Test Translation Program


22 Οκτ 2013 (πριν από 4 χρόνια και 6 μήνες)

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Collaboration Education and

Test Translation Program


Giovanna Spinella, MD

Science and Program Consultant


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








Genetic Alliance

How We Started

May 19

21, 2004 Atlanta, GA


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

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

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


Accepted monthly

Reviewed in 2 month cycle


September 2006

10 approved, 8 in

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

Laboratory genetics

Medical genetics


Primary care

Disease specific advocacy

Review Board

Vet guidelines by which applications are

Evaluates quality of each application

Provides constructive feedback for each

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/

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

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
(first year)

Evidence of Collaboration

All have active roles

Interviews by staff to clarify roles

Referral of patients by clinical lab to

Disease specific advocacy group:

Ensures appropriateness/dissemination
of educational materials

Is resource for patients and families


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

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

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)

Linked Periventricular nodular heteroptopia

(Harvard U)

Rare Diseases Approved for Translations

Multiple Methodology Approach to testing:

Linked Chondrodysplasia

genetic testing in collaboration with
biochemical genetic sterol analysis
mass spectrometry (U Chicago)

Silver Russel Syndrome
(quantitative Taqman) assay and molecular
genetic testing (Emory U)

Experience of CETT Program to Date

Variability in Collaborative Group Composition:

spectrum from fully formed
organizations to individuals willing to help

spectrum from full compliment of
research laboratory expertise and clinical
expertise to predominance of one or the

Approved International research
collaboration and advocacy collaboration

Experience of CETT Program to Date

Need for templates of educational materials
for understanding genetic test and rare
diseases for clinicians and individuals and

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

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

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)


Office of Rare Diseases (ORD)

Stephen Groft, Pharm D, Director

National Institutes of Health