Collaborative Research and Collaborative Research and Development ActivitiesDevelopment Activities

Stephen C. Groft, Pharm.D.Stephen C. Groft, Pharm.D. Office of Rare DiseasesOffice of Rare Diseases

National Institutes of HealthNational Institutes of HealthDepartment of Health and Human Department of Health and Human

ServicesServices__________________________________________________

Genetic Alliance Annual MeetingGenetic Alliance Annual MeetingJuly 28, 2006July 28, 2006

National Institute of Mental Health

National Institute of Neurological Disorders and Stroke

National Library of Medicine

A View of the NIH A View of the NIH

National Cancer Institute

National Institute on Aging

National Heart Lung and Blood Institute

National Eye Institute

Clinical Center Center for Scientific Review

Center for Information Technology

National Institute of Environmental Health Sciences

National Institute of General Medical Sciences

National Institute of Deafness and Other Communication Disorders

National Institute of Dental and Craniofacial Research

John E. Fogarty Center for Advanced Study in the Health Sciences

National Center for Complementary and Alternative Medicine

National Center for Minority Health and Health Disparities

National Center for Research Resources

National Institute of Nursing Research

National Institute of Arthritis and Musculoskeletal and Skin Diseases

National Institute of Allergy and Infectious Disease

National Institute on Alcohol Abuse and Alcoholism

National Institute on Drug Abuse

National Institute of Biomedical Imaging and Bioengineering

National Human Genome Research Institute

National Institute of Diabetes and Digestive and Kidney Diseases

National Institute of Child Health and Human Development

Office of Research on Women’s Health Office of AIDS Research, Office of Dietary Supplements, Office of Behavioral and Social Sciences Research, Office of Disease Prevention, Office of Rare Diseases,

ODDeputy and Associate

DirectorsAdministrative Offices

Advisory Committee to the Director

Rare Diseases Act of 2002Rare Diseases Act of 2002(Rare Disease Prevalence < (Rare Disease Prevalence <

200,000 in USA)200,000 in USA)

Public Law 107-280 (November 6, Public Law 107-280 (November 6, 2002)2002)

Recommend Research and Public Recommend Research and Public Education Agendas at NIHEducation Agendas at NIH

Promote Coordination and Promote Coordination and Collaboration of Rare Diseases Collaboration of Rare Diseases Activities Activities

Develop Information Center (NHGRI)Develop Information Center (NHGRI)

Office of Rare Diseases (ORD)Office of Rare Diseases (ORD)

Intramural Research Program Intramural Research Program • Bench to Bedside Program – IRP/ERPBench to Bedside Program – IRP/ERP• Office of Technology Transfer (Neglected Office of Technology Transfer (Neglected

Diseases, Rare Diseases)Diseases, Rare Diseases)• Clinical and Biochemical Genetics Training Clinical and Biochemical Genetics Training

ProgramProgram• Patient Travel – Angel FlightPatient Travel – Angel Flight

Office of Rare Diseases (ORD)Office of Rare Diseases (ORD)

Extramural Research ProgramExtramural Research Program• Scientific Conferences Scientific Conferences

American Chemical Society American Chemical Society

• Rare Diseases Clinical Research Rare Diseases Clinical Research Network (RDCRN)Network (RDCRN)

• RFA and PA Participation RFA and PA Participation • Office of Policy Analysis and Office of Policy Analysis and

Strategic Initiatives (OPASI) Strategic Initiatives (OPASI)

Office of Rare DiseasesOffice of Rare Diseases Trans-NIH Working Group on Rare Diseases Trans-NIH Working Group on Rare Diseases

ResearchResearch Genetic Testing – CETT ProgramGenetic Testing – CETT Program Bio-specimen Collection, Storage, and Bio-specimen Collection, Storage, and

DistributionDistribution Rare Cancers EmphasisRare Cancers Emphasis AmyloidosisAmyloidosis Future: Need for Special Emphasis Panel Future: Need for Special Emphasis Panel

Review (1987, 1998, 2007 ?)Review (1987, 1998, 2007 ?) Future: Need of Patient/Research RegistryFuture: Need of Patient/Research Registry Future: Survey of Prevalence of Rare Future: Survey of Prevalence of Rare

Diseases in USADiseases in USA

Office of Rare Diseases (ORD)Office of Rare Diseases (ORD) Information Development and Information Development and

Dissemination and Education ActivitiesDissemination and Education Activities• DIRLINE, Clinical Trials.gov, Pub Med, DIRLINE, Clinical Trials.gov, Pub Med,

Gene Tests, OMIMGene Tests, OMIM• Seminars for PAG LeadershipSeminars for PAG Leadership• WebsiteWebsite• Information Center (NHGRI)Information Center (NHGRI)• National Coalition for Health Professional National Coalition for Health Professional

Education in Genetics (NCHPEG)Education in Genetics (NCHPEG)

Rare Diseases Clinical Research Rare Diseases Clinical Research Network (RDCRN)Network (RDCRN)

Rare Diseases Clinical Research Centers Rare Diseases Clinical Research Centers • $1.25 Million/Year for 5 Years – 10 Consortia$1.25 Million/Year for 5 Years – 10 Consortia• Focused on a Subgroup of DiseasesFocused on a Subgroup of Diseases• Consortium of Clinical Investigators, Institutions, Consortium of Clinical Investigators, Institutions,

Patient Support GroupsPatient Support Groups

Data and Technology Coordinating CenterData and Technology Coordinating Center• $2 Million/Year for 5 years $2 Million/Year for 5 years

Utilize Resources of the General Clinical Utilize Resources of the General Clinical Research CentersResearch Centers

http://rarediseasesnetwork.epi.usf.edu/http://rarediseasesnetwork.epi.usf.edu/

Research Network Consortia (2006)Research Network Consortia (2006) http://rarediseasesnetwork.epi.usf.edu/http://rarediseasesnetwork.epi.usf.edu/

Angelman, Rett, Prader-Willi Syndromes – A. BeaudetAngelman, Rett, Prader-Willi Syndromes – A. Beaudet Bone Marrow Failure – J. MaciejewskiBone Marrow Failure – J. Maciejewski Genetic Diseases of Mucociliary Clearance – M. KnowlesGenetic Diseases of Mucociliary Clearance – M. Knowles Genetic Steroid Disorders – M. NewGenetic Steroid Disorders – M. New Nervous System Channelopathies – R. GriggsNervous System Channelopathies – R. Griggs Rare Liver Disorders – R. SokolRare Liver Disorders – R. Sokol Rare Lung Diseases – B. TrapnellRare Lung Diseases – B. Trapnell Rare Thrombotic Disorders – T. OrtelRare Thrombotic Disorders – T. Ortel Urea Cycle Disorders – M. BatshawUrea Cycle Disorders – M. Batshaw Vasculitis Clinical Research – P. MerkelVasculitis Clinical Research – P. Merkel Data and Technology Coordinating Center (DTCC) – J. Data and Technology Coordinating Center (DTCC) – J.

KrischerKrischer

• Collaborative Clinical Research

• Centralized Data Coordination and Technology Development

• Public Resources and Education

• Training

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESU.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of HealthNational Institutes of HealthORD, NCRR, NIAMS, NICHD, NHLBI, NIDDK, ORD, NCRR, NIAMS, NICHD, NHLBI, NIDDK,

NINDS,NINDS,

The Data Technology

Coordinating Center

Coalition of PatientAdvocacy Groups

(CPAG)

Angelman, Rett and

Prader-Willi Syndromes Consortium

Cholestatic Liver

Disease Consortium

CLiC

Genetic Diseases of

Mucociliary Clearance Consortium

Rare Genetic Steroid

Disorders Consortium

Rare Lung

Disease Consortium

Rare Thrombotic

Diseases Consortium

Purposes of Cooperative Rare Diseases Purposes of Cooperative Rare Diseases Clinical Research NetworkClinical Research Network

Facilitate Clinical Research in Rare Diseases Facilitate Clinical Research in Rare Diseases Training of Clinical Investigators in Rare Training of Clinical Investigators in Rare

Diseases ResearchDiseases Research Test Site for Distributed Clinical Data Test Site for Distributed Clinical Data

ManagementManagement Support Collaborative Clinical ResearchSupport Collaborative Clinical Research

• Longitudinal Studies of Patients with Rare Longitudinal Studies of Patients with Rare DiseasesDiseases

• Clinical Pilot or Demonstration ProjectsClinical Pilot or Demonstration Projects• Access to Information Related to Rare Diseases Access to Information Related to Rare Diseases

for Clinicians, Researchers, and the Lay Publicfor Clinicians, Researchers, and the Lay Public

Organization of the RDCRNOrganization of the RDCRNPatients

NIH, ORD, NCRR, NIH, ORD, NCRR, NIAMS,NIAMS,

NICHD, NHLBI, NICHD, NHLBI, NIDDK, NINDS NIDDK, NINDS

Data and TechnologyCoordinating Center PRC

MediaLibrary

Public Website

ResearchersDoctors Educators

PatientCommunity

PharmaceuticalCompanies

Site

Site

Site

RDCCenter

Site

Site

Site

RDCCenter

Site

Site

Site

RDCCenter

Registries

CPAG

SupportGroups

ContactRegistry

Clinical ResearchData Bank

DSMB

Clinical DataStandardization

Groups

Data and Technology Coordinating CenterData and Technology Coordinating CenterDr. Jeffrey KrischerDr. Jeffrey Krischer

• Collaboration in design of clinical protocols, data Collaboration in design of clinical protocols, data management and analysismanagement and analysis

• Develop a coordinated clinical data management Develop a coordinated clinical data management system for the collection, storage and analysis of data system for the collection, storage and analysis of data from multiple diseases and multiple clinical sitesfrom multiple diseases and multiple clinical sites

• Develop tools for web based recruitment and referral, Develop tools for web based recruitment and referral, cross disease data miningcross disease data mining

• Construct a portal for access and integration of public Construct a portal for access and integration of public data resourcesdata resources

• Promote communication and coordination of Network Promote communication and coordination of Network (including internet video conferencing, centralized (including internet video conferencing, centralized secure website)secure website)

Current Accruals - Participants Current Accruals - Participants RegisteredRegistered

Angelman, Rett, & Prader-Willi Syndromes Angelman, Rett, & Prader-Willi Syndromes Consortium – 273Consortium – 273

Bone Marrow Failure Disease Consortium – 67Bone Marrow Failure Disease Consortium – 67 Consortium for Clinical Investigation of Neurologic Consortium for Clinical Investigation of Neurologic

Channelopathies – 18 Channelopathies – 18 Genetic Diseases of Mucociliary Clearance Genetic Diseases of Mucociliary Clearance

Consortium – 17Consortium – 17 Urea Cycle Disorders Consortium – 29 Urea Cycle Disorders Consortium – 29 Vasculitis Clinical Research Consortium – 15 Vasculitis Clinical Research Consortium – 15 Total -419 Patients Total -419 Patients

48 Diseases48 Diseases 34 Patient Advocacy Groups34 Patient Advocacy Groups 18 studies recruiting18 studies recruiting 10 studies not yet recruiting10 studies not yet recruiting 9 International Sites9 International Sites

Inventory and Evaluation of Clinical Inventory and Evaluation of Clinical Research Networks (IECRN) ProjectsResearch Networks (IECRN) Projects

https://www.clinicalresearchnetworks.org/default.asphttps://www.clinicalresearchnetworks.org/default.asp

(>240 Clinical Research Networks)(>240 Clinical Research Networks)

To develop an inventory and database of clinical research To develop an inventory and database of clinical research networks. The inventory will be a searchable data base networks. The inventory will be a searchable data base available as a tool to search for eligible, participating available as a tool to search for eligible, participating clinical networks;clinical networks;

To describe organizational and operational characteristics To describe organizational and operational characteristics

of a sample of networks in several key areas;of a sample of networks in several key areas;

To identify and examine networks best practices that lead To identify and examine networks best practices that lead to successful achievement of specified outcomes, including to successful achievement of specified outcomes, including increased efficiency, promotion of interactivity within the increased efficiency, promotion of interactivity within the network or across networks, and broadening of research network or across networks, and broadening of research scope. scope.

Roadmap for Medical Research, Roadmap for Medical Research, the Office of Portfolio Analysis and the Office of Portfolio Analysis and

Strategic Initiatives (OPASI)Strategic Initiatives (OPASI) Identify ideas for Roadmap initiatives to be Identify ideas for Roadmap initiatives to be

funded in FY2008funded in FY2008 Consultation meetings being held in July Consultation meetings being held in July

and September 2006and September 2006 Solicit additional ideas from the science Solicit additional ideas from the science

and lay communities using a Web-based and lay communities using a Web-based Request for Information (RFI). Request for Information (RFI).

Initial prioritization by IC DirectorsInitial prioritization by IC Directors Review by ACD and NIH Director selectionReview by ACD and NIH Director selection

Criteria for Roadmap InitiativesCriteria for Roadmap Initiatives Goal is to accelerate the discovery and translation of Goal is to accelerate the discovery and translation of

scientific knowledge into public health benefitsscientific knowledge into public health benefits

Is the proposed initiative truly transforming—could it Is the proposed initiative truly transforming—could it dramatically affect how biomedical and/or behavioral dramatically affect how biomedical and/or behavioral research is conducted over the next decade?research is conducted over the next decade?

Will the outcomes from the proposed initiative Will the outcomes from the proposed initiative synergistically promote and advance the individual synergistically promote and advance the individual missions of NIH ICs to benefit health?missions of NIH ICs to benefit health?

Does the proposed initiative require participation Does the proposed initiative require participation from NIH as a whole and/or does it address an area from NIH as a whole and/or does it address an area of science that does not clearly fall within the of science that does not clearly fall within the mission of any one IC or OD program office?mission of any one IC or OD program office?

Is the proposed initiative something that no other Is the proposed initiative something that no other entity is likely or able to do, and is there a public entity is likely or able to do, and is there a public health benefit to having the results of the research health benefit to having the results of the research in the public domain?in the public domain?

Coordinated Efforts for Successful Coordinated Efforts for Successful Orphan Product Development/Rare Orphan Product Development/Rare

Diseases ResearchDiseases Research

Industry (Domestic and International, Large Industry (Domestic and International, Large and Small)and Small)

Academic and Research Community-Academic and Research Community-Multidisciplinary Research EffortsMultidisciplinary Research Efforts

Medical Specialty SocietiesMedical Specialty Societies Patient Advocacy Groups Patient Advocacy Groups Federal GovernmentFederal Government

• RegulatoryRegulatory• ReimbursementReimbursement• ResearchResearch

Intramural Research ProgramIntramural Research Program Extramural Research ProgramExtramural Research Program

Promoting Quality Genetic TestingPromoting Quality Genetic Testing

Formed - National Laboratory Network for Rare Formed - National Laboratory Network for Rare Disease Genetic Testing (NLN) Disease Genetic Testing (NLN) http://www.rarediseasetesting.org http://www.rarediseasetesting.org

Gaining acceptance of global testing servicesGaining acceptance of global testing services CLIA Certification Standards (USA)CLIA Certification Standards (USA) Interpretation of results with appropriate patient Interpretation of results with appropriate patient

counselingcounseling Collaboration, Education, and Genetic Test Collaboration, Education, and Genetic Test

Translation Program (CETT) PrototypeTranslation Program (CETT) Prototype Partnership and networks to improve research Partnership and networks to improve research

translation and data sharing translation and data sharing Between and among research and clinical Between and among research and clinical

laboratories laboratories Among research investigators, clinical laboratories, Among research investigators, clinical laboratories,

patient groups, clinicians, payerspatient groups, clinicians, payers

Challenges and Strategies- Goal: Quicker Challenges and Strategies- Goal: Quicker and Less Expensive Development of and Less Expensive Development of

Orphan ProductsOrphan Products Provide Global Access to Clinical Studies Provide Global Access to Clinical Studies

and Clinical Trials of Private and Public and Clinical Trials of Private and Public SectorsSectors

Develop Globalization of Research Efforts Develop Globalization of Research Efforts and Common Protocols with and Common Protocols with Multidisciplinary Research TeamsMultidisciplinary Research Teams

Continue Efforts for Harmonization of Continue Efforts for Harmonization of Research Data for Regulatory PurposesResearch Data for Regulatory Purposes

Establish Better Definitions of Patient Establish Better Definitions of Patient Responders with Development of Responders with Development of Appropriate Biomarkers and Surrogate Appropriate Biomarkers and Surrogate Endpoints for Safety and EfficacyEndpoints for Safety and Efficacy

Utilize Screening Processes of Industry and Utilize Screening Processes of Industry and Government Chemical LibrariesGovernment Chemical Libraries

Challenges and Strategies- Goal: To Obtain the Challenges and Strategies- Goal: To Obtain the Correct Diagnosis and to Improve Dissemination of Correct Diagnosis and to Improve Dissemination of

InformationInformation Expansion of Newborn Screening Programs Expansion of Newborn Screening Programs

Increased Development of Genetic and Diagnostic Increased Development of Genetic and Diagnostic Tests with Appropriate Counseling - CETT Pilot Tests with Appropriate Counseling - CETT Pilot ProgramProgram

Increase Educational Efforts for the Public and Increase Educational Efforts for the Public and Health Care Providers’ Communities Health Care Providers’ Communities • Diagnostic Criteria Rare Diseases and ConditionsDiagnostic Criteria Rare Diseases and Conditions• Disease Specific Available TreatmentsDisease Specific Available Treatments• Standards of Care for Emergency and Critical Care Standards of Care for Emergency and Critical Care

TreatmentsTreatments• Basis of Genetics and Inherited Disorders Basis of Genetics and Inherited Disorders

Expand Global Linkages of Patient Advocacy Group Expand Global Linkages of Patient Advocacy Group Networks Networks

Develop Inclusive Web-Based Inventory of Global Develop Inclusive Web-Based Inventory of Global Rare Diseases Research Studies/Intervention Rare Diseases Research Studies/Intervention Activities and Information Resources Activities and Information Resources

Challenges and Strategies – Goal: To Challenges and Strategies – Goal: To Meet Patient and Family NeedsMeet Patient and Family Needs

Identify and Expand Worldwide Partnerships Identify and Expand Worldwide Partnerships and Collaborations of Patient Advocacy Groupsand Collaborations of Patient Advocacy Groups

Identify Economic Impact of Rare Diseases on Identify Economic Impact of Rare Diseases on Families and IndividualsFamilies and Individuals

Expand Training Programs on Living and Expand Training Programs on Living and Coping with Rare and Genetic Diseases Coping with Rare and Genetic Diseases

Gaining Acceptance for Disabilities and Gaining Acceptance for Disabilities and Improving Educational Opportunities for Improving Educational Opportunities for PatientsPatients

Maximize Access to Rehabilitation Therapies – Maximize Access to Rehabilitation Therapies – Physical, Hearing, Speech, Vocational, Physical, Hearing, Speech, Vocational, Occupational, Occupational,

Assure Worldwide Access to Safe and Effective Assure Worldwide Access to Safe and Effective Products for the Prevention, Diagnosis, and Products for the Prevention, Diagnosis, and Treatment of Rare DiseasesTreatment of Rare Diseases

ORD WebsiteORD Websitehttp://rarediseases.info.nih.gov/http://rarediseases.info.nih.gov/

Rare Diseases Information – Pub MedRare Diseases Information – Pub Med

Research and Clinical Trials - CRISP, Research and Clinical Trials - CRISP, ClinicalTrials.govClinicalTrials.gov

Patient Support Groups - DIRLINE > 1200 Patient Patient Support Groups - DIRLINE > 1200 Patient Advocacy Groups, NORD, Genetic AllianceAdvocacy Groups, NORD, Genetic Alliance

Patient Travel & LodgingPatient Travel & Lodging

Genetics Information – Gene Tests, OMIM, NCHPEGGenetics Information – Gene Tests, OMIM, NCHPEG Research ResourcesResearch Resources Scientific Workshops, Archived ReportsScientific Workshops, Archived Reports Website TrendsWebsite Trends

• ~ 146,000 Users per Month~ 146,000 Users per Month

• Average Visit – 14 MinutesAverage Visit – 14 Minutes

The Genetic and Rare Diseases The Genetic and Rare Diseases Information Center (NHGRI/ORD)Information Center (NHGRI/ORD)

>14,500 Inquiries (2002 – 2006) >14,500 Inquiries (2002 – 2006)

> 4,000 Rare Diseases or Conditions> 4,000 Rare Diseases or Conditions

Toll-free 1-888-205-3223 (USA)Toll-free 1-888-205-3223 (USA)

International Access Number: 301-International Access Number: 301-519-3194519-3194

Fax: 240-632-9164Fax: 240-632-9164

E-mail: E-mail: GARDinfo@nih.govGARDinfo@nih.gov

Office of Rare DiseasesOffice of Rare DiseasesNational Institutes of HealthNational Institutes of Health

6100 Executive Boulevard 6100 Executive Boulevard

Room 3B-01, MSC - 7518Room 3B-01, MSC - 7518

Bethesda, MD 20892-7518Bethesda, MD 20892-7518

Voice: 301-402-4336Voice: 301-402-4336

Fax: 301-480-9655Fax: 301-480-9655

E-mail: E-mail: ORD@nih.govORD@nih.gov

Website: Website: http://rarediseases.info.nih.gov/http://rarediseases.info.nih.gov/

Office of Rare Diseases - StaffOffice of Rare Diseases - Staff Ms. Mary DemoryMs. Mary Demory Ms. Marita Eddy (Angel Flight)Ms. Marita Eddy (Angel Flight) Dr. John Ferguson (Consultant)Dr. John Ferguson (Consultant) Dr. Stephen C. GroftDr. Stephen C. Groft Dr. Rashmi Gopal-SrivastavaDr. Rashmi Gopal-Srivastava Mr. Christopher GriffinMr. Christopher Griffin Ms. Henrietta Hyatt-KnorrMs. Henrietta Hyatt-Knorr Ms. Sharon MacauleyMs. Sharon Macauley Ms. Geraldine Pollen (Consultant)Ms. Geraldine Pollen (Consultant) Dr. Giovanna Spinella (Consultant)Dr. Giovanna Spinella (Consultant) Dr. William Gahl (Clinical Director, NHGRI)Dr. William Gahl (Clinical Director, NHGRI)