The goal of this meeting is to discuss scientific and ethical principles in clinical trial design in situations where a comparison group might be structured as usual care or as some subset of usual care. Participants will embark on the development of a Points to Consider guidance document for researchers and oversight bodies on considering usual medical care in the design of comparison arms in randomized controlled trials.

November 14, 2005
8:00 a.m. - 8:30 a.m.	Registration
8:30 a.m. - 8:40 a.m.	Welcoming Remarks Raynard S. Kington, M.D., Ph.D. Deputy Director National Institutes of Health Amy P. Patterson, M.D. Director Clinical Research Policy Analysis and Coordination (CRpac) Program Office of Science Policy Office of the Director National Institutes of Health
8:40 a.m. - 9:00 a.m.	Introduction to the Conference The meeting chair will describe the meeting scope and format, including the parameters of the topic at hand, key definitions to be used, meeting objectives, and possible followup activities. Robert J. Levine, M.D. (PDF 8 kb) Professor of Medicine Director Law, Policy and Ethics Core Investigator International Research Core Center for Interdisciplinary Research on AIDS Yale University
9:00 a.m. - 9:40 a.m.	Variation in Medical Practice and Its Implications for the Design of Control Arms in Clinical Trials (30-minute presentation plus 10-minute discussion) During this session, the speaker will describe and give examples of variations in medical practice, including the various roles of clinical trial results, clinician experience, and other data sources in influencing patterns of clinical practice, and discuss national and local variations in practice, secular trends, and individualized treatment and patient subgroups as determinants of variation. John Wennberg, M.D., M.P.H. (PDF 8 kb) Professor Department of Community and Family Medicine Dartmouth Medical School
9:40 a.m. - 10:20 a.m.	Federal Agency Views on the Relevance of Usual Care Control Groups (FDA, NIH, AHRQ, OHRP, CMS) (5-minute presentation for each, with 15-minute Q&A)
10:20 a.m. - 10:40 a.m.	BREAK
10:40 a.m. - 11:20 a.m.	Design Considerations in Randomized Controlled Trials With a Focus on Usual Care Arms I. Basic Principles of Clinical Trial Design (30-minute presentation plus 10-minute discussion) In this talk, the speaker will discuss the fundamental aspects of clinical trial design, including the use of prior randomized controlled trial data and systematic review and meta-analysis in determining appropriate trial design; the selection of study populations and comparability/generalizability issues; the role of historical and observational data and the strength of evidence from these sources; the problem of patient subsets in clinical trials; defining primary and secondary outcomes and comparisons among trials; and the use of composite endpoints. Janet Wittes, Ph.D. (PDF 8 kb) President Statistics Collaborative, Inc.
11:20 a.m. - 11:50 a.m.	Design Considerations in Randomized Controlled Trials (continued) II. FDA Perspectives on Usual Care Control Groups in Regulatory Decisionmaking (30-minute presentation plus 10-minute discussion) In this presentation, an FDA representative will describe the types of control groups that might be acceptable from a regulatory decisionmaking perspective and give examples of how different study designs might be evaluated by the agency. A case study example will be described, involving a description of a clinical trial submitted to FDA that employed a usual care control group. Robert Meyer, M.D. (PDF 8 kb) Director Office of Drug Evaluation II Center for Drug Evaluation and Research U.S. Food and Drug Administration
11:50 a.m. - 12:40 p.m.	Ethical Considerations in Randomized Controlled Trials: Focus on Usual Medical Care and Ethics of Trial Design (30-minute presentation plus 10-minute discussion) The goal of this presentation will be to describe and explain the ethical principles and theories underlying clinical research, specifically the concepts that relate clinical research to clinical care, including equipoise, uncertainty, therapeutic misconception, and patient and physician attitudes toward research. The session also will address how the context of clinical trials affects the evaluation of risks and benefits of research and the utility of clinical trials in setting practice guidelines. Charles Weijer, M.D., Ph.D. (PDF 8 kb) Associate Professor Department of Philosophy Talbot College University of Western Ontario
12:40 p.m. - 1:40 p.m.	Luncheon Speaker The speaker will examine the process of translating the results of systematic scientific investigation into clinical practice, with a focus on the art and science of combining systematic clinical trials data with individualized clinician judgment. This process represents the reverse of the usual care problem, namely, that statistical evidence needs to be combined with individual decisionmaking, based on clinician experience and context, in the practice of evidence-based medicine. Examining this process will help elucidate the complex mix of statistical and individual assessments that go into the practice of medicine. It is this same blend of art and science that informs the design and interpretation of clinical trials. R. Brian Haynes, M.D., Ph.D. (PDF 8 kb) Professor and Chair Department of Clinical Epidemiology and Biostatistics Faculty of Health Sciences McMaster University
1:40 p.m. - 2:20 p.m.	The Acute Respiratory Distress Syndrome Network (ARDSnet): Lessons Learned for the Design of Critical Care Research The speaker will describe scientific and ethical issues arising in clinical trials in a setting where usual medical practice is variable and where an evolving evidence base makes it difficult to determine the most appropriate comparison arms. The aim of this discussion is to understand scientific parameters in the design of critical care research that also occur in other areas of clinical investigation and to look forward to applying lessons learned to continuing challenges in clinical investigation. B. Taylor Thompson, M.D. (PDF 8 kb) Director Medical Intensive Care Unit Medical Director ARDS Network Clinical Coordinating Center Massachusetts General Hospital
2:20 p.m. - 2:45 p.m.	Discussion of ARDSnet
2:45 p.m. - 3:00 p.m.	BREAK
3:00 p.m. - 6:00 p.m.	Case Studies A series of three case studies will be discussed—two on the first day and one on the second day—based on actual clinical trials in three different areas of medical practice. For each case study, a study investigator will present the case, followed by commentary from a clinical trials expert knowledgeable in the field. An interdisciplinary panel will discuss the case, considering the context of the trial, factors leading to specific design choices, and the scientific and ethical implications of the trial design. Panel discussions will include audience participation and will help frame the relevant scientific and ethical issues that apply across diverse areas of clinical research.
3:00 p.m. - 3:30 p.m. Case Presentation: Case Study #1 International Collaborative Ovarian Neoplasm (ICON) Trials of Ovarian Cancer Treatment Ann Marie Swart, M.R.C.P., M.Sc. (PDF 8 kb) Senior Clinical Epidemiologist Cancer Division Clinical Trials Unit UK Medical Research Council Larry J. Copeland M.D. , , a, Michael Bookman M.D.b and Edward Trimble M.D.c Clinical trials of newer regimens for treating ovarian cancer: the rationale for Gynecologic Oncology Group Protocol GOG 182-ICON5 Gynecologic Oncology Volume 90, Issue 2, Supplement 1, August 2003, Pages S1-S7 3:30 p.m. - 3:45 p.m. Commentary on Case Study #1 Joseph L. Pater, M.D., M.Sc. (PDF 10 kb) Edith Eisenhauer Chair in Clinical Cancer Research Director National Cancer Institute of Canada Clinical Trials Group 3:45 p.m. - 4:35 p.m. Panel Discussion of Case Study #1 4:35 p.m. - 5:05 p.m. Case Presentation: Case Study #2 Multimodal Treatment Study of ADHD (MTA) James M. Swanson, Ph.D. (PDF 9 kb) Professor Department of Pediatrics Director Child Development Center School of Medicine University of California, Irvine A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD. Arch Gen Psychiatry. 1999 Dec;56(12):1073-86. http://archpsyc.ama-assn.org/ 5:05 p.m. - 5:20 p.m. Commentary on Case Study #2 Julie Magno Zito, Ph.D. Associate Professor of Pharmacy & Psychiatry Department of Pharmaceutical Health Services Research University of Maryland, Baltimore 5:20 p.m. - 6:00 p.m. Panel Discussion of Case Study #2
November 15, 2005
8:00 a.m. - 8:30 a.m.	Registration
8:30 a.m. - 9:00 a.m.	Case Presentation: Case Study #3 Spine Patient Outcomes Research Trial (SPORT) James N. Weinstein, D.O., M.S. (PDF 9 kb) Professor and Chairman Department of Orthopaedic Surgery Dartmouth Medical School Birkmeyer NJ, Weinstein JN, Tosteson AN, Tosteson TD, Skinner JS, Lurie JD, Deyo R, Wennberg JE. Design of the Spine Patient outcomes Research Trial (SPORT). (PDF 297 kb) Spine. 2002 Jun 15;27(12):1361-72. www.spinejournal.com
9:00 a.m. - 9:20 a.m.	Commentary on Case Study #3 Steven N. Goodman, M.D., Ph.D. (PDF 8 kb) Associate Professor of Oncology, Pediatrics, Epidemiology and Biostatistics Department of Oncology/Division of Biostatistics Johns Hopkins School of Medicine and Bloomberg School of Public Health
9:20 a.m. - 10:10 a.m.	Panel Discussion of Case Study #3
10:10 a.m. - 10:30 a.m.	BREAK
10:30 a.m. - 12:00 noon	Roundtable Discussion: Development of Ethical and Scientific Principles To Guide Considerations of Usual Medical Care in Clinical Trial Design (PDF 267 kb) A moderator will present a preliminary draft set of Points to Consider for designing randomized controlled trials in cases where usual medical care, or components of usual care, might be considered as a comparison group. A roundtable panel, consisting of an interdisciplinary group of clinical trials experts, ethicists, statisticians, and Federal agency representatives knowledgeable in these fields, will discuss the draft. The draft guidance—prepared in advance of the conference—will be open to discussion, debate, and revision during the roundtable. Roundtable members will include speakers from the previous sessions and additional experts. Roundtable Chair: Alan R. Fleischman, M.D. (PDF 9 kb) Chair Federal Advisory Committee Ethics Advisor National Children's Study National Institute of Child Health and Human Development National Institutes of Health
12:00 noon - 1:00 p.m.	LUNCH
1:00 p.m. - 2:30 p.m.	Continued Discussion of Points to Consider The entire panel will continue work on the Points to Consider document.
2:30 p.m. - 2:50 p.m.	BREAK
2:50 p.m. - 4:00 p.m.	Final Discussion and Summary The moderator will lead final discussion of points to consider and will sum up the progress made and next steps for followup activities.
4:00 p.m.	ADJOURNMENT