Transcript Application Review

Collaboration Education and
Test Translation Program
Collaboration Education and
Test Translation Program
www.cettprogram.org
Giovanna Spinella, MD
Science and Program Consultant
NIH ORD CETT Program
Quality, Access, and Sustainability of Biochemical Genetic
Testing Working Meeting
Atlanta, October 6-7, 2006
Quality Testing Rare Genetic Diseases:
Steering Committee
CDC
NIH-ORD
EMORY
HRSA
ASHG
ACMG
SIMD
Genetic Alliance
How We Started
May 19–21, 2004
Atlanta, GA
http://www.phppo.cdc.gov/dls/genetics/RareDiseaseConf.aspx
March 17, 2005
ACMG Satellite
September 26–27, 2005
Washington, DC
CETT Program Objectives
Promote new genetic test development
Translate from research to clinical practice
Educate about each rare genetic disease;
research opportunities & clinical impact
Collect and Store clinical and genetic
information
CETT Program Philosophy
All parties benefit when:
Quality of testing for rare disorders meets or
exceeds existing standards
Clinical laboratories, researchers, clinicians,
and disease specific advocacy groups
collaborate
High-quality educational materials explain
what the test can and cannot tell you and
how best to use the test
CETT Program
First applications accepted Feb-March 2006
Facilitated application process
• Constructive feedback
Applications
• Accepted monthly
• Reviewed in 2 month cycle
Progress
• September 2006 – 10 approved, 8 in
queue
Applicants = Collaborative Group
Clinical (CLIA-certified) laboratory
Researcher (laboratory and/or clinician)
Disease specific advocacy group
The CETT/NCBI Partnership
What can NCBI (National
Center for Biotechnology
Info) do for CETT
Collaborative Groups?
Help develop a useful data
collection scheme
Put data in a broader context
to help advance knowledge
about the disorder
Advocate Mentors
Group of disease specific advocate leaders
Resource to each collaborative group
Assigned early in the process
Review Process
Staff reviews for completeness
One month goal
Review Board evaluates quality
One month goal
Review Board
15 Members
Three teams of five members, one each
from:
• Laboratory genetics
• Medical genetics
• Research
• Primary care
• Disease specific advocacy
Review Board
Vet guidelines by which applications are
evaluated
Evaluates quality of each application
Provides constructive feedback for each
application
Scientific Evidence
How many genes cause the disorder?
What percentage of patients have mutations
in the gene for which testing is proposed?
What percent will be detected compared to
current testing?
Proposed Methodology
Is the approach efficient & cost effective?
How will unusual results be evaluated?
If mutation screening is used, how will
negative results be evaluated?
Are other methods of diagnosis available?
Replace / compliment?
Impact on Healthcare
What are the indications for testing?
How will proposed test change current
diagnostic pathway?
Could correct diagnosis reduce
unnecessary diagnostic testing/facilitate
genetic counseling?
Could early diagnosis reduce morbidity/
mortality?
Laboratory Qualifications
Director’s certification
CLIA or other certification
Number of disorders tested
Staffing for the clinical-laboratory interface:
genetic counselors?, physician consultants?
Data Collection
Clinical information necessary for test
result interpretation collected on a SHORT
form at the time test is ordered
Subset of clinical and genotype
information entered in publicly accessible
database
Multiple pathways suggested
Educational Materials
Provided for three audiences: Medical
geneticists, non-geneticist clinicians, patients
Test ordering
Test result interpretation for negative,
positive, or indeterminate results
Uses of testing in diagnosis,
management, genetic counseling
Create a GeneReview (first year)
Evidence of Collaboration
All have active roles
Interviews by staff to clarify roles
Referral of patients by clinical lab to
researcher
Disease specific advocacy group:
• Ensures appropriateness/dissemination
of educational materials
• Is resource for patients and families
Funding/Commitment
Based on complexity of the test process
Does not include equipment or institutional
costs (or cost of patient test)
Collaborative group provides feedback to
CETT Program for 5 years (from when
genetic test is put in public domain)
Potential Outcomes
Improve understanding of CLIA and quality
standards
Improve dialogue among stakeholders:
Clinical laboratories, reference laboratories,
researchers, clinicians, disease specific
advocates, oversight bodies, payers
Collect genotype/clinical information:
-improve test interpretations
-genotype/phenotype correlations
Program Staff
ORD Program Director:
Project Coordinator:
Scientific Advisor:
Review Board Coordinator:
NCBI Liaison:
Giovanna Spinella, MD
Andrew Faucett, MS
Suzanne Hart, PhD
Roberta Pagon, MD
Lisa Forman, PhD
Rare Diseases Approved for Translations
Molecular Genetic Tests:
 Cherubism (Toronto Sick Children)
 Cornelia de Lange Syndrome (U Chicago) )**Clinically
Available
 Infantile Neuroaxonal Dystrophy (Oregon Health and
Science U)
 Joubert Syndrome (Prevention Genetics)
 Kallman Syndrome (Gene DX)
 Progressive Familial Intrahepatic Cholestasis (8
diseases/3 genes) (Baylor U-Mitochondrial Lab)
 X-Linked Periventricular nodular heteroptopia
(Harvard U)
Rare Diseases Approved for Translations (cont.)
Multiple Methodology Approach to testing:
X-Linked Chondrodysplasia- molecular
genetic testing in collaboration with
biochemical genetic sterol analysis-clinical
mass spectrometry (U Chicago)
Silver Russel Syndrome-methylation
(quantitative Taqman) assay and molecular
genetic testing (Emory U)
Experience of CETT Program to Date
Variability in Collaborative Group Composition:
• Advocacy-spectrum from fully formed
organizations to individuals willing to help
• Research-spectrum from full compliment of
research laboratory expertise and clinical
expertise to predominance of one or the
other
• Approved International research
collaboration and advocacy collaboration
Experience of CETT Program to Date (cont.)
Need for templates of educational materials
for understanding genetic test and rare
diseases for clinicians and individuals and
families
Need for report forms to be interpretable to
non genetic clinicians (example language)
Need for test results to be understandable
and provide limitations of test
Experience of CETT Program to Date (cont.)
Laboratory Issues-molecular genetic testing:
• clinical significance of variance of
unknown significance (VOUS)
• appropriate control samples for test
validation
• reasonable turn around time from test
submission to providing test results
• Informed consent issues regarding testing
and in placing non identifiable data in
public databases
Expanding CETT Program Approaches
(to biochemical)
Modify current application form to
accommodate non molecular genetic testing
approaches and multiple approaches
Add biochemical scientific advisor to CETT
Program staff
Expand Review Board expertise
Develop guidelines for quality control,
quality assurance
Identify guidelines for cost of test
development (where possible)
THANKS TO
Office of Rare Diseases (ORD)
Stephen Groft, Pharm D, Director
National Institutes of Health
www.cettprogram.org