This is the current release of the guideline.

Diseases or conditions for which analysis of gene variations may be used for purposes of guiding the use of medications and related therapeutics

Individuals with genetic variants associated with drug-metabolizing enzymes

Robustness and limitations of test results

For a specific clinical use, pertinent clinical questions were formulated and key search terms were ascertained for the literature search. A time frame of literature searches was conducted from 1995 until December 2009 on MEDLINE or PubMed databases. The specific search terms were pharmacogenetics, pharmacogenomics, clinical applications of pharmacogenetics, personalized medicine and clinical laboratories.

Not stated

Levels of Evidence

1. Evidence includes consistent results from well-designed, well-conducted studies in representative populations.
2. Evidence is sufficient to determine effects, but the strength of the evidence is limited by the number, quality, or consistency of the individual studies; generalizability to routine practice; or indirect nature of the evidence.
3. Evidence is insufficient to assess the effects on health outcomes because of limited number or power of studies, important flaws in their design or conduct, gaps in the chain of evidence, or lack of information. Expert consensus is the basis for the recommendation.

Not stated

Not stated

Strength of Recommendations

A. The National Academy of Clinical Biochemistry (NACB) strongly recommends adoption; there is good evidence that it improves important health outcomes and concludes that benefits substantially outweigh harms.

B. The NACB recommends adoption; there is at least fair evidence that it improves important health outcomes and concludes that benefits outweigh harms.

C. The NACB recommends against adoption; there is evidence that it is ineffective or that harm outweighs benefit.

I. The NACB concludes that the evidence is insufficient to make recommendations; evidence that it is effective is lacking, of poor quality, or conflicting; and the balance of benefits and harms cannot be determined.

A formal cost analysis was not performed and published cost analyses were not reviewed.

This document was approved by the National Academy of Clinical Biochemistry (NACB) Board of Directors in July 2009. The NACB is the Academy of the American Association for Clinical Chemistry.

Definitions of the levels of evidence (I—III) and the strength of recommendations (A, B, C, I) are presented at the end of the "Major Recommendations" field.

Note from the National Academy of Clinical Biochemistry (NACB) and the National Guideline Clearinghouse (NGC): Laboratory Analysis and Application of Pharmacogenetics to Clinical Practice has been divided into individual summaries. In addition to the current summary, the following are available:

• Methodology and quality assurance considerations in pharmacogenetic testing
• Clinical laboratory services considerations
• Clinical practice considerations
• Therapeutic drug monitoring and pharmacogenetics interface considerations
• Ancillary applications: drug prescription/dispensing and forensics
• Regulatory considerations

1. What information should accompany the reported result?

   Recommendation 1

   Laboratories reporting pharmacogenetic genotype test results should be prepared to provide an educational resource to recipients of the test results to explain the complexity of the metabolic pathways involved; also be prepared to provide guidance as to which genes should be tested for a given clinical situation when known (A-II).

2. Should the result be linked to a specific drug usage (as indicator)? Should drug "dosing and usage" information accompany the test result?

   Recommendation 2

   To provide optimum interpretive guidance relative to a specific drug or similar family of drug substrates, a laboratory providing pharmacogenetic (PGx) test results should be able if requested and whenever possible to provide information on drug substrates involved in the clinical situation (B-III).

3. Should laboratories reporting PGx test results provide a consultation component or service available or by referral?

   Recommendation 3

   Laboratories providing PGx test results should be prepared to provide information as to interpretation of those results. Laboratories not equipped to provide test-interpretation capabilities as part of their test-reporting process should seek alternative mechanisms to provide those interpretive services in order to generate a more complete test report (B-II).

4. Should analytical limitations of the PGx test be indicated in the laboratory report?

   Recommendation 4

   A report documenting a PGx test result should provide the recipient of the information sufficient detail documenting the analytical methodology used to obtain the result and address known limitations that may influence the robustness, interpretation, sensitivity, and specificity of the test result (A-I).

5. Are there unique or specific limitations to be considered regarding confidential reporting of PGx test results?

   Recommendation 5

   A pharmacogenetic test result should be documented in a manner consistent with rules pursuant to routine demographics as required for Clinical Laboratory Improvement Amendments (CLIA) compliance and protection of sensitive genetic information required by Health Insurance Portability and Accountability Act (HIPAA), if in the United States, or as may be required in other countries (A-I).

Definitions:

Levels of Evidence

1. Evidence includes consistent results from well-designed, well-conducted studies in representative populations.
2. Evidence is sufficient to determine effects, but the strength of the evidence is limited by the number, quality, or consistency of the individual studies; generalizability to routine practice; or indirect nature of the evidence.
3. Evidence is insufficient to assess the effects on health outcomes because of limited number or power of studies, important flaws in their design or conduct, gaps in the chain of evidence, or lack of information. Expert consensus is the basis for the recommendation.

Strength of Recommendations

A. The National Academy of Clinical Biochemistry (NACB) strongly recommends adoption; there is good evidence that it improves important health outcomes and concludes that benefits substantially outweigh harms.

B. The NACB recommends adoption; there is at least fair evidence that it improves important health outcomes and concludes that benefits outweigh harms.

C. The NACB recommends against adoption; there is evidence that it is ineffective or that harm outweighs benefit.

I. The NACB concludes that the evidence is insufficient to make recommendations; evidence that it is effective is lacking, of poor quality, or conflicting; and the balance of benefits and harms cannot be determined.

None provided

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations").

Appropriate reporting and interpretation of pharmacogenetic test results

Not stated

An implementation strategy was not provided.

Not applicable: The guideline was not adapted from another source.

National Academy of Clinical Biochemistry

The National Academy of Clinical Biochemistry Committee

Committee Members: Roland Valdes Jr, PhD, DABCC, FACB, University of Louisville, Louisville, KY; Deborah A. Payne, PhD, DABMM, DABCC, FACB, Molecular Services, UniPath LLC, Denver, CO; Mark W. Linder, PhD, DABCC, FACB, Department of Pathology and Laboratory Medicine, University of Louisville, Louisville, KY; Gilbert Burckhart, PhD, Pharmacy, University of Southern California, Los Angeles, CA; Daniel H. Farkas, PhD, HCLD, Sequenom Center for Molecular Medicine, Grand Rapids, MI; Felix Frueh, PhD, Medco Health Solutions Inc, Bethesda, MD; Jean-Pierre Morello, PhD, Teva Neuroscience Canada, Montreal, Quebec, Canada; Atiqur Rahman, PhD, Division of Clinical Pharmacology, US Food and Drug Administration, Silver Spring, MD; Gualberto Ruaño, MD, PhD, Genomas Inc and Hartford Hospital, Hartford CT; Les Shaw, PhD, Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA; Saeed Jortani, PhD, DABCC, FACB, Department of Pathology and Laboratory Medicine, University of Louisville, Louisville, KY; Werner Steimer, MD, Department of Clinical Chemistry and Pathobiochemistry, Institut fur Klinische Chemie und Pathobiochemie, Munich, Germany; Steven Wong, PhD, Department of Pathology, Medical College of Wisconsin, Milwaukee, WI; Jeanne Carr, PhD, Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN

Not stated

This is the current release of the guideline.

Electronic copies: Available from the National Academy of Clinical Biochemistry (NACB) Web site .

Print copies: National Academy of Clinical Biochemistry publications are available through American Association for Clinical Chemistry (AACC) Press. To make a purchase or request a catalog, contact AACC Customer Service at 202-857-0717 or custserv@aacc.org.

None available

None available

This NGC summary was completed by ECRI Institute on November 2, 2010. The information was verified by the guideline developer on December 15, 2010.

National Academy of Clinical Biochemistry's (NACB) terms for reproduction of guidelines are posted with each set of guidelines.