Phoenix, AZ—Using the paradigm of individualizing drug therapy based on a patient’s genetics, a group of oncologists and genomic experts have designed a genomic prescribing system that they hope will significantly reduce the staggeringly high rate of adverse drug reactions associated with prescription drugs in the United States. Principal investigator Peter H. O’Donnell, MD, Assistant Professor, Department of Medicine, Section of Hematology/ Oncology, Genitourinary Oncology Program, Committee on Clinical Pharmacology and Pharmacogenomics, Center for Personalized Therapeutics, University of Chicago, IL, discussed the very early results of the 1200 Patients Project at the 2012 Society for Medical Decision Making annual meeting.
“Patients and providers see this as the future of how medicine will be practiced,” Dr O’Donnell told Value-Based Cancer Care (VBCC). “A key advantage of this approach is that all potentially desired pharmacogenomic information is obtained for the patient’s entire drug prescription lifetime, with one single test.”
The model attempts to circumvent the barriers to implementing personalized medicine resulting from the limited and high cost of genetic testing, the delay in their results, and the common disagreement regarding the interpretation of the results. Dr O’Donnell and his colleagues are hoping that this new venture will help to translate the benefits of pharmacogenomics, or personalized medicine, into clinical practice in oncology.
The 1200 Patients Project
The project began in the spring of 2011 and involves preemptive and comprehensive pharmacogenomic genotyping of a large number of consenting patients—at a cost of less than $500 per person—and rapid and cheap electronic dissemination of genotype information (http://cpt.uchicago.edu/page/1200-patients-project). It harnesses the discovery of genetic variants that govern appropriateness of response to, and toxicity from, drugs, but which until now have not been incorporated into prescribing decisions.
In a recent article published in Clinical Pharmacology & Therapeutics, Dr O’Donnell and his team outlined the full scope of the project, which is designed to overcome barriers to the application of routine “pharmacogenomic prescribing” into clinical practice (O’Donnell PH, et al. Clin Pharmacol Ther. 2012;92:446-449). The software and the other technologies for the project were created by Dr O’Donnell’s team, in collaboration with the University of Chicago Center for Research Informatics.
Discussing the rationale for this project, the authors write, “We have carefully considered the alternative option of whole-genome sequencing. Although whole-genome sequencing has the advantage of detecting rare variants…it has the disadvantage of requiring substantially greater costs in quality-control/bioinformatics analysis.” Funding is provided by the Conquer Cancer Foundation of the American Society for Clinical Oncology’s Translational Research Professorship and other institutional and philanthropic sources.
The 1200 patients being recruited for the study are receiving outpatient medical care from 1 of 12 physicians. These include 4 general internists, 3 oncologists, 2 cardiologists, 1 pulmonologist, 1 hepatologist, and 1 gastroenterologist.
The patients undergo testing for a panel of genotypic variants that have been associated with a positive response to, or an adverse reaction to, frequently used medications. The drugs include those that the patients are currently taking and other drugs that they may receive in the future. Newly discovered genetic and pharmacogenomic variants will be incorporated into the testing over time, once they have been confirmed to be clinically relevant.
“A full 674 drugs have been reviewed for inclusion in the genomic prescribing system, with patient- specific information being present when pharmacogenomic information exists,” said Dr O’Donnell.
The patient-specific testing results indicate: Whether the person’s genotypic profile suggests that the patient is likely (or not) to benefit from a particular drug
- What the level of evidence is for this conclusion
- What published studies support these findings.
These data are made available exclusively to the enrolling provider of the specific patient through a research web portal.
Overcoming Clinicians’ Knowledge Gap
The ultimate goals of the project are to determine whether physicians are taking pharmacogenomic information into account during clinic visits, and whether this information alters prescribing to patients who are genetically at high risk for negative outcomes because of adverse drug reactions or for a nonresponse to the specific medication.
“Although a recent survey suggests that 98% of physicians believe ‘patient genetic profiles may influence drug therapy,’ only 13% had ordered a pharmacogenetic test, and only 10% had felt adequately informed about pharmacogenetics,” Dr O’Donnell and colleagues write in their published article.
Approximately 700 patients have been recruited to date, 400 of whom have received pharmacogenomic testing thus far. One physician began using the genomic prescribing system in October 2012, and the other 11 physicians will begin using it “soon,” Dr O’Donnell told VBCC.
The physicians and patients who are involved in the project have expressed “significant enthusiasm,” Dr O’Donnell added. “Patients have little reservation about this type of testing, and physicians are very interested to see what medications have relevant information in our database.”