Download No Slide Title - Lysosomal Disease Network

Rare Diseases Clinical Research Network
Data Management and Coordinating Center
(RDCRN DMCC)
Jeffrey Krischer, PhD
LDN Investigator Meeting at WORLDSymposium 2017
February 17, 2017
The Rare Diseases Clinical Research Network (RDCRN) is coordinated by the Office of Rare Diseases Research (ORDR),
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NCATS. Funding and programmatic support is provided by ORDR in collaboration with participating NIH Institutes.
RDCRN Members Overview
Data as of January 16, 2017
271 clinical centers
(+4 since 2/21/16)
144 patient advocacy groups
3,393 consortium members
(+132 since 2/21/16)
24,781 study participants
currently enrolled
(+3,522 since 2/21/16)
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Active RDCRN Studies
Data as of January 26, 2017
Distribution of Active RDCRN Studies
14%
Number of Active RDCRN Studies by Consortium
16
86%
Other Studies
LDN Studies
Number of Active Studies
14
12
10
8
6
4
2
0
Consortium
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RDCRN Protocol Activation
Data as of December 31, 2016
0.7 yrs
N=99
0.5 yrs
N=53
1.1 yrs
N=38
Median time to activation from initial protocol review
N = number of activated protocols
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LDN Protocol Activation
Data as of December 31, 2016
0.6 yrs
N=125
0.7 yrs
N=26
Median time to activation from initial protocol review
N = number of activated protocols
RDCRN 2nd and
3rd grant cycle
excluding LDN
activated
protocols.
Note: LDN values
represent RDN2 and
RDN3, since LDN
joined the network.
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LDN Accrual/Compliance by
Protocol
Data as of January 21, 2017
Lysosomal Disease Network
Active
Target
Enrollment
15
Enrolled
to Date
9
Protocol
Compliance (%)
100
Active
58
9
100
Active
60
6
100
Active
60
22
99.35
70
39
98.01
16
8
95.68
150
10
30
141
5
6
95.54
82.14
77.78
16
4
77.46
Protocol
Title
Status
6711
Expanded Screening for the Fabry Trait
Podocyturia, a Non-Invasive Predictor of Renal Dysfunction in Fabry
Nephropathy
Determinants of Renal Structural Responses to Enzyme Replacement
Therapy in Fabry Disease Study and Podocytes in Fabry Renal Disease
Natural History and Structural Functional Relationships in Fabry Renal
Disease
Carotid Structure and Function in MPS Syndromes: A Multicenter Study of
Lysosomal Disease Network
6725
6727
6702
6703
6704
6729
Closed to
Accrual
Closed to
A Study of Intrathecal Enzyme Replacement for Cognitive Decline in
Mucopolysaccharidosis I
Accrual
Longitudinal Studies of Brain Structure and Function in MPS Disorders
Active
The Natural History of Mucolipidosis Type IV
Active
Synergistic Enteral Regimen for Treatment of the Gangliosidoses (Syner-G)
Active
6728
An Extension Study of Intrathecal Enzyme Replacement for Cognitive
Decline in Mucopolysaccharidosis I
6720
6714
Active
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LDN Accrual/Compliance by
Protocol
Data as of February 9, 2017
Lysosomal Disease Network
Protocol
6705
6722
6713
67091
67161
67262
Title
Longitudinal Study of Bone and Endocrine Disease in Children with MPS I, II,
and VI
Role of Oxidative Stress and Inflammation in Type 1 Gaucher Disease (GD1):
Potential Use of Antioxidant/Anti-inflammatory Medications
A Natural History Study of the Gangliosidoses
Determination of Cross-Reactive Immunological Material (CRIM) status and
longitudinal follow-up
Genotype-Phenotype Correlations of Late Infantile Neuronal Ceroid
Lipofuscinosis
The Hunter James Kelly Research Institutes Clinical Database of Children with
Krabbe Disease
1Compliance
2Compliance
Status
Target
Enrolled
Protocol
Enrollment to Date Compliance (%)
Active
55
55
72.28
Active
50
13
70.50
Active
52
34
43.64
Active
300
155
-
Active
75
41
-
Active
60
0
-
information will become available pending data entry
information will become available pending participant accrual
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Collaboration with Industry
Protocol
LDN6703
LDN6705
LDN6707
LDN6708
LDN6709
Pharmaceutical Company
Genzyme Corporation, Shire HGT
Shire HGT
Shire HGT
Genzyme Corporation
Genzyme Corporation
LDN6711 Amicus Therapeutics, Shire HGT,
Genzyme Corporation
LDN6714 BioMarin Pharmaceutical, Inc.
LDN6722 Pfizer Inc., Shire HGT
Type of Support
Supplemental funding
Supplemental funding
Supplemental funding
Supplemental funding
Funding for processing of whole blood sample,
skin fibroblasts and mutation analysis
Supplemental funding
Supplemental funding (vials of Aldurazyme from
commercial source)
Supplemental funding
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LDN Data Submitted to dbGaP
Data submitted to the federal repository:
•
•
•
•
•
•
•
LDN6702: Natural History and Structural Functional Relationships in Fabry Renal Disease
LDN6703: Longitudinal Studies of Brain Structure and Function in MPS Disorders
LDN6704: The Natural History of Mucolipidosis Type IV
LDN6705: Longitudinal Study of Bone and Endocrine Disease in Children with MPS I, II, and VI
LDN6707: Characterizing the Neurobehavioral Phenotype(s) in MPS III
LDN6709: Determination of Cross-Reactive Immunological Material (CRIM) status and
longitudinal follow-up of individuals with Pompe disease
LDN6716: Genotype-Phenotype Correlations of Late Infantile Neuronal Ceroid Lipofuscinosis
LDN6719: Immune Response to Intrathecal Enzyme Therapy in Mucopolysaccharidosis 1 Patients
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ClinicalTrials.gov Update
Data as of January 21, 2017
All RDCRN studies should be registered
• Study Chair is responsible for registering study and uploading results.
LDN is currently 100% compliant with study registration.
• RDCRN report tracks registration and result status for each protocol
o GEN.I.14.ClinicalTrials.gov Protocol Status Report can be found on the
Members’ Website by navigating to the ‘Network Reports’ folder
• All NIH funded clinical trials (in whole or in part) should have
results posted to CT.gov within 1 year of completion date
• RDCRN CT.gov training available on Media Center
https://www.federalregister.gov/documents/2016/09/21/2016-22379/nih-policy-on-the-dissemination-of-nih-fundedclinical-trial-information
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Electronic Regulatory Binder
The Electronic Regulatory Binder (E-Reg Binder) is an online
interface for receiving and tracking regulatory documents
• Benefits of E-Reg Binder
o Centralized repository for all study related documents
o Increase efficiency by streamlining document storage and auditing
o Allows for the review of all regulatory documents remotely, thereby
reducing time spent on-site during audit visits
o Reduce costs and undue administrative burden at the local sites
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Single IRB NIH Requirement
RDN III protocols (current grant cycle):
• Plan for single IRB implementation if an active study will
continue into next grant cycle
• Multi-center studies that are listed in current grant application,
but are not yet activated, are not required to use single IRB until
grant renewal in 2018
In the 2018 competitive grant renewal submission, consortium
are expected to include a plan for implementation of single IRB
model
If preferred, single IRB model can be implemented prior to the
submission of the 2018 application
http://osp.od.nih.gov/sites/default/files/sIRB_Extramural_FAQs.pdf
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OneIRB Coordinating Center
The OneIRB CC interacts
directly with the single
IRB of Record on
consortium’s behalf to:
• Submit initial IRB
applications,
amendments, continuing
reviews, and reportable
events
• Respond to IRB queries
• Distribute IRB approval
letters and stamped
consent forms to sites
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LDN Sites and OneIRB
LDN Sites Utilizing OneIRB
Children's Hospital of Pittsburgh
Cincinnati Children's Hospital Medical Center
Mayo Clinic - Rochester
Oregon Health & Science University
University of California, Los Angeles
University of California, San Francisco
University of Chicago
University of Miami
University of Minnesota
University of Rochester
University of Utah
LDN Sites with Plans to Implement OneIRB
Baylor College of Medicine
Cedars-Sinai Medical Center
Duke University
Emory University
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RDCRN Contact Registry
Data as of January 16, 2017
Goals: To inform registrants about RDCRN studies available;
To disseminate information about RDCRN activities
Overall (All consortia):
• 19,975 total registrations
• 109 countries
• 177 diseases represented
LDN Contact Registry:
• 70 total registrations
• 11 countries
• 24 diseases represented
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Joining the RDCRN LDN Contact
Registry
“How Did You Hear About the RDCRN LDN Contact Registry?”
3%
4% 3%
Internet Search
6%
Medical Professional
Support Group or Foundation
13%
Other
56%
15%
Missing
Publication
Word of Mouth
http://www.rarediseasesnetwork.org/LDN/registry/index.htm
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RDCRN LDN Contact Registry
Enrollment
Opportunities for increasing LDN Contact Registry Enrollment:
• Addition of link to the RDCRN Contact Registry
o LDN public website
o PAG website(s)
o Social media
• Distribution of Contact Registry Interest Form
o In clinic/at study visits
o At Patient Advocacy Group (PAG) meetings
• Auto-enrollment of longitudinal study participants into contact registry
• Use google analytics to determine demand for public facing registry
http://www.rarediseasesnetwork.org/documents/LDNContactRegistryForm.pdf
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Recent Contact Registry
Enhancements
o Mobile friendly webpages
o Updated enrollment form content
 Ability to enroll unaffected family members (for the 16 consortia who
opted in to this feature: UCDC, RLD, MCC, BVMC, RKSC, INC, LDN,
NEPTUNE, PIDTC, STAIR, PC, NAMDC, BBD, CEGIR, DSC, CReATe)
 Ability to enroll multiple affected family members at the same time (ex.
one parent enrolling multiple affected children)
 Ability to select diseases across consortia
o Option for registrants to create a login so they can update their enrollment
information in the future and access a customized dashboard which includes:
 Area where participants can complete surveys, view completed surveys,
and update information
 Area to echo information to participants on the number of participants
enrolled, gender, age, disease, location, etc. (Participant Summary)
 Network and consortium announcements
 Consortia and PAG social media links
 Ability for participants to easily send a template Contact Registry invitation
email to others
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Recent Contact Registry
Enhancements
 Utilization Update:
o 908 new registrants have joined the Contact Registry since the enhancements
went live
 750 of the new registrants (83%) chose to set-up a username and
password
 43 of the new registrants have enrolled multiple patients (ex. registrant is a
patient and has a child who is a patient, registrant has two children who
are both patients)
o 98 registrants who had joined the Contact Registry prior to the enhancements
promotion have since returned to update their username and password and
login to the dashboard
 Note: The enhancements have not been advertised to registrants. These are people that returned to the
Contact Registry login page on their own and updated their information.
o 52 emails have been sent by registrants to invite others to join the Contact
Registry through the “More Ways to Help” tool on the dashboard
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RDCRN Contact Registry
Enhancements
Enrollment
Member Homepage
Participant Summary
(Statistics)
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RDCRN Tools: Patient Portal
• Participants and parents
can complete forms at
home or online in clinic.
• Login information is the
Participant ID and Local ID.
• If interested, this could be
implemented in LDN
protocols in the future.
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RDCRN Enhancements
Enhancements:
•
•
•
•
•
•
•
•
•
Data Sharing Policy template development
Remote and risk-based auditing
Electronic Site Delegation Log (E-SDL)
OneIRB
Provision and utilization of third party applications, such as REDCap
Interactive study data (accessible by participants)
Cross-consortia/cross-study collaboration
Outreach and awareness via Social Media
Patient Advocacy Groups (PAGs) engagement
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Thank you
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