595specifi ed based on the companion diagnostic. Clear separation is generally required
of the data used for developing the diagnostic test, including their threshold of posi-
tivity, from the data used for evaluating treatment effectiveness in subsets determined
by the test. Adaptive analysis can be used to provide fl exibility to the analysis but the
use of such methods requires careful planning and prospective defi nition in order to
assure that the pivotal trial adequately limits the chance of erroneous conclusions.
Role of Drug Delivery in Personalized Medicine
Along with other technologies, refi nements in drug delivery will play an important
role in the development of personalized medicine. One well known example is glu-
cose sensors regulating the release of insulin in diabetic patients. Gene therapy, as a
sophisticated drug delivery method, can be regulated according to the needs of indi-
vidual patients. ChipRx Inc is developing a true “responsive therapeutic device” in
which biosensors, electronic feedback and drug/countermeasure release are fully
integrated.
Repositioning of Drugs for Personalized Medicine
Repositioning or repurposing of a drug means its use for an indication other than
originally intended. The pharmaceutical industry is exploring this approach because
of high failure rate of drugs in development and paucity of new drugs in pipelines.
The advantage of repositioning the drug is shortening of development time as the
drug has already passed toxicity testing and safety assessment and needs only late
stage clinical trials for the new indication. For an approved drug, development of an
additional indication may be initiated by feedback from clinicians’ off-label use of
the drug. With increasing knowledge of genomic basis of diseases, repositioning
may be useful for matching the right drug to the right patient.
There are numerous examples of drugs that have been repositioned. Gabapentin
and pregabalin, originally developed as antiepileptic drugs, are used more often for
neuropathic pain. Sildenafi l (Viagra) was initially developed and studied for use in
hypertension and angina pectoris, for which it was not adequately effective.
Observation of penile erection as side effect led to its development for erectile dys-
function. Other indications are also being explored.
Bisphosphonates are a commonly prescribed therapy for osteoporosis and skel-
etal metastases. The drugs have also been associated with reduced tumor burden in
some patients, but the mechanism is unknown. A study has provided evidence that
bisphosphonates inhibit EGFR (HER) receptor tyrosine kinase, including the com-
monly mutated forms that drive NSCLC, as well as a resistance mutation (Stachnik
et al. 2014 ). This new mechanism lays the basis for the repositioning of bisphospho-
nates for the prevention and therapy of HER family-driven cancers.
Role of Pharmaceutical Industry