14 4
companies are building large electronic databases of clinical and genomic information
that the FDA believes can be useful in tracking ADRs in a post-marketing setting. It
may be possible to investigate if customers with certain genetic polymorphisms are
on certain drugs and have experienced certain ADRs. As a part of FDA Amendment
Act, which was signed into law in 2008, pharmaceutical companies are required to
submit results from post-marketing studies to a clinical trial registry. By partnering
with personal genomics companies, the FDA would gain access to genomic data that
may provide additional insight into ADRs that have genetic underpinnings. Such a
collaborative project would probably not be possible until companies were at the
point where they had genotyped at least 100,000 patients on high-density arrays. One
current potential drawback to an alliance between the FDA and personal genomics
fi rms is that, at the moment, the cost for such services is out of reach for the average
consumer, which could limit the diversity of individuals contained in a database.
Recommendations for the Clinical Use of Pharmacogenetics
Due to the rapid development of cost-effective methods for genotyping and the need
to genotype only once in the lifetime of a patient, it would be advisable to include the
genotype in the patient’s record. It is also desirable to include the genotypes of trans-
port proteins and drug receptors, which can reveal highly predictive genetic informa-
tion. This would provide the physician with valuable information to individualize the
treatment. Besides development of personalized medicines, the impact of genotyping
on medical practice would shift the emphasis from present diagnosis- based treatment
to detection of disease prior to clinical manifestation and preventive treatment with
appropriate medicine and a dose that is most effective and safest for an individual.
Predicted clinical developments from application of pharmacogenetics are:
- Establishment of prescribing guidelines, based on clinical studies, for drugs that
are subject to substantial polymorphic metabolism - Prescribing advice will relate dose to genotype and will highlight the possibility
of drug interactions when multiple drugs are prescribed concomitantly - Establishment and recording of individual patient genotypes that is, “personal
pharmacogenetic profi les” - Pharmacogenetic testing will substantially reduce the need for hospitalization,
and its associated costs, because of adverse drug reactions - Development of new drugs for patients with specifi c genotypes that is, “drug
stratifi cation”
Limitations of Pharmacogenetics
Inherited component of the response to drugs is often polygenic. Furthermore, the
drug response is probably affected by multiple genes, each gene with multiple poly-
morphisms distributed in the general population. Racial differences add further
4 Pharmacogenetics