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Application Instructions
Guidelines for Submitting Funding Requests
Click here to download a Microsoft Word version of this document. CETT Program Application Instructions The CETT Program released
the third version of the Application and Instructions in June 2008. All Applications
must now be submitted in CETTrack. CETTrack is a secure electronic program for
tracking all CETT Program processes. Applicants can develop their Collaborative
Group application and track the process through review, disposition and post
funding activities. We strongly
encourage all applicants to contact Andy Faucett, CETT Program Coordinator
(info@CETTProgram.org or 404-778-8420), early in the process to obtain assistance. He will REGISTER your Collaborative
Group and potential Application in CETTrack. He is available to provide an
early review of individual application sections to a Collaborative Group seeking
additional guidance or to address other issues throughout the application
process. Collaborative
Groups submitting applications which are not DNA sequence-based assays or
applications which have multiple testing platforms must contact the CETT
Program Coordinator for guidance. The letters in the instructions refer to the
letters in the application document. 1. Register the Collaborative Group
in CETTrack The lead person
for each Application must contact the CETT Program Coordinator and initiate the
Registration process. Each member of the Collaborative Group must be registered
in CETTrack. The Collaborative Group is expected to include the following:
More than one
individual may be registered in each category. There may be multiple
individuals for each role (e.g. researchers, clinicians, and patient
advocates). Collaborative Groups that
need additional assistance identifying members for the requested roles should
contact the CETT Program Coordinator for further assistance. In the Application
include a brief description to explain why the members of the Collaborative
Group are the appropriate individuals to translate and support this new or
improved clinical test. If any of the
Required Members of the Collaborative Group are missing this should be
discussed with the CETT Program Coordinator and a backup plan should be
provided in the Application. For example if there is no specific Advocacy
organization, how will this critical role be filled. 2. Letters of
commitment and roles of collaborative group members a. Each member of the Collaborative
Group should independently upload a personal letter of commitment in CETTrack. b. In the letters of collaboration, specify the
actual work plan and the role for each member. Consider the following guidance in your
answers: What will the role of the patient advocate group be in the project? Do
they have adequate staffing? What is the relationship between the clinical
laboratory and the research laboratory? How will they work together on new
findings, etc? Who will provide clinical c. Describe the plan for regular communication
between all members of the Collaborative Group.
Regular communication among the laboratory, researcher, and advocate is
encouraged during the application process and once the test is available. NOTE: Joint
Letters of Collaboration are no longer accepted per the Review Board. 4. Genes b. For sequenced-based molecular tests,
complete Table 2. How well does the proposed test identify mutations in the
gene? By completing Table 2, estimate
the power of the approach to detect the various types of mutations in that gene.
For non-sequence-based tests, provide the proposed method,
the target tested for, the proportion of disease attributed to the test target,
and the detection of the target using the proposed method. 5. Test methods Although
the majority of applications to date rely on DNA sequencing, the CETT Program
accepts applications for any appropriate testing platform. Contact Andy
Faucett, CETT Program Coordinator, for further guidance on non-molecular testing
platforms. a. Identify the test type(s) and
describe in detail the methods to be used in the proposed test. Why was this method chosen? How does it
compare with other methods? If more than one test method is necessary to
achieve the detection rate included in Table 2, include information on each of
the methods. b. For sequenced-based tests: v. Have large deletions been looked for
and/or reported for this gene? Cite
methods used to identify large deletions, their frequency, and sources for this
information. How will your proposed testing scheme assess large deletions? How will you consider UPD and single or
multiple exon deletions in test result interpretation? Consider addressing
apparent homozygosity in autosomal dominant and recessive disorders. e. For example, assume that 100 samples
that meet your minimum eligibility criteria are submitted to the laboratory. In
the flow sheet, take these 100 samples through your testing plan and include
the anticipated outcome (i.e., number of positive, negative, and indeterminate
test results). From what source or
reference is this estimate derived? g. If the proposed test targets specific
findings or is limited to specific regions of the gene/chromosome, how will new
findings be added to expand the testing strategy? For example, if the
researcher identifies a mutation in exon 10 of the gene, and the proposed test
sequences only exons 4-8, how will the clinical laboratory incorporate this new
information into the proposed test? For molecular tests, describe why whole
gene sequencing is or is not needed. 6. Project cost of test setup and
Funding Request For
non-sequencing based tests, contact the CETT Program Coordinator before
completing this section. The CETT Program does not fund indirect costs; if indirect
costs are required by the applicants institution, they should be included in
the projected cost of test setup. a. Prepare a translation budget that
includes materials, labor and other costs associated with test translation, not
test development. Equipment costs over $500 cannot be included. The CETT
Program funding is intended to supplement test translation funding provided by
the clinical laboratory and/or patient advocacy organization. Indicate the
laboratorys contribution for test translation. Outline other promised or
potential sources of funding. As of June
2008 the CETT Program is providing additional funding to support the
development of the collaboration; the participation of the researcher in test translation
and consultation on unusual results; and the development of educational
materials. In the Application indicate how the funds will be distributed.
Funding will be provided from the NIH Office of Rare Diseases Research via a procurement
contract. The CETT Program prefers to distribute funds to a single member of
the Collaborative Group and then that member will distribute funds to the other
members as indicated in the Application. 8. Current diagnostic pathway and proposed
diagnostic pathway When
answering these questions, assume that the reviewer is not familiar with the current diagnostic criteria and
pathway. Describe the diagnostic
criteria and pathway in detail. It is helpful to use the same format when
presenting the current and proposed diagnostic pathways. Some applicant teams have indicated that PowerPoint
is a user-friendly program for creating flow diagrams. Requested elements of the diagnostic &
test pathways should be discussed in the written response as well as in the
flow diagrams. a. Are the diagnostic criteria
published? Provide the reference. If
they are not published or if the published criteria are out of date, explain
the basis of the current diagnostic criteria. c. For the proposed diagnostic
pathway that includes the new test discuss if the pathway may change once
additional data are collected. d. Discuss if the proposed testing will
be tiered (i.e., done in stages) and how the ordering for each subsequent test
will be accomplished. Will additional
testing be reflexive or will the ordering physician need to order the next tier
of the test? c. If more than one test method is
necessary to achieve the detection rate included in Table 2, identify each of
the methods in the flow diagram for the proposed diagnostic pathway. e. This information may be used to justify testing to payers. 9. Test result interpretation b. Refer to the CETT Program guidelines
for evaluation of indeterminate results. Indicate if the clinical laboratorys
process for evaluating VOUS has been previously reviewed and approved by the
CETT Program. If yes, indicate if you anticipate any changes specific to this
test. c. What role will the researcher play
in evaluating VOUS or other indeterminate results? Is there a functional assay to evaluate VOUS? If family studies are needed to evaluate
novel mutations and/or VOUS, will the family members be charged? h. For applications that use sequence-based molecular
testing: iii. Can carriers for an autosomal
recessive disorder or X-linked disorder be reliably detected using the proposed
test methods? Discuss testing for both the sibling of an affected individual
and for the spouse/partner of a known carrier. 10. Test result reports a. Provide a draft report for each of the result types. Each
report should address the critical elements in the CETT Program Result Report
Template. The Report Templates and additional
information in the PowerPoint presentation on laboratory reports are located on
the CETT Program website. If your institution has guidelines or restrictions on
test result report format changes, please describe those in this section. 11. References Provide a
brief summary of the active research on this condition. Highlight important
findings in the selected references. Include data that expand understanding of
expected test results or test interpretations. Additional preprints and unpublished
data that expand the understanding of identified mutations are appreciated. 12. 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
guidelines to be addressed in the application. i. Explain the laboratory experience in
assay validation. For further information, refer to the PowerPoint available on
the CETT Program website. 13. Potential impact of the test
on health a. A clinical laboratory usually offers
testing in all of the listed scenarios. For each NO response, justify your
reasoning for not offering testing in that particular scenario. iii. Partners of known carriers includes:
a) new partners of obligate carrier parents, and b) partners of relatives of a
proband, who are at risk to be a carrier.
If you are providing carrier testing for partners of known carriers (2)
but not for general population screening, describe whether data are available
to explain this difference. b. How will the proposed test results
potentially change patient care? This might include health care management, need
for additional tests, impact on the time-to-diagnosis (medical odyssey), and/or recurrence risk counseling? Describe
any impact on age of diagnosis Are there
therapies to reduce morbidity and/or mortality? If yes, describe. Describe how a laboratory representative or
genetic counselor would justify use of the test to a clinician and to a payer. 14. Laboratory-Clinical interface a. b. Who in
the clinical laboratory will respond to clinician inquiries about test
ordering, test report interpretation, test cost and reimbursement, test methods
and sensitivity, who to test, and who to test first, etc? Who will respond to
patient inquiries? If not provided elsewhere, state the name and certification
of these individuals. c. How will the researcher and advocate
group be involved in laboratory-clinical interface? How will activities with the researcher or
research laboratory be coordinated? Will there be regular communication between
all members of the Collaborative Group? 15. Educational materials CETT Program
policy requires that the clinical laboratory be an information source for all
potential consumers of the proposed test. Since clinical tests developed using
the CETT Program are initially offered by one laboratory, there are limited or
no other information resources. The laboratory must be willing to discuss
testing with clinicians, patients, and families by telephone and/or email. You are
required to contact the CETT Program Education Coordinator ed@CETTProgram.org prior to submission of
the Application. The Education Coordinator and the CETT Program website have a
number of resources to assist in the development of appropriate educational
materials. A blank template for each of the target audiences with points and
questions to consider is available to help guide development. Also posted to the CETT Program website are
examples of educational materials that have been reviewed by the CETT Program.
Finally, the Power Point slides from the CETT Review Board Meeting (March 6-7,
2007) are posted and discuss the development of educational materials and the
types of information that should be included. In
developing initial drafts of educational materials for a new test, you may
start by cutting and pasting from the examples provided. It is important to
develop educational materials for patients and families with a reading level
suitable for families just learning about the condition. In general the
synopsis (abstract) should be written at a 6th to 8th grade level and
additional sections should be written at or below the 8th to 10th grade reading
level. It is anticipated that each test (condition) will have specific issues
that may need to be highlighted. Each laboratory is encouraged to use their own
format, style and graphics to identify the educational materials as coming from
their own institution. The CETT
Program realizes that the test translation and educational material development
timelines will be different for each application. The Collaborative Group is
encouraged to submit draft educational materials with the application. Option B
allows for submission of these after evaluation but well before the test in
introduced. In general Option B should be avoided if the clinical laboratory
has been working on test development during the application process and
anticipates that the test will be available shortly after approval. The CETT
Program Coordinator and CETT Program Education Coordinator are available to
assist with the development of educational materials, the distribution plan and
the plan to announce the test. You are encouraged to contact the CETT Program
Staff before, during and after the application process. All educational
materials MUST BE REVIEWED AND POSTED before the test is announced. 16. Data collection plan The CETT Program partners
with the Each CETT Program-sponsored
test must have a one-page clinical form for the clinician requesting the test
to complete at the time the patients sample is submitted. The primary purpose of these clinical data is
to aid the clinical testing laboratory in interpretation of test results.
However, it is further recognized that newly available clinical genetic tests
for rare genetic disorders present unique opportunities. In most cases, the first-time clinical
availability of a test may result in the accumulation of a significant
knowledge base about the genetic and clinical scope and breadth of the disorder
as more affected individuals are identified.
Therefore, the CETT program seeks to leverage the individual
genotype/phenotype data for each test it CETT Program
applicants must contact NCBI (cett@ncbi.nlm.nih.gov)
prior to submitting their application to coordinate data collection tasks. NCBI
will:
Assist CETT Program Collaborative Groups with the initial design of their
collection plan.
Create user-friendly electronic clinical data forms for each project in
order to facilitate data collection, storage and sharing.
Organize and store genotype and clinical data collected from individuals
evaluated by their new test.
Discuss and help applicants develop individualized approaches to creating
publicly accessible data that may aid understanding about the disorder and its
treatments. 17. GeneReview The
GeneReview should be completed within 12 months of funding. Refer to the FAQs on
the CETT Program website for the GeneReview outline or see Author Instructions
on the GeneTests website (www.genetests.org)
select About GeneTests on the navigation bar. Applicants should contact Bonnie Pagon (bpagon@u.washington.edu) early in the
application process. The Collaborative Group is responsible for ensuring that a
GeneReview is completed; however, recruitment of experts outside the
Collaborative Group as authors is welcome. 19. Annual Report The Collaborative Group is
required to submit a report to the CETT Program annually for a total of 5 years.
Typically, the clinical laboratory is the entity responsible for coordinating
the annual report and submitting the information to the CETT Program
Coordinator. Contact
the CETT Program Coordinator for current submission guidelines and required
elements. Currently report elements should include:
Status of Testing o
Length
of time between application approval and release of the clinical test o
Date
the clinical test was released o
Volume
of tests including indication for test (diagnostic, carrier, prenatal, etc.) o
Number
of positive, negative, and indeterminate results o
Breakdown
of mutations identified (nonsense, missense, frameshift, deletion, duplication,
VOUS) o
Detection
rate observed in tested samples
Status of Educational Materials o
In
what format are educational materials available? (Print, web) o
Are
educational materials posted on web sites for each member of the Collaborative
Group? Provide URL address for each o
Release
date for educational materials o
Date
of most recent update of educational materials o
Frequency
of contact by clinicians or families with questions about testing. (Calls to
each member of the Collaborative Group) o
Status
of GeneReview
Status of Data Collection o
Date
that online clinical data collection form was posted o
Proportion
of tests with clinical data collection form o
How
often does the laboratory contact the ordering clinician to request missing
clinical information? What is the process? o
Dates
of data uploads to NCBI
Status of Collaboration within the
Collaborative Group o
Frequency
and type of scheduled communications among the Collaborative Group o
Frequency
of interactions between the clinical lab and researcher for consultation on new
findings o
Are
websites of the Collaborative Group linked? o
Is
information about research opportunities provided with test result report? How? o
Any
publications, presentations, or posters by the Collaborative Group? o
Number
of patients/families referred to researcher for further study and if so, was it
helpful to the interpretation o
Frequency
of individuals referred for clinical testing by researcher and/or advocacy? o
Any
unexpected issues observed o
Discuss
plans, if any, to change the testing paradigm o
Changes
in laboratory staff and Collaborative Group participation
Application Specific Feedback o
Other
specific reports indicated in the original application, as applicable Email Andy Faucett with questions. Updated: July, 2008 Application page |
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