The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) initiative: methods of the EGAPP Working Group

http://www.nature.com/gim/journal/v11/n1/full/gim20092a.html

The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) initiative: methods of the EGAPP Working Group

Steven M Teutsch¹, Linda A Bradley², Glenn E Palomaki³, James E Haddow³, Margaret Piper⁴, Ned Calonge⁵, W David Dotson^2,6, Michael P Douglas^2,6 and Alfred O Berg⁷ Chair, on behalf of the EGAPP Working Group

1. ¹Merck & Company, Inc., West Point, Pennsylvania
2. ²National Office of Public Health Genomics, CDC, Atlanta, Georgia
3. ³Department of Pathology and Laboratory Medicine (Research), The Warren Alpert Medical School of Brown University, Providence, Rhode Island
4. ⁴Blue Cross/Blue Shield Association Technology Evaluation Center, Chicago, Illinois
5. ⁵Colorado Department of Public Health and Environment, Denver, Colorado
6. ⁶McKing Consulting Corp., Atlanta, Georgia
7. ⁷Department of Family Medicine, University of Washington, Seattle, Washington

Correspondence: Linda A. Bradley, PhD, National Office of Public Health Genomics, Centers for Disease Control and Prevention, 4770 Buford Highway, MS K-89, Atlanta, GA 30341. E-mail: lbradley@cdc.gov.

Received 10 April 2008; Accepted 13 June 2008

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.Disclosure: Steven M. Teutsch is an employee, option and stockholder in Merck & Co., Inc. W. David Dotson is a former employee and current stockholder in Novo Nordisk, Inc.

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Abstract

The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Initiative, established by the National Office of Public Health Genomics at the Centers for Disease Control and Prevention, supports the development and implementation of a rigorous, evidence-based process for evaluating genetic tests and other genomic applications for clinical and public health practice in the United States. An independent, non-federal EGAPP Working Group (EWG), a multidisciplinary expert panel selects topics, oversees the systematic review of evidence, and makes recommendations based on that evidence. This article describes the EGAPP processes and details the specific methods and approaches used by the EWG.

Keywords: 

Evidence-based medicine; review; systematic

The completion of the Human Genome Project has generated enthusiasm for translating genome discoveries into testing applications that have potential to improve health care and usher in a new era of “personalized medicine.”^1–4 For the last decade however, questions have been raised about the appropriate evidentiary standards and regulatory oversight for this translation process.^5–10The US Preventive Services Task Force (USPSTF) was the first established national process to apply an evidence-based approach to the development of practice guidelines for genetic tests, focusing on BRCA1/2 testing (to assess risk for heritable breast cancer) and on HFE testing for hereditary hemochromatosis.^11,12 The Centers for Disease Control and Prevention-funded ACCE Project piloted an evidence evaluation framework of 44 questions that defines the scope of the review (i.e., disorder, genetic test, clinical scenario) and addresses the previously proposed^6,7 components of evaluation: Analytic andClinical validity, Clinical utility and associated Ethical, legal and social implications. The ACCE Project examined available evidence on five genetic testing applications, providing evidence summaries that could be used by others to formulate recommendations.^13–16 Systematic reviews on genetic tests have also been conducted by other groups.^17–20

Genetic tests tend to fit less well within “gold-standard” processes for systematic evidence review for several reasons.^21–24 Many genetic disorders are uncommon or rare, making data collection difficult. Even greater challenges are presented by newly emerging genomic tests with potential for wider clinical use, such as genomic profiles that provide information on susceptibility for common complex disorders (e.g., diabetes, heart disease) or drug-related adverse events, and tests for disease prognosis.^25,26 The actions or interventions that are warranted based on test results, and the outcomes of interest, are often not well defined. In addition, the underlying technologies are rapidly emerging, complex, and constantly evolving. Interpretation of test results is also complex, and may have implications for family members. Of most concern, the number and quality of studies are limited. Test applications are being proposed and marketed based on descriptive evidence and pathophysiologic reasoning, often lacking well-designed clinical trials or observational studies to establish validity and utility, but advocated by industry and patient interest groups.