Dominic Mitchell

Economic Evaluation of a Pharmacogenomics Test for Statin-Induced Myopathy in Cardiovascular High-Risk Patients Initiating a Statin

BackgroundStatins are the mainstay hypercholesterolemia treatment and reduce the risk of cardiovascular events in patients. However, statin therapy is often interrupted in patients experiencing musculoskeletal pain or myopathy, which are common in this patient group. Currently, the standard tests for diagnosing statin myopathies are difficult to interpret. A pharmacogenomics (PGx) test to diagnose statin-induced myopathy would be highly desirable.MethodsWe developed a Markov state model to assess the cost-effectiveness of a hypothetical PGx test, which aims to identify statin-induced myopathy in high-risk, secondary prevention cardiovascular patients. The alternative strategy hypothesized is that physicians or patients interrupt the statin therapy in the presence of musculoskeletal pain. Our model includes health states specific to the PGx test outcome which assesses the impact of test errors.ResultsAssuming a perfect test, the results indicate that the PGx test strategy dominates when the test costs less than CAN

Burden of illness of bone metastases in prostate cancer patients in Québec, Canada: A population-based analysis

356, when the strategy is cost neutral. These results are robust to deterministic and probabilistic sensitivity analyses.ConclusionOur base-case results show that a PGx test for statin-induced myopathy in a high-risk, secondary prevention of a cardiovascular event population would be a dominant solution for a test cost of CAN

Economic Evaluation Of A Pharmacogenomic Test For Statin-Induced Myopathy In Cardiovascular High-Risk Patients Initiating A Statin.

356 or less. Furthermore, the modelling of the complete range of diagnostic test outcomes provide a broader understanding of the economic value of the pharmacogenomics test.

Bias within economic evaluations - the impact of considering the future entry of lower-cost generics on currently estimated incremental cost-effectiveness ratios of a new drug.

INTRODUCTION Metastasis of prostate cancer (PC) to bone (metastatic bone disease, MBD) increases morbidity, but Canadian data are lacking on the associated healthcare resource utilization (HCRU) and costs. We quantified MBD-related HCRU and associated costs in this population, and assessed skeletal-related events (SREs), such as pathologic fracture, spinal cord compression, bone radiotherapy, and bone surgery. METHODS We conducted a retrospective, population-based cohort study using the Québec health insurance agency database. Prescription drug and medical services data were retrieved for patients with ≥1 healthcare claim in 2001 with a PC diagnosis (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] code of 185.xx). Patients with ≥2 MBD-related claims or an SRE were compared with a matched-control group of PC patients without MBD. Patients were followed until death, loss to follow-up, or the end of available data (August 31, 2010). Costs (in 2012 Canadian dollars) were adjusted for age, year of MBD diagnosis, general health status, and baseline resource utilization. RESULTS Compared with controls (n = 1671), MBD patients (n = 626) had significantly higher HCRU. Adjusted mean (95% confidence interval) all-cause healthcare costs were

Value of a Hypothetical Pharmacogenomic Test for the Diagnosis of Statin-Induced Myopathy in Patients at High Cardiovascular Risk

11 820 (7248-16 058) higher, and MBD-related costs were

Maximal expected benefits from lowering cholesterol in primary prevention for a high-risk population

3 091 (1267-4861) higher in MBD patients than in controls. Nearly 50% of MBD patients received radiotherapy within 2.5 years of their MBD diagnosis, but most exited the study without experiencing other SREs. CONCLUSION MBD imposes a heavy HCRU and cost burden among patients with PC in Canada. Effective therapy is needed to reduce the clinical and economic impact of MBD in this population.

A Discrete Event Simulation Model to Assess the Economic Value of a Hypothetical Pharmacogenomics Test for Statin-Induced Myopathy in Patients Initiating a Statin in Secondary Cardiovascular Prevention

Background Statins are the mainstay hypercholesterolemia treatment and reduce the risk of cardiovascular events in patients. However, statin therapy is often interrupted in patients experiencing musculoskeletal pain or myopathy, which are common in this patient group. Currently, the standard tests for diagnosing statin myopathies are difficult to interpret. A pharmacogenomics (PGx) test to diagnose statin-induced myopathy would be highly desirable.

A Discrete Event Simulation Model For A Pharmacogenomics Test For Statin-Induced Myopathy In Patients Initiating A Statin In Secondary Cardiovascular Prevention

Background Most economic evaluation models compare a new patented drug (NPRx) to a generic comparator. Drug costs within these models are usually limited to the retail cost of both drugs at the time of model conception. However, the retail cost of the NPRx is expected to drop once generic versions of this molecule are introduced following the expiration of the NPRx’s patent. The objective of this study was to examine the impact on the incremental cost-effectiveness ratio (ICER) of the future introduction of lower-cost generic versions of the NPRx within the model’s time horizon. Methods We examined the impact of this parameter with the use of two approaches: 1) a mathematical proof identifying its impact on the NPRx’s ICER; and 2) applying this parameter to a previously published economic model comparing a NPRx to a generic comparator and identifying what would have been the NPRx’s ICER had this model considered this parameter. Results As expected, both the mathematical proof and the application to the previously published economic model showed that considering the future introduction of lower-cost generic versions of the NPRx within the model’s time horizon lowers the NPRx’s ICER. The timing of the future entry of lower-cost generic molecules, their relative price compared to that of the patented version, and the discount rate applied to future costs all influenced the results. Conclusion An ICER estimated within economic evaluations comparing NPRx to generic comparators which ignore the future introduction of lower-cost generic versions of the NPRx within the model’s time horizon will tend to be overestimated. Inclusion of this parameter should be considered within future economic evaluations.

Framework for the cost-effectiveness of secondary prevention strategies in cardiovascular diseases: A Canadian theoretical modelbased analysis

We recently conducted two economic evaluations of a hypothetical pharmacogenomic test for statin-induced myopathy (SIM) in patients at high cardiovascular risk. Although the models differed in modeling technique and data inputs, both yielded similar results. We believe our approach to assessing the economic value of a diagnostic test was highly advantageous as it characterized the complete range of false-negative and false-positive test outcomes. We used a broad interpretation of test parameters that reflected physician and patient behavioral responses to the test results and accounted for patient adherence to treatment. Both economic evaluations indicated that a highly accurate pharmacogenomic test for SIM would provide a positive incremental net monetary benefit (INMB) for a provincial payer in Canada. However, the value of the test would depend on its ability to accurately diagnose patients when they experience musculoskeletal pain symptoms and guide patients with a test result indicating no SIM to adhere to treatment. Interestingly, our results indicated that a highly inaccurate test would still yield a positive INMB. We found this surprising result was driven by the imbalance of the risk of cardiovascular events outweighing the risk of rhabdomyolysis in patients at high cardiovascular risk. A highly accurate pharmacogenomic test for SIM in patients at high cardiovascular risk would provide economic value for payers. However, the economic and clinical value of the test would depend on the credibility of the test results and their success in influencing patients without SIM to adhere to therapy.

Development of a Pharmacoeconomic Model to Assess the Cost Effectiveness of Pharmacogenomics Tests in Chronic Heart Failure: The Case of Ivabradine

Abstract Aims: The objective of this study was to estimate the maximal clinical benefit that could be reasonably expected from a cholesterol-lowering intervention. Materials and methods: We used a hypothetical population at high risk of cardiovascular disease events from three risk assessment models including the Framingham risk function, the Score Canada and the Pooled Cohort Risk Assessment Equations. Our source population were all 55-year-old smoking men with diabetes, hypertension and low HDL. From this population, we identified two different subpopulations named “high” and “low”, referring to their cholesterol levels which were set at 8.60 and 4.14 mmol/L respectively. Both subpopulations were identified for each risk assessment model in order to estimate the maximal impact of lowering cholesterol on cardiovascular disease events. Results: Our extrapolations estimated that the maximal theoretical efficacy of a cholesterol-lowering intervention corresponds to a risk ratio ranging between 0.46 and 0.66 over a 10-year period. The number of events prevented during this period were between 21 and 29 per 100 patients which corresponds to a number needed to treat varying from 3.47 to 4.76. Conclusions: Our estimation showed the maximal clinical benefit that could be reasonably expected by an intervention that would lower total cholesterol in high-risk patients.