Genetic Testing

Tables

Tier 1
Tier 2
Tier 3

Genomic Tests and Family Health History by Levels of Evidence

The CDC Office of Public Health Genomics ranks the following list for levels of evidence of genomic tests and family health history in practice . This approach was based on a paper by Khoury

and updated in accordance with criteria presented by a 2014 paper in Clinical Pharmacology and Therapeutics . The criteria are shown in the following figure to provide additional information to our readers. This list is updated on an ongoing basis andprovided only for informational purposes to researchers, healthcare providers, public health programs and others.

Green

FDA label requires use of test to inform choice or dose of a drug
CMS covers testing
Clinical practice guidelines based on systematic review supports testing

Yellow

FDA label mentions biomarkers*
CMS coverage with evidence development
Clinical practice guideline, not based on systematic review, supports use of test
Clinical practice guideline finds insufficient evidence but does not discourage use of test
Systematic review, without clinical practice guideline, supports use of test
Systematic review finds insufficient evidence but does not discourage use of test
Clinical practice guideline recommends dosage adjustment, but does not address testing

Red

FDA label cautions against use
CMS decision against coverage
Clinical practice guideline recommends against use of test
Clinical practice guideline finds insufficient evidence and discourages use of test
Systematic review recommends against use
Systematic review finds insufficient evidence and discourages use
Evidence available only from published studies without systematic reviews, clinical practice guidelines, FDA label or CMS labels coverage decision

*Can be reassigned to Green of Red of one or more conditions in these categories apply

Tier 3/Red category: represents genomic and family health history applications either have synthesized evidence culminating in recommendations against use (or discouraging use), OR no relevant synthesized evidence was identified. Such applications are not ready for routine practice, but may be considered in clinical and population research.

Gene, Gene/Drug, Test, or Family Health History	Disorder/Indication	Use*	Synthesized Evidence Sources
HFE	hereditary hemochromatosis	population screening	USPSTF (2006)
routine BRCA genetic counseling, routine BRCA testing	Hereditary breast/ovarian cancer, in women whose family health history is not associated with an increased risk of BRCA mutations	population screening	USPSTF (2013)
panels for various genetic risk factors	common diseases	risk assessment, disease prevention	Multiple sources, for example:EGAPP (2010)
next generation sequencing/whole genome sequence	various common diseases	risk prediction	Rapidly evolving landscape; gaps in knowledge exist for analytic validity, clinical validity and clinical utility
SNP panels	type 2 diabetes	risk prediction	EGAPP [PDF 242.05 KB] (2013)
TCF7L2 genotyping	type 2 diabetes	risk prediction	EGAPP [PDF 242.05 KB] (2013)
NRAS or PIK3CA mutation analysis and/or testing for loss of PTEN or AKT protein expression/anti-EGFR therapy	metastatic colorectal cancer	PGx	EGAPP [PDF 456.16 KB] (2013) Systematic review (2011)
CYP450 testing/SSRIs	non-psychotic depression	PGx, PGx-dose	EGAPP (2007)
tumor gene expression analysis (Prolaris®, Oncotype Dx® Prostate	prostate cancer	prognostic, management	BCBS TEC (2014)
emerging genomic tests in the CDC'sGAPP Finder of theGAPP Knowledge Base	various disorders	various uses	Almost all of these applications (except when listed above) have insufficient information on analytic or clinical validity, or clinical utility

*Pharmacogenomic applications have been classified in the Use column as either PGx (which may relate to drug choice, prevention of adverse events, or other uses of the information gained through testing), or PGx-dose (when specific dosing-related guidance is provided, or mention of a potential effect on dose is noted in the evidence sources cited). Additional Use categories include: screening, cascade testing, risk prediction, diagnostic, and prognostic.

Source Abbreviations: Agency for Healthcare Research and Quality (AHRQ), American College of Medical Genetics and Genomics (ACMG), American Society of Clinical Oncology (ASCO), Centers for Medicare and Medicaid Services (CMS), Clinical Pharmacogenetics Implementation Consortium (CPIC), Evaluation of Genomic Applications in Practice and Prevention (EGAPP), National Comprehensive Cancer Network (NCCN), National Institute for Health and Care Excellence (NICE), National Institutes of Health (NIH), Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children (SACHDNC), US Department of Health and Human Services (DHHS), US Food and Drug Administration (FDA), United States Preventive Services Task Force (USPSTF)

Other Abbreviations: estrogen receptor (ER), progesterone receptor (PgR), pharmacogenomics (PGx), single-nucleotide polymorphism (SNP)