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Funding for Genetic Testing
Guidelines for Submitting Funding Requests
The CETT Program released a revised application in July 2007. Collaborative groups are encouraged to use the new application immedietly. Applications conforming to previous verions should not be submitted after September 1, 2007. CETT
Program Application Submission Checklist Letters of Commitment from the
Collaborative Group Genetic Counselor (Clinical Laboratory) Current Draft Test Result Report Forms Variant of Unknown Significance/Indeterminate Molecular Tests: AR Disorder
with 1 Mutation Identified Table of Tests & Similar Methods
Currently Offered by the Clinical Laboratory Letter of Medical Necessity for Proposed
Test Non-genetic Health Care Professionals Genetics Health Care Professionals Clinical Data Collection Sheet CETT Program Application This document provides the CETT
Program Application.
1.
Identify the Collaborative
Group* Provide the main contact (name,
title, email, phone number, and website) for each participant category. Include a brief description of each person’s previous
and current activities related to the condition tested. Clinical Laboratory (CLIA) ______________________________________ Genetic Counselor (Clinical Laboratory) ___________________________ Research Laboratory (Researcher) _______________________________ Consulting Clinician (Research preferred) _________________________ Advocate Organization & Contact________________________________ If an advocacy organization is not involved in this application, please
explain. Others ____________________________________________________ 2.
Letters of
commitment and roles of Collaborative Group members a.
Attach a letter
from every member of the Collaborative Group outlining each individual’s:* ·
Proposed
activities related to the condition tested. ·
Role in the
collaboration. ·
Commitment to the
translation process. ·
Agreement to work
together to ensure that testing is available for a minimum of five (5) years. ·
Role(s) in the
work plan (see sections 13, 14, 15, 16). b.
Describe the
plan for regular communication between all members of the Collaborative Group. Specifically, identify the plans for: * i.
Interaction between
the clinical laboratory and the researcher/research laboratory. ii.
Interaction between
the patient advocate group, clinical laboratory, and researcher. Include the letters as
PDFs with an electronic application or mail signed copies to the CETT Program
Coordinator, Andy Faucett (email info@CETTProgram.org) 3.
Disease name and clinical description a.
Name of the
disorder for which testing is proposed: b.
OMIM
number(s) for the disorder: c.
Mode of
inheritance of the disorder: d.
In paragraph
form, describe the condition including the clinical features, natural history,
penetrance (for all disorders regardless of mode of inheritance), prevalence,
and, if known, incidence variation by population. e.
What is
known about the association of the disease (i.e., phenotype) and the proposed
test? Provide specific correlations
between the test results and phenotype.
How strong are the correlations? 4.
Genes a.
Complete
Table 1. Table
1. All genes known to be involved in this condition.
***This should be the sequence that you will use as your
reference sequence. b.
Complete
Table 2. * Table
2. Ability of proposed test method to identify mutations in this gene.
1
What percent of individuals with the condition have mutations in this
gene? 2
Proportion of affected individuals with a mutation(s) as classified by
gene/locus, phenotype, population group, and/or test method. c.
Is locus
heterogeneity known to exist for this condition? Is yes, please elaborate. d.
Are there
other phenotypes associated with mutations in this gene or test target? Provide the disease name and OMIM number for
each alternate phenotype. 5.
Test methods* a.
Identify the
test type(s) to be used in the proposed test. * Molecular Biochemical Cytogenetic Array Other b.
For
molecular tests describe in detail the methods: i.
Provide the
number and types of mutations in this gene identified to date (i.e. nonsense,
missense, frameshift, whole gene deletions, etc.). ii.
Give the
source of this information. iii. Have large deletions that require a test method other
than sequence analysis for detection been looked for and/or reported for this
gene and with what frequency? iv. How will such deletions be assessed? v.
What is the
plan to address situations such as possible UPD, homozygosity for autosomal
dominant or recessive mutations, etc. * c.
For
quantitative tests describe in detail the methods: i.
Provide the
reference range for affected and unaffected individuals and identify the source
of reference range. ii.
Do the reference
ranges overlap? d.
How will
ambiguous test results be interpreted? e.
For patients
who meet diagnostic criteria what is the probability of finding a positive test
result, negative test result, and indeterminate test result? * f.
What
limitations of the test influence this detection rate? g.
If the
initial testing is targeted, how will new findings be added to expand the
testing strategy? For molecular tests, describe why whole gene sequencing is or
is not needed. * h.
Provide the
plan for assay validation of the proposed test. i.
Does the
validation plan require positive controls? Discuss the availability of positive
control material and other reference material.
j.
Are any of
the control materials synthetic? Provide citations for all synthetic control
materials. 6.
Projected cost of test setup, test price, and test
turn-around time a.
What is the
estimated setup cost to the laboratory?
Include reasoning behind the estimate. * b.
What is the
estimated charge for the initial proband on a fee-for-service basis? Provide
the turnaround time. If the testing is offered in tiers, provide the price for
each tier and include the turnaround time for each tier. Include CPT codes and
units proposed. c.
What is the
estimated charge and turnaround time for testing family members? d.
What is the
anticipated volume of tests for the first year? On which of the following is the estimate in
(d) based upon (check all that apply): ____ disease incidence, ____ historical
requests, ____ survey of support group members, ____ other e.
If the
volume of testing were to be 10 times higher or lower than anticipated, are you
still prepared to offer the test? ____ No ____ Yes f.
Are there
patent issues with the proposed methodology? ____ No ____ Yes. g.
If yes, have
you negotiated an agreement with the patent holders? ____No ____Yes. Describe
the agreement or plan for discussion. 7.
Current diagnostic pathway and proposed diagnostic pathway a.
Provide the
current diagnostic criteria for the disorder. * b.
Current
diagnostic pathway. Provide a narrative and flow diagram of the current
diagnostic pathway. Include any exclusionary findings. In your narrative,
detail the cost and turnaround time for each laboratory test. c.
Proposed
diagnostic pathway. Provide a narrative and flow diagram of the diagnostic
pathway that includes the proposed test(s). Describe how the proposed test(s)
would be used with, or instead of, the testing in the current diagnostic pathway
detailed in (b) above. Does the proposed test(s) reduce/change the need for
other tests included in the current diagnostic pathway detailed in (b) above? d.
Discuss if the
proposed testing will be tiered (i.e., done in stages) and how the ordering for
each subsequent tier will be ordered. * e.
Discuss the
clinical finding(s) that should be present in a patient to warrant ordering the
proposed test; i.e., if these findings are not present, the yield on the test
will very low. f.
How will the
clinical laboratory handle a sample that has been submitted on a patient who
does not meet the minimum criteria in (e) above? g.
How will the
clinical laboratory handle a sample for which no clinical data are provided? 8.
Test result interpretation a.
Define a
positive and negative test result. b.
Explain in
detail how indeterminate results (e.g., variants of unknown significance (VOUS)
or borderline quantitative results) will be evaluated before being reported. c.
Will
patients who meet diagnostic criteria and have a negative or indeterminate test
result be referred to the researcher? If
so, how? * d.
Describe how
the test result interpretation is influenced by the phenotypic spectrum of the
condition. e.
Is there
enough evidence to interpret the significance of a “mild” phenotype associated
with specific mutations or results in an indeterminate range? f.
Discuss
whether penetrance and variable expressivity affect test result interpretation
and how this will be reported. g.
For biochemical
or other testing, does the sample type (e.g., fibroblasts vs. blood cells) affect
the test result and/or test result interpretation? h.
For molecular
genetic testing: i.
For autosomal
recessive disorders, in what proportion of patients will one allele be
identified and in what proportion of patients will both alleles be identified? ii.
How will the
test result report address the issue of large deletions? iii. Can carriers for an autosomal recessive disorder or
X-linked disorder be reliably detected using the proposed test methods? * 9.
Test result reports a.
Provide
a draft test result report form for each of the following test result types. * i.
Positive/abnormal ii.
Negative iii. Variants of unknown significance (VOUS) /
indeterminate results iv. For molecular testing of autosomal recessive
disorders when only one mutation is identified 10. References a.
Provide one
or more published references that address the issues above. Indicate the best
article to b.
Provide a brief
summary of the active research on this condition and gene. 11. Technical
experience of the clinical laboratory in diagnostic testing If
this is the first rare disease test to be performed by the clinical laboratory,
contact Dr. Suzanne Hart (shart@mail.nih.gov) for additional information that
may be needed in the application. Date Dr. Hart was contacted: ______. a.
Name and
certification(s) of laboratory director(s): b.
CLIA
certification number and expiration date: c.
Other
certification(s) of the laboratory: d.
Provide a
table that includes all tests currently performed by the laboratory, test
method, annual volume, and whether the test uses a kit or is laboratory
developed (homebrew). Indicate which
laboratory tests are for rare diseases (prevalence of less than 200,000 cases per
year in the e.
Total number
of disorders tested by a method similar to that proposed in the clinical
laboratory. f.
Total number
of tests offered by the laboratory. g.
Annual
volume of all genetic tests: _____>10 samples, _____ <100 samples, _____
100-500, _____ 501-1,000, _____ >1,000 h.
Briefly
describe the previous experience of the clinical laboratory in testing for rare
disorders and how that experience will be helpful in the current proposal. i.
Explain the
laboratory experience in assay validation. * j.
List the
members of the laboratory staff, their certification (AGT, other), number of years
each technician has worked in CLIA-certified diagnostic laboratories. k.
List the laboratory
genetic counselors, their certification, and source of funding (% laboratory, %
clinical responsibilities, % research, and % other). l.
Do you
anticipate staffing changes if this proposal is funded? ____ No ____ Yes If yes, discuss the specific
changes. 12. Potential
impact of the test on health a.
Indicate the
clinical laboratory’s commitment to offer testing in all of the following
scenarios. For each NO response, justify your reasoning for not offering testing.
i.
Diagnostic
testing YES
/ NO ii.
Confirmatory
diagnostic testing YES /
NO iii. Carrier testing * ·
At risk family
members YES / NO ·
Partners of
known carriers YES / NO ·
General
population testing YES / NO iv. Predictive or presymptomatic testing YES / NO v.
Prenatal
diagnosis YES
/ NO vi. Pre-implantation genetic diagnosis YES / NO If
the clinical laboratory does not
offer PGD, what steps will be taken to facilitate PGD testing at other
laboratories that offer this service? b.
How will the
results of the proposed test potentially change patient care? Describe how a laboratory representative,
such as a genetic counselor would justify use of the test to a clinician and to
a payer. * c.
Include a
letter of medical necessity that a clinician could submit to a payer to
facilitate reimbursement. 13. Laboratory-Clinical
interface a.
Describe the
interface between clinicians ordering tests and the clinical laboratory. * b.
Who will
provide medical consultation for test ordering and test result interpretation
for referring clinicians? Provide name certification of these individuals. How
will the researcher be part of this process? c.
How will the
researcher and advocate group be involved in laboratory-clinical interface? * d.
Are there clinical
experts who are part of a national network who might be involved in follow-up of
patients? Have you contacted this network? Describe any planned collaborations. 14. Educational materials * a.
Describe the work
plan(s) to develop educational materials for each of the three target
audiences: ·
Patients and
family members ·
Non-genetic
(primary care) healthcare professionals ·
Genetic health
care professionals In addition to providing a plan for specifically how the materials will
be developed, include the following information: i.
Names, experience and
expertise of the individuals involved and their specific responsibilities. ii.
Process and frequency
of updating these materials, including the individual(s) responsible. iii.
Distribution plan
for educational materials for each of the target audiences. iv.
Marketing plan for
the proposed test, including how it will be announced and to which target
audiences. b.
Select either
Option A or Option B below regarding submission and CETT Program review of
educational materials. Note: Both submission options require that revisions be
submitted to the CETT Program Coordinator for final review at least 4 weeks
prior to the start of clinical testing. i.
Option A – Submit draft versions for each target
audience with the Application. Indicate the primary author and the review
process to date. Feedback will be provided with the Review Board written
evaluation. ·
This is the
preferred option and should be used by applicants who anticipate that testing will
be ready for clinical use shortly after CETT Program approval ii.
Option B – Submit a timeline for development and
review of draft educational materials before release of the clinical test.
Drafts must be submitted to the CETT Program Coordinator no later than 6 weeks
after receipt of the written evaluation. The timeline should allow for feedback
and revision before the planned start of clinical testing. Initial feedback
from the CETT Staff and CETT Review Board will be provided approximately 4
weeks after receipt by the CETT Staff. ·
This option can be
used by applicants who believe that test translation will take several months. c.
Indicate whether
you are requesting the $1,000 to 15. Data
collection plan * a.
Applicants should
contact NCBI (cett@ncbi.nlm.nih.gov)
early in the application process to develop the data collection plan that will
include: ·
Creation and use
of electronic clinical submission sheets. ·
Secure URL for
data management. ·
Approaches to the
creation of de-identified data sharing. Date of contact to NCBI: ________ b.
Describe in detail
the plan for collecting, storing, and potentially evaluating clinical
information and genetic test results. Provide a description of the individuals,
responsibilities, and methods for collection and storage of results and
clinical information. Include the extent and timeframe for release of
information to public databases. |