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

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