Predictive ability of direct-to-consumer pharmacogenetic testing: when is lack of evidence really lack of evidence?

Rachel RJ Kalf, Rachel Bakker & A Cecile JW Janssens^*

* Author for correspondence

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For several years personal genome tests have been offered directly to consumers via the internet. Based on single genome scans, these direct-to-consumer (DTC) tests predict susceptibility to common multifactorial diseases, such as Type 2 diabetes, coronary heart disease and nonfamilial cancer, inform about predisposition to drug response, report carrier status for monogenic diseases, or provide all of the above. The market is served by a few major players, such as 23andMe and deCODEme, and numerous lesser-known companies such as YouScript, GenePlanet and Theranostics [101–105].

The market for DTC personal genome testing is steadily increasing, even though the evidence on the predictive ability and clinical utility of these tests is limited. The few available studies have shown that predicted risks of multifactorial diseases differed between companies and were sometimes even contradictory for the same individual [1,106], but large-scale studies on the predictive ability are lacking. From prediction studies that investigated genetic risk models based on different but comparable selections of SNPs, we know that the predictive ability of genetic testing for multifactorial diseases is low to moderate, except when one or more SNPs had substantial impact on disease risk [2]. From this indirect evidence it is concluded that the DTC offer of genetic testing for multifactorial diseases is premature.
To date, most of the discussion about DTC personal genome tests has focused on the prediction of these multifactorial diseases and less attention has been given to the predictive ability and clinical utility of pharmacogenetic testing. Yet, many companies offer pharmacogenetic testing to inform about the genetic susceptibility to drug response and side effects of treatment [3], such as the efficacy of clopidogrel and the risk of side effects from abacavir treatment. A recent comparison of eight DTC companies showed that genetic testing was clearly recommended by the US FDA for only four out of 30 drugs reviewed [3]. It may be that many of the remaining drugs have not been approved either because empirical studies demonstrated that their predictive ability is insufficient, or because they have not yet been investigated in empirical studies.