Economic modelling of costs associated with outcomes reported for type 2 diabetes mellitus (T2DM) patients in the CANVAS and EMPA-REG cardiovascular outcomes trials

Aims: To model direct medical costs associated with reductions in cardiovascular disease (CVD) events in T2DM patients reported in the CANVAS and EMPA-REG trials, which assessed the cardiovascular safety of canagliflozin and empagliflozin, respectively.

Materials and methods: Costs were modeled from a US managed care organization (MCO) perspective for the CVD outcomes included in both trials: three-point major adverse cardiovascular event (MACE) and its components (cardiovascular-related death, nonfatal myocardial infarction, nonfatal stroke), as well as heart failure requiring hospitalization. The rate of CVD events averted (difference between study drug and placebo) was projected to the portion of an MCO T2DM population matching the respective trial’s inclusion criteria. A targeted literature search for paid amounts directly associated with each CVD event provided the unit costs, which were applied to the projected number of events averted, to calculate costs avoided per member per year (PMPY). One-way sensitivity analyses were performed on events averted, unit costs, and percentages of trial-applicable patients.

Results: Based on three-point MACE events averted, costs avoided PMPY of $6.17 (range: $1.27–$10.94) for CANVAS and $2.75 ($0.19–$4.83) for EMPA-REG were estimated. Costs avoided for individual components of MACE ranged from $0.77 to $3.84 PMPY for CANVAS and from -$0.97 (additional costs) to $1.54 for EMPA-REG. PMPY costs avoided for heart failure were $2.72 for CANVAS and $1.32 for EMPA-REG.

Limitations and conclusions: Models assumed independent, non-recurrent outcomes and were restricted to medical costs directly associated with the trial-reported events. The reductions in CVD events in T2DM patients reported for both CANVAS and EMPA-REG project to a positive cost avoidance for these events in an MCO population. The analysis did not include an assessment of the impact on total cost, as the costs associated with adverse events, drug utilization or other clinical outcomes were not examined.     

Cost-effectiveness of rivaroxaban compared with enoxaparin plus a vitamin K antagonist for the treatment of venous thromboembolism

Background:

Venous thromboembolism (VTE), comprised of deep vein thrombosis (DVT) and pulmonary embolism (PE), is commonly treated with a low-molecular-weight heparin such as enoxaparin plus a vitamin K antagonist (VKA) to prevent recurrence. Administration of enoxaparin?+?VKA is hampered by complexities of laboratory monitoring and frequent dose adjustments. Rivaroxaban, an orally administered anticoagulant, has been compared with enoxaparin?+?VKA in the EINSTEIN trials. The objective was to evaluate the cost-effectiveness of rivaroxaban compared with enoxaparin?+?VKA as anticoagulation treatment for acute, symptomatic, objectively-confirmed DVT or PE.

Methods:

A Markov model was built to evaluate the costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios associated with rivaroxaban compared to enoxaparin?+?VKA in adult patients treated for acute DVT or PE. All patients entered the model in the ‘on-treatment’ state upon commencement of oral rivaroxaban or enoxaparin?+?VKA for 3, 6, or 12 months. Transition probabilities were obtained from the EINSTEIN trials during treatment and published literature after treatment. A 3-month cycle length, US payer perspective ($2012), 5-year time horizon and a 3% annual discount rate were used.

Results:

Treatment with rivaroxaban cost $2,448 per-patient less and was associated with 0.0058 more QALYs compared with enoxaparin?+?VKA, making it a dominant economic strategy. Upon one-way sensitivity analysis, the model’s results were sensitive to the reduction in index VTE hospitalization length-of-stay associated with rivaroxaban compared with enoxaparin?+?VKA. At a willingness-to-pay threshold of $50,000/QALY, probabilistic sensitivity analysis showed rivaroxaban to be cost-effective compared with enoxaparin?+?VKA approximately 76% of the time.

Limitations:

The model did not account for the benefits associated with an oral and minimally invasive administration of rivaroxaban. ‘Real-world’ applicability is limited because data from the EINSTEIN trials were used in the model. Also, resource utilization and costs were based on the US healthcare system.

Conclusion:

Rivaroxaban is a cost-effective option for anticoagulation treatment of acute VTE patients.     

Length of stay and economic consequences with rivaroxaban vs enoxaparin/vitamin K antagonist in patients with DVT and PE: findings from the North American EINSTEIN clinical trial program

Objective:

Venous thromboembolism (VTE) (deep vein thrombosis [DVT] and pulmonary embolism [(PE]) represents a substantial economic burden to the healthcare system. Using data from the randomized EINSTEIN DVT and PE trials, this North American sub-group analysis investigated the potential of rivaroxaban to reduce the length of initial hospitalization in patients with acute symptomatic DVT or PE.

Methods:

A post-hoc analysis of hospitalization and length-of-stay (LOS) data was conducted in the North American sub-set of patients from the randomized, open-label EINSTEIN trial program. Patients received either rivaroxaban (15?mg twice daily for 3 weeks followed by 20?mg once daily; n?=?405) or dose-adjusted subcutaneous enoxaparin overlapping with (guideline-recommended ‘bridging’ therapy) and followed by a vitamin K antagonist (VKA) (international normalized ratio?=?2.0–3.0; n?=?401). The open-label study design allowed for the comparison of LOS between treatment arms under conditions reflecting normal clinical practice. LOS was evaluated using investigator records of dates of admission and discharge. Analyses were carried out in the intention-to-treat population using parametric tests. Costs were applied to the LOS based on weighted mean cost per day for DVT and PE diagnoses obtained from the Healthcare Cost and Utilization Project dataset.

Results:

Of 382 patients hospitalized, 321 (84%), had acute symptomatic PE; few DVT patients required hospitalization. Similar rates of VTE patients were hospitalized in the rivaroxaban and enoxaparin/VKA treatment groups, 189/405 (47%) and 193/401 (48%), respectively. In hospitalized VTE patients, rivaroxaban treatment produced a 1.6-day mean reduction in LOS (median?=?1 day) compared with enoxaparin/VKA (mean?=?4.5 vs 6.1; median?=?3 vs 4), translating to total costs that were $3419 lower in rivaroxaban-treated patients.

Conclusion:

In hospitalized North American patients with VTE, treatment with rivaroxaban produced a statistically significant reduction in LOS. When treating DVT and PE patients, clinicians should consider newer anti-coagulants with less complex treatment regimens.     

Erratum to: ‘Statistical estimate of the proportional hazard premium of loss’

The asymptotic variance of the risk premium estimator, proposed by Necir et al. (2007), is revised, by using the right asymptotic approximation of the uniform empirical quantile process.     

Stabilization and the aftermarket prices of initial public offerings

The paper examines the determinants of stabilization and its impact on the aftermarket prices. We use a unique dataset to relax several assumptions in the stabilization literature. We find that underwriters support IPO prices shortly after listing, particularly in cold markets and when demand is weak. We also show that stabilized IPOs are more common amongst reputable underwriters. This finding suggests that stabilization may be used as a mechanism to protect the underwriter’s reputation. It also implies that reputable underwriters may possess private information and price IPOs closer to their true values (i.e., higher than those indicated by the weak premarket demand). Consistent with the latter view, we show that stabilized IPOs are offered at higher prices and suffer less underpricing than those indicated by the premarket demand, firm characteristics and market-wide conditions. The post-IPO performance results indicate that stabilized IPOs are unlikely to be mispriced as their prices do not exhibit any significant reversal after the initial stabilization period. We conclude that stabilization may be superior to underpricing as it protects investors from purchasing overpriced IPOs, benefits issuers by reducing the total money “left on the table” and enhances the overall profitability of underwriters.     

Communications About Resilience Enhancing Activities By English Local Authorities

Abstract

The Civil Contingencies Act (2004 Civil Contingencies Act. 2004. Contingency Planning Regulations 2005, London: The Stationery Office. No. 2042 Statutory Instruments [Google Scholar]) in the United Kingdom introduced new responsibilities for public authorities regarding Business Continuity Management (BCM) and other emergency planning activities. Using content analysis techniques, this study examined thirty-four English county councils' websites to examine the extent to which this online medium communicated these new responsibilities to stakeholders. Using key-word-in-context (KWIC) and content clustering, this exploratory study found that local authorities' websites were far from generic in their web-based communications about their new Civil Contingencies Act responsibilities and BCM activities, and it reveals a number of differing website traits, motivations and orientations.     

UNSEASONED EQUITY OFFERINGS MBO-IPOs vs NON-MBO-IPOs

In this paper we examine the degree of under-pricing of two different types of unseasoned equity offerings (IPOs), namely MBO-IPOs and non-MBO-IPOs. Since, MBO-IPOs were previously subsidiaries or divisions of publicly listed companies which were taken private by a group of managers and then reverted back to public ownership; there should be a lower level of information asymmetry between the market on the one hand and the company and its underwriters on the other. Thus, if under-pricing is mainly the result of uncertainty about the market value of the issuing firm, the information asymmetry hypothesis would predict that, compared with the non-MBO-IPOs, MBO-IPOs should exhibit a significantly lower degree of under-pricing. The results show that MBO-IPOs are less under-priced than non-MBO-IPOs. However, the difference is not statistically significant.     

The gender wage gap among recent post‐secondary graduates in Canada: a distributional approach

Using the National Graduates Survey, we examine the trends in the gender wage gap among recent post‐secondary graduates in Canada between 1988 and 2007. Female graduates earn on average 6–14% less than males during the period two to five years after graduation. Decompositions show that observable personal characteristics and job attributes can explain only a small portion of the wage gap. We also find that men earn more than women at every point of the distribution. Interestingly, the wage difference shrank in the lower half of the distribution in recent years, while it increased in the upper half.