Cost-effectiveness of pazopanib in advanced soft-tissue sarcoma in Canada.

BACKGROUND: In the phase iii palette trial of pazopanib compared with placebo in patients with advanced or metastatic soft-tissue sarcoma (sts) who had received prior chemotherapy, pazopanib treatment was associated with improved progression-free survival (pfs). We used an economic model and data from palette and other sources to evaluate the cost-effectiveness of pazopanib in patients with advanced sts who had already received chemotherapy. METHODS: We developed a multistate model to estimate expected pfs, overall survival (os), lifetime sts treatment costs, and quality-adjusted life-years (qalys) for patients receiving pazopanib or placebo as second-line therapy for advanced sts. Cost-effectiveness was calculated alternatively from the health care system and societal perspectives for the province of Quebec. Estimated pfs, os, incidence of adverse events, and utilities values for pazopanib and placebo were derived from the palette trial. Costs were obtained from published sources. RESULTS: Compared with placebo, pazopanib is estimated to increase qalys by 0.128. The incremental cost of pazopanib compared with placebo is CA$20,840 from the health care system perspective and CA$15,821 from the societal perspective. The cost per qaly gained with pazopanib in that comparison is CA$163,336 from the health care system perspective and CA$124,001 from the societal perspective. CONCLUSIONS: Compared with placebo, pazopanib might be cost-effective from the Canadian health care system and societal perspectives depending on the threshold value used by reimbursement authorities to assess novel cancer therapies. Given the unmet need for effective treatments for advanced sts, pazopanib might nevertheless be an appropriate alternative to currently used treatments.

Cost-effectiveness of lapatinib plus letrozole in her2-positive, hormone receptor-positive metastatic breast cancer in Canada.

BACKGROUND: The cost-effectiveness of first-line treatment with lapatinib plus letrozole for postmenopausal women with hormone receptor-positive (hr+), human epidermal growth factor receptor 2-positive (her2+) metastatic breast cancer (mbc) has not been assessed from the Canadian health care system and societal perspectives. METHODS: A partitioned survival analysis model with 3 health states (alive, pre-progression; alive, post-progression; dead) was developed to estimate direct and indirect costs and quality-adjusted life years (qalys) with lapatinib-letrozole, letrozole, anastrozole, or trastuzumab-anastrozole as first-line treatment. Clinical inputs for lapatinib-letrozole and letrozole were taken from the EGF30008 trial (NCT00073528). Clinical inputs for anastrozole and trastuzumab-anastrozole were taken from a network meta-analysis of published studies. Drug costs were obtained from the manufacturer's price list, the Quebec list of medications, and imsBrogan. Other costs were taken from the Ontario Health Insurance Plan's Schedule of Benefits and Fees and published studies. A 10-year time horizon was used. Costs and qalys were discounted at 5% annually. Deterministic and probabilistic sensitivity analyses were performed to assess the effects of changes in model parameters. RESULTS: Quality-adjusted life years gained with lapatinib-letrozole were 0.236 compared with trastuzumab-anastrozole, 0.440 compared with letrozole, and 0.568 compared with anastrozole. Assuming a health care system perspective, incremental costs were $5,805, $67,029, and $67,472 respectively. Given a cost per qaly threshold of $100,000, the probability that lapatinib-letrozole is preferred was 21% compared with letrozole, 36% compared with anastrozole, and 68% compared with trastuzumab-anastrozole. Results from the societal perspective were similar. CONCLUSIONS: In postmenopausal women with hr+/her2+ mbc receiving first-line treatment, lapatinib-letrozole may not be cost-effective compared with letrozole or anastrozole, but may be cost-effective compared with trastuzumab-anastrozole.

Landscape characteristics influence ranging behavior of Asian elephants at the human-wildlands interface in Myanmar.

CONTEXT: Asian elephant numbers are declining across much of their range driven largely by serious threats from land use change resulting in habitat loss and fragmentation. Myanmar, holding critical range for the species, is undergoing major developments due to recent sociopolitical changes. To effectively manage and conserve the remaining populations of endangered elephants in the country, it is crucial to understand their ranging behavior. OBJECTIVES: Our objectives were to (1) estimate the sizes of dry, wet, and annual ranges of wild elephants in Myanmar; and quantify the relationship between dry season (the period when human-elephant interactions are the most likely to occur) range size and configurations of agriculture and natural vegetation within the range, and (2) evaluate how percentage of agriculture within dry core range (50% AKDE range) of elephants relates to their daily distance traveled. METHODS: We used autocorrelated kernel density estimator (AKDE) based on a continuous-time movement modeling (ctmm) framework to estimate dry season (26 ranges from 22 different individuals), wet season (12 ranges from 10 different individuals), and annual range sizes (8 individuals), and reported the 95%, 50% AKDE, and 95% Minimum Convex Polygon (MCP) range sizes. We assessed how landscape characteristics influenced range size based on a broad array of 48 landscape metrics characterizing aspects of vegetation, water, and human features and their juxtaposition in the study areas. To identify the most relevant landscape metrics and simplify our candidate set of informative metrics, we relied on exploratory factor analysis and Spearman's rank correlation coefficient. Based on this analysis we adopted a final set of metrics into our regression analysis. In a multiple regression framework, we developed candidate models to explain the variation in AKDE dry season range sizes based on the previously identified, salient metrics of landscape composition. RESULTS: Elephant dry season ranges were highly variable averaging 792.0 km2 and 184.2 km2 for the 95% and 50% AKDE home ranges, respectively. We found both the shape and spatial configuration of agriculture and natural vegetation patches within an individual elephant's range play a significant role in determining the size of its range. We also found that elephants are moving more (larger energy expenditure) in ranges with higher percentages of agricultural area. CONCLUSION: Our results provide baseline information on elephant spatial requirements and the factors affecting them in Myanmar. This information is important for advancing future land use planning that takes into account space-use requirements for elephants. Failing to do so may further endanger already declining elephant populations in Myanmar and across the species' range.

Validation of the Seegene RV15 multiplex PCR for the detection of influenza A subtypes and influenza B lineages during national influenza surveillance in hospitalized adults.

Background. The Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN SOS) has been performing active influenza surveillance since 2009 (ClinicalTrials.gov identifier: NCT01517191). Influenza A and B viruses are identified and characterized using real-time reverse-transcriptase polymerase chain reaction (RT-PCR), and multiplex testing has been performed on a subset of patients to identify other respiratory virus aetiologies. Since both methods can identify influenza A and B, a direct comparison was performed.Methods. Validated real-time RT-PCRs from the World Health Organization (WHO) to identify influenza A and B viruses, characterize influenza A viruses into the H1N1 or H3N2 subtypes and describe influenza B viruses belonging to the Yamagata or Victoria lineages. In a subset of patients, the Seeplex RV15 One-Step ACE Detection assay (RV15) kit was also used for the detection of other respiratory viruses.Results. In total, 1111 nasopharyngeal swabs were tested by RV15 and real-time RT-PCRs for influenza A and B identification and characterization. For influenza A, RV15 showed 98.0 % sensitivity, 100 % specificity and 99.7 % accuracy. The performance characteristics of RV15 were similar for influenza A subtypes H1N1 and H3N2. For influenza B, RV15 had 99.2 % sensitivity, 100 % specificity and 99.8 % accuracy, with similar assay performance being shown for both the Yamagata and Victoria lineages.Conclusions. Overall, the detection of circulating subtypes of influenza A and lineages of influenza B by RV15 was similar to detection by real-time RT-PCR. Multiplex testing with RV15 allows for a more comprehensive respiratory virus surveillance in hospitalized adults, without significantly compromising the reliability of influenza A or B virus detection.

Examining Ontario's universal influenza immunization program with a multi-strain dynamic model.

Seasonal influenza imposes a significant worldwide health burden each year. Mathematical models help us to understand how changes in vaccination affect this burden. Here, we develop a new dynamic transmission model which directly tracks the four dominant seasonal influenza strains/lineages, and use it to retrospectively examine the impact of the switch from a targeted to a universal influenza immunization program (UIIP) in the Canadian province of Ontario in 2000. According to our model results, averaged over the first four seasons post-UIIP, the rates of influenza-associated health outcomes in Ontario were reduced to about half of their pre-UIIP values. This is conservative compared to the results of a study estimating the UIIP impact from administrative data, though that study finds age-specific trends similar to those presented here. The strain interaction in our model, together with its flexible parameter calibration scheme, make it readily extensible to studying scenarios beyond the one explored here.