[Federal Register Volume 76, Number 240 (Wednesday, December 14, 2011)]
[Notices]
[Pages 77833-77834]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-32047]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Healthcare Research and Quality


Scientific Information Request on CYP2C19 Variants and Platelet 
Reactivity Tests

AGENCY: Agency for Healthcare Research and Quality (AHRQ), HHS.

ACTION: Request for Scientific Information Submissions.

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SUMMARY: The Agency for Healthcare Research and Quality (AHRQ) is 
seeking scientific information submissions from manufacturers of 
CYP2C19 variants and platelet reactivity tests. Scientific information 
is being solicited to inform our Comparative Effectiveness Review of 
Testing of CYP2C19 Variants and Platelet Reactivity for Guiding 
Antiplatelet Treatment, which is currently being conducted by the 
Evidence-based Practice Centers for the AHRQ Effective Health Care 
Program. Access to published and unpublished pertinent scientific 
information on this device will improve the quality of this comparative 
effectiveness review. AHRQ is requesting this scientific information 
and conducting this comparative effectiveness review pursuant to 
Section 1013 of the Medicare Prescription Drug, Improvement, and 
Modernization Act of 2003, Public Law 108-173.

DATES: Submission Deadline on or before January 13, 2012.

ADDRESSES: Online submissions: http://effectivehealthcare.AHRQ.gov/index.cfm/submit-scientific-information-packets/. Please select the 
study for which you are submitting information from the list of current 
studies and complete the form to upload your documents.
    Email submissions: ehcsrc@ohsu.edu (please do not send zipped 
files--they are automatically deleted for security reasons).
    Print submissions: Robin Paynter, Oregon Health and Science 
University, Oregon Evidence-based Practice Center, 3181 SW Sam Jackson 
Park Road, Mail Code: BICC, Portland, OR 97239-3098.

FOR FURTHER INFORMATION CONTACT: Robin Paynter, Research Librarian, 
Telephone: (503) 494-0147 or Email: ehcsrcohsu.edu.

SUPPLEMENTARY INFORMATION: In accordance with Section 1013 of the 
Medicare Prescription Drug, Improvement, and Modernization Act of 2003, 
Public Law 108-173, the Agency for Healthcare Research and Quality has 
commissioned the Effective Health Care (EHC) Program Evidence-based 
Practice Centers to complete a comparative effectiveness review of the 
evidence for testing of CYP2C19 variants and platelet reactivity for 
guiding antiplatelet treatment.
    The EHC Program is dedicated to identifying as many studies as 
possible that are relevant to the questions for each of its reviews. In 
order to do so, we are supplementing the usual manual and electronic 
database searches of the literature by systematically requesting 
information (e.g., details of studies conducted) from medical device 
industry stakeholders through public information requests, including 
via the Federal Register and direct postal and/or online solicitations. 
We are looking for studies that report on CYP2C19 variants and platelet 
reactivity tests, including those that describe adverse events, as 
specified in the key questions detailed below. The entire research 
protocol, including the key questions, is also available online at: 
http://effectivehealthcare.AHRQ.gov/index.cfm/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productid=854#3962.
    This notice is a request for industry stakeholders to submit the 
following:
     A current product label, if applicable (preferably an 
electronic PDF file).
     Information identifying published randomized controlled 
trials and observational studies relevant to the clinical outcomes. 
Please provide both a list of citations and reprints if possible.
     Information identifying unpublished randomized controlled 
trials and observational studies relevant to the clinical outcomes. If 
possible, please provide a summary that includes the following 
elements: study number, study period, design, methodology, indication 
and diagnosis, proper use instructions, inclusion and exclusion 
criteria, primary and secondary outcomes, baseline characteristics, 
number of patients screened/eligible/enrolled/lost to withdrawn/follow-
up/analyzed, and effectiveness/efficacy and safety results.
     Registered ClinicalTrials.gov studies. Please provide a 
list including the ClinicalTrials.gov identifier, condition, and 
intervention.
    Your contribution is very beneficial to this program. AHRQ is not 
requesting and will not consider marketing material, health economics 
information, or information on other indications. This is a voluntary 
request for information, and all costs for complying with this request 
must be borne by the submitter.
    In addition to your scientific information please submit an index 
document outlining the relevant information in each file along with a 
statement regarding whether or not the submission comprises all of the 
complete information available.

    Please Note:  The contents of all submissions, regardless of 
format, will be available to the public upon request unless 
prohibited by law.The draft of this review will be posted on AHRQ's 
EHC program Web site and available for public comment for a period 
of 4 weeks. If you would like to be notified when the draft is 
posted, please sign up for the email list at: http://effectivehealthcare.AHRQ.gov/index.cfm/join-the-email-list1/.

The Key Questions

Key Question 1

    In patient populations who are candidates for clopidogrel therapy, 
does

[[Page 77834]]

genetic testing for CYP2C19 variants predict intermediate and clinical 
outcomes following treatment initiation?
    a. What is the analytic validity (technical test performance) of 
the various assays used for CYP2C19 genetic testing?
    b. What is the clinical validity (predictive accuracy) of genetic 
testing for predicting intermediate and clinical outcomes in patients 
who are receiving clopidogrel therapy?
    c. Do the following factors modify the association between genetic 
test results and clinical outcomes?
    i. Co-medications.
    ii. Patient-level factors (e.g., race or ethnicity, age, sex, 
disease severity, or comorbidities).
    iii. Test-related factors (e.g., between-assay differences).
    iv. System-level factors (e.g., settings where testing is 
performed).

Key Question 2

    In patient populations receiving clopidogrel therapy, does 
phenotypic testing of platelet reactivity predict intermediate and 
clinical outcomes?
    a. What is the analytic validity (technical test performance) of 
the various assays used in phenotypic testing of platelet reactivity?
    b. What is the clinical validity (predictive accuracy) of 
phenotypic testing for predicting intermediate and clinical outcomes in 
patients who are receiving clopidogrel therapy?
    c. Do the following factors modify the association between 
phenotypic test results and clinical outcomes?
    i. Co-medications.
    ii. Patient-level factors (e.g., race or ethnicity, age, sex, 
disease severity, or comorbidities).
    iii. Test-related factors (e.g., between-assay differences).
    iv. System-level factors (e.g., settings where testing is 
performed).

Key Question 3

    What is the comparative effectiveness of alternative test-and-treat 
strategies (including a no-testing strategy) for therapeutic decision 
making regarding antiplatelet therapy among patients who are candidates 
for clopidogrel-based treatment?
    a. What is the comparative effectiveness of the following testing 
strategies on therapeutic decision making, platelet reactivity during 
followup, and clinical outcomes in patients who are candidates for 
antiplatelet treatment?
    i. Genetic testing for CYP2C19.
    ii. Genetic testing for CYP2C19 followed by phenotypic testing for 
platelet reactivity.
    iii. Phenotypic testing for platelet reactivity.
    iv. No testing.
    b. How do modifying factors (e.g., race or ethnicity, age, sex, 
comorbidities, diet, or the time between conducting the test and 
obtaining results) affect the association of alternative phenotypic or 
genetic test-and-treat strategies and patient outcomes? Alternative 
test-guided treatments can include non-clopidogrel antiplatelet agents 
or high-dose clopidogrel regimens.

Key Question 4

    What are the potential adverse effects or harms from genetic or 
phenotypic testing per se or from test-directed treatments?

    Dated: December 2, 2011.
Carolyn M. Clancy,
AHRQ, Director.
[FR Doc. 2011-32047 Filed 12-13-11; 8:45 am]
BILLING CODE 4160-90-M