Rare Diseases Research Activities at the National Institutes of Health : Rare Diseases Research Activities at the National Institutes of Health
Stephen C. Groft, Pharm.D.
Office of Rare Diseases, National Institutes of Health
Department of Health and Human Services
National Organization for Rare Disorders
Annual Conference
Roadmap for Rare Diseases Research
October 1, 2006
Slide2 : The View of the NIH - A Complex Organization OD
Deputy and Associate Directors
Administrative Offices Advisory Committee to the Director
Goals of Global Approach to Rare Diseases and Orphan Products : Goals of Global Approach to Rare Diseases and Orphan Products Mobilize Health Professionals and Society to Take Action
Obtain Cooperative and Collaborative Support From All Nations and Partners in Health Research and Product Development
Improve Health Literacy of Populations to Enable Information-Based Decision Making
Reduce Disparities in Global Health with Ready Access to Information and Interventions for Diagnosis, Prevention, and Treatment of Rare Diseases
Benefits of Rare Diseases Research and Orphan Products Development : Benefits of Rare Diseases Research and Orphan Products Development More Rapid Access to Investigational and Approved Orphan Products to Meet Patient and Family Needs
Improved Information Development and Dissemination Activities
Establish Collaborative and Cooperative Research Partnerships (Multiple Principal Investigators on Grants)
Reduce Time to Diagnosis and Improve Genetic Testing Procedures
Quicker and Less Expensive Development of Orphan Products
Coordinated Efforts for Successful Orphan Products Development/Rare Diseases Research : Coordinated Efforts for Successful Orphan Products Development/Rare Diseases Research Pharmaceutical, Biotechnology, and Medical Devices Industries
Academic and Private Foundation Research Communities-Multidisciplinary Research Efforts
Medical Specialty Societies and Healthcare Providers
Patient Advocacy Groups
Federal Government
Regulatory
Reimbursement
Research
Health Care Services
Prevention
Selected Outcomes of the Scientific Conferences Program : Selected Outcomes of the Scientific Conferences Program Identify Research Opportunities
Establish Research Priorities
Develop Program Announcements and Solicit R01 Applications
Establish Diagnostic and Monitoring Criteria
Develop Animal Models
Support Registries - Patient and Tissue
Develop Research Protocols, Collaborative Research Arrangements, and Plan Clinical Trials
Disseminate Results to Targeted Professional and Voluntary Health Organizations
Co-Sponsor with Patient Advocacy Groups, Academic Investigators, Industry, Foundations, Intramural and Extramural Research Programs
Quicker and Less Expensive Development of Safe and Effective Orphan Products : Quicker and Less Expensive Development of Safe and Effective Orphan Products Provide Global Access to Clinical Studies and Clinical Trials of Private and Public Sectors
Develop Globalization of Research Efforts and Common Protocols with Multidisciplinary Research Teams
Continue Efforts for Harmonization of Research Data for Regulatory Purposes
Natural History Studies to Establish Better Definitions of Patient Responders with Development of Appropriate Biomarkers and Surrogate Endpoints for Safety and Efficacy
Utilize Screening Processes of Industry and Government Chemical Libraries
Obtaining the Correct Diagnosis and Improving Dissemination of Information About Rare Diseases and Orphan Products : Obtaining the Correct Diagnosis and Improving Dissemination of Information About Rare Diseases and Orphan Products Expansion of Newborn Screening Programs
Increased Development of Genetic and Diagnostic Tests with Appropriate Patient and Family Counseling
Increase Educational Efforts for the Public and Health Care Providers’ Communities
Better Diagnostic Criteria for Rare Diseases
Available Treatments for Specific Diseases
Standards of Care for Emergency and Critical Care Treatments
Expand Global Linkages and Collaborations of Patient Advocacy Group Networks
Develop Inclusive Web-Based Inventory of Global Rare Diseases Research Studies/Intervention Activities and Information Resources
NLM- ClinicalTroials.gov
Promoting Quality Genetic Testing : Promoting Quality Genetic Testing
Gaining Acceptance of Global Testing Services and Certification Standards
Interpretation of Results with Appropriate Patient Counseling
Foster Development of Collaboration, Education, and Genetic Test Translation Program - (CETT) Prototype
Genome-Wide Association Studies - RFI
http://grants.nih.gov/grants/gwas/index.htm
Establish Partnerships and Networks to Improve Research Translation and Data Sharing
Between and among research and clinical laboratories
Slide10 : Collaboration
Education
Test (Genetic)
Translation
Program for Rare Genetic Diseases
Dr. Roberta Pagon, Andrew Faucett, Dr. Giovanna Spinella, and Dr. Suzanne Hart
ORD “CETT” Program
Slide11 : Model of Cooperation between researcher, diagnostic laboratory and patient advocate group to translate diagnostic tests from research to a clinical laboratory
Flexibility of process to allow for development of different types of genetic tests, collaborations and sources of test development
Development of clinical materials and data collection to improve understanding of the genetic test and understanding of the rare disease. Key Features of CETT
Slide12 : Application must be submitted by team
Patient advocate group
Clinical (CLIA-certified) laboratory
Researcher (laboratory and/or clinician)
Preliminary review by Program Coordinator & Program Scientific Advisor Process
Slide13 : Application forwarded to Review Board Coordinator
Reviewed by 4 members of Review Board (clinician, molecular/biochemical geneticist, patient advocate, clinical geneticist)
Accepted for translation or
Returned to submission team with questions and suggestions – “facilitated process” Process
Slide14 : Information about the correlation between the disease and the test
Information about the potential impact of the test on healthcare management
Evidence that the clinical lab is experienced in diagnostic testing (e.g., number of tests, experience of staff, genetic counselors, CLIA certification)
Proposed method(s) of testing is the most appropriate methods for the disorder
Projections for cost of tests set-up and charge for individual test
Requirements
Slide15 : Statement of collaborative commitments between researcher, clinical lab and advocacy group
Educational materials in a standardized format for clinical care providers and for patients to address correlation between the disease and the test, potential impact of the test on healthcare management, test ordering, test interpretation, and the benefits and risks of testing Requirements
Slide16 : Phenotype / genotype data collection plan to improve understanding of the disease and test interpretation including the method of storage for the phenotype and genotype data
Annual report form on volume of testing, detection rate, mutations found to be used to update “Gene Reviews” Requirements
Slide17 : September 2005 – January 2007
Development of web site
Submission criteria and forms
Examples of educational / information materials
Laboratory experts
Appointment of Review Board
Clinical genetic experts
Patent advocate
Development of review process
Broad publicity for program
January/February 2006
Acceptance of first proposals
Goal of 4-6 week turn-around
Facilitated process
Winter 2006/2007
Evaluation of program
Projected Timeline
Slide18 : Hosted through ORD website
http://rarediseases.info.nih.gov/
Questions
Giovanna Spinella – spinellg@od.nih.gov
Andy Faucett – afaucett@genetics.emory.edu Contacts
Meeting Patient and Family Needs : Meeting Patient and Family Needs
Identify Economic Impact of Rare Diseases on Families and Individuals
Expand Training Programs for PAG on Living and Coping with Rare and Genetic Diseases
Gaining Acceptance for Disabilities and Improving Educational Opportunities for Patients
Maximize Access to Rehabilitation Therapies – Physical, Hearing, Speech, Vocational, Occupational
Provide Worldwide Access to Safe and Effective Products for the Prevention, Diagnosis, and Treatment of Rare Diseases
Provide Ready Access to Information About Rare Diseases
Mission of the RDCRN : Mission of the RDCRN To develop improved diagnostic methods & treatments for rare diseases by facilitating translational research and collaboration between investigators, patient support groups, and the NIH
To utilize translational research to improve the lives of individuals affected by rare diseases
To develop innovative, scalable techniques for conducting clinical research in rare diseases
Goals of RDCRN : Goals of RDCRN Develop innovative tools to collect and manage geographically distributed clinical research data using standardized data elements
Conduct clinical-translational research on multiple rare diseases including:
Longitudinal studies, Diagnostics, and Therapeutic trials
Provide training in clinical research on rare diseases
Improve (Web) access to information about rare diseases; involvement of PAGs
http://rarediseasesnetwork.epi.usf.edu/
Slide22 : Data and Technology Coordinating Center RARE DISEASES CLINICAL RESEARCH NETWORK Rare Genetic Steroid Disorders Consortium Consortium for Clinical Investigation of Neurological Channelopathies Angelman, Rett, and Prader-Willi Syndromes Consortium Urea Cycle Disorders Consortium Cholestatic Liver Disease Consortium Genetic Diseases of Mucociliary Clearance Consortium Rare Lung Disease Consortium Rare Thrombotic Diseases Consortium Vasculitis Clinical Research Consortium Bone Marrow Failure Disease Consortium
Geographic Distribution - Centers : Geographic Distribution - Centers CLiC RLDC ARPWC GDMCC UCDC VCRC BMFDC CINCH RGSDC RTDC NIH DTCC
Geographic Distribution - Clinical Sites : Geographic Distribution - Clinical Sites Toronto, Canada Paris, France Edinburgh, UK Cambridge,
UK Groningen,
Netherlands Tokyo Japan Melbourne, Australia Sao Paulo, Brazil Lyon, France Quebec Canada Bad Bramstedt,
Germany London 55 Medical institutions
32 GCRCs
34 Patient Advocacy Groups : 34 Patient Advocacy Groups Alpha-1 Fdn
Alagille Syndrome Alliance
American Liver Fdn
Androgen Insensitivity Support Group
Angelman Syndrome Fdn
Aplastic Anemia and MDS International Fdn
CARES Fdn
Churg-Strauss Syndrome Assn
Children’s Liver Assn for Support Services
Children’s Liver Disease Fdn
CSS Patient Group
Cystic Fibrosis Fdn
Genetic Alliance
International Rett Syndrome Assn
LAM Fdn
Magic Foundation
Muscular Dystrophy Assn
National Adrenal Diseases Fdn
National Ataxia Fdn
National Organization for Rare Diseases
National Urea Cycle Disorders Fdn
Pediatric Interstitial Lung Disease Family Network Fdn
Periodic Paralysis Assn
Platelet Disorder Support Assn
PNH Support Group
Polyarteritis Nodosa Support Group
Prader-Willi Syndrome Assn (USA)
Primary Ciliary Dyskinesia Fdn
Pulmonary Alveolar Proteinosis Fdn
Pulmonary Fibrosis Fdn
Takayasu's Arteritis Research Assn
The Angelman Syndrome Fdn
United Mitochondrial Disease Fdn
Wegener's Granulomatosis Assn
Integrated Network : NIH ORD, NCRR, NIAMS, NICHD, NHLBI, NIDDK, NINDS Data and Technology Coordinating Center Media Library Researchers Doctors Educators Patient Community Pharmaceutical Companies RDC Center Registries Integrated Network Contact
Registry Clinical Research Data Bank Clinical Data Standardization Groups
Rare Diseases Under Study n=45 : Rare Diseases Under Study n=45 Alagille Syndrome
Alpha-1 Antitrypsin Deficiency
Amegakaryocytic Thrombocytopenic Purpura
Andersen-Tawil Syndrome
Androgen Receptor Defects
Angelman's Syndrome
Antiphospholipid Antibody Syndromes
Aplastic Anemia
Apparent Mineralocorticoid Excess
Arginase Deficiency
Argininosuccinate Lyase Deficiency Argininosuccinate Synthetase Deficiency
Autoimmune Neutropenia
Bile Acid Synthesis Disorders
Carbamyl Phosphate Synthetase Deficiency
Catastrophic Antiphospholipid Ab Syndrome
Churg-Strauss Syndrome
Citrin Deficiency
Congenital Adrenal Hyperplasia
Cystic Fibrosis
Episodic Ataxias
Giant Cell Arteritis
Heparin-induced Thrombocytopenia
Rare Diseases Under Study (cont.) : Rare Diseases Under Study (cont.) Hereditary Interstitial Lung Disease
Large Granular Lymphocyte Leukemia
Lymphangioleiomyomatosis
Microscopic Polyangiitis
Mitochondrial Hepatopathies
Myelodysplastic Syndromes
N-Acetylglutamate Synthase Deficiency
Non-dystrophic Myotonic Disorders
Ornithine Transcarbamylase Deficiency
Ornithine Translocase Deficiency Syndrome Paroxysmal Nocturnal Hemoglobinuria
Polyarteritis Nodosa
Prader-Willi Syndrome
Primary Ciliary Dyskinesia
Progressive Familial Intrahepatic Cholestasis
Pseudohypoaldosteronism
Pulmonary Alveolar Proteinosis
Pure Red Cell Aplasia
Rett Syndrome
Takayasu's Arteritis
Thrombotic Thrombocytopenic Purpura
Wegener’s Granulomatosis
National Standards : National Standards Use of standardized terminology/ vocabulary (e.g., SNOMED)
Incorporated into protocols, data collection forms, database, adverse event reporting, etc.
Innovative data collection techniques
cell phone call-in and reports by participants that populate database for CINCH
Standardization of Protocol Development and Implementation : Standardization of Protocol Development and Implementation Standardized Protocol and Consent Formats
Standardized Checklist for submission for approval from DTCC, PRC and DSMB
Manual of Operations template
Protocol Monitoring Plan
Electronic AE and SAE reporting and review
Studies Open and Enrolling : Studies Open and Enrolling Enrolling since Jan., 2006
25 approved protocols
20 enrolling patients – assistance of PAGs
21 studies under development or current review by the PRCs or DSMBs, including:
Novel therapeutic trials
Longitudinal studies
Diagnostic studies
Demonstration Projects
Information Development, Dissemination, and Education Activities : Information Development, Dissemination, and Education Activities
National Library of Medicine Gateway http://gateway.nlm.nih.gov/gw/Cmd
DIRLINE > 1200 Patient Advocacy groups (NORD Assistance)
Clinical Trials.gov
Rare Diseases – 5,429 Studies Recruiting for 875 Rare Diseases ( 11,676 Total for 1,024 Rare Diseases)
WHO Meta-Register of Clinical Trials
Pub Med/MEDLINE – 4800 Journals from 70 Countries, 750 Million Searches/year
Gene Tests (1294 Diseases)
1134 Clinics - 1000 Diseases Clinical Tests
606 Laboratories - 294 Diseases Research Only Laboratories
Regional Meetings (ORD/NORD) Seminars for PAG Leadership
National Coalition for Health Professional Education in Genetics (NCHPEG)
ORD Present and Future Emphasis and Needs : ORD Present and Future Emphasis and Needs Genetic Testing – CETT Program
Inventory of Bio-specimen Collection, Storage, and Distribution Repositories (Biobanks)
Need for Patient/Research Registry Standards
Develop Acceptable Method of Determining Prevalence of Rare Diseases
Bench to Bedside Grant Program – IRP/ERP
http://clinicalcenter.nih.gov/ccc/btb/awards.shtml
Office of Technology Transfer (Neglected Diseases, Rare Diseases) Available Technology from Government ( >750 technologies) and Academic Laboratories and Clinics (Future)
Patient Travel – Angel Flight
Undiagnosed Diseases
Items of Interest from ORD/NIH : Items of Interest from ORD/NIH
Genome-Wide Association Studies - RFI on Genome Wide Association Studies. Submit genetic data (genotype) with Relevant health Information (Phenotypes) to a Central Data Repository
http://grants.nih.gov/grants/gwas/index.htm
Annual Report on Rare Diseases Research Advances
Office of Rare Diseases, National Institutes of Health
http://rarediseases.info.nih.gov/html/reports/fy2005/Annual_Report_FY_05_Final.pdf
Multiple Principal Investigators web site:
http://grants.nih.gov/grants/multi_pi/index.htm
The Genetic and Rare Diseases Information Center (NHGRI/ORD) : The Genetic and Rare Diseases Information Center (NHGRI/ORD) >15,600 Inquiries (2002 – 2006)
> 4,640 Rare Diseases or Conditions
> 6,740 Related Terms
Next Step – National Library of Medicine Collaboration
Toll-free 1-888-205-3223 (USA)
International Access Number: 301-519-3194
Fax: 240-632-9164
E-mail: GARDinfo@nih.gov
ORD Website http://rarediseases.info.nih.gov/ : ORD Website http://rarediseases.info.nih.gov/ Rare Diseases Information – Pub Med
Research and Clinical Trials - CRISP, ClinicalTrials.gov
Patient Support Groups - DIRLINE > 1200 Patient Advocacy Groups, NORD, Genetic Alliance
Patient Travel & Lodging
Genetics Information – Gene Tests, OMIM, NCHPEG
Research Resources
Scientific Workshops, Archived Reports
Office of Rare Diseases - Staff : Office of Rare Diseases - Staff Ms. Mary Demory
Ms. Marita Eddy (Angel Flight)
Dr. John Ferguson (Consultant)
Dr. Stephen C. Groft
Dr. Rashmi Gopal-Srivastava
Mr. Christopher Griffin
Ms. Henrietta Hyatt-Knorr
Ms. Sharon Macauley
Ms. Geraldine Pollen (Consultant)
Dr. Giovanna Spinella (Consultant)
Dr. William Gahl (Clinical Director, NHGRI)
Office of Rare Diseases National Institutes of Health : Office of Rare Diseases National Institutes of Health 6100 Executive Boulevard
Room 3B-01, MSC - 7518
Bethesda, MD 20892-7518
Voice: 301-402-4336
Fax: 301-480-9655
E-mail: ORD@nih.gov
Website: http://rarediseases.info.nih.gov/