Test Translation Program

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22 Οκτ 2013 (πριν από 3 χρόνια και 9 μήνες)

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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



Collaboration Education and

Test Translation Program

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


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 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

ORD Program Director:

Project Coordinator:

Scientific Advisor:

Review Board Coordinator:

NCBI Liaison:

Program Staff

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


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 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