis and interpretation of clinical trials implicitly rely on PK and PD concepts and the purpose of this workshop is to describe a variety of PK/PD concepts, including population methods, and some applications and experiences in clinical trial settings. Drug level monitoring during routine clinical visits in the course of Phase II and Phase III clinical trials provides a means to document pharmacokinetic.
373
Final Program TUESDAY, MAY 12, 1992 (Continued) 2:00 PM - 3:30 PM
Three Simultaneous Workshops (continued) Workshop V (continued) Salon C & D Issues in PharmacoklneUcs and Pharmacodynamlcs in Clinical Trials variability in a patient population and to examine variation among relevant subgroups of the patient population which may provide insight to optimal efficacy or minimal toxicity from administered doses. Clinical tdal designs have been proposed which use PK and PD data (i.e., dose and/or drug concentration response data) advocating randomizing study subjects to steady-state drug concentrations rather than to a fixed administered dose. Implementation requires some Bayesian estimation strategies to adjust subject doses to desired levels. Evaluation of the relationship of changing dose patterns and efficacy patterns within individual subjects also provides insight into treatment strategies, dose response and variation within and among subjects responses.
Chairperson: Robert O'Neill, Food and Drug Administration Ted Grasela, SUNY Buffalo Carl Peck, Food and Drug Administration John Rodman, St. Jude's Children's Research Hospital Diecussant: Gordon Pledger, R.W. Johnson Pharmaceutical Research Institute
Workshop Vl Designs for Specialized Clinical Trial Situations
Salon E & F
Frequently, a particular clinical trial will pose problems that are not readily addressable by standard textbook approaches to trial design and analysis. Speakers in this session will discuss =nonstandard" situations calling for specialized designs. These include: 1. Designs to =match" preferred treatments .to patient subgroups based on psychological, demographic and behavioral characteristics and their application to studies of the clinical management of alcoholism; 2. Studies of acute illness in which treatment must be initiated prior to completion of a definitive eligibility workup, thereby requiring that the primaryanalysis be performed on a subset of the randomized patients; 3. Situations in which the unit of randomization must be =clusters" of patients rather than individuals; e.g., clinics, neighborhoods, or even cities.
Chairperson: Janet Wittes, New England Research Institute, Inc. Larry Muenz, Consultant, National Institute on Alcohol Abuse and Alcoholism Corsee Dating, Centocor, Inc. Allan Donner, University of Western Ontario 3:30 PM - 4:00 PM
Break
Exhibit Center
374
Final Program TUESDAY, MAY 12, 1992 (Continued) Plenary Session IV
4:00 PM - 5:30 PM
Salon C & D
Women and Clinical Trials: Politics versus Science Have women been discriminated against in clinical research? The dimensions and underlying causes of the "gender gap" have provoked considerable controversy. Recently, major attempts have been made to address this issue, including The Women's Health Initiative, a large multi-component study targeting cardio-vascular disease, cancer, and osteoporosis, and a National Institutes of Health policy aimed at ensuring representation in studies for both women and minorities. A corollary issue is the determination of when it is scientifically or medically necessary to conduct separate trials in males and females or to replicate in one gender results that have been shown in the other. The Food and Drug Administration has considered this question from a regulatory perspective. Speakers in this session will address these issues from both a scientific and a political point of view. An example will be given of a new trial designed to study the effects of aspirin on heart disease in women, based on the findings in males.
Chairperson: Blossom Patterson, National Cancer Institute William Harlan, National Institutes of Health Eileen Leonard, Food and Drug Administration Julie Buring, Harvard Medical School Discussant: Viv!an Pinn, National Institutes of Health Cocktail Banquet Invited Speaker: Bemadine Healy, M.D. Director, National Institutes of Health
6:30 PM
WEDNESDAY, MAY 13, 1992 8:00 AM - 12:00 PM
Registration
8:00 AM - 12:00 PM
Exhibit Program
8:00 AM - 10:00 AM
Contributed Paper Session III
Grand Ballroom Foyer Exhibit Center
(four [4] simultaneous sessions)
Session IliA: Patient and Physician Accrual Into Clinical Trials Chairperson: Jeffrey Probsffield
Salon A & B
8:00 AM
36
Understanding Physician Accrual of Eligible Patients to North American Symptomatic Carotid Endarterectomy Trial (NASCET); Kathryn Taylor, York University
8:20 AM
37
Are Habitual Volunteers a Problem in Clinical Trials?; Mary Morris, University of Washington
8:40 AM
38
A Low Cost Screening Survey to Assess Sample Yield and Refine Study Entry Criteria; Mae Gordon, Washington University
9:00 AM
39
On Entry Cdteria for Clinical Trials; Janet Wittes, Statistics Collaborative
375
Final Program WEDNESDAY, MAY 13, 1992 (Continued) Contributed Paper Session III (continued) (four [4] simultaneous sessions)
8:00 AM - 10:00 AM
9:20 AM
40
Screening Rules for Determining Blood Pressure Status in Clinical Trials: Application to the Trials of Hypertension Prevention; Nancy Cook, Harvard Medical School
9:40 AM
41
Multistage Screening for a Lipid-Restricted Population: The VA HDL Intervention Trial (HIT); Marika Iwane, VA Medical Center, West Haven
Session IIIB: Clinical Trials Logistics Chairperson: Jennifer Gassman
Salon E & F
8:00 AM
42
Crisis Management: A Coordinating Center's Experience with the Suspension of a AIDS Treatment Protocol for a Clinical Trial; Janet Holbrook, The Johns Hopkins University
8:20 AM
43
Recruitment of Clinical Centers in an Investigator-Initiated Multicenter Clinical Trial; Virginia Howard, Bowman Gray School of Medicine
8:40 AM
44
Form Enhances Content: Development of a Generic Protocol (GP); Nancy Paul, Queen's University
9:00 AM
45
Developing Clinical Trial Quality Management Principles; Christopher Barker, Syntex Research
9:20 AM
46
Remote Entry to Integrated Clinical Project Database: On-Line Reporting of Clinical Trial Site Visit Information by Clinical Research Associates; Barbara Nagle, Bio-Pharm Clinical Services
9:40 AM
47
Patient Charges/Costs in the Home Intravenous Antibiotic Trial; Frances Mather, Tulane University
Session IIIC: Qualify of Life Chairperson: Richard Berzon
Constitution Ballroom
8:00 AM
48
Quality of Life Before and After Knowledge of a Trial's Results; Laurie Fitch, University of Minnesota
8:20 AM
49
Assessing Patient Satisfaction in Randomized Clinical Trials: Some Design and Measurement Issues; David Moher, University of Ottawa
8:40 AM
50
Subjective Quality of Life Assessment: A New Instrument, the "SQLP"; Paul Gerin, Unit~ de Pharmacologie Clinique
9:00 AM
51
Random Time Versus Fixed Time Sampling in Clinical Trials Among Drug Addicts; Ram Jain, National Institute on Drug Abuse
9:20 AM
52
Estimating Sensitivity, Specificity and Prevalence from Clinical Trials of Multiple Screening Tests; Timothy Church, University of Minnesota
9:40 AM
53
Comparison of Two Methods of Classification of Cause of Death in a Cardiovascular Clinical Trial; George Feldman, Kaiser Permanente Research Foundation
376
Final Program WEDNESDAY, MAY 13, 1992 (Continued) Contributed Paper Session III (continued) (four [4] simultaneous sessions) Session IIID: General Issues in Data Management Chairperson: Joseph Collins
Salon C & D
8:00 AM
54
An ABC of Information Management in Primary Prevention Trials; David Duncan, University of Glasgow
8:20 AM
55
Planning for Computer Migration During the Course of a Clinical Trial; Frances LoPresti, Maryland Medical Research Institute
8:40 AM
56
Computer-Assisted Eligibility Review and Randomization; M. Marvin Newhouse, The Johns Hopkins University
9:00 AM
57
The Importance of Quality and Accuracy in the Conduct of Clinical Trials: EORTC Quality Assurance Measures; Kris Vantongelen, University Hospital St. Rafael
9:20 AM
58
R.E.A.C.T.--A Hand-Held Computer System to Facilitate Clinical Trials; Martin Schneider, Westchester Distribution Systems, Inc.
9:40 AM
59
Development of a Computerized 24 Hour-a-day Randomization Service; Julie Weston, University of Toronto
10:00 AM - 10:30 AM
Break
10:30 AM - 12:00 PM
Plenary Session V Disseminating the Results of Clinical Trials
Exhibit Center Salon C & D
Increasing attention has been directed at the issue of how information concerning the closure of an ongoing trial should be communicated to involved and interested parties, including investigators, treating physicians, patients both in and outside the trial setting, journal editors, and the press. NIH held a conference on this topic in January 1990 which examined several examples of such terminated studies and indicated that substantial differences existed within NIH in how such circumstances were approached and responded to. With this conference as a background, we intend to highlight the most significant current areas of debate: who should decide when information should be disseminated outside of the traditional avenues, when should such information be disseminated, to whom should it be communicated, who should assume responsibility for such communication, and what level of detail should be made available. We will provide comment from representatives of the NIH, investigators, treating physicians, and the press. Chairperson: Maureen Myers, Boehringer-lngelheim Michael Friedman, National Cancer Institute Gina Kolata, New York Times David Miller, Community Physician Gerald Medoff, Washington University Curtis Meinert, Johns Hopkins University Michael Walker, Laboratory of Immunoregulation, NIAID 12:00 PM
Adjournment
PROGRAM SUNDAY, MAY 10, 1992
7:30 AM - 2:00 PM
Registration for Pre-Conference Workshops
9:00 AM - 5:00 PM
Pre-Conference Workshops Pre-Conference I Design and Analysis of Longitudinal Clinical Trials
Grand Ballroom Foyer
Constitutional
Ballroom
Longitudinal designs are now widely used in clinical research to assess the effects of treatment on changes in physiologic or clinical measures of health status over time. This workshop will describe modern methods for the design and analysis of longitudinal clinical trials, with an emphasis on the issues that arise in randomized clinical trials with longitudinal designs. The workshop will discuss: • • • • •
design of longitudinal clinical trials choice of outcome measure modeling the mean and covariance structure sample size calculations data analysis, including models for handling attrition and missing data
Software for the analysis of longitudinal data, including REML program for growth curve analysis, the GEE program developed by Liang and Zeger, and BMD P5V, will be discussed. These presentations will make extensive use of examples from recent clinical trials research.
Speakers: Nan M, Laird James H. Ware
356 0197-2456/92/$5.00
Controlled Clinical Trials 13:356-376 0992) © Elsevier Science Publishing Co., Inc. 1992 655 Avenue of the Americas, New York, New York 10010
357
Final Program SUNDAY, MAY 10, 1992 (Continued) Pra-Conforence II Ancillary Studies In Clinical Trials: A Workshop for Clinical Trial Coordinstora
Salon A & B
This workshop will address issues related to the development of ancillary studies in clinical trials which would be of importance to nursing science. The objectives of the workshop include: (1) the identification of questions of relevance to nursing science which could be addressed in ancillary studies; (2) identification of the concerns of clinical trial investigators in the consideration of ancillary studies; (3) review of the approval process; (4) identification of funding opportunities; and (5) design issues in the development of ancillary studies. The format will include a combination of lecture and discussion. Clinical trial coordinators attending need have no previous experience with ancillary studies.
Speakers: Jacqueline Dunbar-Jacob Susan Thomas Pra-Conference III
Salon E & F
Survival Analysls-A Non-Technical Workshop on Statistical Aspects In the Planning end Analysis of Survival Studies The treatment or prevention of chronic diseases often involves evaluation of a "time-to-event" end point. The analysis of such end points, call generically "survival analysis," requries specialized statistical methods. This workshop will provide a nontechnical review of key aspects of the design, monitoring and analysis of clinical trials with time-to-event end points. Topics to be covered include end point selection, estimation of survival distributions, planning sample sizes, statistical significance tests of treatment effects, regression analysis for survival data, sequential monitoring of survival trials, competing risks and evaluating surrogate end points. Ample time will be provided for discussion and questions. The presentations will be non-technical and will emphasize case studies. Speakers: Frank E. Harrell, Jr. G. Gordon Lan Richard Simon 12:00 PM - 5:00 PM
Board of Directors Meeting
President's Ballroom
4:00 PM - 8:00 PM
Registration
Grand Ballroom Foyer
7:00 PM - 10:00 PM
Evening Social Reception
Salon A, B, & C
MONDAY, MAY 11, 1992
7:30 AM - 5:00 PM
Registration
Grand Ballroom Foyer
358
Final Program MONDAY, MAY 11, 1992 (Continued)
8:30
AM
-
Exhibit Program
5:00 PM
8:30 AM - 8:45 AM
Welcome Genell L. Knatterud, President Society for Clinical Trials
8:45 AM - 10:15 AM
Plenary Session I Sharing Clinical Trials Data
Exhibit Center Grand C & D
Clinical trials typically generate substantial quantities of high quality data on the clinical course of a disease. Considering the high costs of performing a clinical trial, it is appropriate to maximize the usefulness of the effort through widely sharing the resulting database. These data may constitute unique research resources which would be invaluable to other scientists exploring related questions. In addition, the sharing of these data may lead to improvement of such methodologic techniques as study design, outcome measurement and analytic approach, and help identify reliable surrogate endpoints and prognostic indicators. Traditionally, investigators tend to be very possessive of the data collected in their studies, and often rightly so. Premature release of study data may al!ow others to "scoop" the main study results or perform a number of ancillary analyses before the original investigators have their opportunity to fully explore their data. Speakers in this session will discuss the benefits of and concerns about sharing data from ongoing and completed clinical trials. Issues such as NIH policy regarding sharing research data, possible conditions placed on data release, the timing and extent of data release, the work involved in study data documentation, and possible mechanisms for data dissemination, will be addressed. Chairperson: Peter Gilbert, National Institutes of Health Stephen Fienberg, York University Toronto Genell Knatterud, Maryland Medical Research institute George Williams, Merck, Sharp & Dohme Research Laboratories David Amato, Harvard School of Public Health 10:15 AM - 10:45 AM
Break
Exhibit Center
10:30 AM - 4:00 PM
Poster S e u l o n I (Poster Prlmatlme 10:30- 11:30 AM)
Exhibit Center
P01
Strategies for Educating and Training Clinicians to Conduct Community-Based Research: A Report from the Community Programs for Clinical Research on AIDS; Geraldine Maiatico, National Institutes of Health
P02
The Use of Computer-Assisted Instruction (CAI) for Protocol Training; Sharon Rolnick, University of Minnesota
P03
Features of Manuals of Procedures for Multicenter Randomized Clinical Trials; Claudia Moy, The Johns Hopkins University
359
Final Program MONDAY, MAY 11, 1992 (Continued) 10:30 AM - 4:00 PM
Poster Session I (continued) (Poster PrlmeUme - 10:30 - 11:30 AM)
Exhibit Center
P04
Performance Evaluation of Centers Participating in a Multicenter Clinical Trials Group: A Model Developed for the Community Programs for Clinical Research on AIDS (CPCRA); Michael Hedderman, National Institutes of Allergy and Infectious Diseases
P05
Performance Evaluation in Multicenter Clinical Trials: Development of a Model by the AIDS Clinical Trials Group (ACTG); Linda Rosendorf, National Institutes of Allergy and Infectious Diseases
P06
Monitoring Investigator Compliance; Tamara Odom-Maryon, City of Hope National Medical Center
P07
CAST Coordinator Survey; Joyce Kellen, University of Calgary
P08
Determinants of Clinical Center Staff Size: Ophthalmologists and Ophthalmic Photographers Certified in a Large Multi-Center Trial; Lee McCaffrey, The Johns Hopkins University
P09
Facilitating Investigator Recruitment; Laurie Halloran, PAREXEL International Corporation
P10
Fiscal Administration of Clinics by Coordinating Centers: A Survey of Multi-Center Eye Trials; Charlotte Gerczak, The Johns Hopkins University
P11
Collaboration Between Universities and the Pharmaceutical Industry - A European Perspective; lan Ford, Glasgow University
P12
The Development of a National Perinatal Clinical Trials Network in Canada: The First Step; Mary Hannah, University of Toronto
P13
Evaluation of the Impact of Legal Regulations on the Quality of Trials in Spain; Femando Garcia-Lopez, The Johns Hopkins University
P14
Chiropractic and Pharmaceutical Treatment for Muscle Tension Headaches: A Randomized Clinical Trial; Patrick Boline, Northwestern College of Chiropractic
P15
Simplifying Large Trials: An Example from the Community Programs for Clinical Research on AIDS; John Matts, University of Minnesota
P16
Organization, Goals, and Logistical Challenges of the Community Programs for Clinical Research on AIDS; Marcia Carlyn, National Institutes of Health
P17
Are Science and Seeding Trials" Compatible?; Jean-Pierre Boissel, Unit(~ de Pharmacologie Clinique
360
Final Program MONDAY, MAY 11, 1992 (Continued)
10:30 AM - 4:00 PM
Poster Session I (continued) (Poster Prlmetlme - 10:30 - 11:30 AM)
Exhibit Center
P18
Cooperative Clinical Trials in Health Services Research in the Department of Veterans Affairs; William Henderson, VA Hospital
P19
Blocked Randomized Assignment of Treatments to Patients in Clinical Trials Using SAS (Statistical Analysis System); Maria Deloria, National Institutes of Health
P20
The Analysis of a Single-Patient Efficacy Trial of an Investigational Antiepileptic Drug; J. Todd Sahlroot; National Institutes of Health
P21
Methodological and Ethical Issues in a Series of Exploratory Multiple Crossover Double-Blind Studies in Individual Patients with Dementia to Assess the Efficacy and Safety of CGS 5649B; Tim Standish, McMaster University
P22
Low Dose Oral Anticoagulation and Cardiac Valvular Replacement: Application of the Eligibility Oriented Randomization Scheme; Nadine Bossard, Unit6 de Pharmacologie Clinique
P23
An Application of an Extended Greco-Latin Square Design to Study Gender and Race Bias; Sue Marcus, University of Pennsylvania
P24
A Controlled Clinical Trial in Ophthalmology: Formal Randomization May Not be Ethical; Margaret Ballantyne, Queen's University
P25
Conducting Clinical Trials with Database Controls; James Murphy, University of Colorado Medical School
P26
Social Security Number - - An Appropriate Algorithm for Randomization in a Community Hospital Setting?; Dawn Blackhurst, The Greenville Hospital System
P27
Assessing Quality of Life in Clinical Trials; Robert Hoop, Marion Merrell Dow Inc.
P28
Simplified Assessment of Lab Parameters in Clinical Trials - Basic Considerations; Maria Grazia Pochobradsky, Helsinn SA
P29
A Sample Size Formula for Case-Control Studies with an Independent Variable that is Continuous; Bruce Thompson, Maryland Medical Research Institute
P30
Statistical Considerations in Monitoring the Systolic Hypertension in the Elderly Program; Barry Davis, The University of Texas School of Public Health
P31
Sample Size Determination Using an Interim Analysis; David Bristol, Schering-Plough Corporation
P32
Bayesian Decision-Theoretic Clinical Trials: Monte Carlo Comparison with Classical Group Sequential Methods; Roger Lewis, Harbor-UCLA Medical Center
361
Final Program MONDAY, MAY 11, 1992 (Continued)
10:30 AM - 4:00 PM
Poeter Session I (continued) (Poster Prlmetime - 10:30 - 11:30 AM)
Exhibit Center
P33
Computer Models for Editing Study Data; Susan Karabelas, Maryland Medical Research Institute
P34
The Development of Data Collection Tools to Assist in Protocol Management; Collette Houston, Memorial Sloan-Kettering Cancer Center
P35
Parent: A Strategy for Automation of Data Management Tasks in Clinical Trials and Registries; Jeffrey Martin, University of Pittsburgh
P36
Computer-Assisted Clinic Monitoring: The COMS Experience; Kelly Manos, The Johns Hopkins University
P37
Data Entry Manual for a Clinical Trial; Scott Corely, University of Washington
P38
An Inventoried Editing System: Efficient Maintenance of High Standards in Data Quality; Sharon Lawlor, University of Pittsburgh
P39
NHLBI Growth and Health Study Remote Clinical Data Systems: 5 Years Later; Ellis Clarke, Maryland Medical Research Institute
P40
Use of a Relational Database to Track Correspondence Regarding Requested Corrections to Case Data Records; Patrick McGrath, University of Missouri
P41
Databases - A Relational Design: The Pros and Cons; Paul Wainwright, University of Birmingham
P42
Selecting A RDBMS for a Multi-Disciplinary Clinical Research Database; Danny Wu, Memorial Sloan-Kettering Cancer Center
P43
Confidence Intervals for the Difference of Two Survival Probabilities: A Comparative Study; Young Jack Lee, National Institutes of Health
P44
Graphical Methods for Visualizing the Timing of Follow-up in Clinical Studies; Martin Lesser, North Shore University Hospital Cornell
P45
Graphical Display of Kaplan-Meier Plots; Mark Van Natta, The Johns Hopkins University
P46
Cox Regression Analyses Using SAS/PHREG; Michele Donithan, The Johns Hopkins University
P47
Selection of Covadates in the Cox Model: Simulations; Franca Barton, Maryland Medical Research Institute
362
Final Program MONDAY, MAY 11, 1992 (Continued) 10:30 AM - 4:00 PM
Poster Session I (continued) (Poster Prlmetlme - 10:30 - 11:30 AM)
10:45 AM - 11:30 AM
Poster Discussion Topic: Meta-Analysis Discussant: Curt Furberg
Exhibit Center
P48
Randomized Clinical Trials on Medical Treatment of Glaucoma: Are they Appropriate to Guide Clinical Practice?; Luca Rossetti, Instituto di Ricerche Farmacologiche "Mario Negri"
P49
Publication of Randomized Clinical Trials in Vision Research Submitted as Abstracts to the National Ophthalmology Meetings; Roberta Scherer, University of Maryland
P50
A Comparison of Statistical Methods of Pooling Randomized Control Trials (RCTs): An Assessment of 45+ Meta-Analyses (M-As); Joseph Lau, VA Medical Center, Boston
P51
Advantages and Limitations of Meta-Analytic Regressions of Clinical Trials Data; Jesse Berlin, University of Pennsylvania
P52
Meta-Analysis or Quantitative Overview - Is There any Difference?; Lesley Stewart, MRC Cancer Trials Office
P53
Meta-Analysis of Randomized Controlled Trials of the Benefits of Screening Women Ages 40-49; Kenneth Chu, National Cancer institute
Contributed Paper Session I (four [4] simultaneous sessions)
11:00 AM - 12:00 PM
Session IA: Statistical Methods for Special Designs in Clinical Trials Salon A & B Chairperson: Dennis Dixon 11:00 AM
01
Bayesian Guidelines for Phase II Clinical Trial Design and Analysis; Peter Thall, M.D. Anderson Cancer Center
11:20 AM
02
A Likelihood-Based Graphical Method for Meta-Analysis; Steven Goodman, The Johns Hopkins University
11:40 AM
03
An Illustrative Statistical Analysis of Cutoff-Based Randomized Clinical Trials; Joseph Cappelleri, Harvard School of Public Health
Session IB: Analysis of Surrogate End Points Chairperson: Lawrence Hauptman
Salon E & F
11:00 AM
04
Predictive Value of Repeated Measurements of CD4 Lymphocyte Counts on Progression to AIDS; Florent Boutitie, London School of Hygiene and Tropical Medicine
11:20 AM
05
Design Issues for Studies Based on UItrasonographic Measurement of the Carotid Artery IntimaI-Medial Thickness; Mark Espeland, Bowman Gray School of Medicine
11:40 AM
06
Evaluation of Coronary Arteriography Changes as a Surrogate Endpoint for Atherosclerotic Cardiac Events; John Matts, University of Minnesota
363
Final Program MONDAY, MAY 11, 1992 (Continued) Contributed Paper Session I (continued) (four [4] simultaneous sessions) Session IC: Early Stopping Chairperson: William Blackwelder
Constitution Ballroom
11:00 AM
07
Estimation in Clinical Trials that Stop Early; Maria Mori Brooks, University of Washington
11:20 AM
08
One-Sided Test for Clinical Trials with Group Sequential Design that Allow Early Acceptance of Negative Result; Benny Zee, Queen's University
11:40 AM
09
When Should Randomization to Untreated Control Groups Stop?; Thomas Chalmers, Harvard School of Public Health
Session ID: Student Scholarship Chairperson: Theodore Karrison
Salon C & D
11:00 AM
10
Cost Utility Analysis of Maintenance Treatment for Recurrent Depression; Nancy Paul, Carnegie Mellon University
11:20 AM
11
The Analysis of Incomplete Data in the Three-Period TwoTreatment Crossover Design for Clinical Trials; Barbra Richardson, UCLA
11:40 AM
12
Prognostic Indices: Who Needs Them?; Janet Dunn, University of Birmingham Exhibit Center
12:00 PM - 1:30 PM
Lunch
1:30 PM - 3:00 PM
Workshop I ConatltuUon Ballroom Data Management Symposium Approaches for managing data collected in clinical trials have changed rapidly over the past decade as computer technology has advanced. For those involved in data coordinating centers for clinical trials there is little published to help in planning or managing data centers. Two companion workshops will address current methods and technologies employed by a variety of coordinating centers in various settings.
Organization and function of a clinical trials coordinating center Herman Mitchell, New England Research Institute; Brent Blumenstein, Bonnie Hermanson, Kenneth James. This paper will lead off the discussion by providing an overview of the structure(s) of data coordinating centers and a description of their functions. Guidelines for planning a data coordinating center for various types of studies will b discussed.
Approaches to data management Eleanor McFadden, Eastern Cooperative Ontology Group; Anna Bagniewska, Fran LoPresti In this presentation, the options for data base management designs will be discussed with the relative merits of various models and systems. Requirements for adequate software and hardware will be discussed and techniques for specific data management requirements such as encoding of adverse reactions and diseases will be described.
364
Final Program 1:30 PM - 3:00 PM
Workshop I (continued) Data Management Symposium
Constitution Ballroom
Support for the development of these workshops and the ensuing manuscripts is being provided by the Johns Hopkins Center for Clinical Trials.
Chairpersons: Ruth McBride, University of Washington Steve Singer, Dedicated Response
Workshop II Adjusting the Treatment Comparison for Covarlate Imbalance
Salon C & D
In randomized clinical trials, we usually collect a large amount of information at baseline about the patients. These data can comprise patient characteristics, clinical observations, and biochemical, radiographic or pathologic test results. Some of the variables mays36have been found previously to relate to prognosis but the evidence for the prognostic importance of each variable may vary from definite to possible to weak to non-existent. Although on average, randomization will balance treatment groups with respect to these variables, any individual trial will have a degree of imbalance, and in some the imbalance may be substantial. Various statistical strategies have been proposed for dealing with covariate imbalances in the analysis and these range from reliance on the unconditional randomization distribution (no adjustment) to inclusion of all "apparently" important covariates in a statistical model. Speakers will present their own approaches to this problem, followed by criticism and discussion lead by formal discussants.
Chairperson: Laurence Freedman, National Cancer Institute Lincoln Moses, Stanford University John Tukey, Princeton University
Discussant: Paul Meier, University of Chicago Workshop III Adverse Experiences with Investlgatlonal Drugs
Salon E & F
Clinical trials of investigational drugs are primarily aimed at assessing whether the drug under study, compared with either a placebo or the current standard treatment, is efficacious in the treatment of a specific disorder. Equally important, however, is determination of the test drug's safety profile which would, at the end of the trial, allow one to conclude whether the test drug does more good than harm. These safety data are most commonly labelled as adverse experiences or events, side-effects, or adverse reactions. However, in most clinical trials the tendency to place our emphasis on operational issues relating to the "collection" and "processing" of this information without due attention to some of the conceptual issues relating to the reporting of adverse experience. These issues, if considered appropriately at the start of a trial, could indirectly affect the resolution of potential problems during the collection and processing stages. This workshop will address a number of conceptual issues including:
365
Final Program MONDAY, MAY 11, 1992 (Continued)
1:30 PM - 3:00 PM
Workshop III (continued) Adverse Experiences with InvseUgstlonal Drugs
Salon E & F
• should we, and if yes, how do we, distinguish between any newly reported signs/symptoms and adverse experiences • appropriateness of causal assessment • what constitutes an ~episode" in the context of adverse experiences and does this differ from a "report" • which study efficacy outcome events should be reported as adverse experiences • the need to meet the requirements of different regulatory authorities in an international collaborative trial • how regulatory authorities and safety monitoring committees interact with respect to serious adverse experiences during the course of a trial • the delegation of responsibility for monitoring safety to an external safety committee Chairperson: Robin Roberts, McMaster University Bruce Davidson, Wyeth-Ayerst Research Andreas Laupacis, University of Ottawa Robert Temple, Food and Drug Administration 3:00 PM - 3:30 PM
Break
3:30 PM - 5:00 PM
Plenary Saselon II
Exhibit Center Salon C & D
Cost Conslderstlons In Clinical Trials Randomized clinical trials are expensive to design and to carry out. Costs are associated with the individual participants in the trials, the investigators, the clinical centers, the various staffs, the central laboratories, and the data coordinating center. The literature on clinical trials includes a number of papers on the ultimate economic benefit of a trial to the population at large. Little has been written, however, on methods for designing trials with a view toward minimizing costs. The aim of this session is to open a discussion on methods for formal incorporation of economic considerations into the design of randomized clinical trials. The session will deal with two specific aspects of using cost considerations to help design clinical trials. First, in the context of community-based randomized trials in AIDS, the session will discuss various approaches to structuring the trials with the view toward efficient designs. The methods have potential applicability to diseases other than AIDS. The second topic will be a proposal to use formal cost functions to aid in the design of trials. By analogy with methods in common use in the design of sample surveys, a cost function can be constructed that will allow a design to minimize cost for fixed precision or to maximize precision for fixed cost. Examples of the use of such a function will be presented. Chairperson: Peter Peduzzi, VA Cooperative Study Program Group James Neaton, University of Minnesota Sonja McKinlay, New England Research Institute Inc. Joel Verter, Henry Ford Hospital
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Final Program MONDAY, MAY 11, 1992 (Continued) 5:15 PM
Business Mectlng
Salon C & D
TUESDAY, MAY 12, 1992
7:30 AM - 5:00 PM
Registration
8:00 AM - 5:00 PM
Exhibit Program
8:30 AM - 10:00 AM
Plenary Session III
Grand Ballroom Exhibit Center Salon C & D
The Role of the Government, Industry, and Academia In the Conduct of Large-Scale Clinical Trials There are two major sources for funding large-scale clinical trials: government agencies and the pharmaceutical industry. Those who fund clinical trials accomplish the collection and analysis of the data derived from the trials by one of three methods: in-house; through contractual relationships with free-standing academic coordinating centers; or in collaborative partnership among government, the pharmaceutical industry and academic coordinating centers. As the costs and complexities of clinical trials increase, the pressure for collaboration is increasing. However, the interests of each group may differ at each stage of conducting a trial: in the initial planning of the trial (including framing the hypotheses to be tested), in selecting the rules by which the data are collected and analyzed in the oversight of the trial as it progresses, and in the final assembly and reporting of the data, both to the FDA and to the general public. The speakers in this session will present their individual viewpoints, representing federal funding sources, the pharmaceutical companies' perspective, and the position of the academic coordinating center. The speakers will describe their past experience with shared clinical trials, giving insight into past performance and future promise of the collaboration. Chalrperaon: Daniel Deykin, Veterans Administration Cooperative Studies Program Edward Scolnick, Merck, Sharp & Dohme Laboratories Michael Gent, Hamilton Civic Hospital Research Centre 10:00 AM - 10:30 AM
Break
Exhibit Center
10:00 AM - 4:00 PM
Poster Session II (Poster Primstime 10:15 - 11:30 AM)
Exhibit Center
P54
Clinical Trial Enrollers Versus Nonenrollers: Recruitment and Enrollment Assessment in Clinical Trials (REACT) Project; Larry Gorkin, Institute for Behavioral Medicine
367
Final Program TUESDAY, MAY 12, 1992 (Continued) 10:00 AM - 4:00 PM
Poster S e s s i o n II ( c o n t i n u e d ) ( P o s t e r P r l m e t l m e - 10:15 - 11:30 A M )
Exhibit C e n t e r
P55
The Use of Focus Groups in the Design of Cholesterol Education Intervention Programs; Rebecca Masters, The Johns Hopkins University School of Medicine
P56
Non-Ulcer Dyspepsia and the Randomized Multiple Cross-Over Model; Kornelia HOschen, SmithKline Beecham Pharma Munich
P57
Problems in Assessing Left Ventricular Function in Clinical Trials; Sylvie Ahn, University of Louvain
P58
Termination Issues in Long-Term Clinical Trial Research; Judith Jensen, St. Louis University Medical Center
P59
Long Term Adherence in Patients Who Fail the Initial Prerandomization Adherence Screen. The Studies of Left Ventricular Dysfunction Experience; Milena Henzlova, University of Alabama
P60
Predicting Noncompliance Among HIV Positive Asymptomatic Individuals in a Randomized Controlled Clinical Trial; Richard Berzon, Burroughs Wellcome Company
P61
Methodological Issues in Screening for Relapse in Early Breast Cancer; Roldano Fossati, Istituto di Ricerche Farmacologiche =Mario Negri"
P62
Population Screening for Randomization into Large Scale Cholesterol Reduction Clinical Trials; John Norrie, University of Glasgow
P63
Developing a Prognostic Index for Stomach Cancer; Janet Dunn, University of Birmingham
P64
Regression to the Mean in Clinical Trials with Entry Based on Counting Events; Robert McMahon, Maryland Medical Research Institute
P65
The Paradox of Rapid Accrual; Michael Palmer, National Cancer Institute of Canada
P66
A Predictive Model of Inclusion Rates in a Very Large Scale Clinical Trial with General Practitioners; Yves Alamercery, Societe R.C.T.s
P67
A Deming Approach to Recruiting: The National Institute of Neurological Disorders and Stroke (NINDS) t-PA Stroke Trial Experience; Barbara Tilley, Henry Ford Health Sciences Center
P68
Recruitment Experience in the Home Intravenous Antibiotic Trial; Frances Mather, Tulane University
P69
Lessons for Coordinating Center Management from a Centralized, Computer-Assisted Randomization System; Townes Coates, The Johns Hopkins University
P70
A Software for Registration and Stratified Randomization in MulUcenter Clinical Trials: The Experience of the European Lung Cancer Working Party; Marianne Paesmans, Institut Jules Bordet
368
Final Program TUESDAY, MAY 12, 1992 (Continued)
10:00 AM - 4:00 PM
Poster Session II (continued) (Poster Prlmetlme - 10:15 - 11:30 AM)
Exhibit Center
P71
Quality Assurance & Multicenter Clinical Trials; Beverly Koski, Queen's University
P72
Standardization Description of Dose-Ranging Trial Protocols; Jean-Pierre Boissel, Unit~ de Pharmacologie Clinique
P73
Continuing Review of Trials by Local Ethics Boards: A Reminder System for Keeping Participating Centres on Track; Nancy Paul, Queen's University
P74
Impact of a Randomized Trial on Transfusion Practice in Orthopedic Surgery; Lenore Dickson, McMaster University
P75
Health Care Directives in the Elderly and Health Care Utilization; Bonnie Rush, McMaster University & Geriatric Research Group
P76
Are there Gender-Related Differences Among Attitudes of Patients in Heart Failure Trials?; Glenda Blackburn, University of Alabama Medical Center
P77
Retrospective Psychometric Reports are Poor Estimates of Treatment Success; Jocelyne Feine, Universite de Montreal
P78
Variation in Resource Center Workload and Productivity Over a 13-Year Period; Barbara Hawkins, The Johns Hopkins University
P79
Registry of Resource Centers for Multicenter Clinical Studies; Nancy Fink, The Johns Hopkins University
P80
A Comparison of Three Database Packages, SIR, Paradox and DBaselV with Respect to Their Ability to Perform Data Management Tasks; Julie Weston, University of Toronto
P81
Difficulties in the Data Management of Recurrent and Transient Events in Prospective Randomized Clinical Trials: Example from a Randomized Trial Comparing Two Different Brachytherapy Dose Rates in Gynaecological Cancer; Jeannine Bouzy, Institute Gustave Roussy
P82
Common Toxicity Criteria: The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) Experience; Nancy Wainman, National Cancer Institute of Canada
P83
The Measurement of Visual Analogue Scale Data Is Not a Burden; Michael Palmer, Queen's University
P84
Development of a Composite Index for Noncompliance Patients in Clinical Trials; Marisa De Rosa, CINECA - Inter University Computing Center
P85
A Coding System for Medication Use Based on the American Hospital Formulary Service; June Pierce, Bowman Gray School of Medicine
369
Final Program TUESDAY, MAY 12, 1992 (Continued) Poster Session II (continued) (Poster Prlmstime - 10:15 - 11:30 AM)
10:00 AM - 4:00 PM
Exhibit Center
P86
Online With WHO: Electronic Medication Coding; Kathleen Gallinger, PAREXEL International Corporation
P87
Comparison Between Two Drug Titration Systems Developed for the POST CABG Studies Clinical Trial; Evelyn Mirenzi, Maryland Medical Research Institute
P88
Subject File Checklists to Facilitate Clinical Trial Close-Out Activities; Rita Pelusio, University of Rochester
P89
Techniques for Editing Longitudinal Growth Data; Bruce Barton, Maryland Medical Research Institute
P90
Pursuing High Quality Data Through Structured Form Design; Nancy Remaley, University of Pittsburgh
P91
Computer Generated Drug Distribution and Accountability for a Clinical Trial; Patrick McGrath, University of Missouri
P92
Using SAS to Monitor Tdal Supplies - Experience Gained in a Multicenter Trial; Caroline Gould, Bard Limited
P93
Simulation Study Comparing Cumulative Mean Change with Slope Estimate Summaries: Application to a Comparative Trial of Venlafaxine, Imipramine and Placebo; A. Richard Entsuah; WyethAyerst Research
P94
Analysis of Risk Factors for Conditions Defined by Extremes of a Distribution; Bruce Barton, Maryland Medical Research Institute
P95
Conventions for Handling Missing Data; Linda Ward, University of Birmingham
P96
Rank Statistics for Analysis of a Clinical Trial with Multiple Events Per Patient: The Multicentar Study of Hydroxyurea in Sickle Cell Anemia (MSH); Robert McMahon, Maryland Medical Research Institute
P97
Problems in Drawing Conclusions in Barrier Contraceptive Clinical Tdals with Compliance Problems; Inder Sharma, Family Health Intamational
P98
Comparing Trials for the Treatment of Myelomatosis; Janet Dunn, University of Birmingham
P99
Documentation and Analysis of Adverse Event Data in Clinical Tdals: The German Chronic Myeloid Leukemia Study Experience; Joerg Hasford, Biometric Center for Therapeutic Studies
370
Final Program TUESDAY, MAY 12, 1992 (Continued)
10:30 AM - 12:30 PM
Contributed Paper Session II (four [4] simultaneous sessions)
session IIA: Logistic Regression and Survival Analysis Chairperson: Mohan Beltangady
Salon A & B
10:30 AM
13
Clinical Use of Logistic Regression Models to Predict Treatment Efficacy in the Presence of Treatment-Covariate Interaction; Thomas Moritz, VA Medical Center, Hines
10:50 AM
14
Patient Compliance as an Explanatory Variable in the Aspirin Myocardial Infarction Study; David Zurakowski, University of Chicago
11:10 AM
15
Modelling the Time-Varying Course of Compliance in a Clinical Trial; Robert Glynn, Harvard Medical School
11:30 AM
16
Nonparametric Survival Regression Trees and Application to Three Radiation Therapy Oncology Group (RTOG) Malignant Glioma Trials; Charles Scott, Radiation Therapy Oncology Group
11:50 AM
17
Observational Analyses with Time Dependency and Missing Values in the Thrombolysis in Myocardial Infarction (TIMI) II Clinical Trial; Michael Terrin, Maryland Medical Research Institute
12:10 PM
18
Parametric Approaches to Quality Adjusted Survival Analysis; Bernard Cole, Dana-Farber Cancer Institute seselon liB: Data Management Issues In Drug Toxicity and Drug Dispensation Chairperson: Michael Hamrell
Salon E & F
10:30 AM
19
Lessons Learned and Pitfalls to be Avoided in the Design of Study Drug Titration Systems; Norma Lynn Fox, Maryland Medical Research Institute
10:50 AM
20
Adverse Medical Events in Clinical Trials: Reporting and Evaluation; Philip Day, VA Medical Center, Albuquerque
11:10 AM
21
Bar-Coding in Validating Investigational Drug Packaging; Mark Jones, VA Medical Center, Albuquerque
11:30 AM
22
Toxicity Grading Systems; Hilary Franklin, The Netherlands Cancer Institute
11:50 AM
23
ARGO: An On-Line Prescription Monitoring System; Marisa DeRosa, CINECA Session IIC: Phase I - II Designs Chairperson: Judith Feinberg
10:30 AM
24
Salon C & D
Design and Implementation of the NHLBI and the VA Cooperative Studies Program Collaborative Study, "Trial to Evaluate the Effect of Digitalis on Mortality in Heart Failure"; William Williford, VA Medical Center, Perry Point
371
Final Program TUESDAY, MAY 12, 1992 (Continued) Contributed Paper Session II (continued) (four [4] simultaneous sessions)
10:30 AM - 12:30 PM
10:50 AM
25
Design of the Veterans Administration Cooperative Study of Active Immunotherapy of HIV Infection; Peter Peduzzi, VA Medical Center, West Haven
11:10 AM
26
Mean Daytime Diastolic Blood Pressure as an Entry Criterion in a Parallel Factorial Design Study to Assess the Antihypertensive Efficacy of Nebivolol (NEB) Alone or in Combination with Hydrochlorothiazide; Jean Lefebvre, Centre Hospitalier de I'Universite Laval
11:30 AM
27
A Phase II Elimination Procedure of Treatments for a Serious Illness; Christopher Palmer, University of Cambridge
11:50 AM
28
Preliminary Safety and Activity Evaluation of New Agents for the Treatment of HIV-1 Infection: Recommended Guidelines for Trial Design; Daniel Stein, National Institute of Allergy and Infectious Diseases
12:10 PM
29
Randomized, Three-Step Trial Design for Phase 1 Study of Chemopreventive Agents; Paul Carbone, Wisconsin Comprehensive Cancer Center
Session liD: Classification for Design Analysis Chairperson: Joseph Pater
Constitution Ballroom
10:30 AM
30
Assessing Disease-Specific Causes of Death in a Trial of AllCause Mortality; Jan Markowitz, The Johns Hopkins University
10:50 AM
31
A Questionnaire to Measure Morbidity in Patients Receiving Radiation Therapy for Head and Neck Cancer; Peter Skingley, McMaster University
11:10 AM
32
Improving the Classification of Stage: A Potential Problem for Comparative Studies; Linda Ward, Cancer Research Campaign Trials Unit
11:30 AM
33
Classification of Protocol Deviations in a Complex Study; Claudia Moy, The Johns Hopkins University
11:50 AM
34
Eligible-Non-Randomized Patients: Their Impact on Generalizability; Deborah Marcellus, McMaster University
12:10 PM
35
Effect of Selective Decontamination of the Digestive Tract (SDD) Upon Mortality; Luca Brazzi, Instituto di Ricerche Farmacologiche 'Mario Negri"
12:30 PM - 2:00 PM
Lunch
Exhibit Center
372
Final Program TUESDAY, MAY 12, 1992 (Continued) 2:00 PM - 3:30 PM
Three Simultaneous Workshops Workshop IV Constitution Ballroom Data Management Symposium (Continued) The second of two companion workshops on data management will focus on current methodologies in data collection, quality assurance, reporting and archiving.
Data collection and transcription Jim Hosking, University of North Carolina; Lance Bailey, Barbara Hawkins, Marvin Newhouse Data collection, the measurement and recording of data, is perhaps the most crucial stage in the overall data management process. This paper will describe current methodologies in forms design, data entry, data coding and transfer of data. Data quality assurance and monitoring Jennifer Gassman, Cleveland Clinic; Duke Owen This presentation will examine quality control strategies for the study database. It will discuss decisions related to which items to check, where to check them, how to handle discrepant data and reporting data quality.
Study reporting, archlvlng and cloeeout Ruth McBride, University of Washington; Steve Singer, John Matts What should be included in monitoring and other reports requires careful consideration as does the format of presentation. The first part of this talk will discuss design and production of various types of reports from clinical trials. At the termination of a clinical trial, the focus of the coordinating center shifts to issues related to close-out. This period will be the final opportunity to make sure that data are as complete and accurate as possible. During this period the database and other materials will need to be finally archived. The second part of this presentation will discuss issues and methodologies related to close-out and archiving. 2:00 PM - 3:30 PM
Workshop V Issues In PhsrmacoklneUcs and Phsrmacodynamlca In Clinical Trials
Salon C & D
Pharmacokinetics (PK) refers to the time-course of drugs and their metabolites in various tissues of the body. Pharmacodynamics (PD) refers to the relationship between drug levels and the pharmacologic effects of drugs. The planning, design, analysis and interpretation of clinical trials implicitly rely on PK and PD concepts and the purpose of this workshop is to describe a variety of PK/PD concepts, including population methods, and some applications and experiences in clinical trial settings. Drug level monitoring during routine clinical visits in the course of Phase II and Phase III clinical trials provides a means to document pharmacokinetic.
373
Final Program TUESDAY, MAY 12, 1992 (Continued) 2:00 PM - 3:30 PM
Three Simultaneous Workshops (continued) Workshop V (continued) Salon C & D Issues in PharmacoklneUcs and Pharmacodynamlcs in Clinical Trials variability in a patient population and to examine variation among relevant subgroups of the patient population which may provide insight to optimal efficacy or minimal toxicity from administered doses. Clinical tdal designs have been proposed which use PK and PD data (i.e., dose and/or drug concentration response data) advocating randomizing study subjects to steady-state drug concentrations rather than to a fixed administered dose. Implementation requires some Bayesian estimation strategies to adjust subject doses to desired levels. Evaluation of the relationship of changing dose patterns and efficacy patterns within individual subjects also provides insight into treatment strategies, dose response and variation within and among subjects responses.
Chairperson: Robert O'Neill, Food and Drug Administration Ted Grasela, SUNY Buffalo Carl Peck, Food and Drug Administration John Rodman, St. Jude's Children's Research Hospital Diecussant: Gordon Pledger, R.W. Johnson Pharmaceutical Research Institute
Workshop Vl Designs for Specialized Clinical Trial Situations
Salon E & F
Frequently, a particular clinical trial will pose problems that are not readily addressable by standard textbook approaches to trial design and analysis. Speakers in this session will discuss =nonstandard" situations calling for specialized designs. These include: 1. Designs to =match" preferred treatments .to patient subgroups based on psychological, demographic and behavioral characteristics and their application to studies of the clinical management of alcoholism; 2. Studies of acute illness in which treatment must be initiated prior to completion of a definitive eligibility workup, thereby requiring that the primaryanalysis be performed on a subset of the randomized patients; 3. Situations in which the unit of randomization must be =clusters" of patients rather than individuals; e.g., clinics, neighborhoods, or even cities.
Chairperson: Janet Wittes, New England Research Institute, Inc. Larry Muenz, Consultant, National Institute on Alcohol Abuse and Alcoholism Corsee Dating, Centocor, Inc. Allan Donner, University of Western Ontario 3:30 PM - 4:00 PM
Break
Exhibit Center
374
Final Program TUESDAY, MAY 12, 1992 (Continued) Plenary Session IV
4:00 PM - 5:30 PM
Salon C & D
Women and Clinical Trials: Politics versus Science Have women been discriminated against in clinical research? The dimensions and underlying causes of the "gender gap" have provoked considerable controversy. Recently, major attempts have been made to address this issue, including The Women's Health Initiative, a large multi-component study targeting cardio-vascular disease, cancer, and osteoporosis, and a National Institutes of Health policy aimed at ensuring representation in studies for both women and minorities. A corollary issue is the determination of when it is scientifically or medically necessary to conduct separate trials in males and females or to replicate in one gender results that have been shown in the other. The Food and Drug Administration has considered this question from a regulatory perspective. Speakers in this session will address these issues from both a scientific and a political point of view. An example will be given of a new trial designed to study the effects of aspirin on heart disease in women, based on the findings in males.
Chairperson: Blossom Patterson, National Cancer Institute William Harlan, National Institutes of Health Eileen Leonard, Food and Drug Administration Julie Buring, Harvard Medical School Discussant: Viv!an Pinn, National Institutes of Health Cocktail Banquet Invited Speaker: Bemadine Healy, M.D. Director, National Institutes of Health
6:30 PM
WEDNESDAY, MAY 13, 1992 8:00 AM - 12:00 PM
Registration
8:00 AM - 12:00 PM
Exhibit Program
8:00 AM - 10:00 AM
Contributed Paper Session III
Grand Ballroom Foyer Exhibit Center
(four [4] simultaneous sessions)
Session IliA: Patient and Physician Accrual Into Clinical Trials Chairperson: Jeffrey Probsffield
Salon A & B
8:00 AM
36
Understanding Physician Accrual of Eligible Patients to North American Symptomatic Carotid Endarterectomy Trial (NASCET); Kathryn Taylor, York University
8:20 AM
37
Are Habitual Volunteers a Problem in Clinical Trials?; Mary Morris, University of Washington
8:40 AM
38
A Low Cost Screening Survey to Assess Sample Yield and Refine Study Entry Criteria; Mae Gordon, Washington University
9:00 AM
39
On Entry Cdteria for Clinical Trials; Janet Wittes, Statistics Collaborative
375
Final Program WEDNESDAY, MAY 13, 1992 (Continued) Contributed Paper Session III (continued) (four [4] simultaneous sessions)
8:00 AM - 10:00 AM
9:20 AM
40
Screening Rules for Determining Blood Pressure Status in Clinical Trials: Application to the Trials of Hypertension Prevention; Nancy Cook, Harvard Medical School
9:40 AM
41
Multistage Screening for a Lipid-Restricted Population: The VA HDL Intervention Trial (HIT); Marika Iwane, VA Medical Center, West Haven
Session IIIB: Clinical Trials Logistics Chairperson: Jennifer Gassman
Salon E & F
8:00 AM
42
Crisis Management: A Coordinating Center's Experience with the Suspension of a AIDS Treatment Protocol for a Clinical Trial; Janet Holbrook, The Johns Hopkins University
8:20 AM
43
Recruitment of Clinical Centers in an Investigator-Initiated Multicenter Clinical Trial; Virginia Howard, Bowman Gray School of Medicine
8:40 AM
44
Form Enhances Content: Development of a Generic Protocol (GP); Nancy Paul, Queen's University
9:00 AM
45
Developing Clinical Trial Quality Management Principles; Christopher Barker, Syntex Research
9:20 AM
46
Remote Entry to Integrated Clinical Project Database: On-Line Reporting of Clinical Trial Site Visit Information by Clinical Research Associates; Barbara Nagle, Bio-Pharm Clinical Services
9:40 AM
47
Patient Charges/Costs in the Home Intravenous Antibiotic Trial; Frances Mather, Tulane University
Session IIIC: Qualify of Life Chairperson: Richard Berzon
Constitution Ballroom
8:00 AM
48
Quality of Life Before and After Knowledge of a Trial's Results; Laurie Fitch, University of Minnesota
8:20 AM
49
Assessing Patient Satisfaction in Randomized Clinical Trials: Some Design and Measurement Issues; David Moher, University of Ottawa
8:40 AM
50
Subjective Quality of Life Assessment: A New Instrument, the "SQLP"; Paul Gerin, Unit~ de Pharmacologie Clinique
9:00 AM
51
Random Time Versus Fixed Time Sampling in Clinical Trials Among Drug Addicts; Ram Jain, National Institute on Drug Abuse
9:20 AM
52
Estimating Sensitivity, Specificity and Prevalence from Clinical Trials of Multiple Screening Tests; Timothy Church, University of Minnesota
9:40 AM
53
Comparison of Two Methods of Classification of Cause of Death in a Cardiovascular Clinical Trial; George Feldman, Kaiser Permanente Research Foundation
376
Final Program WEDNESDAY, MAY 13, 1992 (Continued) Contributed Paper Session III (continued) (four [4] simultaneous sessions) Session IIID: General Issues in Data Management Chairperson: Joseph Collins
Salon C & D
8:00 AM
54
An ABC of Information Management in Primary Prevention Trials; David Duncan, University of Glasgow
8:20 AM
55
Planning for Computer Migration During the Course of a Clinical Trial; Frances LoPresti, Maryland Medical Research Institute
8:40 AM
56
Computer-Assisted Eligibility Review and Randomization; M. Marvin Newhouse, The Johns Hopkins University
9:00 AM
57
The Importance of Quality and Accuracy in the Conduct of Clinical Trials: EORTC Quality Assurance Measures; Kris Vantongelen, University Hospital St. Rafael
9:20 AM
58
R.E.A.C.T.--A Hand-Held Computer System to Facilitate Clinical Trials; Martin Schneider, Westchester Distribution Systems, Inc.
9:40 AM
59
Development of a Computerized 24 Hour-a-day Randomization Service; Julie Weston, University of Toronto
10:00 AM - 10:30 AM
Break
10:30 AM - 12:00 PM
Plenary Session V Disseminating the Results of Clinical Trials
Exhibit Center Salon C & D
Increasing attention has been directed at the issue of how information concerning the closure of an ongoing trial should be communicated to involved and interested parties, including investigators, treating physicians, patients both in and outside the trial setting, journal editors, and the press. NIH held a conference on this topic in January 1990 which examined several examples of such terminated studies and indicated that substantial differences existed within NIH in how such circumstances were approached and responded to. With this conference as a background, we intend to highlight the most significant current areas of debate: who should decide when information should be disseminated outside of the traditional avenues, when should such information be disseminated, to whom should it be communicated, who should assume responsibility for such communication, and what level of detail should be made available. We will provide comment from representatives of the NIH, investigators, treating physicians, and the press. Chairperson: Maureen Myers, Boehringer-lngelheim Michael Friedman, National Cancer Institute Gina Kolata, New York Times David Miller, Community Physician Gerald Medoff, Washington University Curtis Meinert, Johns Hopkins University Michael Walker, Laboratory of Immunoregulation, NIAID 12:00 PM
Adjournment