Do Physicians Think Genomic Medicine Will Be Useful for Patient Care?

Sridharan Raghavan; Jason L Vassy


Personalized Medicine. 2014;11(4):425-433. 

In This Article

Drug Selection

Pharmacogenetics, the use of genetic testing to guide drug treatment choices, may be the most anticipated application of so-called personalized medicine. In oncology, testing tumor pathology specimens – through either direct probing of DNA or RNA or through detection of gene products – has become increasingly important to target therapies to specific cancer-promoting mutations.[24] In recent years, many different tumor types have been sequenced, allowing the identification of the mutation spectrum of different cancers, raising the possibility of increasingly personalized chemotherapy.[25] For certain medications in more widespread use, common genetic variation is associated with efficacy or risk of adverse effects, either of which might be used to tailor drug therapy. For example, studies demonstrated wide variation in the dose of the anticoagulant warfarin needed to achieve therapeutic effect, depending on genetic variation at a few loci in the VKORC1 gene that were differentially distributed across racial backgrounds, with potential implications for the safe initiation of the drug without risk of bleeding.[26] Similarly, GWAS have revealed a SNP in the SLCO1ref-1 gene that increases one's risk of life-threatening muscle damage from treatment with simvastatin, a commonly prescribed medication for hypercholesterolemia.[27] Since these medications are for common conditions often managed by primary care physicians, pharmacogenetics may be the domain for which genomic testing has the greatest impact in widespread patient care. In 2009, Grant et al. found that approximately 50% of physician respondents would recommend a test to guide diabetes drug therapy for their patients, if available. Enthusiasm for pharmacogenetics might vary with its predicted purpose: Haga et al. found that, among primary care physicians surveyed, 78% reported that pharmacogenetic testing was 'Very important' to predict adverse response to treatment, whereas only 48% responded that testing was 'Very important' to predict treatment nonresponse.[28]

Despite the general physician optimism about the application of genomic testing to drug therapy, the actual penetration of pharmacogenetic testing into clinical practice is difficult to assess. Stanek et al., in a national survey of 10,300 generalists and specialists across nonsurgical and surgical fields, found that 98% of respondents felt that genetics could influence a patient's response to a medication, but only 13% of physicians had ordered a pharmacogenetic test in the 6 months prior to being surveyed.[29] Among physicians who had ordered a genetic test to guide drug therapy, however, Stanek et al. observed that comparable numbers of physicians reported prevention of drug toxicity (80%) and improving drug effectiveness (73%) as motivations for ordering tests.[29]

Physicians have expressed a desire for clinical trial evidence or expert consensus regarding the application of pharmacogenomic testing. Grant et al. found that only 5–7% of physicians would be willing to order a pharmacogenetic test prior to clinical trial evidence demonstrating benefit. Similarly, Stanek et al. find that 72–80% of physician survey respondents reported that scientific publication, US FDA recommendation or expert guidelines were 'Important/Very Important' when considering ordering pharmacogenetic testing.[29] It seems, then, that physicians may perceive that genomic testing will be useful in optimizing drug therapy, but its uptake among generalists is limited at present. The application of pharmacogenomic testing to the initiation of warfarin therapy is one of the best studied and exemplifies some of the inherent challenges of pharmacogenomics, even before recent randomized trials called into question the benefit of genetic testing in this context.[30–32] Despite the presence of FDA guidelines issued in 2010 for the application of genetic testing for warfarin susceptibility prior to initiation of therapy, Bernhardt et al. found in their survey of primary care physicians that 89% of those physicians who had started a patient on warfarin had never ordered a genomic test prior to treatment initiation.[12] In fact, in a theoretical survey scenario, only 32% of respondents would use pharmacogenetic testing to guide initiation of warfarin therapy, despite 70% of respondents acknowledging its potential usefulness to guide treatment. The case of warfarin demonstrates that favorable attitudes toward genomic testing and translation into clinical practice are highly divergent. Furthermore, it suggests that expert guidelines, while cited as a potential barrier to uptake of genomic medicine,[11] may be necessary but are not sufficient for generalized adoption of genomic medicine.