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.
*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)