Cost-Utility Analysis of Venous Thromboembolism Prophylaxis Strategies for People Undergoing Elective Total Hip and Total Knee Replacement Surgeries in the English National Health Service

Background: Major orthopedic surgery, such as elective total hip replacement (eTHR) and elective total knee replacement (eTKR), are associated with a higher risk of venous thromboembolism (VTE) than other surgical procedures. Little is known, however, about the cost-effectiveness of VTE prophylaxis strategies in people undergoing these procedures. Aim: The aim of this work was to assess the cost-effectiveness of these strategies from the English National Health Service perspective to inform NICE guideline (NG89) recommendations. Materials and Methods: Cost-utility analysis, using decision modeling, was undertaken to compare 15 VTE prophylaxis strategies for eTHR and 12 for eTKR, in addition to “no prophylaxis” strategy. The analysis complied with the NICE Reference Case. Structure and assumptions were agreed with the guideline committee. Incremental net monetary benefit (INMB) was calculated, vs. the model comparator (LMWH+ antiembolism stockings), at a threshold of £20,000/quality-adjusted life-year (QALY) gained. The model was run probabilistically. Deterministic sensitivity analyses (SAs) were undertaken to assess the robustness of the results. Results: The most cost-effective strategies were LMWH for 10 days followed by aspirin for 28 days (INMB = £530 [95% CI: -£784 to £1,103], probability of being most cost-effective = 72%) for eTHR, and foot pump (INMB = £353 [95% CI: -£101 to £665]; probability of being most cost-effective = 18%) for eTKR. There was considerable uncertainty regarding the cost-effectiveness ranking in the eTKR analysis. The results were robust to change in all SAs. Conclusions: For eTHR, LMWH (standard dose) for 10 days followed by aspirin for 28 days is the most cost-effective VTE prophylaxis strategy. For eTKR, the results are highly uncertain but foot pump appeared to be the most cost-effective strategy, followed closely by aspirin (low dose). Future research should focus on assessing cost-effectiveness of VTE prophylaxis in the eTKR population.Peer reviewe

Systematic review of economic evaluations and cost analyses of guideline implementation strategies

Objectives To appraise the quality of economic studies undertaken as part of evaluations of guideline implementation strategies; determine their resources use; and recommend methods to improve future studies. Methods Systematic review of economic studies undertaken alongside robust study designs of clinical guideline implementation strategies published (1966-1998). Studies assessed against the BMJ economic evaluations guidelines for each stage of the guideline process (guideline development, implementation and treatment). Results 235 studies were identified, 63 reported some information on cost. Only 3 studies provided evidence that their guideline was effective and efficient. 38 reported the treatment costs only, 12 implementation and treatment costs, 11 implementation costs alone, and two guideline development, implementation and treatment costs. No study gave reasonably complete information on costs. Conclusions Very few satisfactory economic evaluations of guideline implementation strategies have been performed. Current evaluations have numerous methodological defects and rarely consider all relevant costs and benefits. Future evaluations should focus on evaluating the implementation of evidence based guidelines. Keywords: Cost-effectiveness analysis, physician (or health care professional) behaviour, practice guidelines, quality improvement, systematic review.Peer reviewedAuthor versio

Meta regression analysis to indirectly compare dalteparin to enoxaparin for the prevention of venous thromboembolic events following total hip replacement

<p>Abstract</p> <p>Background</p> <p>Patients undergoing elective total hip replacement (THR) surgery are at an increased risk for venous thromboembolic events (VTEs). Dalteparin and enoxaparin are recommended as thromboprophylaxis for at least 10 days in these patients. Even though both agents have proven clinical effectiveness through placebo controlled studies, there have been no head to head trials to assess comparative effectiveness. Indirect statistical techniques were used to compare safety and efficacy between dalteparin and enoxaparin following THR surgery.</p> <p>Methods</p> <p>A literature search was conducted from January 1980 to November 2009 for randomized trials evaluating dalteparin or enoxaparin prophylaxis in THR patients. In trials where a common control was used (e.g. placebo), indirect statistical comparisons between dalteparin and enoxaparin were performed using meta regression analysis with active drug as the primary independent variable.</p> <p>Results</p> <p>A total of nine placebo controlled enoxaparin (n = 5) and dalteparin (n = 4) trials met the inclusion criteria. THR patients treated with enoxaparin or dalteparin had a 50% VTE risk reduction compared to the placebo control (RR = 0.50, p < 0.001). This benefit was achieved without a significant increase in the risk for major bleeds (RR = 1.19, p = 0.76), heparin induced thrombocytopenia (HIT) (RR = 1.13, p = 0.83) or death (RR = 0.72, p = 0.59). The indirect comparison was not able to find significant differences between enoxaparin and dalteparin in terms of VTEs (p = 0.36), major bleeds (p = 0.45), HIT (p = 0.48) and death (p = 0.86).</p> <p>Conclusions</p> <p>The findings suggested comparable safety and efficacy between dalteparin and enoxaparin in TKR patients. Therefore, treatment decisions should be based on other considerations, such as patient or physician preference, ease of administration and cost.</p

Safety and Efficacy of nab-Paclitaxel in the Treatment of Patients with Breast Cancer

Taxanes are highly active chemotherapeutic agents in the treatment of early-stage and metastatic breast cancer. Novel formulations have been developed to improve efficacy and decrease toxicity associated with these cytotoxic agents. nab-paclitaxel is a solvent free, albumin-bound 130-nanometer particle formulation of paclitaxel (Abraxane®, Abraxis Bioscience), which was developed to avoid toxicities of the Cremophor vehicle used in solvent-based paclitaxel. In a phase III clinical trial, nab-paclitaxel demonstrated higher response rates, better safety and side-effect profile compared to conventional paclitaxel, and improved survival in patients receiving it as second line therapy. Higher doses can be administered over a shorter infusion time without the need for special infusion sets or pre-medications. It is now approved in the US for treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant therapy, where prior therapy included an anthracycline. Recently, several phase II studies have suggested a role for nab-paclitaxel as a single agent and in combination with other agents for first-line treatment of metastatic breast cancer

Development of a value based pricing index for new drugs in metastatic colorectal cancer

Background: Worldwide, prices for cancer drugs have been under downward pressure where several governments have mandated price cuts of branded and generic products. A better alternative to mandated price cuts would be the estimation of a launch price based on drug performance, cost effectiveness and a country’s ability to pay. In this study, the development of a global pricing index for new drugs that encompasses all of these attributes in patients with metastatic colorectal cancer (mCRC) is described. Methods: A pharmacoeconomic model was developed to simulate clinical outcomes in mCRC patients receiving chemotherapy with the addition of a “new drug” that improves survival by 1.4, 3 and 6 months. Cost and health state utility data were obtained from cancer centers and oncology nurses (total n=112) in Canada (n=24), Spain (n=24), India (n=24), South Africa (n=16) and Malaysia (n=24). A price per dose was estimated for each survival increment using a target value threshold of three times the per capita gross domestic product (GDP) for each country, as recommended by the World Health Organisation (WHO). Multivariable analysis was then used to develop the pricing index, which considers survival benefit, per capita GDP and income dispersion as measured by the Gini coefficient as predictor variables. Results: Higher survival benefits were associated with elevated drug prices, especially in wealthier countries such as Canada and Spain. For a nation like Argentina with a per capita GDP of $15,000 and a Gini coefficient of 51, it is estimated that for a drug which provides a 4 month survival benefit in mCRC, the value based price would be$US 630 per dose. In contrast, the same drug in a wealthier country like Norway could command a price of $US 2,775 and still be considered cost effective according to the WHO criteria. Conclusions: A global pricing index was presented that can be used to estimate a value based price in different countries for new drugs in mCRC. The application of this index to estimate a price based on cost effectiveness would be a good starting point for opening dialogue between the key stakeholders and a better alternative to governments’ mandated price cuts

Development of a value based pricing index for new drugs in metastatic colorectal cancer

Background: Worldwide, prices for cancer drugs have been under downward pressure where several governments have mandated price cuts of branded and generic products. A better alternative to mandated price cuts would be the estimation of a launch price based on drug performance, cost effectiveness and a country’s ability to pay. In this study, the development of a global pricing index for new drugs that encompasses all of these attributes in patients with metastatic colorectal cancer (mCRC) is described. Methods: A pharmacoeconomic model was developed to simulate clinical outcomes in mCRC patients receiving chemotherapy with the addition of a “new drug” that improves survival by 1.4, 3 and 6 months. Cost and health state utility data were obtained from cancer centers and oncology nurses (total n=112) in Canada (n=24), Spain (n=24), India (n=24), South Africa (n=16) and Malaysia (n=24). A price per dose was estimated for each survival increment using a target value threshold of three times the per capita gross domestic product (GDP) for each country, as recommended by the World Health Organisation (WHO). Multivariable analysis was then used to develop the pricing index, which considers survival benefit, per capita GDP and income dispersion as measured by the Gini coefficient as predictor variables. Results: Higher survival benefits were associated with elevated drug prices, especially in wealthier countries such as Canada and Spain. For a nation like Argentina with a per capita GDP of $15,000 and a Gini coefficient of 51, it is estimated that for a drug which provides a 4 month survival benefit in mCRC, the value based price would be$US 630 per dose. In contrast, the same drug in a wealthier country like Norway could command a price of $US 2,775 and still be considered cost effective according to the WHO criteria. Conclusions: A global pricing index was presented that can be used to estimate a value based price in different countries for new drugs in mCRC. The application of this index to estimate a price based on cost effectiveness would be a good starting point for opening dialogue between the key stakeholders and a better alternative to governments’ mandated price cuts

The hope and reality of long‐acting hemophilia products

Recombinant DNA technology and protein engineering are creating hope that we can address ongoing challenges in hemophilia care such as reducing the costs of therapy, increasing the availability to the developing world, and improving the functional properties of these proteins. Technological advances to improve the half‐life of recombinant clotting factors have brought long‐acting clotting factors for hemophilia replacement therapy closer to reality. Preclinical and clinical trial results are reviewed as well as the potential benefits and risks of these novel therapies. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91179/1/23146_ftp.pd

Body surface area and baseline blood pressure predict subclinical anthracycline cardiotoxicity in women treated for early breast cancer.

BACKGROUND AND AIMS: Anthracyclines are highly effective chemotherapeutic agents which may cause long-term cardiac damage (chronic anthracycline cardiotoxicity) and heart failure. The pathogenesis of anthracycline cardiotoxicity remains incompletely understood and individual susceptibility difficult to predict. We sought clinical features which might contribute to improved risk assessment. METHODS: Subjects were women with early breast cancer, free of pre-existing cardiac disease. Left ventricular ejection fraction was measured using cardiovascular magnetic resonance before and >12 months after anthracycline-based chemotherapy (>3 months post-Trastuzumab). Variables associated with subclinical cardiotoxicity (defined as a fall in left ventricular ejection fraction of ≥5%) were identified by logistic regression. RESULTS: One hundred and sixty-five women (mean age 48.3 years at enrollment) completed the study 21.7 months [IQR 18.0-26.8] after starting chemotherapy. All received anthracyclines (98.8% epirubicin, cumulative dose 400 [300-450] mg/m2); 18% Trastuzumab. Baseline blood pressure was elevated (≥140/90mmHg, mean 147.3/86.1mmHg) in 18 subjects. Thirty-four subjects (20.7%) were identified with subclinical cardiotoxicity, independent predictors of which were the number of anthracycline cycles (odds ratio, OR 1.64 [1.17-2.30] per cycle), blood pressure ≥140/90mmHg (OR 5.36 [1.73-17.61]), body surface area (OR 2.08 [1.36-3.20] per standard deviation (0.16m2) increase), and Trastuzumab therapy (OR 3.35 [1.18-9.51]). The resultant predictive-model had an area under the receiver operating characteristics curve of 0.78 [0.70-0.86]. CONCLUSIONS: We found subclinical cardiotoxicity to be common even within this low risk cohort. Risk of cardiotoxicity was associated with modestly elevated baseline blood pressure-indicating that close attention should be paid to blood pressure in patients considered for anthracycline based chemotherapy. The association with higher body surface area suggests that indexing of anthracycline doses to surface area may not be appropriate for all, and points to the need for additional research in this area

The EGALITY study:A confirmatory, randomised, double-blind study comparing the efficacy, safety and immunogenicity of GP2015, a proposed etanercept biosimilar, versus the originator product in patients with moderate to severe chronic plaque-type psoriasis

BACKGROUND: GP2015 is a proposed etanercept biosimilar.OBJECTIVE: To demonstrate equivalent efficacy, and comparable safety and immunogenicity of GP2015 and etanercept originator (ETN, Enbrel(®) ) in patients with moderate to severe chronic plaque-type psoriasis.METHODS: 531 eligible patients were randomised 1:1 to self-administer GP2015 or ETN twice-weekly subcutaneously. Patients with a 50% improvement in psoriasis area and severity index (PASI 50) at week 12 were re-randomised to continue the same treatment on a once-weekly dosing schedule or to undergo a sequence of 3 treatment switches between GP2015 and ETN until week 30. Thereafter, patients continued treatment with the product they had been assigned to last, up to week 52.RESULTS: The difference in PASI 75 (75% improvement from baseline PASI score) response rates at week 12 between GP2015 and ETN (primary endpoint) was -2.3%. The 95% confidence interval (-9.85, 5.30) was well contained within the pre-specified margin range of (-18, 18). Incidence of treatment-emergent adverse events up to week 52 was comparable between continued GP2015 (59.8%) and ETN (57.3%); switching treatments revealed comparable safety profiles. Anti-drug antibodies, all non-neutralising, were limited to 5 patients on ETN during treatment period 1, and 1 patient in the switched ETN group, who had been treated with GP2015 for 12 weeks at time of the finding.CONCLUSION: The EGALITY study demonstrated equivalent efficacy and comparable safety and immunogenicity of GP2015 and ETN. The study results provided the final clinical confirmation of biosimilarity and contributed to the totality-of-the-evidence proposing that GP2015 is an etanercept biosimilar. This article is protected by copyright. All rights reserved.</p