Clinical utility of combinatorial pharmacogenomic testing in depression: A Canadian patient- and rater-blinded, randomized, controlled trial.

The pharmacological treatment of depression consists of stages of trial and error, with less than 40% of patients achieving remission during first medication trial. However, in a large, randomized-controlled trial (RCT) in the U.S. ("GUIDED"), significant improvements in response and remission rates were observed in patients who received treatment guided by combinatorial pharmacogenomic testing, compared to treatment-as-usual (TAU). Here we present results from the Canadian "GAPP-MDD" RCT. This 52-week, 3-arm, multi-center, participant- and rater-blinded RCT evaluated clinical outcomes among patients with depression whose treatment was guided by combinatorial pharmacogenomic testing compared to TAU. The primary outcome was symptom improvement (change in 17-item Hamilton Depression Rating Scale, HAM-D17) at week 8. Secondary outcomes included response (≥50% decrease in HAM-D17) and remission (HAM-D17 ≤ 7) at week 8. Numerically, patients in the guided-care arm had greater symptom improvement (27.6% versus 22.7%), response (30.3% versus 22.7%), and remission rates (15.7% versus 8.3%) compared to TAU, although these differences were not statistically significant. Given that the GAPP-MDD trial was ultimately underpowered to detect statistically significant differences in patient outcomes, it was assessed in parallel with the larger GUIDED RCT. We observed that relative improvements in response and remission rates were consistent between the GAPP-MDD (33.0% response, 89.0% remission) and GUIDED (31.0% response, 51.0% remission) trials. Together with GUIDED, the results from the GAPP-MDD trial indicate that combinatorial pharmacogenomic testing can be an effective tool to help guide depression treatment in the context of the Canadian healthcare setting (ClinicalTrials.gov NCT02466477).

Cost-effectiveness of combinatorial pharmacogenomic testing for depression from the Canadian public payer perspective.

Aim: Evaluate the cost-effectiveness of combinatorial pharmacogenomic (PGx) testing, versus treatment as usual (TAU), to guide treatment for patients with depression, from the Canadian public healthcare system perspective. Materials & methods: Clinical and economic data associated with depression were extracted from published literature. Clinical (quality-adjusted life years; QALYs) and economic (incremental cost-effectiveness ratio) outcomes were modeled using combinatorial PGx and TAU treatment strategies across a 5-year time horizon. Results: With the combinatorial PGx strategy to guide treatment, patients were projected to gain 0.14-0.19 QALYs versus TAU. Accounting for test price, combinatorial PGx saved CAD $1,687-$3,056 versus TAU. Incremental cost-effectiveness ratios ranged from -$11,861 to -$16,124/QALY gained. Conclusion: Combinatorial PGx testing was more efficacious and less costly compared with the TAU for depression.

Economic Burden of Depression and Associated Resource Use in Manitoba, Canada.

OBJECTIVES: To characterize the health-care utilization and economic burden associated with depression in Manitoba, Canada. METHODS: Patient-level data were retrieved from the Manitoba Centre for Health Policy administrative, clinical, and laboratory databases for the study period of January 1, 1996, through December 31, 2016. Patients were assigned to the depression cohort based on diagnoses recorded in hospitalizations and outpatient physician claims, as well as antidepressant prescription drug claims. A comparison cohort of nondepressed subjects, matched with replacement for age, gender, place of residence (urban vs. rural), and index date, was created. Demographics, comorbidities, intentional self-harm, mortality, health-care utilization, prescription drug utilization, and costs of health-care utilization and social services were compared between depressed patients and matched nondepressed patients, and incidence rate ratios and hazard ratios were reported. RESULTS: There were 190,065 patients in the depression cohort and 378,177 patients in the nondepression cohort. Comorbidities were 43% more prevalent among depressed patients. Intentional self-harm, all-cause mortality, and suicide mortality were higher among patients with depression than the nondepression cohort. Health-care utilization-including hospitalizations, physician visits, physician-provided psychotherapy, and prescription drugs-was higher in the depression than the nondepression cohort. Mean health-care utilization costs were 3.5 times higher among depressed patients than nondepressed patients ($10,064 and $2,832, respectively). Similarly, mean social services costs were 3 times higher ($1,522 and $510, respectively). Overall, depression adds a total average cost of $8,244 (SD = $40,542) per person per year. CONCLUSIONS: Depression contributes significantly to health burden and per patient costs in Manitoba, Canada. Extrapolation of the results to the entire Canadian health-care system projects an excess of $12 billion annually in health system spending.

Combinatorial pharmacogenomics and improved patient outcomes in depression: Treatment by primary care physicians or psychiatrists.

Failed medication trials are common in the treatment of major depressive disorder (MDD); however, the use of combinatorial pharmacogenomics to guide medication selection has been previously associated with improved outcomes in the psychiatric care setting. The utility of combinatorial pharmacogenomics in patients with MDD in primary care and psychiatric care settings was evaluated here. Patients enrolled in a naturalistic, open-label, prospective study [Individualized Medicine: Pharmacogenetics Assessment and Clinical Treatment (IMPACT)] with MDD were evaluated (N = 1871). Pharmacogenomic testing was performed for all patients and medications were categorized based on gene-drug interactions. Beck's Depression Inventory (BDI) was evaluated at baseline and follow-up (weeks 8-12). Symptom improvement (percent decrease in BDI), response (≥50% decrease in BDI), and remission (BDI≤10) at follow-up were evaluated according to provider type and whether medications were genetically congruent (little/no gene-drug interactions). There was a 27.9% reduction in depression symptoms at follow-up, as well as response and remission rates of 25.7% and 15.2%, respectively. Outcomes were significantly better among patients treated by primary care providers versus psychiatrists (symptom improvement 31.7% versus 24.9%, p < 0.01; response rate 30.1% versus 22.3%, p < 0.01; remission rate 19.5% versus 12.0%, p < 0.01). There was a 31% relative improvement in response rate among patients taking congruent versus incongruent medications, with slightly higher congruence among primary care providers (87.6%) versus psychiatrists (85.2%). Following combinatorial pharmacogenomic testing, outcomes were significantly improved among patients treated by primary care providers compared to psychiatrists, which supports the use of pharmacogenomics in broader treatment settings.

Effectiveness of a bundled approach to reduce urinary catheters and infection rates in trauma patients.

BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) are common nosocomial infections. In 2015, the Centers for Medicare and Medicaid Services began imposing financial penalties for institutions where CAUTI rates are higher than predicted. However, the surveillance definition for CAUTI is not a clinical diagnosis and may represent asymptomatic bacteriuria. The objective of this study was to compare rates of urinary catheterization and CAUTI before and after the implementation of a bundled intervention. METHODS: This retrospective review evaluated trauma patients from January 2013-January 2015. The bundled intervention optimized the urinary catheterization process and culturing practices to reduce false positives. The CAUTI rate was defined as a positive surveillance CAUTI divided by total catheter days multiplied by 1,000 days. RESULTS: A total of 6,236 patients were included (pre: n = 5,003; post: n = 1,233). Fewer patients in the post bundle group received a urinary catheter (pre: 25% vs post: 16%; P < .001). After bundle implementation, the CAUTI rate reduced over one third (pre: 4.07 vs post: 2.56; incidence rate ratio, 0.63; 95% confidence interval, 0.19-2.07). CONCLUSIONS: Although the number of patients exposed to urinary catheters and catheter days was decreased, optimization of culturing practices was essential to prevent the CAUTI rate from increasing from a reduced denominator. Implementation of a CAUTI prevention bundle works synergistically to improve patient safety and hospital performance.