CYP2D6 copy number distribution in the US population.

The cytochrome P450 2D6 (CYP2D6) gene is perhaps the most well characterized gene involved in drug metabolism and is known to have both gene duplication and deletion variants that are inheritable and stable. In a set of over 30,000 deidentified clinical samples we found that 12.6% of all patients tested had zero, one, or three or more copies of the CYP2D6 gene. On the basis of the combined frequency and impact of these variants, we believe that CYP2D6 copy number variation may account for the single most impactful genetic anomaly as it relates to pharmacogenetic directed therapies.

Cost-Effectiveness of a Pharmacogenetic Test to Guide Treatment for Major Depressive Disorder.

BACKGROUND: Recent clinical trials indicate that pharmacogenetic-guided treatment of major depressive disorder (MDD) results in higher treatment response rates by genetically matching patients to medications and avoiding a trial-and-error process. OBJECTIVE: To evaluate the cost-effectiveness of a pharmacogenetic test (IDGx) that has demonstrated effectiveness compared with standard of care (SOC) medication management among patients with varied MDD severity. METHODS: Data from a large prospective, randomized controlled trial of treatment-naive patients or patients with inadequately controlled MDD in general practice and psychiatric treatment settings were used to build a Markov state-transition probability model. Analyses were conducted from the societal perspective. Treatment response rates, mortality rates, direct and indirect medical costs, and utility inputs were derived from the reference study and published scientific literature. The cost of the pharmacogenetic test was $2,000. A 3% discount rate was used to discount costs and effects. Univariate one-way sensitivity analyses were performed to determine the effect of input parameters on net monetary benefit. RESULTS: For moderate to severe MDD, the model estimated a cumulative effect over 3 years of 2.07 quality-adjusted life-years (QALYs) for the pharmacogenetic-guided treatment group and 1.97 QALYs for the SOC group, including a lower probability of death from suicide (0.328% and 0.351%, respectively). Total costs over 3 years were $44,697 (IDGx) and $47,295 (SOC). This difference includes a savings of $2,918 in direct medical costs and $1,680 in indirect costs. Results were more pronounced when only severely depressed patients were evaluated. CONCLUSIONS: Pharmacogenetic testing among moderate to severe MDD patients improved QALYs and resulted in cost savings. Sensitivity analyses supported the robust nature of the current findings of the dominant IDGx test to guide treatment. DISCLOSURES: Funding for this analysis was provided by AltheaDx, which is the manufacturer of the IDgenetix test. AltheaDx personnel assisted in the study design, data collection, and review of the manuscript. Maciel and Garces are employed by AltheaDx. Groessl has received funding as a consultant from American Specialty Health.

Improved efficacy with targeted pharmacogenetic-guided treatment of patients with depression and anxiety: A randomized clinical trial demonstrating clinical utility.

The objective of this study was to evaluate the effect of pharmacogenetics-guided treatment on patients diagnosed with depression and/or anxiety, in a diverse set of clinical settings, as compared to the standard of care. The trial design followed a prospective, randomized, subject- and rater-blinded approach enrolling 685 patients from clinical providers specializing in Psychiatry, Internal Medicine, Obstetrics & Gynecology, and Family Medicine. The NeuroIDgenetix® test uses a genetic variant panel of ten genes, along with concomitant medications, to make medication management recommendations based on gene-drug and drug-drug interactions for over 40 medications used in the treatment of depression and anxiety. Pharmacogenetic testing was performed at the initial screening visit and baseline patient assessments were determined using the 17-item Hamilton Rating Scale for Depression (HAM-D17) and the Hamilton Rating Scale for Anxiety (HAM-A). Following enrollment and randomization, pharmacogenetic results for subjects assigned to the experimental group were provided to physicians to guide treatment selection, while control subjects were treated according to the usual standard of care. HAM-D17 and HAM-A assessments were collected at 4 weeks, 8 weeks, and 12 weeks after baseline to assess the efficacy of therapeutic selection. In patients diagnosed with depression, response rates (p = 0.001; OR: 4.72 [1.93-11.52]) and remission rates (p = 0.02; OR: 3.54 [1.27-9.88]) were significantly higher in the pharmacogenetics-guided group as compared to the control group at 12 weeks. In addition, patients in the experimental group diagnosed with anxiety showed a meaningful improvement in HAM-A scores at both 8 and 12 weeks (p = 0.02 and 0.02, respectively), along with higher response rates (p = 0.04; OR: 1.76 [1.03-2.99]). From these results, we conclude that pharmacogenetic-guided medication selection significantly improves outcomes of patients diagnosed with depression or anxiety, in a variety of healthcare settings.

Economic Evaluation of Implementing a Novel Pharmacogenomic Test (IDgenetix®) to Guide Treatment of Patients with Depression and/or Anxiety.

BACKGROUND: The response to therapeutics varies widely in patients with depression and anxiety, making selection of an optimal treatment choice challenging. IDgenetix®, a novel pharmacogenomic test, has been shown to improve outcomes by predicting the likelihood of response to different psychotherapeutic medications. OBJECTIVE: The objective of this study was to estimate the cost effectiveness of implementing a novel pharmacogenomic test (IDgenetix®) to guide treatment choices in patients with depression and/or anxiety compared with treatment as usual from the US societal perspective. METHODS: We developed a discrete event simulation to compare clinical events, quality-adjusted life-years, and costs of the two treatment strategies. Target patients had a Hamilton Rating Scale for Depression Score ≥ 20 and/or a Hamilton Rating Scale for Anxiety score ≥ 18 at baseline. Remission, response, and no response were simulated based on the observed rates in the IDgenetix® randomized controlled trial. Quality-adjusted life-years and direct and indirect costs attributable to depression and anxiety were estimated and compared over a 3-year time horizon. We conducted extensive deterministic and probabilistic sensitivity analyses to assess the robustness of the results. RESULTS: The model predicted cumulative remission rates of 78 and 66% in IDgenetix® and treatment as usual groups, respectively. Estimated discounted quality-adjusted life-years were 2.09 and 1.94 per patient for IDgenetix® and treatment as usual, respectively, which resulted in 0.15 incremental quality-adjusted life-years (95% credible interval 0.04-0.28). The total costs after accounting for a US$2000 test cost were US$14,124 for IDgenetix® compared with US$14,659 for treatment as usual, suggesting a US$535 (95% credible interval - 2902 to 1692) cost saving per patient in the IDgenetix® group. Incremental quality-adjusted life-year gain (0.49) and cost savings (US$6800) were substantially larger in patients with severe depression (Hamilton Rating Scale for Depression score ≥ 25). CONCLUSION: Using the IDgenetix® test to guide the treatment of patients with depression and anxiety may be a dominant strategy, as it improves quality-adjusted life-years and decreases overall costs over a 3-year time horizon.

Clinical Impact of Pharmacogenetic-Guided Treatment for Patients Exhibiting Neuropsychiatric Disorders: A Randomized Controlled Trial.

Objective: Pharmacogenetic testing holds promise as a personalized medicine tool by permitting individualization of pharmacotherapy in accordance with genes influencing therapeutic response, side effects, and adverse events. The authors evaluated the effect on outcomes for patients diagnosed with neuropsychiatric disorders of pharmacogenetics (PGx)-guided treatment compared to usual standard of care. Methods: This was a prospective, randomized study of 237 patients at an outpatient community-based psychiatric practice conducted between April 2015 and October 2015. Baseline patient assessments and a buccal swab were collected for pharmacogenetic testing at study initiation. For the experimental group, PGx results were provided to the clinicians as guides to treatment. Control subjects were treated according to the usual standard of care with no clinician reference to their PGx results. Neuropsychiatric Questionnaire (NPQ) and Symbol Digit Coding Test (SDC) scores and adverse drug events, hospitalizations, and medication information were collected at 30, 60, and 90 days. Results: More than half (53%) of patients in the control group reported at least 1 adverse drug event compared to 28% of patients with PGx-guided medication management (P = .001). NPQ and SDC scores improved for both groups, but no statistical difference in efficacy as measured by these assessments was observed within the 90-day observation period. Conclusions: Pharmacogenetic testing may facilitate psychiatric drug therapy with greater tolerability and similar efficacy compared to standard of care. Trial Registration: ClinicalTrials.gov Identifier: NCT02411123​​.

Initial assessment of the benefits of implementing pharmacogenetics into the medical management of patients in a long-term care facility.

The health care costs associated with prescription drugs are enormous, particularly in patients with polypharmacy (taking more than five prescription medications), and they continue to grow annually. The evolution of pharmacogenetics has provided clinicians with a valuable tool that allows for a smarter, more fine-tuned approach to treating patients for a number of clinical conditions. Applying a pharmacogenetics approach to the medical management of patients can provide a significant improvement to their care, result in cost savings by reducing the use of ineffective drugs, and decrease overall health care utilization. AltheaDx has begun a study to look at the benefits associated with incorporating pharmacogenetics into the medical management of patients who are on five or more medications. Applying pharmacogenetic guided PharmD recommendations across this patient population resulted in the elimination and/or replacement of one to three drugs, for 50% of the polypharmacy patient population tested, and an estimated US$621 in annual savings per patient. The initial assessment of this study shows that there is a clear opportunity for concrete health care savings solely from prescription drug management when incorporating pharmacogenetic testing.