The Rare Diseases Clinical Research Network (RDCRN)

Data current as of October 22, 2014

Rare Diseases Clinical Research Network (RDCRN) is coordinated by Office of Rare Diseases Research, NCATS. Funding and programmatic support is provided by ORDR in collaboration with participating NIH Institutes.

Rare/Orphan Diseases

• The FDA defines an orphan disease as:• A condition affecting <200,000 Americans Or• A disease with greater prevalence but no

reasonable expectation that drug development costs are recoverable by U.S. sales

• There are an estimated 6,000 rare diseases• Approximately 25 million Americans have a

rare disease

Challenges for Rare Diseases Research

• Disease often not well characterized or defined• Rarity means:

– Recruitment for trials is usually quite difficult– Study populations become widely dispersed– Few expert centers for diagnosis, management,

and research• Often little high-quality evidence available to

guide treatment

Goals of the RDCRN

• Facilitate clinical research by:– Creation of Consortia focused on related diseases– Cost-sharing research infrastructures– Establishing uniform protocols for data collection – Making meaningful large-scale studies possible

• Longitudinal cohorts, pilot projects, and randomized trials

• Directly engage patients and their advocates

• Train new investigators in rare diseases research

RDCRN

- Established by the Office of Rare Diseases Research- Started in 2003--currently in 3rd 5 year cycle - 1st cycle (10 Consortia) supported by ORDR, NCRR, NINDS, NIAMS, NICHD, NHLBI, NIDDK - 2nd cycle (19 Consortia) supported by ORDR, NINDS, NIAMS, NICHD, NHLBI, NIDDK, NIAID, NIDCR, NCI - 3rd cycle (22 Consortia) supported by ORDR, NINDS, NIAMS, NICHD, NHLBI, NIDDK, NIAID, NIDCR, NCI, NIMH- Currently involves 258 institutions world-wide- Collectively studying >200 diseases- 32836 patients enrolled in studies (during all 3 grant cycles)

•Collaborative Clinical Research

•Centralized Data Coordination and Technology Development

•Public Resources and Education

•Training

DHHS-NIHORDR, NINDS, NIAMS, NICHD, NHLBI, NIDDK,

NIDCR, NIAID, NCI, NIMH

The Data Management and Coordinating Center

Coalition of PatientAdvocacy Groups

(CPAG)DystoniaCoalition

Brain VascularMalformation Consortium

Genetic Disorders of Mucociliary Clearance Consortium

Chronic Graft Versus Host Disease Consortium

Nephrotic SyndromeRare Disease Clinical

Research Network

Primary Immune DeficiencyTreatment Consortium

LysosomalDisease Network

Autonomic Rare DiseasesClinical Research Consortium

Inherited NeuropathiesConsortium

Rare KidneyStone Consortium

Urea Cycle DisordersConsortium

Vasculitis ClinicalResearch Consortium

Porphyria Rare DiseaseClinical Research Consortium

Rett Syndrome, MECP2 Duplications, and Rett-related

Disorders Consortium Clinical Research in ALS and

Related Disorders for Therapeutic Development

Sterol and IsoprenoidDiseases Consortium

North America MitochondrialDiseases Consortium

Consortium for Eosinophilic Gastrointestinal Disease Researchers

Rare Lung Disease Consortium

Brittle Bone Disease Consortium

Frontotemporal Lobar Degeneration Clinical Research Consortium

Development Synaptopathies

Consortium

•Collaborative Clinical Research

•Public Resources and Education

•Centralized Data Coordination and

Technology Development

•Training

DHHS-NIHORDR, NCATS, NINDS, NIAMS, NICHD,

NHLBI, NIDDK, NIDCR, NIAID, NCI, NIMH, ODS

The Data Management and Coordinating Center

Coalition of PatientAdvocacy Groups

(CPAG)

Rett Syndrome, MECP2 Duplications, and Rett-related Disorders Consortium

Frontotemporal Lobar Degeneration Clinical Research Consortium

Clinical Research in ALS and Related Disorders for Therapeutic Development

Brittle Bone Disorders Consortium

Developmental Synaptopathies Consortium

Rare Lung Diseases Consortium

Coalition of Patient Advocacy Groups (CPAG) (> 95 PAGs)

Coalition of Patient Advocacy Groups (CPAG) (> 95 PAGs)

Data Management and Coordinating Center (DMCC)

Data Management and Coordinating Center (DMCC)

Urea Cycle Disorders Consortium

RDCRN Consortia, DMCC and CPAG

RDCRN Consortia, DMCC and CPAGSteering CommitteeSteering Committee OSMBs/DSMBsOSMBs/DSMBs

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

Rare Lung Diseases Consortium

Sterol and Isoprenoid Disorders Consortium

Vasculitis Clinical Research Consortium

Rare Kidney Stone Consortium

Primary Immune Deficiency Treatment Consortium

Porphyrias Consortium

North American Mitochondrial Disease Consortium

Nephrotic Syndrome Study Network

Lysosomal Disease Network

Inherited Neuropathies Consortium

Genetic Disorders of Mucociliary Clearance Consortium

Frontotemporal Lobar Degeneration Clinical Research Consortium

Dystonia Coalition

Development Synaptopathies Consortium

Clinical Research in ALS and Related Disorders for Therapeutic Development Consortium

Rett Syndrome, MECP2 Duplications, and Rett-related Disorders Consortium

Autonomic Rare Diseases Clinical Research Consortium Brain Vascular Malformation

Consortium Brittle Bone Disorders

Consortium Chronic Graft Versus Host

Disease Consortium

Consortium for Eosinophilic Gastrointestinal Disease Researchers

NIDCRNIDCRNIAMSNIAMS NIDDKNIDDK ODSODSNCINCI NINDSNINDSNHLBINHLBI NIMHNIMHNIAIDNIAID

ORDR/NCATSORDR/NCATSProgram Coordination

ORDR/NCATSORDR/NCATSProgram Coordination

NIHNIH

NICHDNICHD

RDCRN Data Management and Coordinating Center (DMCC)

• Supports RDCRN by providing technologies, tools, and support of study design and data analysis

• On-line protocol management system– Patient enrollment/randomization– Data entry and collection with data standards– Adverse event reporting

• Protocol training for research staff • Members’ website: documentation, databases• Hosts RDCRN public website (>2 million hits/year)• Oversees the RDCRN Contact Registry

RDCRN Websitehttp://rarediseasesnetwork.org

• Portal to websites for each Consortium

• Portal to members’ website

• Portal for patient advocacy groups

• RDCRN Contact Registry

• RDCRN Media Center

RDCRN Web Stats for Last 12 Month Period

Consortium Visits HitsAutonomic Rare Diseases Clinical Research Consortium 179584 1678884Porphyrias Consortium 105456 789571Urea Cycle Disorders Consortium 86952 494469Vasculitis Clinical Research Consortium 84297 633843Dystonia Coalition 80243 589469North America Mitochondrial Diseases Consortium 65341 498576Inherited Neuropathies Consortium 48655 306774Nephrotic Syndrome Rare Disease Clinical Research Network 47259 315286Angelman, Rett, & Prader-Willi Syndromes Consortium 45242 365717Brain Vascular Malformation Consortium 43507 208216Sterol and Isoprenoid Disease Consortium 33196 144332Rare Kidney Stone Consortium 32462 145263Primary Immune Deficiency Treatment Consortium 32417 201525Genetic Disorders of Mucociliary Clearance Consortium 27300 109832Chronic Graph Versus Host Disease Consortium 23071 119096Salivary Gland Carcinomas Consortium 12740 53183Lysosomal Disease Consortium 10038 17354

Hit: Each file requested by a visitor registers as a hit. There can be several hits on each page.Visit: The number of times a visitor viewed at least one page.

RDCRN Protocol Activity

- 21 Consortia with NIH approved protocols- 79 Accruing protocols- 11 Accrual goal met- 258 Clinical Sites

Consortia Protocol Accrual

Total Participants Registered as of October 22,

2014Consortium Cumulative Current Calendar Year

Autonomic Rare Diseases Clinical Research Consortium 646 114Brain Vascular Malformation Consortium 1699 179Chronic GVHD Consortium 1303 156Dystonia Coalition 3995 436Genetic Disorders of Mucociliary Clearance Consortium 1202 19Inherited Neuropathies Consortium 6295 1918Lysosomal Disease Network 568 33Nephrotic Syndrome Study Network 1113 135North American Mitochondrial Disease Consortium 1582 919Porphyrias Consortium 1482 338Primary Immune Deficiency Treatment Consortium 1011 156Rare Kidney Stone Consortium 2161 1093Rare Lung Disease Consortium 340 0Rett Syndrome, MECP2 Duplications, and Rett-related Disorders Consortium 2812 33Sterol and Isoprenoid Research Consortium 53 3Urea Cycle Disorders Consortium 846 43Vasculitis Clinical Research Consortium 5728 524

32836 6099

Protocol by NIH Institute

Institute ConsortiumProtocols in

developmentActive

ProtocolsClosed

ProtocolsNCI Chronic Graft vs Host Disease 3 1 0NHLBI Mucociliary Clearance 3 1 0NIAID Primary Immune Deficiency 0 4 0NIAMS Brittle Bone Disorders 4 0 0

Vasculitis 10 10 1NICHD Sterol and Isoprenoid Diseases 2 3 0

Urea Cycle Disorders 3 4 2NIDCR Salivary Gland Carcinomas 0 0 2NIDDK Nephrotic Syndrome 2 2 0

Porphyria 0 7 0 Rare Kidney Stone 2 11 0

NINDS Autonomic Rare Diseases 3 3 1 Brain Vascular Malformation 1 5 0 Eosinophilic Gastrointestinal Disease 0 0 0 ALS and Related Disorders 1 0 0 Dystonia Coalition 0 2 0 Development Synaptopathies 1 0 0 Frontotemporal Lobar Degeneration 0 0 0 Inherited Neuropathies 5 5 0 Lysosomal Disease Network 4 11 5 North America Mitochondrial Diseases 1 10 0

RDCRN Patient Contact Registry

- Enrollment open to patients with diseases under study by Consortia- Provides international on-line system for communication, recruitment, research- 187 Diseases represented- 14019 Registrations

Contact Registry Accrual

RDCRN U.S. Sites

RDCRN North America Sites

RDCRN European Sites

RDCRN World Sites

U.S. Geographic Distribution of Contact Registrants

North America Geographic Distribution of Contact Registrants

European Geographic Distribution of Contact Registrants

World Geographic Distribution of Contact Registrants

Start of Consortium-Specific Slides

BVMC U.S. Sites

BVMC North America Sites

BVMC European Sites

BVMC World Sites

BVMC U.S. Geographic Distribution of Contact Registrants

BVMC North America Geographic Distribution of Contact Registrants

BVMC European Geographic Distribution of Contact Registrants

BVMC World Geographic Distribution of Contact Registrants

BVMC Contact Registrants by Disease

Disease N PercentFamilial Cavernous Malformations (CCM) - Common Hispanic Mutation 33 25%

Hereditary Hemorrhagic Telangiectasia (HHT) - Brain Arteriovenous Malformation (BAVM) 30 23%

Multiple Diseases 3 2%

Sturge-Weber Syndrome (SWS) - Leptomeningeal Angiomatosis 65 50%

131 100%

BVMC Contact Registry Accrual Over Time

BVMC Accrual by Protocol

RDCRNProtocol Number Title

Enrollment goal

Target Enrollment

To DateEnrolled to Date

6201 Project 1: Modifier Genes in Cerebral Cavernous Malformations 500 454 222

6202 Project 2: Innovative approaches to gauge progression of Sturge-Weber Syndrome

300 253 134

6203 Project 3: Cerebral Hemorrhage Risk in Hereditary Hemorrhagic Telangiectasia 3500 3126 976

6204 Establishing reliability for Quantitative EEG, Transcranial Doppler, behavioral outcomes and Optical Coherence Tomography in SWS: The next step toward biomarker development

40 40 39

6205 Project 1 Pilot Protocol: Permeability MRI in Cerebral Cavernous Malformations Type 1 in New Mexico: Effects of Statins

30 30 8

6207 Topical Anti-angiogenic Therapy for Telangiectasia in HHT: Proof of Concept 10 10 0

BVMC Accrual (cumulative) by Protocol

BVMC Accrual (cumulative) Over Time

BVMC Trainees

BVMC Recent Publications

www.rarediseasesnetwork.org

www.rarediseasesnetwork.org/bvmc