Collaboration Education and
Test Translation Program
www.cettprogram.org
Giovanna Spinella, MDScience and Program Consultant
NIH ORD CETT ProgramQuality, Access, and Sustainability of Biochemical Genetic
Testing Working MeetingAtlanta, October 6-7, 2006
Collaboration Education andTest Translation Program
Quality Testing Rare Genetic Diseases:Steering Committee
CDC NIH-ORD EMORYHRSA
ASHGACMGSIMD Genetic Alliance
How We Started
May 19–21, 2004 Atlanta, GAhttp://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 practiceEducate about each rare genetic disease;
research opportunities & clinical impactCollect 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 2006Facilitated application process
• Constructive feedbackApplications
• Accepted monthly• Reviewed in 2 month cycle
Progress• September 2006 – 10 approved, 8 in
queue
Applicants = Collaborative Group
Clinical (CLIA-certified) laboratoryResearcher (laboratory and/or clinician)Disease specific advocacy group
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
The CETT/NCBI Partnership
Advocate Mentors
Group of disease specific advocate leadersResource to each collaborative groupAssigned early in the process
Review Process
Staff reviews for completenessOne month goal
Review Board evaluates qualityOne month goal
Review Board
15 MembersThree 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 applicationProvides 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 certificationCLIA or other certificationNumber 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 resultsUses of testing in diagnosis,
management, genetic counselingCreate a GeneReview (first year)
Evidence of Collaboration
All have active rolesInterviews by staff to clarify rolesReferral of patients by clinical lab to
researcherDisease specific advocacy group:
• Ensures appropriateness/dissemination of educational materials
• Is resource for patients and families
Funding/Commitment
Based on complexity of the test processDoes 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
ORD Program Director: Project Coordinator:
Scientific Advisor:Review Board Coordinator:
NCBI Liaison:
Program Staff
Giovanna Spinella, MDAndrew Faucett, MSSuzanne Hart, PhDRoberta Pagon, MDLisa 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
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
Experience of CETT Program to Date (cont.)
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 expertiseDevelop guidelines for quality control,
quality assuranceIdentify guidelines for cost of test
development (where possible)
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