Briefly describe a specific question, or set of related questions, about a health care test or treatment that this program should consider.

Does the use of Cytochrome P450 2C19 (CYP2C19) testing to predict response to clopidogrel in people: (1) with acute coronary syndrome, (2) who have suffered other cardiovascular disease-related events (e.g., ischemic stroke, symptomatic peripheral arterial disease), or (3) undergoing percutaneous coronary intervention, lead to improvements in health outcomes compared to a no-testing strategy, or are test results useful in medical, personal, or public health decision-making?

Does your question include a comparison of different health care approaches? (If no, your topic will still be considered.)

yes

If yes, explain the specific technologies, devices, drugs, or interventions you would like to see compared:

Health outcomes following therapy guided by CYP2C19 pharmacogenetic testing, to predict clopidogrel response, versus a no-testing strategy.

What patients or group(s) of patients does your question apply to? (Please include specific details such as age range, gender, coexisting diagnoses, and indications for therapy.)

1. Patients with acute coronary syndrome, 2) patients who have suffered other cardiovascular disease-related events (e.g., ischemic stroke, symptomatic peripheral arterial disease), or 3) patients undergoing percutaneous coronary intervention.

Are there subgroups of patients that your question might apply to? (For example, an ethnic group, stage or severity of a disease.)

Prevalence of having one or two copies (corresponding to intermediate- and poor-metabolizer phenotypes, respectively) of reduced- or loss-of-function CYP2C19 variants is estimated to be higher among Asians than African-Americans or Caucasians.

Describe the health-related benefits you are interested in. (For example, improvements in patient symptoms or problems from treatment or diagnosis.)

Interested in the potential for improved clinical outcomes (reduction in recurrent ischemic events, reduction of stent thromboses, reduction of cardiovascular-disease related morbidity and mortality) as a result of modifications in treatment decisions.

Describe any health-related risks, side effects, or harms that you are concerned about.

Potential for 1) misinterpretation or misclassification of drug metabolizer status, along with the possibility that it might result in excessive or inadequate dosing, and 2) selection of alternate drug that proves to be less effective or to have more severe side effects (e.g., severe bleeding).

Appropriateness for EHC Program

Does your question include a health care drug, intervention, device, or technology available (or likely to be available) in the U.S.?

yes

Which priority area(s) and population(s) does this topic apply to? (check all that apply)

EHC Priority Conditions (updated in 2008)

• Cardiovascular disease, including stroke and hypertension

AHRQ Priority Populations

• Minority groups
• Women
• Elderly

Federal Health Care Program

• Medicaid
• Medicare

Importance

Describe why this topic is important.

While clopidogrel may decrease morbidity and mortality associated with several cardiovascular diseases, individual patient response to clopidogrel can vary substantially. Pharmacogenetic testing for CYP2C19 variants that could affect clopidogrel response is commercially available. Evidence-based review and guidelines are needed, however, to determine whether and how these tests should be used in clinical practice to predict clopidogrel response in a way that could effectively improve health outcomes.

What specifically motivated you to ask this question? (For example, you are developing a clinical guideline, working with a policy with large uncertainty about the appropriate approach, costly intervention, new research you have read, items in the media you may have seen, a clinical practice dilemma you know of, etc.)

This is a topic under consideration by the EGAPP Working Group, who may develop evidence-based guidelines based on the results of this systematic review.

Does your question represent uncertainty for clinicians and/or policy-makers? (For example, variations in clinical care, controversy in what constitutes appropriate clinical care, or a policy decision.)

yes

If yes, please explain:

Uncertainty for clinicians and policy-makers regarding whether information gained through current testing strategies will result in improved health outcomes.

Potential Impact

How will an answer to your research question be used or help inform decisions for you or your group?

This is a topic under consideration by the EGAPP Working Group, who may develop evidence-based guidelines based on the results of this systematic review.

Describe the timeframe in which an answer to your question is needed.

Ideally within 1 year.

Describe any health disparities, inequities, or impact on vulnerable populations your question applies to.

Nominator Information

Other Information About You: (optional)

Please choose a description that best describes your role or perspective: (you may select more than one category if appropriate)

This is a topic under consideration by the EGAPP Working Group, who may develop evidence-based guidelines based on the results of this systematic review.

Are you making a suggestion as an individual or on behalf of an organization?

Organization

Please tell us how you heard about the Effective Health Care Program