Lorlatinib Effectiveness and Quality-of-Life in Patients with ALK-Positive NSCLC Who Had Failed Second-Generation ALK Inhibitors: Canadian Real-World Experience.

Lorlatinib is the only targeted therapy approved in Canada to treat patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) whose tumor has progressed despite treatment with second-generation ALK tyrosine kinase inhibitor (TKI), a patient population with high unmet need and lack of publicly reimbursed targeted treatments in Canada. We prospectively examined the real-world effectiveness and impact of lorlatinib on quality-of-life in 59 lorlatinib-treated patients, characterized as: median age of 62.0 years; 47.5% were female; 32.2% had central nervous system metastases; 50.8% had 2+ prior ALK TKI lines; and alectinib was the most common ALK TKI (72.9%) administered before lorlatinib, including 44.1% who received first-line alectinib. With a median follow-up of 15.3 months (IQR: 6.2-19.2), median time-to-treatment discontinuation of lorlatinib was 15.3 months (95% CI: 7.9-not reached), with 54.2% (95% CI: 40.8-65.9%) of patients without treatment discontinuation at 12 months. At baseline, the mean health utility score (HUS) was 0.744 (SD: 0.200). At 3 months, patients receiving lorlatinib demonstrated a 0.069 (95% CI: 0.020-0.118; p = 0.007) average HUS increase over baseline; HUS was maintained at 6 and 12 months. Thus, patients with ALK-positive NSCLC post second-generation ALK TKI remained on lorlatinib for a meaningful duration of time while their quality-of-life was preserved.

Cost-effectiveness of alternative strategies for vaccination of adolescents against serogroup B IMD with the MenB-FHbp vaccine in Canada.

OBJECTIVE: Serogroup B meningococci (MnB) are now the largest cause of invasive meningococcal disease (IMD) in Canada. We assessed the clinical and economic impact of 3 adolescent MenB-FHbp immunization strategies. METHODS: A population-based dynamic transmission model was developed to simulate the transmission of MnB among the entire Canadian population over a 30-year time horizon. Age group-based IMD incidence, bacterial carriage and transmission, disease outcomes, costs, and impact on quality of life were obtained from Canadian surveillance data and published literature. The vaccine was assumed to provide 85% protection against IMD and 26.6% against carriage acquisition. The model estimated the impact of routine vaccination with MenB-FHbp in 3 strategies: (1) age 14, along with existing school-based programs, with 75% uptake; (2) age 17 with 75% uptake, assuming school vaccination; and (3) age 17 with 30% uptake, assuming vaccination outside of school. Costs were calculated from the Canadian societal perspective. RESULTS: With no vaccination, an estimated 3974 MnB cases would be expected over 30 years. Vaccination with strategies 1-3 were estimated to avert 688, 1033, and 575 cases, respectively. These outcomes were associated with incremental costs per quality-adjusted life-year of $976,000, $685,000, and $490,000. CONCLUSIONS: Our model indicated that if the vaccine reduces risk of carriage acquisition, vaccination of older adolescents, even at lower uptake, could have a significant public health impact. Due to low disease incidence, MnB vaccination is unlikely to meet widely accepted cost-effectiveness thresholds, but evaluations of new programs should consider the overall benefits of the vaccination.

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: Statin (HMG-CoA reductase inhibitor) therapy is the mainstay dyslipidemia treatment and reduces the risk of a cardiovascular (CV) event (CVE) by up to 35%. However, adherence to statin therapy is poor. One reason patients discontinue statin therapy is musculoskeletal pain and the associated risk of rhabdomyolysis. Research is ongoing to develop a pharmacogenomics (PGx) test for statin-induced myopathy as an alternative to the current diagnosis method, which relies on creatine kinase levels. The potential economic value of a PGx test for statin-induced myopathy is unknown. METHODS: We developed a lifetime discrete event simulation (DES) model for patients 65 years of age initiating a statin after a first CVE consisting of either an acute myocardial infarction (AMI) or a stroke. The model evaluates the potential economic value of a hypothetical PGx test for diagnosing statin-induced myopathy. We have assessed the model over the spectrum of test sensitivity and specificity parameters. RESULTS: Our model showed that a strategy with a perfect PGx test had an incremental cost-utility ratio of 4273 Canadian dollars ($Can) per quality-adjusted life year (QALY). The probabilistic sensitivity analysis shows that when the payer willingness-to-pay per QALY reaches $Can12,000, the PGx strategy is favored in 90% of the model simulations. CONCLUSION: We found that a strategy favoring patients staying on statin therapy is cost effective even if patients maintained on statin are at risk of rhabdomyolysis. Our results are explained by the fact that statins are highly effective in reducing the CV risk in patients at high CV risk, and this benefit largely outweighs the risk of rhabdomyolysis.

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

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. METHODS: We 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. RESULTS: Assuming a perfect test, the results indicate that the PGx test strategy dominates when the test costs less than CAN$356, when the strategy is cost neutral. These results are robust to deterministic and probabilistic sensitivity analyses. CONCLUSION: Our 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$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.

A model to assess the cost-effectiveness of pharmacogenomics tests in chronic heart failure: the case of ivabradine.

Pharmacogenomics (PGx) tests have the potential of improving the effectiveness of expensive new drugs by predicting the likelihood, for a particular patient, to respond to a treatment. The objective of this study was to develop a pharmacoeconomic model to determine the characteristics and the cost-effectiveness of a hypothetical PGx test, which would identify patients who are most likely to respond to an expensive treatment for chronic heart failure. For this purpose, we chose the example of ivabradine. Our results suggest that the use of a PGx test that could select a subgroup of patients to be treated with an expensive drug has the potential to provide more efficient drug utilization.

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

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.