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Guideline Summary
Guideline Title
Clinical laboratory services considerations. In: Laboratory medicine practice guidelines: guidelines and recommendations for laboratory analysis and application of pharmacogenetics to clinical practice.
Bibliographic Source(s)
Linder MW, Steimer W. Clinical laboratory services considerations. In: Valdes R Jr, Payne DA, Linder MW, editor(s). Laboratory medicine practice guidelines: guidelines and recommendations for laboratory analysis and application of pharmacogenetics to clinical practice. Washington (DC): National Academy of Clinical Biochemistry (NACB); 2010. p. 15-8. [8 references]
Guideline Status

This is the current release of the guideline.

Scope

Disease/Condition(s)

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

Guideline Category
Assessment of Therapeutic Effectiveness
Evaluation
Technology Assessment
Clinical Specialty
Medical Genetics
Pathology
Pharmacology
Intended Users
Advanced Practice Nurses
Clinical Laboratory Personnel
Health Care Providers
Pharmacists
Physician Assistants
Physicians
Guideline Objective(s)

To provide evidence based recommendations for establishing appropriate utilization of pharmacogenetic information in clinical practice

Target Population

Individuals with genetic variants associated with drug-metabolizing enzymes

Interventions and Practices Considered
  1. Qualification of personnel performing pharmacogenetic testing to perform "high complexity testing"
  2. Use of whole blood or validated alternative sample for testing
  3. Inclusion of report information to establish structural features of tested gene and test results
  4. Pharmacogenetic assays to include genetic alterations of target locus as indicated
  5. Establishment of criteria to determine which genetic variants to include in diagnostic assays
Major Outcomes Considered

Quality assurance of pharmacogenetic testing

Methodology

Methods Used to Collect/Select the Evidence
Searches of Electronic Databases
Description of Methods Used to Collect/Select the Evidence

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.

Number of Source Documents

Not stated

Methods Used to Assess the Quality and Strength of the Evidence
Weighting According to a Rating Scheme (Scheme Given)
Rating Scheme for the Strength of the Evidence

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.
Methods Used to Analyze the Evidence
Systematic Review
Description of the Methods Used to Analyze the Evidence

Not stated

Methods Used to Formulate the Recommendations
Expert Consensus
Description of Methods Used to Formulate the Recommendations

Not stated

Rating Scheme for the Strength of the Recommendations

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.

Cost Analysis

The guideline developers reviewed published cost analyses.

Method of Guideline Validation
Peer Review
Description of Method of Guideline Validation

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.

Recommendations

Major Recommendations

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:

  1. What level of certification should be required for clinical laboratories and personnel performing pharmacogenetics testing?

    Recommendation 1

    Whenever possible, and when required for laboratory compliance with local regulations, personnel performing pharmacogenetic testing in the United States must be qualified to perform "high complexity testing" as defined by Clinical Laboratory Improvement Amendments (CLIA) Subpart A Sec 493.17(a) or as required by individual states. In other countries or municipalities, the appropriate accrediting agency will dictate appropriate regulations (A-I).

    The table below lists the scoring based on the consensus of the authors of this document.

    Tests having a cumulative score of >12 are considered to be of high complexity (CLIA regulations subpart 493.17)
    Criteria Rank
    Scientific knowledge 3
    Training and experience 3
    Reagents and materials preparation 2-3
    Characteristics of operational steps 2-3
    Calibration, quality control (QC), and proficiency testing materials 3
    Test system troubleshooting and maintenance 2-3
    Interpretation and judgment 3
    Cumulative score 18-21
  1. What are the recommended specimens for testing?

    Recommendation 2

    The recommended specimen for testing is whole blood or a properly validated alternative sample (B-II).

  1. What analytical information should be included with the test result?

    Recommendation 3

    The report should include sufficient information to establish the structural features of the tested gene and the results of that testing (A-I). The committee is cautious about recommending a specific format for reporting variants at this time.

  1. What criteria should be used to establish which genetic variants of a locus should be included for diagnostics purposes?

    Recommendation 4

    Pharmacogenetic (PGx) assays designed for clinical application should include genetic alterations of the target locus for which there is a well-defined influence on the function of the locus product or for which there is a clear relationship between the structural characteristic and observable influence on drug pharmacokinetics, pharmacodynamics, and/or toxicology (B-III).

    Recommendation 5

    NACB recommends that criteria be established to guide the selection of which genetic variants to include in diagnostic assays (A-III).

  1. Is it necessary for there to be evidence to demonstrate cost effectiveness before recommending clinical use of PGx tests?

    Recommendation 6

    Clinical laboratories should provide testing services when there is a convincing rationale for doing so. Criteria should be established to demonstrate this (A-III).

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.

Clinical Algorithm(s)

None provided

Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

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

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

Utilization of well-established and rigorous laboratory practices in pharmacogenetic testing and consideration of processes that ensure adequate compliance

Potential Harms

Not stated

Implementation of the Guideline

Description of Implementation Strategy

An implementation strategy was not provided.

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need
Getting Better
IOM Domain
Effectiveness

Identifying Information and Availability

Bibliographic Source(s)
Linder MW, Steimer W. Clinical laboratory services considerations. In: Valdes R Jr, Payne DA, Linder MW, editor(s). Laboratory medicine practice guidelines: guidelines and recommendations for laboratory analysis and application of pharmacogenetics to clinical practice. Washington (DC): National Academy of Clinical Biochemistry (NACB); 2010. p. 15-8. [8 references]
Adaptation

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

Date Released
2010
Guideline Developer(s)
National Academy of Clinical Biochemistry - Professional Association
Source(s) of Funding

National Academy of Clinical Biochemistry

Guideline Committee

National Academy of Clinical Biochemistry Committee

Composition of Group That Authored the Guideline

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

Financial Disclosures/Conflicts of Interest

Not stated

Guideline Status

This is the current release of the guideline.

Guideline Availability

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

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.

Availability of Companion Documents

None available

Patient Resources

None available

NGC Status

This NGC summary was completed by ECRI Institute on October 27, 2010. The information was verified by the guideline developer on December 15, 2010.

Copyright Statement

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

Disclaimer

NGC Disclaimer

The National Guideline Clearinghouse™ (NGC) does not develop, produce, approve, or endorse the guidelines represented on this site.

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