RARE DISEASE WORKSHOP SERIES

Improving the Clinical Development Process

Clinical Evaluation of Rare Disease Treatments
June 14-15, 2011
L'Enfant Plaza Hotel, Washington, D.C.

Presentation slides can be accessed by clicking on the links within the agenda.
Click here for a summary of the entire Workshop.

Day 1 – Morning

Clinical evaluation of rare disease: lessons learned in common diseases relevant to rare diseases
8:30 am	Welcome Emil Kakkis, M.D., Ph.D., President,EveryLife Foundation for Rare Diseases
8:40 am	Introduction to Some Important Issues in Evaluating Efficacy Thomas R, Ph.D., Prof. of Biostatistics, University of Washington
9:00 am	General Considerations in Endpoint Development John Powers, III, M.D., Senior Medical Scientist, NIH
9:20 am	Selection of Meaningful Endpoints Anne Pariser, M.D., Associate Director for Rare Diseases, CDER, FDA
9:40 am	Discussion: What is the conceptual framework allowing one to first take into consideration all of the appropriate potential endpoints for a clinical trial by looking at the disease as a whole, then select the most worthwhile and feasible of these endpoints to be measured in a clinical trial? When should a previously used endpoint versus an untested endpoint be used? How do we go about qualifying a new endpoint that has not been tested before?

Assessing minimum important difference/responder definition in clinical evaluation of rare diseases
• Strategies for developing and using MID in clinical efficacy evaluation
10:40 am	Minimal Important Difference: what is it, how to estimate Applying the MID: proportion who benefit Gordon Guyatt, M.D., Prof. of Clinical Epidemiology and Biostatistics, McMaster University
11:10 am	Discussion
11:20 am	Considerations in Interpretation of Outcomes Measures John Powers, III, M.D., Senior Medical Scientist, NIH
11:50 am	Assessments and Endpoints: Demonstrating Effectiveness Marc Walton, M.D., Ph.D., Associate Director for Translational Medicine, Office of Translational Sciences, CDER, FDA
• Assessing the responder definition in rare disease situations
12:20 pm	Assessing Responders for Aldurazyme in MPS I Gerry Cox, M.D., Ph.D., Vice President, Clinical Development, Genzyme Corporation
12:40 pm	Interpretation of Health Outcomes Data within Rare Disease Clinical Trials Kathy Wyrwich, Ph.D., Senior Research Scientist, Center for Health Outcomes Research, United BioSource Corporation
1:20 pm	Discussion: How should MID/responder definition be determined in rare disease situations: translation from other diseases or empirical testing in natural history or clinical data? How should MID/responder definition be analyzed: As a method to interpret clinical meaningfulness of data after obtaining a positive statistical result, or built into the primary analysis?

Day 1 – Afternoon

• Exploring patient reported outcomes to support a label claim or to support the results of clinical outcomes

2:00 pm	Patient Reported Outcomes: Challenges for Rare Diseases Emil Kakkis, M.D., Ph.D., President,EveryLife Foundation for Rare Diseases
2:05 pm	Exploring Clinical Outcome Assessments in Rare Disease Trials Laurie Burke, R.Ph., MPH, Associate Director for Study Endpoints and Labeling, Office of New Drugs, CDER, FDA
2:50 pm	PROMIS: Patient-Reported Outcomes Measurement Information System James Witter, M.D., Ph.D., Chief Science Officer, NIH/NIAMS
3:20 pm	Addressing Content Validity of PRO Measures: The Unique Case of Rare Diseases Nancy Kline Leidy, Ph.D., Senior Vice President, Scientific Affairs, United BioSource Corporation
3:50 pm	Discussion: For rare diseases, when should developers adopt existing common instruments as their primary strategy for using PROs, and when should they develop new, disease-specific instruments? How should a developer meet the guidelines set forth in the FDA PRO Guidance to qualify an endpoint while managing the challenges posed by rare disease drug development, both in adopting an existing instrument and developing one from scratch? Can PROs be used to support the clinical meaningfulness of clinical outcomes?
4:50 pm	Wrap-up of Day 1
4:55 pm	End of Day 1

Day 2 – Morning
8:30 am	Welcome Day 2 Emil Kakkis, M.D., Ph.D., President,EveryLife Foundation for Rare Diseases

• Examples of development of clinical evaluation tools to assess degree of clinical benefit in neurological and rare diseases
8:50 am	Gene Therapy for CNS Manifestations of the Lysosomal Storage Disorders Ron Crystal, M.D., Prof. of Genetic Medicine, Weill Cornell Medical College
9:20 am	Development of Rare Disease Evaluation Tools Ali Skrinar, M.A., MPH, Senior Director, Clinical Research & Regulatory Affairs, Enobia Pharma
10:10 am	Use of Registries for Clinical Evaluation of Rare Diseases P.K. Tandon, Ph.D., Senior Vice President, Global Biomedical Data Sciences and Informatics, Genzyme Corporation
10:40 am	“Successful” Application of Patient Reported Outcome in Multiple Sclerosis Andrew R. Blight, Ph.D., Chief Scientific Officer, Acorda Therapeutics
11:10 am	Discussion: What are the key challenges observed in rare disease-specific instrument development and what practical solutions might allow for better development, utilization, and qualification of such measures? What is the critical information that might be derived from similar disease states to the one being studied that might support the qualification of an evaluative tool as reasonable for a rare disease?

Day 2 - Afternoon
• Evaluation of clinical benefit across multiple clinical domains
12:55 pm	The Necessity for Improving the Accessibility to Multi-Domain Assessments in rare disease treatments Emil Kakkis, M.D., Ph.D., President,EveryLife Foundation for Rare Diseases
1:25 pm	How to combine information from multiple endpoints for comparing two treatment groups? L.J. Wei, Ph.D., Professor of Biostatistics, Harvard University
1:45 pm	Statistical Analyses for Multi-Domain Outcomes James Signorovitch, Ph.D., Manager, Analysis Group
2:15 pm	Discussion: How do we capture and interpret the real effect of a treatment on patients using multi-domain endpoints? How would we then interpret clinical data from multi-domain results and accurately make labeling claims based on the result of a multi-domain analysis?
3:00 pm	Closing remarks
3:30 pm	End of workshop