The interest in genomics continues to grow. In oncology, genomics is adding to the level of confidence that particular chemotherapeutics will have the desired effects against specific tumor types. The FDA, recognizing the promise of these new technologies, has recently revised some drug labels—warfarin, for example—to make clinicians aware that gene variations may affect drug sensitivity.

The case of warfarin addresses the role genomics is beginning to play in optimizing dosages as well as helping to minimize adverse drug reactions (ADRs). Indeed, the costs of the ever-increasing number of drug side effects continue to escalate. It was estimated that cost of drug-related problems exceed $177.4 billion annually in the U.S. (which includes untreated indication, improper drug selection, subtherapeutic dosage, and failure to receive drugs, overdosage, adverse drug reactions, drug interactions, and drug use without indication).¹

Beyond the economic impact, of course, there is the individual patient: ADRs are a major component of poor drug compliance and, thus, represent a lost opportunity to maintain or improve health.²

The use of AAPs in the non-institutionalized U.S. population has increased dramatically since being introduced in 1996 from a rate of 0.15% in 1996 to 1.06% in 2005.³ While AAPs have been shown to dramatically reduce hospitalizations for schizophrenia and related indications, they carry a risk of cardiometabolic side effects, including significant weight gain, elevated triglycerides and elevated blood glucose leading to diabetes.

Improved compliance with AAPs could result in 30 to 100 avoided behavioral health inpatient admissions per 1,000,000 typical commercial (non-Medicare, non-Medicaid) members over one year, as well as lower prevalence rates of diabetes. This incremental annual cost amounts to about $11,000 per AAP patient who develops diabetes.

In the population taking statins, there is an under-appreciated set of sometimes debilitating symptoms including myalgia and myositis. The incidence rate reported in prescribing information ranges from 1% to 5% but much higher rates of 10% for new patients have been reported in the literature.⁴

Although a common complaint, physicians frequently miss the connection between symptoms and statins.⁵ The JUPITER study published in the New England Journal of Medicine and presented at this year's American College of Cardiology meeting could mean more physicians will consider statin therapy for their patients.⁶

We found 15.3% of new statin takers experienced myopathy, using claims coded with a myalgia ICD-9 code or a creatine kinase test claim dated 30 days to 12 months after the first statin script, using 2006 claims data covering a commercially insured population of 190 million. The incidence reaches almost 23% for the cohort having suffered an acute coronary artery disease event in the 12 months before statin initiation. The burden of statin-induced neuro-myopathy on healthcare costs could represent a 40% increase compared to patients on statins not developing side effects.

Thus, DNA-guided diagnostics for drug selection has implications for patient well being, outpatient and inpatient treatment costs of side effects, and ongoing monitoring costs. In addition, it is expected that drug compliance will be enhanced since the risk of non-compliance increases for patients experiencing side effects. Identifying an individual's sensitivity to drug classes and the individual drugs within them could allow for optimized dosing, the prescribing of alternative medications, or closer monitoring and counseling of patients for the development of side effects.

Bringing DNA-based diagnostic tests to the practice of medicine will require a platform that provides clinicians with new decision support tools. Operationally, these must include three components: an ensemble of inherited, stable DNA markers from several genes; a bio-clinical algorithm validated in clinical studies for ascertaining the clinical significance of a patient's DNA marker configuration, and a reporting system for doctors to select drugs based on each patient's individual risk of developing common, clinically intensive side effects.

But having advanced technology and standardized methods won't be enough. Moving forward, it will be crucial for healthcare providers and patients to understand both the benefits and limitations of what personalized medicine can and cannot deliver. We need to identify the gaps in public understanding so that we can help to ensure appropriate utilization and that people are able to benefit from the information that resides in their own bodies.

Gualberto Ruaño, M.D., Ph.D. is President and CEO of Genomas, Inc. and Director of Genetics Research at Hartford Hospital

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2. Chan M, Nicklason F, Vial JH. Adverse drug events as a cause of hospital admission. Internal Medicine Journal. 2001;31:199–205.

3. Domino ME, Swartz MS. Who are the new users of antipsychotic medications? Psychiatric Services. 2008;59:507-514.

4. Bruckert E, Hayem G, Dejager S et al. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients – The Primo Study. Cardiovascular Drugs and Therapy. 2005;19:403-414.

5. Golomb, BA, McGraw, JJ, Evans, MA, Dimsdale, JE. Physician Response to Patient Reports on Drug Adverse Effects. Drug Safety. 2007;30(8): 669-675.

6. Glynn, RJ, Danielson, E, Francisco A.H. Fonseca, FAH et al. A Randomized Trial of Rosuvastatin in the Prevention of Venous Thromboembolism. New England Journal of Medicine. 2009; published on-line March 29.