Personalized Medicine - Translational Informatics: Realizing the Promise of Knowledge-Driven Healthcare - page 43

over many millennia, while mutations affecting drug response have only relatively
recently become relevant [ 22 ].
Warfarin is a prime example of a drug for which genetic information may affect
prescribing. It is an anticoagulant, initially developed as rat poison in the mid-
1900s. The drug itself has a very narrow therapeutic index: too low a dose and there
is no therapeutic effect, too high a dose and the patient may bleed out. Two genes in
particular, VKORC1 and CYP2C9, are known to affect the activity of warfarin,
causing the FDA to include this information on the drug label. Various resources
(e.g. websites, smartphone “apps”) exist to provide clinical decision support that
incorporates genotype data for initial dosing, though clinical studies to date have
reached different conclusions regarding improved outcomes through use of genetic
information in dosing [ 23 , 24 ].
Other examples of pharmacogenomics success stories in recent years include
targeted use of ivacaftor (Kalydeco™) to treat cystic fi brosis in patients with G551D
CFTR mutations [ 25 ], approval of crizotinib (Xalkori™) for ALK positive non-
small cell lung cancer [ 26 ], and Vemurafenib, the fi rst drug approved for BRAF-
mutant cancer [ 27 ].

3.4.2 Direct to Consumer (DTC) Genetic Testing

The direct to consumer (DTC) genetic testing landscape has been an evolving one
since deCODE and 23andMe fi rst launched their services in 2007, with others to
follow soon after. These companies varied fairly widely in terms of cost, number of
mutations tested, and degree of support provided. In general, the customer would
provide a biospecimen, e.g. by spitting into a test tube or taking a buccal swab, and
send the specimen back to the company to be processed. The test results were then
made available to the customer through a secure web interface (see Fig. 3.6 ). Some
companies focused primarily on actionable, disease-related traits. 23andMe, the
main player still standing by 2014, included both health traits (at least initially, see
below) and other more recreational information, such as wet versus dry earwax, and
the ability to smell a metabolite of asparagus in one's urine. They also introduced
functionality around tracing ancestry, and the ability to participate in surveys,
thereby furthering biomedical research.
DTC testing has been somewhat controversial from a regulatory perspective.
It was, and at some level still is, unclear to what extent these services are or should be
regulated by the FDA. Through 2010 and 2011, the FDA approached companies indi-
vidually, with communications suggesting that their services might qualify as devices
and therefore require FDA review and approval for use. They requested that the com-
panies either explain why this was not the case, or how they intended to pursue agency
approval. In late 2013, the FDA issued a letter to 23andMe ordering that it cease to
market its service until FDA authorization was received. Shortly thereafter, the com-
pany stopped airing a television advertisement in which they promoted the service's