One of the most important but unresolved problems in therapy with potent and often toxic drugs has been inability to describe, understand, and quantify the relationships and variability between drug doses, concentrations in blood, and the interplay between therapeutic and toxic drug effects. Defining drug action and inter-patient variability has been, for the most part, limited to simplistic descriptions of average maximum and minimum drug dosages. Until recently, this has not permitted true individualization of therapy for each patient.
Although significant inter-individual variability has been known to exists in the response to most medications, medication selection has historically used empiric data rather than individualized. This is despite the fact that the FDA is increasingly recognizing the importance of the genetic contribution to the individual variation in response to therapy. Nevertheless, the main reason that physicians have not incorporated genetic and non-heritable host factors into treatment plans is the lack of applicable, easy to use algorithms that translate the patient’s characteristics into clinical recommendations.
Cincinnati Children’s Hospital Medical Center (CCHMC) recently received U.S. Patent No. 8,589,175, titled Optimization and individualization of medication selection and dosing, which may change the way individual variability based on genetic make-up is utilized in order to both select and prescribe certain medicines. The CCHMC patent specifically covers methods for optimizing dosing regimens for medications utilizing population models, genotype, and clinical information to treat patients with neuropsychiatric and other disorders. Assurex Health is the exclusive worldwide licensee of the technology covered under the CCHMC patent and has developed pharmacogenomic tests for psychiatric, ADHD, and pain medications.
The invention disclosed in the ‘175 patent incorporates computerized methods of targeting drug therapy, particularly dosing regimens and compound selection, to an individual subject or patient. The methods incorporate genetic and non-heritable factors into drug selection and prescription. The invention provides computational algorithms for recommending a dosing regimen for a particular patient utilizing population models, genotype information, and clinical information. The methods of the invention allow iterative integration of patient information and clinical data. The methods of the invention provide timely, easy to understand, and easy to implement recommendations. Further, the invention provides proactive identification of patients potentially requiring more in-depth assessment by a clinical pharmacology specialist.
In essence, the invention provides a mechanism for translating “one size fits all” drug dosing into individualized dosing based on a person’s genetic and non-heritable characteristics. Patient-specific genetic factors involve unidirectional, pharmacokinetic or pharmacodynamic, drug-gene interactions. Unidirectional refers to the effect of the genetic variation on the pharmacokinetic or pharmacodynamic action of the drug. A pharmacokinetic drug-gene interaction is considered potentially clinically significant if there is a documented interaction that shows the genetic factor either increases or reduces the activity of a specific enzyme associated with the metabolism of the drug by ≧20%. A pharmacodynamic drug-gene interaction is considered potentially clinically significant if there is a documented interaction that shows the genetic factor alters (either positively or negatively) the action of the drug by 20% or greater .
The methods of the invention can be applied to correct for the variability seen in drug metabolism due to genetic polymorphisms combined with the variability resulting from non-genetic factors. The results provide a way to standardize the impact of various fixed factors, such as a patient’s genetic variability, and dynamic factors, such as drug-drug and drug-environment interactions or patient drug-adherence. As a result, the starting and target doses for neuropsychiatric and other medications can be determined without the need for metabolic data.
The hope of CCHMC and Assurex is that by prescribing a medication that may be more likely to succeed because it is tailored to an individual patient’s genetic profile, clinicians will be better able manage their patient’s condition and improve outcomes.
Early studies suggest that the CCHMC innovation is working. In fact, on December 5, 2013, Assurex announced the publication of a third clinical study providing evidence for the effectiveness of the combinatorial pharmacogenomic test over the current method for selecting psychotropic medications. The study results were published in the November 2013 issue of Discovery Medicine, and are consistent with two previous clinical trials. This latest study concluded that patients are more than twice as likely to respond when treatment is guided using the CCHMC invention as compared to treatment as usual.
Tags: Assurex Health, Cincinnati Children's Hospital Medical Center, patent, patents, prescribing drugs
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