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Prostate Cancer Lab #25: Pharmacogenomics and Dosing (Kristine Ashcraft)

“Pharmacogenomics is germline genetic testing that helps us understand when our genes would dictate that for a growing list of medications, whether we need a higher dose, a lower dose, or a different medication altogether.” – Kristine Ashcraft

Meeting Summary

We’re being overdosed, underdosed, and misdrugged. People are being given drugs that are ineffective, or in tragic cases fatal, which testing could have predicted. We should get tested at birth to identify our personal drug risks and to inform personalized dosing levels. Our system of drug delivery should be tuned to dose at the right level for individuals, and eventually by measuring the effective level of the drug in the body, and then modulate the dose empirically, as opposed to prescriptively. Instead we have one-size-fits-all (not personalized) rules for prescriptions and a bias to prescribe the maximum tolerable dose, which makes sense for some drugs, but not others.

Kristine Aschcraft has been an innovator in precision medicine and pharmacogenomics since 2000, co-authoring and assisting in study design for some of the most cited publications on the clinical and economic benefits of pharmacogenomics in high risk polypharmacy patients. She led the team that created the first pharmacogenomic-guided clinical decision support tool to be integrated in the clinical workflow in AllScripts, Epic, and Cerner; winning a HIMSS Health 2.0 Open APP challenge award in 2013. She has helped coordinate multiple population-based programs aiming to reduce medication risk and associated adverse outcomes and costs with targeted pharmacogenomic testing and improved clinical decision support. She is committed to catalyzing the adoption of precision medicine to improve care and reduce healthcare costs.

“Pharmacogenomics” is testing that looks at our hereditary (“germline”) genes to help us understand when, for a growing list of medications, we need a higher dose, a lower dose, or a different medication altogether. In cancer care, greater than 99% of patients will have a pharmacogenetic variation that impacts their response to on average more than 10 commonly prescribed medications.

There are guidelines for administering every drug based on drug-gene interactions developed by the Clinical Pharmacogenetics Implementation Consortium (CPIC). This is a great reference to determine if a gene test should be considered before administering that drug. You can key in any medication that is being offered and see whether there is a CPIC guideline for drug or dose change guidance or FDA guidance on how that medication would be modified and which gene is impacted.

Unfortunately, guidelines and reimbursement policies do not align with current evidence. They’re outdated. Awareness of these specific drug-gene interactions should be widespread and tested for. This is something that can be done once in a lifetime. Although there aren’t many cancer medications that have drug-gene guidance, a lot of the other medications that cancer patients need are impacted by pharmacogenomics and should be considered. 

Meeting Recording

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