Pharmacogenomics: CLINICAL TRIALS

A recent English-language Medline search for the phrase “pharmacogenomics and clinical use” from 2003 to the present revealed 369 articles from every specialty of health care, disease identification, patient monitoring, and therapeutics. At present, large clinical trials are under way to establish the correlation between genomic information and therapeutic response.

A study called GenHAT (Genetics of Hypertension-Associated Treatment), an ancillary to ALLHAT (Antihypertensive and Lipid-Lowering to Prevent Heart Attack Trial) and GENECARD (A Genome-wide Scan for Early-Onset Coronary Artery Disease) are just two examples. Upon its completion, GenHAT will be able to characterize genetic variations in hypertension and establish correlation to therapeutic response. GENECARD aims to identify chromosomal regions as well as specific SNPs related to the early onset of coronary artery disease.

Numerous smaller clinical trials are elucidating the impact of genomic variability in drug response and applying this information to an array of medications. Researchers at the University of Kentucky have published a small study on the metabolism of risperidone (Janssen), ADEs, and drug discontinuation. Using inpatient samples from 325 patients who experienced ADEs and 212 patients who discontinued, genomic assay techniques, including the AmpliChip™ CYP450, have been used in conjunction with logistic regression to determine the association of genomic enzyme data and response. Researchers have determined that when the CYP450 2D6 poor metabolizer phenotype was corrected for confounders, it was associated with both ADEs (OR 3.4; 95% CI: 1.4-8) and a discontinuation of risperidone canadian (6.0; 95% CI: 1.4-25.4). The authors emphasize that larger trials are needed, but the data hold promise.

Jefferson et al. have investigated aspirin resistance and polymorphic differences in four candidate genes known for their role in platelet aggregation. Blood samples of 330 Caucasian men from the Cleveland Clinic with a medical history that includes a percutaneous coronary intervention (PCI), MI, and a daily dose of aspirin (81-325 mg) have been screened for aspirin resistance. After correcting for confounders, researchers found that one polymorphic change in the P2RY1 gene was associated with a 2.7-fold increase (95% CI: 1.12-6.57; P = .03) in aspirin resistance. Again, this was a small trial in a limited population but a harbinger of what is to come.

Both of the aforementioned trials, while interesting, provide little information to clinicians. The small sample sizes and limited populations diminish external validity. Moreover, validation of study results from either trial in a large clinical setting is lacking at this time. Until the results can be reproduced, pharmacogenomic testing will remain experimental and nonessential in clinical medicine.

The number of trials using genomic data could double within a year—this is exciting but daunting news to health care professionals. Armed with genetic information, a clinician has the power to evaluate a patient for drug dosing and response before initiating therapy, further reducing the possibility of serious ADEs and negative clinical outcomes. The clinical impact of pharmacogenomics is potentially tremendous. For example, genomic data will assist in identifying aspirin-resistant patients at the time therapeutic decisions are made, thus helping clinicians in selecting pharmacotherapy and possibly preventing the devastating consequences of a stroke. canadian antibiotics


The predictive power of pharmacogenomics is not without a substantial initial investment. The cost of the AmpliChip™ CYP450 assay is $500 to the patient, but specialized equipment and laboratory personnel are required. Although the fee is nominal in relation to other health care procedures, the information derived is basic phenotypic data; third-party payers do not routinely cover the assay because it is considered nonessential. Future pharmacogenomic studies will evaluate more complex interactions and probably at a higher cost, as foreshadowed by receptor-based therapeutics such as epidermal growth factor (EGF) inhibitors; however, the economic impact of pharmacogenomics remains to be determined.

Knowing that ADEs are prevalent and costly to the health care system, the pharmacoeconomic implications of genomic monitoring are conceivably extensive and favorable when the long-term savings of better clinical outcomes and improved quality of life are considered. Cost-benefit analyses that encompass total costs and long-term benefits will advance the acceptance of pharmacogenomics in clinical medicine; in the near future, pharmacogenomics will be synonymous with standard of care.


With the gross influx of information and the jargon of molecular biology infiltrating health care at an accelerated pace, several questions arise:

  • How will health care teams handle genomic data in a patient’s profile?
  • Is it the physician’s responsibility to order and interpret genomic data before giving treatment?
  • Is it the pharmacist who will effectively evaluate genomic data and provide not only therapeutic recommendations but also patient counseling?
  • Is it the nurse who must understand and add genomic profiles to a long list of monitoring parameters?
  • Does everyone in the multidisciplinary approach to patient care share in the responsibility of pharmacogenomics?
  • Will adding another professional (a molecular biologist or geneticist) to the patient-care team potentially thwart cost-reduction efforts?

Such questions must be answered as we move into the genomic era of medicine.


Where does pharmacogenomics stand in the field of clinical medicine? Just as Alice (in Wonderland) fell for a seemingly long time to the bottom of the rabbit hole with one key and numerous doors surrounding her, clinical medicine has embarked on the initial phases of pharmacogenomic medicine with the completion of the sequence identification of the human genome as the key in hand. Unlike the vivid dream in the beloved children’s tale, however, pharmacogenomics is a very real scientific endeavor into the complexity of drug response.

Currently, the primary key—the complete human genome sequence—has unlocked only a few doors in drug-response pathways. Many doors remain locked, and there are more questions than answers. Nonetheless, with the accelerated pace of molecular biology research, clinicians can be assured that the discovery of additional keys in the structure-function relationship of the human genome will revolutionize patient care and improve outcomes. online pharmacy uk

Category: Main

Tags: Pharmacogenomics

Leave a Reply

Your email address will not be published. Required fields are marked *