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

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 use of complementary and alternative medicines among patients with locally advanced breast cancer – a descriptive study

BACKGROUND: Complementary and alternative medicine (CAM) use is common among cancer patients. This paper reviews the use of CAM in a series of patients with locally advanced breast cancer (LABC). METHODS: Women with LABC attending a specialist clinic at a single Canadian cancer centre were identified and approached. Participants completed a self-administered survey regarding CAM usage, beliefs associated with CAM usage, views of their risks of developing recurrent cancer and of dying of breast cancer. Responses were scored and compared between CAM users and non-users. RESULTS: Thirty-six patients were approached, 32 completed the questionnaire (response rate 89%). Forty-seven percent of LABC patients were identified as CAM users. CAM users were more likely to be younger, married, in a higher socioeconomic class and of Asian ethnicity than non-users. CAM users were likely to use multiple modalities simultaneously (median 4) with vitamins being the most popular (60%). Motivation for CAM therapy was described as, "assisting their body to heal" (75%), to 'boost the immune system' (56%) and to "give a feeling of control with respect to their treatment" (56%). CAM therapy was used concurrently with conventional treatment in 88% of cases, however, 12% of patients felt that CAM could replace their conventional therapy. Psychological evaluation suggests CAM users perceived their risk of dying of breast cancer was similar to that of the non-Cam group (33% vs. 35%), however the CAM group had less severe anxiety and depression. CONCLUSION: The motivation, objectives and benefits of CAM therapy in a selected population of women with LABC are similar to those reported for women diagnosed with early stage breast cancer. CAM users display less anxiety and depression and are less likely to believe they will die of their breast cancer. However the actual benefit to overall and disease free survival has yet to be demonstrated, as well as the possible interactions with conventional therapy. Consequently more research is needed in this ever-growing field

External influences and priority-setting for anti-cancer agents: a case study of media coverage in adjuvant trastuzumab for breast cancer

<p>Abstract</p> <p>Background</p> <p>Setting priorities for the funding of new anti-cancer agents is becoming increasingly complex. The funding of adjuvant trastuzumab for breast cancer has brought this dilemma to the fore. In this paper we review external factors that may influence decision-making bodies and present a case study of media response in Ontario, Canada to adjuvant trastuzumab for breast cancer.</p> <p>Methods</p> <p>A comprehensive search of the databases of Canadian national and local newspapers and television was performed. Articles pertaining to trastuzumab in adjuvant breast cancer as well as 17 other anti-cancer drugs and indications were retrieved. The search period was from the date when individual trial results were announced to the date funding was made available in Ontario.</p> <p>Results</p> <p>During the 2.6 months between the release of the trastuzumab results to funding approval in Ontario, we identified 51 episodes of media coverage. For the 17 other drugs/indications (7 breast and 10 non-breast), the median time to funding approval was 31 months (range 14–46). Other recent major advances in oncology such as adjuvant vinorelbine/cisplatin for resected NSCLC and docetaxel for advanced prostate cancer received considerably less media attention (17 media reports for each) than trastuzumab. The median number of media reports for breast cancer drugs was 4.5 compared to 2.5 for non-breast cancer drugs (p = 0.56).</p> <p>Conclusion</p> <p>Priority-setting for novel anti-cancer agents is a complex process that tries to ensure fair use of constrained resources to fund therapies with the best evidence of clinical benefit. However, this process is subject to external factors including the influence of media, patient advocates, politicians, and industry. The data in this case study serve to illustrate the significant involvement one (or all) of these external factors may play in the debate over priority-setting.</p

Clinical and Economic Considerations of Empirical Antibacterial Therapy of Febrile Neutropenia in Cancer

Febrile neutropenia is a condition that can develop in patients with cancer following the administration of myelosuppressive chemotherapy or radiation therapy. The current standard of patient management involves the empirical use of a combination of antibacterials or a single broad spectrum agent to offer extensive antibacterial coverage of both Gram-positive and Gram-negative microorganisms. Over the past 25 years, febrile neutropenia has changed from a condition that was fatal in over 50% of patients to a condition with an infection-related mortality rate of less than 10%. A major reason behind these extraordinary advances in patient care has been the many well-designed randomised trials of empirical antibacterial therapy that have been conducted over this period of time. In contrast to this finding, a review of the literature revealed limited economic data on the empirical treatment of febrile neutropenia in patients with cancer. Therefore, there is a definite need to conduct more pharmacoeconomic research in this area and to develop methods of implementing the findings of such studies.Reviews-on-treatment, Immunocompromised-infections, Antibacterials, Immunocompromised-infections, Quality-of-life, Cost-analysis, Neutropenia, Cancer, Colony-stimulating-factors

Impact of Regulatory Approval Status on CADTH Reimbursement of Oncology Drugs and Role of Real-World Evidence on Conditional Approvals from 2019 to 2021

Real-world evidence (RWE) is health and outcomes data generated from a patient&rsquo;s journey through the health care system or disease process (i.e., real-world data). RWE is now having an increasingly important role in regulatory/reimbursement decisions. This article examines reimbursement recommendations by the Canadian Agency for Drugs and Technology in Health (CADTH) on oncology drugs approved between 2019 and 2021. Oncology drugs with a Summary Basis of Decision (SBD) for original marketing approvals were used to generate a corresponding list of CADTH final clinical recommendations for review. Of the 45 oncology drugs approved by Health Canada, CADTH granted positive funding recommendations to all 11 drugs that had priority review approvals. Two of the 17 drugs with standard reviews did not file to CADTH and 3 received a negative recommendation. Of the 17 drugs with Notice of Compliance with Conditions (NOCc) status, three were not filed to CADTH and four were under active reviews. Of the ten completed NOCc reviews, all contained RWE from sponsors and six received a negative decision on their first review. No significant differences in review times were found between the three approval statuses. Regulatory approval status appeared to influence reimbursement outcomes in Canada and evaluation of 10 NOCc approvals provided little insight regarding robustness of RWE required for more favorable considerations