Guidelines on treatment and algorithms
Gene activity status, gene-drug interactions and clinical recommendations found in your PGx report are based on CPIC / FDA and guideline evidence ratings (CPIC level A, B, C or D) and links to additional drug information. These guidelines are curated by international consortia and updated regularly.
“CPIC’s goal is to address this barrier to clinical implementation of pharmacogenetic tests by creating, curating, and posting freely available, peer-reviewed, evidence-based, updatable, and detailed gene/drug clinical practice guidelines (click here for all CPIC publications). CPIC guidelines follow standardized formats, include systematic grading of evidence and clinical recommendations, use standardized terminology, are peer-reviewed, and are published in a leading journal (in partnership with Clinical Pharmacology and Therapeutics) with simultaneous posting to cpicpgx.org, where they are regularly updated.”
Follow the link for more information on the Clinical Pharmacogenetics Implementation Consortium (CPIC®): https://cpicpgx.org/ and the FDA https://www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling
Clinical Resources for some of the relevant treatment areas:
What are the limitations of the test?
The Mediclinic Precise Pharmacogenetics test analyses genetic variations in your DNA and provides a summary of result-specific guidelines. These guidelines link functional variations of genes coding the Cytochrome P450 metabolic enzymes, and specific drug transporters or drug target genes, to altered drug response, reduced drug clearance or activation according to drug label information and established clinical guidelines (Please see reference to guidelines above).
The Mediclinic Precise Pharmacogenetics test might not be able to provide you with a result of one or more markers, because you may have a new unique variant for which a drug-gene relationship has not yet been reported/published.
Many key genes in pharmacogenomics use a 'star allele' system, where a single star allele (e.g. *3) defines a certain combination of one or more genetic variants that are found together in that allele. Genes can have many star alleles; the enzyme CYP2C9, for example, has over 60 known star alleles. PGx tests tend to only test for some of the most common star alleles, meaning that rare alleles will not be detected. This is due to not all star alleles having been documented, having good enough clinical evidence published on them (i.e. classified as ‘uncertain function’), and therefore would not provide clinically relevant information yet.
This test will not detect all reported/known genetic variations that result in altered gene activity. *1 or wild-type alleles are reported by default if those specifically tested for in the Mediclinic Precise Pharmacogenetics test were not detected. IND values are conservatively assigned to alleles that could not be determined with complete certainty. Only listed mutations are tested for and the absence of a detected mutation does not rule out the possibility of sensitivity to a specific medication due to the presence of other mutations or other environmental factors.
Additional genetic testing (e.g., using other PGx tests, or through sequencing) might uncover or clarify other functional variations you may carry that also affect the medication response but were not detected in this analysis.
It’s possible that the report will indicate there are no issues with any of the medications the patient is taking (for example, they’re all in the Green category), yet they may still feel they are having issues. There may be other factors involved in how they respond to medications (such as their medical condition, age, liver, and kidney function, etc.).
Not all medications available on the market are listed in the report. This is because there is still not enough scientific evidence to conclude about their drug-gene relationships. The treatment guidelines will be updated as more testing is done and more evidence is gathered on medications. The PGx report report will be updated as these sources of information are updated.