Economic evaluations of pharmacogenetic and pharmacogenomic screening tests : a systematic review : second update of the literature

Objective : Due to extended application of pharmacogenetic and pharmacogenomic screening (PGx) tests it is important to assess whether they provide good value for money. This review provides an update of the literature. Methods : A literature search was performed in PubMed and papers published between August 2010 and September 2014, investigating the cost-effectiveness of PGx screening tests, were included. Papers from 2000 until July 2010 were included via two previous systematic reviews. Studies' overall quality was assessed with the Quality of Health Economic Studies (QHES) instrument. Results : We found 38 studies, which combined with the previous 42 studies resulted in a total of 80 included studies. An average QHES score of 76 was found. Since 2010, more studies were funded by pharmaceutical companies. Most recent studies performed cost-utility analysis, univariate and probabilistic sensitivity analyses, and discussed limitations of their economic evaluations. Most studies indicated favorable cost-effectiveness. Majority of evaluations did not provide information regarding the intrinsic value of the PGx test. There were considerable differences in the costs for PGx testing. Reporting of the direction and magnitude of bias on the cost-effectiveness estimates as well as motivation for the chosen economic model and perspective were frequently missing. Conclusions : Application of PGx tests was mostly found to be a cost-effective or cost-saving strategy. We found that only the minority of recent pharmacoeconomic evaluations assessed the intrinsic value of the PGx tests. There was an increase in the number of studies and in the reporting of quality associated characteristics. To improve future evaluations, scenario analysis including a broad range of PGx tests costs and equal costs of comparator drugs to assess the intrinsic value of the PGx tests, are recommended. In addition, robust clinical evidence regarding PGx tests' efficacy remains of utmost importance

Effects of Pharmacogenetic Screening for CYP2D6 Among Elderly Starting Therapy With Nortriptyline or Venlafaxine:A Pragmatic Randomized Controlled Trial (CYSCE Trial)

PURPOSE/BACKGROUND: The duration of untreated depression is a predictor for poor future prognosis, making rapid dose finding essential. Genetic variation of the CYP2D6 isoenzyme can influence the optimal dosage needed for individual patients. The aim of this study was to determine the effectiveness of CYP2D6 pharmacogenetic screening to accelerate drug dosing in older patients with depression initiating nortriptyline or venlafaxine. METHODS/PROCEDURES: In this randomized controlled trial, patients were randomly allocated to one of the study arms. In the intervention arm (DG-I), the specific genotype accompanied by a standardized dosing recommendation based on the patients' genotype and the prescribed drug was directly communicated to the physician of the participant. In both the deviating genotype control arm (DG-C) and the nonrandomized control arm, the physician of the participants was not informed about the genotype and the associated dosing advise. The primary outcome was the time needed to reach adequate drug levels: (1) blood levels within the therapeutic range and (2) no dose adjustments within the previous 3 weeks. FINDINGS/RESULTS: No significant difference was observed in mean time to reach adequate dose or time to adequate dose between DG-I and DG-C. Compared with the nonrandomized control arm group, adequate drug levels were reached significantly faster in the DG-I group (log-rank test; P = 0.004), and there was a similar nonsignificant trend for the DG-C group (log-rank test; P = 0.087). IMPLICATIONS/CONCLUSIONS: The results of this study do not support pharmacogenetic CYP2D6 screening to accelerate dose adjustment for nortriptyline and venlafaxine in older patients with depression

A Model Based Cost-Effectiveness Analysis of Routine Genotyping for CYP2D6 among Older, Depressed Inpatients Starting Nortriptyline Pharmacotherapy

Objective Genotyping for CYP2D6 has the potential to predict differences in metabolism of nortriptyline. This information could optimize pharmacotherapy. We determined the costs and effects of routine genotyping for old aged Dutch depressed inpatients. Methods With a decision-tree, we modelled the first 12 weeks of nortriptyline therapy. Direct costs of genotyping, hospitalization, therapeutic drug monitoring and drugs were included. Based on genotype, patients could be correctly, sub-, or supratherapeutically dosed. Improvement from sub-or supratherapeutically dosed patients to correctly dosed patients was simulated, assuming that genotyping would prevent under-or overdosing of patients. In the base case, this improvement was assumed to be 35%. A probabilistic sensitivity analysis (PSA) was performed to determine uncertainty around the incremental cost-effectiveness ratio (ICER). Results In the base case analysis, costs for genotyping were assumed sic200 per test with a corresponding ICER at sic1 333 000 per QALY. To reach a sic50 000 per QALY cut-off, genotyping costs should be decreased towards sic40 per test. At genotyping test costs <sic35 per test, genotyping was dominant. At test costs of sic17 per test there was a 95% probability that genotyping was cost-effective at sic50 000 per QALY. Conclusions CYP2D6 genotyping was not cost-effective at current genotyping costs at a sic50 000 per QALY threshold, however at test costs below sic40, genotyping could be costs-effective

A clinical validation study for application of DBS in therapeutic drug monitoring of antidepressants

BACKGROUND: A bridging study of plasma and DBS concentrations for therapeutic drug monitoring of antidepressants was performed. Results & methodology: Potassium-based hematocrit analysis was included. In addition, we defined acceptance criteria based on the differences between individual data points of plasma and DBS concentrations. These criteria were applied to test acceptability of error found in predicted nortriptyline plasma concentrations. Potassium-based hematocrit predicted a negative bias for DBS concentrations of amitriptyline, but not for the other compounds. To predict plasma concentrations of antidepressants based on DBS concentrations, a factor of 0.8, 0.65, 0.84 and 0.78 was found for nortriptyline, desmethylclomipramine, venlafaxine and desmethylvenlafaxine, respectively. DISCUSSION & CONCLUSION: Application of the factor and newly formulated acceptance criteria demonstrated prediction of nortriptyline plasma concentrations based on DBS concentrations

Model structure for the treatment of major depressive disorder with nortriptyline during the first 12 weeks.

<p>Patients who receive a dosage which led to therapeutic plasma concentrations (i.e. “correct”) did not receive a next dose evaluation. Patients who quit nortriptyline pharmacotherapy entered a wash out period with a disutility of 0.20 for 14 days. After this period, pharmacotherapy with 6 tranylcypromine was initiated for the remaining time in the model. PM = poor metabolizer, IM = intermediate metabolizer, EM = extensive metabolizer, UM = ultrarapid metabolizer.</p

Probability on cost-effectiveness at €50 000 per QALY (solid line) or probability of test costs to break even with cost-savings (broken line) shown at different CYP2D6 genotyping test costs.

<p>Probability on cost-effectiveness at €50 000 per QALY (solid line) or probability of test costs to break even with cost-savings (broken line) shown at different CYP2D6 genotyping test costs.</p