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34 | SEPTEMBER 1, 2016 | GENengnews.com | Genetic Engineering & Biotechnology News Pharmacogenetics Continued from page 33 duce confusion among clinicians and pro- vide a resource that is usable both now and in the future." Preemptive Pharmacogenetic Testing While the CPIC guidelines are shaping up nicely, other institutions are working on integrating genetic data with their EHRs. "Normally, pharmacogenetic testing is done after the fact," states Stuart Scott, Ph.D., as- sistant professor of genetics and genomic sci- ences, Icahn School of Medicine at Mount Sinai. "We see this as less helpful for patients and advocate doing pharmacogenetic testing beforehand—preemptively," Before preemptive pharmacogenetic test- ing can be implemented, certain elements may have to be in place. According to Dr. Scott, these elements include suitable clinical guidelines, duly informed clinicians, dem- onstrations of cost-effectiveness, and assur- ances that insurance companies will honor reimbursement plans. At Mount Sinai, Dr. Scott is participating in programs that preemptively test patients for genes involved in drug response variabil- ity. Patient-specific gene-drug information is added to the patient's EHR, where it sits un- til the doctor orders a drug for which there is pertinent genetic information. Ordering such a drug essentially pulls an informational trig- ger—the relevant test result is retrieved and presented to the ordering physician with CPIC therapy recommendations. Certain specialties such as cardiology, psychiatry, on- cology, and pain management already have well-known cases of gene-drug pairs, which were the first to be included in the implemen- tation programs at Mount Sinai. "With approximately 2,000 patients enrolled since 2013, the system now 'fires' point-of-care pharmacogenetic results and recommendations about once every two weeks," notes Dr. Scott. "The physician re- ceives a message through the EHR. For ex- ample, the message might say, 'patient is a poor metabolizer of Drug A—consider X, Y, and Z alternatives.'" Initially, Dr. Scott was concerned that it would be necessary to genotype 10,000 people before "triggering" would occur. However, activation of the pharmacogenet- ics functionality in Mount Sinai's EHR sys- tem is occurring with only one-fifth of that number enrolled. "We think it's important to give physicians options, not orders, as physicians ultimately know the clinical context of their patients bet- ter than anyone," insists Dr. Scott. "The can be rejected for any reason. We are carefully measuring provider feedback and experience using the EHR system. This information from clinicians informs how we refine our pharma- cogenetic implementation programs without adding more work for physicians." Dr. Scott feels that doctors need educa- tion on using pharmacogenetics, as most have never had formal training before. To this end, medical students at Mount Sinai have the option of having their own person- al pharmacogenetic tests performed. Later, when the students attend Dr. Scott's lectures, the de-identified clinical results are reviewed. Dr. Scott envisions patients receiving ge- netic testing for a drug response panel during initial visits to the doctor's office. This infor- mation can then follow them for the rest of their lives via their EHRs, and potentially also through smart phone apps and other personal electronic devises. International Initiatives International efforts to incorporate phar- macogenetics into routine medical practice can be seen in European countries. One am- bitious undertaking, sponsored by the Euro- pean Union (EU), is a multicenter study to evaluate the cost-benefit ratio of preemptive pharmacogenetic advice in comparison to conventional treatment considerations. This will be undertaken by the Ubiquitous Phar- macogenetics consortium. "Six different healthcare centers through- out Europe will enroll patients, says Mag- nus Ingelman-Sundberg, Ph.D., professor and section head, department of physiology and pharmacology, Karolinska Institute. "At each center, one patient group will be treated based on pharmacogenetic information of the patient's genome, and another control group will receive conventional medical care. By comparing the two regimens, we can do a cost-benefit analysis to determine the value of using preemptive pharmacogenetics testing." Dr. Ingelman-Sundberg concurs with the idea that it is important to keep track of the latest developments in pharmacogenetics and drug-genome interactions. The Euro- pean Medicines Agency (EMA) fulfills the function of the FDA in the EU. "Employing DNA to predict a patient's reaction to a particular drug is easier, safer, and less costly than testing for the phenotype by in vivo studies," Dr. Ingelman-Sundberg points out. "However, we are still research- ing exactly what the individual's DNA se- quence means for the expression of drug- metabolizing enzymes, drug transporters, and drug targets in the patient. "Many rare mutations which are now not present in the commonly used genotyp- ing platforms influence drug response. We still do not know all the mutations out there and how they affect the phenotype. These unknown rare mutations confound current preemptive genotyping for many drugs and have to subsequently be incorporated into the future genotyping platforms." Other factors in Europe lend themselves to clinical evaluation of pharmacogenetics. 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