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Guideline Summary
Guideline Title
Recommendations from the EGAPP Working Group: can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan?
Bibliographic Source(s)
Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Recommendations from the EGAPP Working Group: can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan. Genet Med. 2009 Jan;11(1):15-20. PubMed External Web Site Policy
Guideline Status

This is the current release of the guideline.

Scope

Disease/Condition(s)

Metastatic colorectal cancer

Guideline Category
Evaluation
Management
Risk Assessment
Technology Assessment
Clinical Specialty
Gastroenterology
Internal Medicine
Medical Genetics
Oncology
Intended Users
Advanced Practice Nurses
Health Care Providers
Health Plans
Managed Care Organizations
Physician Assistants
Physicians
Utilization Management
Guideline Objective(s)

To provide recommendations regarding UGT1A1 genotyping in adult patients with metastatic colorectal cancer to be treated with irinotecan, and to summarize the supporting scientific evidence

Target Population

Patients with metastatic colorectal cancer treated with irinotecan

Interventions and Practices Considered

UGT1A1 genotyping

Major Outcomes Considered

Analytic Validity

Analytic specificity and sensitivity of commonly tested alleles

Clinical Validity

Association of UGT1A1 genotype with:

  • Incidence of severe neutropenia
  • Incidence of severe diarrhea
  • Rate of tumor response
  • Circulating levels of drug metabolites

Clinical Utility

  • Influence of UGT1A1 genotyping results on irinotecan prescribing decisions
  • Health-related patient outcomes following use of UGT1A1 genotyping to guide choice or dose of irinotecan

Methodology

Methods Used to Collect/Select the Evidence
Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases
Searches of Unpublished Data
Description of Methods Used to Collect/Select the Evidence

Note from the National Guideline Clearinghouse (NGC): An evidence review commissioned by the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group and was funded under contract by the Office of Public Health Genomics (NOPHG) at the Centers for Disease Control and Prevention (CDC). An evidence report was prepared by CDC-based EGAPP staff, working in conjunction with investigators from Institute for Preventive Medicine and Medical Screening (IPMMS) and Research Triangle Institute (RTI) International. (See the "Availability of Companion Documents" field).

Key Questions Relating to the Analytic Framework

Key Question 1. Does testing for UGT1A1 mutations in patients with metastatic colorectal cancer (CRC) treated with irinotecan lead to improvement in outcomes (e.g., irinotecan toxicity, response to treatment, morbidity and mortality) compared with no testing? (Overarching question)

Key Question 2. What is the analytic validity of the test(s) that identify key UGT1A1 mutations?

Key Question 3. What is the clinical validity of UGT1A1 testing?

  1. How well does UGT1A1 testing predict phenotypic markers (e.g., increased plasma SN-38 levels or decreased enzyme activity) and associated adverse drug reactions (e.g., diarrhea or neutropenia)?
  2. How well does UGT1A1 testing in patients with metastatic CRC predict morbidity and mortality?
  3. Do other factors (e.g., race/ethnicity, other medications) independently affect clinical validity?

Key Question 4. What are the benefits and harms (clinical utility) related to UGT1A1 testing for patients with metastatic CRC treated with irinotecan?

  1. Based on UGT1A1 test results, what are the management options for patients?
  2. Do these options improve patient outcomes or management decisions by patients or providers?

Literature Search

Research Triangle Institute (RTI) International staff conducted a MEDLINE literature search (through May 2006) for studies addressing the clinical validity and utility of UGT1A1 genotyping in metastatic CRC patients treated with irinotecan. Articles were also identified by search of the references included in selected articles. Based on the key questions and discussion with the UGT1A1 Technical Expert Panel, a list of article inclusion and exclusion criteria was generated. RTI reviewed abstracts against these criteria to determine inclusion in the review, abstracted data into evidence tables, assessed the quality of individual articles, and prepared a preliminary report. When the RTI report was submitted, members of the Centers for Disease Control and Prevention-sponsored Evaluation of Genomic Applications in Practice and Prevention (EGAPP) initiative team and EGAPP consultants performed searches for and reviewed articles on the analytic validity of UGT1A1 genotyping and on UGT1A1 allele/genotype frequencies, and updated the clinical validity and utility searches through December 2006. They also performed additional summarization and statistical analyses, integrated the component sections, and produced a draft evidence report for consideration by the EGAPP Working Group (EWG).

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

The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group has developed criteria for assessing the quality of the body of evidence for the individual components of evaluation, analytic validity, clinical validity, and clinical utility. The adequacy of information to answer the key questions related to each evaluation component is classified as Convincing, Adequate, or Inadequate.

Short summaries were developed for all individual studies included for analytic and clinical validity and clinical utility, and included EGAPP and RTI quality ratings for comparison. Overall quality assessments of Good, Fair, or Marginal were provided for analytic and clinical validity and clinical utility.

  • Good quality indicated existence of reliable data to support conclusions that are not likely to change based on further studies.
  • Fair quality indicated that, while some reasonable quality data were available, they were insufficient to allow firm conclusions to be drawn.
  • Marginal quality indicated insufficient data, or flaws in study design or conduct, that would not allow any conclusions to be drawn.

Teutsch SM, Bradley LA, Palomaki GE, Haddow JE, Piper M, Calonge N, Dotson WD, Douglas MP, Berg AO; EGAPP Working Group. The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) initiative: methods of the EGAPP Working Group. Genet Med. 2009 Jan;11(1):3-14.

Methods Used to Analyze the Evidence
Meta-Analysis
Review of Published Meta-Analyses
Systematic Review with Evidence Tables
Description of the Methods Used to Analyze the Evidence

Note from the National Guideline Clearinghouse (NGC): An evidence review commissioned by the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group (EWG) was funded under contract by the Office of Public Health Genomics (OPHG) at the Centers for Disease Control and Prevention (CDC). An evidence report was prepared by CDC-based EGAPP staff, working in conjunction with investigators from Institute for Preventive Medicine and Medical Screening (IPMMS) and Research Triangle Institute (RTI) International. (See the "Availability of Companion Documents" field).

With a focus on the application of study data to specific key questions, the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) reviewers assessed the quality of evidence for the evaluation components (i.e., analytic and clinical validity, clinical utility) based on standard criteria, including study design and conduct, consistency and generalizability of data, and appropriateness of statistical analyses. Short summaries were written for all individual studies included for assessment of analytic validity, clinical validity, and clinical utility, and included EGAPP and RTI International quality ratings.

Key questions (see the "Description of Methods Used to Collect/Select the Evidence" field) were developed by the EGAPP Working Group (EWG) and further refined in discussions with a Technical Expert Panel. Key question 1 is the overarching question: "Does testing for UGT1A1 mutations in patients with metastatic colorectal cancer (CRC) treated with irinotecan lead to improvement in outcomes (e.g., irinotecan toxicity, response to treatment, morbidity and mortality) compared to no testing?" If direct evidence was insufficient to answer key question 1, key questions 2 through 4 were used to elicit intermediate information to address the overarching question through a "chain of evidence." In reviewing the available evidence, questions from the ACCE (Analytic validity, Clinical validity, Clinical utility, and Ethical, Legal and Social implication) review framework were used to identify and organize the specific information needed to address the key questions.

The adequacy of the information to answer the key questions related to each evaluation component is classified as Convincing, Adequate, or Inadequate. This information is critical to assess the "strength of linkages" in the chain of evidence.*

Based on the evidence available, the overall level of certainty of net health benefit is categorized as High, Moderate, or Low.* High certainty is associated with consistent and generalizable results from well-designed and conducted studies, making it unlikely that estimates and conclusions will change based on future studies. When the level of certainty is Moderate, some data are available, but limitations in data quantity, quality, consistency, or generalizability reduce confidence in the results, and, as more information becomes available, the estimate or effect may change enough to alter the conclusion. Low certainty is associated with insufficient or poor quality data, results that are not consistent or generalizable, or lack of information on important outcomes of interest; as a result, conclusions are likely to change based on future studies.

Teutsch SM, Bradley LA, Palomaki GE, Haddow JE, Piper M, Calonge N, Dotson WD, Douglas MP, Berg AO; EGAPP Working Group. The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) initiative: methods of the EGAPP Working Group. Genet Med. 2009 Jan;11(1):3-14.

*Sawaya GF, Guirguis-Blake J, LeFevre M, et al. Update on methods of the U.S. Preventive Services Task Force: estimating certainty and magnitude of net benefit. Ann Intern Med 2007;147:871-5.

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

Note from the National Guideline Clearinghouse (NGC): An evidence review commissioned by the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group was funded under contract by the Office of Public Health Genomics (OPHG) at the Centers for Disease Control and Prevention (CDC). An evidence report was prepared by CDC-based EGAPP staff, working in conjunction with investigators from Institute for Preventive Medicine and Medical Screening (IPMMS) and Research Triangle Institute (RTI) International. (See the "Availability of Companion Documents" field).

EGAPP Working Group members reviewed the evidence report, examined other sources of information as needed to address specific gaps in the evidence, and considered contextual issues related to implementation of testing in clinical practice. The final recommendation was formulated based on magnitude of effect, certainty of evidence, and consideration of contextual factors.

Key factors considered in the development of a recommendation are: the relative importance of the outcomes selected for review; the benefits (e.g., improved clinical outcome, reduction of risk) that result from the use of the test and subsequent actions or interventions (or if not available, maximum potential benefits); the harms (e.g., adverse clinical outcome, increase in risk or burden) that result from the use of the test and subsequent actions/interventions (or if not available, largest potential harms); and the efficacy and effectiveness of the test and follow-up compared with currently used interventions (or doing nothing). Simple decision models or outcomes tables may be used to assess the magnitudes of benefits and harms, and estimate the net effect. Consistent with the terminology used by the USPSTF, the magnitude of net benefit (benefit minus harm) may be classified as Substantial, Moderate, Small, or Zero.*

Standard EGAPP language for recommendation statements uses the terms: Recommend For, Recommend Against, or Insufficient Evidence (Table 6 in Teutsch et al., 2009). Because the types of emerging genomic tests addressed by EGAPP are more likely to have findings of Insufficient Evidence, three additional qualifiers may be added. Based on the existing evidence and consideration of contextual issues and modeling, Insufficient Evidence could be considered "Neutral" (not possible to predict with current evidence), "Discouraging" (discouraged until specific gaps in knowledge are filled or not likely to meet evidentiary standards even with further study), and "Encouraging" (likely to meet evidentiary standards with further studies or reasonable to use in limited situations based on existing evidence while additional evidence is gathered).

Teutsch SM, Bradley LA, Palomaki GE, Haddow JE, Piper M, Calonge N, Dotson WD, Douglas MP, Berg AO; EGAPP Working Group. The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) initiative: methods of the EGAPP Working Group. Genet Med. 2009 Jan;11(1):3-14.

*Sawaya GF, Guirguis-Blake J, LeFevre M, et al. Update on methods of the U.S. Preventive Services Task Force: estimating certainty and magnitude of net benefit. Ann Intern Med 2007;147:871-5.

Rating Scheme for the Strength of the Recommendations

Recommendations Based on Certainty of Evidence, Magnitude of Net Benefit, and Contextual Issues

High or Moderate Recommend for:
  • If the magnitude of net benefit is Substantial, Moderate, or Small, unless additional considerations warrant caution.
  • Consider the importance of each relevant contextual factor and its magnitude or finding.
Recommend against:
  • If the magnitude of net benefit is Zero or there are net harms.
  • Consider the importance of each relevant contextual factor and its magnitude or finding.
Low Insufficient evidence:
  • If the evidence for clinical utility or clinical validity is insufficient in quantity or quality to support conclusions or make a recommendation.
  • Consider the importance of each contextual factor and its magnitude or finding.
  • Determine whether the recommendation should be Insufficient (neutral), Insufficient (encouraging), or Insufficient (discouraging).
  • Provide information on key information gaps to drive a research agenda.

Teutsch SM, Bradley LA, Palomaki GE, Haddow JE, Piper M, Calonge N, Dotson WD, Douglas MP, Berg AO; EGAPP Working Group. The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) initiative: methods of the EGAPP Working Group. Genet Med. 2009 Jan;11(1):3-14.

Cost Analysis

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

Method of Guideline Validation
External Peer Review
Internal Peer Review
Description of Method of Guideline Validation

The evidence report (see "Availability of Companion Documents" field) and the recommendation statement were each peer reviewed before being finalized.

Recommendations

Major Recommendations

Summary of Recommendation

The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group found that the evidence is currently insufficient to recommend for or against the routine use of UGT1A1 genotyping in patients with metastatic colorectal cancer (CRC) who are to be treated with irinotecan, with the intent of modifying the dose as a way to avoid adverse drug reactions (severe neutropenia).

Rationale

The EGAPP Working Group (EWG) found no intervention trials showing that targeted dosing of irinotecan based on UGT1A1 genotyping could reduce the rates of two specific adverse drug events, severe (Grade 3-4) neutropenia or diarrhea. Observational studies indicate a significant association between UGT1A1 genotypes, particularly *28/*28 and *1/*28, and the occurrence of severe neutropenia. Observational studies also indicate a possible association between severe diarrhea and these UGT1A1 genotypes, but the association is not statistically significant. An additional finding was the suggestion that reducing irinotecan dose may result in patient harms due to diminished effectiveness of treatment in highest risk individuals (*28/*28 homozygotes), and that a higher dose might be warranted among individuals at lower risk of adverse drug events (*1/*1 and *1/*28 genotypes). This review did not consider higher risk patients (e.g., having previous adverse reactions to irinotecan or additional risk factors for neutropenia).

Analytic Validity: The EWG found adequate evidence to conclude that analytic sensitivity and specificity were high for the commonly tested alleles, but evidence was inadequate for rarer alleles.

Clinical Validity: The EWG found adequate evidence of a significant association between UGT1A1 genotype and the incidence of severe neutropenia at standard doses of irinotecan. The EWG found adequate evidence of a possible association between genotype and severe diarrhea, but the effect was smaller and not statistically significant. The EWG found adequate evidence of a significantly higher rate of tumor response to standard irinotecan dosing among individuals with the genotype at highest risk of adverse drug events (*28/*28).

Clinical Utility: The EWG found no evidence to support clinical utility in the proposed clinical scenario. Preliminary modeling suggests that, even if targeted dosing were to be highly effective, it is not clear that benefits (reduced adverse drug events) outweigh harms (unresponsive tumors).

Contextual Issues: Addressing patient preferences regarding risk of side effects and quality of life, versus aggressive treatment to potentially improve effectiveness, is expected practice. In addition, a recent study reported that risk for neutropenia was lower at lower irinotecan doses. For treatment regimens utilizing lower irinotecan doses, UGT1A1 genotype may not be a useful indicator of risk for adverse drug events. Further rigorous evaluation of UGT1A1 genotyping using current and promising irinotecan treatment protocols is warranted.

Clinical Considerations

Patient Population under Consideration

Colorectal cancer (CRC) will be diagnosed in an estimated 150,000 individuals in 2007, resulting in 52,000 deaths. No direct estimate of irinotecan use is available, but about 15% of cases (22,500) have "distant" CRC and may be candidates for irinotecan therapy.

Testing (UGT1A1 Genotyping)

Of the 60 or more UGT1A1 gene variants, two are responsible for 98-99% of the genotypes found in the US white population. These are named *1 (the "wild" sequence of (TA)6TAA) and *28 (with an extra TA repeat or (TA)7TAA).

  • 44% of the US white population are homozygous for *1 (genotype *1/*1)
  • 45% are heterozygous (genotype *1/*28)
  • 11% (about 1 in 10) are homozygous for *28 (genotype *28/*28)

Reliable UGT1A1 genotyping is available using the US Food and Drug Administration (FDA)-cleared kit or through a laboratory developed test. FDA clearance provides assurance that the test is analytically valid, and the results are related to an outcome of interest, but FDA does not evaluate clinical utility.

Clinical Implications

When compared with individuals with the *1/*1 genotype, individuals with the *28/*28 genotype:

  • Metabolize the active form of irinotecan (SN-38) more slowly and, therefore, have a longer time-weighted exposure
  • Have a significant 3.5-fold increase in the rate of severe (Grade 3/4) neutropenia (heterozygotes are intermediate with a nonsignificant 1.8-fold increase)
  • Have a nonsignificant 1.6-fold increase in the rate of severe (Grade 3/4) diarrhea (heterozygotes are intermediate with a nonsignificant 1.4-fold increase)
  • Have a significant 1.7-fold increase in the tumor response rate to treatment (heterozygotes are similar to the reference category, with a nonsignificant 1.1-fold increase).

Clinical Utility of UGT1A1 Genotyping

The clinical utility of routine reduction of initial irinotecan dose in *28 homozygotes based on UGT1A1 genotyping is unknown. No study has prospectively documented the potential benefits (reduced adverse drug events) or harms (reduced proportion of responsive tumors).

Clinical Caveats

  • Some evidence exists that when lower doses of irinotecan are routinely used, the lower rate of adverse drug events is not related to UGT1A1 genotype. However, the clinical effectiveness of lower dosing is not clear.
  • Selective genotyping based on patient preferences is possible. Among those individuals wanting aggressive treatment, genotyping might allow higher dosing among the *1/*1 and *1/*28 groups. Alternatively, individuals wanting to maximize quality of life may choose lower dosing if found to be *28/*28.
  • Alternate drug use is possible, based on patient preference (e.g., cetuximab or bevacizumab) without genotyping, or if a *28/*28 individual is identified.
  • The National Comprehensive Cancer Network recommends pretreatment with colony-stimulating factors for individuals with a 20% or greater risk of febrile neutropenia.
  • The rate of severe neutropenia is as high as 36% among *28/*28 individuals, but the proportion with associated fever is unknown.

Contextual Issues Important to the Recommendation

There is insufficient evidence to support a recommendation for or against use of UGT1A1 testing in adults with metastatic CRC treated with irinotecan. In the absence of evidence supporting clinical utility, additional contextual issues were taken into account in formulating the final EWG recommendation.

Contextual Issues That Suggest the Potential Benefits of UGT1A1 Genotyping

  • CRC is a major public health problem in the United States, causing substantial morbidity and mortality.
  • Irinotecan is a commonly used chemotherapeutic agent that appears to be effective as a first-line or second-line agent.
  • Potentially avoidable irinotecan-related adverse reactions, such as severe neutropenia and diarrhea, are relatively common. Depending on severity, these adverse reactions can reduce overall quality of life and, in some cases, be life threatening.
  • A number of therapeutic regimens are available for the treatment of CRC, including regimens that do not involve irinotecan. Therefore, individuals identified to be at increased risk for serious adverse reactions related to irinotecan may have alternative treatment options.
  • UGT1A1 genetic testing may be of benefit in individual cases when used by knowledgeable practitioners who are informed about the potential benefits and harms of genotyping in this context.
  • Considering patient preferences may be reasonable on a case by case basis to address patient preferences about risk factors and quality of life versus aggressive treatment to potentially improve effectiveness.
  • Limited evidence for improved survival among *28 homozygotes suggests the possibility that wild genotype individuals are being under dosed.

Contextual Issues That Suggest the Potential Harms of UGT1A1 Genotyping

  • Utilization of UGT1A1 testing in this clinical scenario and impact on physician decision making is not known.
  • Reductions in irinotecan dosage resulting from information gained through UGT1A1 genotyping may reduce tumor response and survival.

Other Contextual Issues Regarding UGT1A1 Genotyping

  • Although the cost of UGT1A1 genotyping on an individual level may be relatively low in the context of cancer treatment, the potential for increased cost of widespread use may not be justifiable without evidence supporting clinical utility and improved outcomes.
  • Other options may be considered for individuals who are homozygous for UGT1A1*28. For example, the National Comprehensive Cancer Network recommends pretreatment with colony stimulating factor for individuals at a 20% or higher risk of febrile neutropenia. (NCCN Myeloid Growth Factors Panel Members, 2008)

Definitions:

Recommendations Based on Certainty of Evidence, Magnitude of Net Benefit, and Contextual Issues

High or Moderate Recommend for:
  • If the magnitude of net benefit is Substantial, Moderate, or Small, unless additional considerations warrant caution.
  • Consider the importance of each relevant contextual factor and its magnitude or finding.
Recommend against:
  • If the magnitude of net benefit is Zero or there are net harms.
  • Consider the importance of each relevant contextual factor and its magnitude or finding.
Low Insufficient evidence:
  • If the evidence for clinical utility or clinical validity is insufficient in quantity or quality to support conclusions or make a recommendation.
  • Consider the importance of each contextual factor and its magnitude or finding.
  • Determine whether the recommendation should be Insufficient (neutral), Insufficient (encouraging), or Insufficient (discouraging).
  • Provide information on key information gaps to drive a research agenda.

Teutsch SM, Bradley LA, Palomaki GE, Haddow JE, Piper M, Calonge N, Dotson WD, Douglas MP, Berg AO; EGAPP Working Group. The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) initiative: methods of the EGAPP Working Group. Genet Med. 2009 Jan;11(1):3-14.

Clinical Algorithm(s)

None provided

Evidence Supporting the Recommendations

References Supporting the Recommendations
Type of Evidence Supporting the Recommendations

The type of supporting evidence is not specifically stated for each recommendation.

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits
  • Improved professional and consumer understanding of the use of UGT1A1 genotyping for the treatment of metastatic colorectal cancer with irinotecan.
  • Inform a translational research agenda by identifying gaps in knowledge that might be addressed in future research.
Potential Harms

Not stated

Qualifying Statements

Qualifying Statements
  • This recommendation statement is a product of the independent Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Although the Centers for Disease Control and Prevention (CDC) provides support to the EGAPP Working Group, including staff support in the preparation of this document, recommendations made by the EGAPP Working Group should not be construed as official positions of the CDC or the US Department of Health and Human Services.
  • In general, evaluation of clinical validity was limited by the small number of studies. Further, some of the included studies did not focus exclusively on colorectal cancer (CRC) patients. The majority of studies reported patients with Grade 3 and Grade 4 neutropenia as one group, making individual analysis for Grade 4 neutropenia not feasible. The clinical validity of UGT1A1 variants other than that of *28 in whites was not assessed. See the original guideline document for a detailed list of gaps in the research.

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
Living with Illness
IOM Domain
Effectiveness
Patient-centeredness
Safety

Identifying Information and Availability

Bibliographic Source(s)
Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Recommendations from the EGAPP Working Group: can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan. Genet Med. 2009 Jan;11(1):15-20. PubMed External Web Site Policy
Adaptation

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

Date Released
2009 Jan
Guideline Developer(s)
Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group - Independent Expert Panel
Guideline Developer Comment

This recommendation statement is a product of the independent EGAPP Working Group. Although the Centers for Disease Control and Prevention (CDC) provides support to the EGAPP Working Group, including staff support in the preparation of this document, recommendations made by the EGAPP Working Group should not be construed as official positions of the CDC or the US Department of Health and Human Services.

Source(s) of Funding

United States Government

Guideline Committee

The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group

Composition of Group That Authored the Guideline

Group Members: Alfred O. Berg, MD, MPH (University of Washington) (Chair); Katrina Armstrong, MD, MSCE (University of Pennsylvania School of Medicine); Jeffrey Botkin, MD, MPH (University of Utah); Ned Calonge, MD, MPH (Colorado Department of Public Health and Environment); James Haddow, MD (The Warren Alpert Medical School of Brown University); Maxine Hayes, MD, MPH (Washington State Department of Health); Celia Kaye, MD, PhD (University of Colorado School of Medicine); Kathryn A. Phillips, PhD (University of California, San Francisco); Margaret Piper, PhD, MPH (Blue Cross/Blue Shield Association Technology Evaluation Center); Carolyn Sue Richards, PhD, FACMG (Oregon Health & Science University); Joan A. Scott, MS, CGC (Johns Hopkins University); Ora L. Strickland, PhD, DSc (Hon.), RN, FAAN (Emory University); Steven Teutsch, MD, MPH (Merck & Co.)

Financial Disclosures/Conflicts of Interest

Steven Teutsch is an employee, option and stock holder in Merck & Co., Inc.

Guideline Status

This is the current release of the guideline.

Guideline Availability
Availability of Companion Documents

The following are available:

Patient Resources

None available

NGC Status

This NGC summary was completed by ECRI Institute on February 19, 2008. The information was verified by the guideline developer on July 22, 2009.

Copyright Statement

This NGC summary is based on the original guideline: Recommendations from the EGAPP Working Group: can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan. Genet Med 2009 Jan;11(1):15-20. ©American College of Medical Genetics. Reprinted with permission of Lippincott Williams & Wilkins.

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