16 research outputs found
The Price of Innovative Anticancer Drugs
Many new anticancer drugs enter the market at a relatively high price. Some healthcare authorities have made the rare decision not to fund new anticancer drugs due to their high prices. Decision-makers fear that these expensive new anticancer drugs are not generating net social benefits. The following work investigates the relationship between prices and clinical benefits of anticancer drugs that have come to market over the past decade. We show that the relationship between drug prices and clinical benefits is not linear. In fact, modern drug prices appear to rise exponentially. Drug manufacturers explain their pricing strategy with concerns towards the high cost of innovating in the pharmaceutical industry. Accordingly, a discussion of innovation in anticancer research is included. The discussion also provides insight into cancer control in the upcoming generation of personalized medicines. The aim is to gain an understanding of the social benefits received from these innovative new treatments
Health Care Utilization & Costs in Lung Cancer Screening Participantsâa Propensity Matched Economic Analysis
Quality of Life and Socioeconomic Indicators Associated with Survival of Myeloid Leukemias in Canada
Understanding how patientâreported quality of life (QoL) and socioeconomic status (SES) relate to survival of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) may improve prognostic information sharing. This study explores associations among QoL, SES, and survival through administration of the EuroâQoL 5âDimension, 3âlevel and Functional Assessment of Cancer TherapyâLeukemia and financial impact questionnaires to 138 adult participants with newly diagnosed AML or MDS in a longitudinal, panâCanadian study. Cox regression and lasso variable selection models were used to explore associations among QoL, SES, and established predictors of survival. Secondary outcomes were changes in QoL, performance of the QoL instruments, and lost income. We found that higher QoL and SES were positively associated with survival. The Lasso model selected the visual analog scale of the EQâ5Dâ3L as the most important predictor among all other variables (P = .03; 92% selection). Patients with AML report improved QoL after treatment, despite higher mean outâofâpocket expenditures compared with MDS (up to 239 for MDS; P = .05), greater loss of productivityârelated income (reaching id="mce_marker"786/month for AML vs $709 for MDS; P < .05), and greater caregiver effects (65% vs 35% caregiver productivity losses for AML vs MDS; P < .05). Our results suggest that including patientâreported QoL and socioeconomic indicators can improve the accuracy of survival models
Resource utilization and costs during the initial years of lung cancer screening with computed tomography in Canada
Background
It is estimated that millions of North Americans would qualify for lung cancer screening and that billions of dollars of national health expenditures would be required to support population-based computed tomography lung cancer screening programs. The decision to implement such programs should be informed by data on resource utilization and costs.
Methods
Resource utilization data were collected prospectively from 2059 participants in the Pan-Canadian Early Detection of Lung Cancer Study using low-dose computed tomography (LDCT). Participants who had 2% or greater lung cancer risk over 3 years using a risk prediction tool were recruited from seven major cities across Canada. A cost analysis was conducted from the Canadian public payer's perspective for resources that were used for the screening and treatment of lung cancer in the initial years of the study.
Results
The average per-person cost for screening individuals with LDCT was USD453 (95% confidence interval [CI], USD400âUSD505) for the initial 18-months of screening following a baseline scan. The screening costs were highly dependent on the detected lung nodule size, presence of cancer, screening intervention, and the screening center. The mean per-person cost of treating lung cancer with curative surgery was USD33,344 (95% CI, USD31,553âUSD34,935) over 2 years. This was lower than the cost of treating advanced-stage lung cancer with chemotherapy, radiotherapy, or supportive care alone, (USD47,792; 95% CI, USD43,254âUSD52,200; p = 0.061).
Conclusion
In the Pan-Canadian study, the average cost to screen individuals with a high risk for developing lung cancer using LDCT and the average initial cost of curative intent treatment were lower than the average per-person cost of treating advanced stage lung cancer which infrequently results in a cure
RGD-containing ligands for targeting liposomal nanoparticles
The use of a targeting ligand to enhance the delivery of liposomal nanoparticles (LNs) to specific cells in diseased tissue is an attractive strategy that has progressed very slowly since the idea originated over 25 years ago. The slow progress can be attributed, in part, to the difficulties involved in producing well-defined targeted LN systems. This work concerns the development of peptide-based ligands for targeting LNs to cells that overexpress the α[sub v]ÎČâ integrin, which is considered a unique marker of the tumor-associated endothelium. Initial work focused on using Fab' fragments of monoclonal antibodies as targeting ligands and employing literature techniques for coupling these proteins to lipids that can then be inserted in preformed LNs. However, it was found that the coupling procedures resulted in low yields of poorly defined lipid-ligand conjugates that were difficult to quantitate when incorporated into LN. Attention was then given to the development of a peptide-targeting agent that could be incorporated into an LN at the time that the LN is made. The RGD-containing cyclic peptide, eRGDfK, was employed as the targeting ligand. In order to characterize its binding to the α[sub v]ÎČâ integrin, a fluorescently labeled analogue, cRGDfK-488, was synthesized and capillary electrophoresis was employed for analysis. This procedure proved advantageous for studying receptor ligand interactions, since it allowed for the binding to be characterized in solution without the need for covalent modification of receptor or ligand. A 2:1 RGD ligand to integrin specific binding stoichiometry was revealed with the second binding event having a similar affinity as the first binding event. The next phase of these studies investigated the ability of cRGDfK-488 to bind to integrins on human umbilical vascular endothelial cells (HUVEC) and subsequently undergo endocytosis. This was compared to the binding and uptake properties of a fluorescently labeled monoclonal antibody, LM609X, which specifically binds α[sub v]ÎČâ integrin. Using flow cytometry and fluorescence microscopy, it is shown that the RGD ligand exhibited considerably greater uptake following incubation at endocytosis permitting temperatures (37°C) as compared to endocytosis inhibiting temperatures (4°C). A 7.4-fold increase in uptake of the RGD-lipid was observed following a one-hour incubation with HUVEC at 37°C, as compared to 4°C. In contrast, only a 1.9 fold increase in cell-associated fluorescence was observed on incubation with LM609X at 37°C as compared to 4°C. It is suggested that this ability of RGD ligands to stimulate endocytosis may be of utility for achieving enhanced intracellular delivery of ligand-associated drugs in anti-angiogenic applications. The cyclic peptide was then used to construct a fluorescently labeled RGD-spacer-lipid construct of defined molecular weight that could be incorporated into LN at the time of manufacture. It is shown that the resulting RGD-LNs bind to HUVEC with increasing avidity as the amount of RGD-spacer-lipid incorporated is increased. Further, these RGD-LNs are straightforward to make and can load and retain anti-cancer drugs such as doxorubicin. It is shown that RGD-LNs loaded with doxorubicin and incubated with HUVEC selectively deliver the drug to the cytosol while non-targeted LNs are not internalized by the cell, suggesting potential utility as targeted drug delivery systems in vivo.Medicine, Faculty ofBiochemistry and Molecular Biology, Department ofGraduat
Total Chemical Synthesis of a 27 kDa TASP Protein Derived from the MscL Ion Channel of M. tuberculosis
A TimeâTrend Economic Analysis of Cancer Drug Trials
BackgroundScientific advances have led to the discovery of novel treatments with high prices. The cost to publicly fund high-cost drugs may threaten the sustainability of drug budgets in different health care systems. In oncology, there are concerns that health-benefit gains are diminishing over time and that the economic evidence to support funding decisions is too limited.MethodsTo assess the additional costs and benefits gained from oncology drugs over time, we used treatment protocols and efficacy results from U.S. Food and Drug Administration records to calculate cost-effectiveness ratios for drugs approved to treat first- and second-line metastatic or advanced breast, colorectal, and non-small cell lung cancer during the years 1994-2013. We assessed reimbursement recommendations reached by health technology assessment agencies in the U.K., Australia, and Canada.ResultsCost-effectiveness ratios were calculated for 50 drugs approved by the U.S. regulator. The more recent approvals were often based on surrogate efficacy outcomes and had extremely high costs, often triple the costs of drugs approved in previous years. Over time, the effectiveness gains have increased for some cancer indications; however, for other indications (non-small cell lung and second-line colorectal cancer), the magnitude of gains in effectiveness decreased. Reimbursement recommendations for drugs with the highest cost-effectiveness ratios were the most inconsistent.ConclusionEvaluation of the clinical benefits that oncology drugs offer as a function of their cost has become highly complex, and for some clinical indications, health benefits are diminishing over time. There is an urgent need for better economic evidence from oncology drug trials and systematic processes to inform funding decisions.Implications for practiceHigh-cost oncology drugs may threaten the ability of health care systems to provide access to promising new drugs for patients. In order to make better drug-funding decisions and enable equitable access to breakthrough treatments, discussions in the oncology community should include economic evidence. This study summarizes the extra benefits and costs of newly approved drugs from pivotal trials during the postgenomic era of drug discovery. The reader will gain an appreciation of the need for economic evidence to make better drug-reimbursement decisions and the dynamics at play in today's oncology drug market
A TimeâTrend Economic Analysis of Cancer Drug Trials
BACKGROUND. Scientific advances have led to the discovery of novel treatments with high prices. The cost to publicly fund high-cost drugs may threaten the sustainability of drug budgets in different health care systems. In oncology, there are concerns that health-benefit gains are diminishing over time and that the economic evidence to support funding decisions is too limited. METHODS. To assess the additional costs and benefits gained from oncology drugs over time, we used treatment protocols and efficacy results from U.S. Food and Drug Administration records to calculate cost-effectiveness ratios for drugs approved to treat first- and second-line metastatic or advanced breast, colorectal, and non-small cell lung cancer during the years 1994â2013. We assessed reimbursement recommendations reached by health technology assessment agencies in the U.K., Australia, and Canada. RESULTS. Cost-effectiveness ratios were calculated for 50 drugs approved by the U.S. regulator. The more recent approvals were often based on surrogate efficacy outcomes and had extremely high costs, often triple the costs of drugs approved in previous years. Over time, the effectiveness gains have increased for some cancer indications; however, for other indications (non-small cell lung and second-line colorectal cancer), the magnitude of gains in effectiveness decreased. Reimbursement recommendations for drugs with the highest cost-effectiveness ratios were the most inconsistent. CONCLUSION. Evaluation of the clinical benefits that oncology drugs offer as a function of their cost has become highly complex, and for some clinical indications, health benefits are diminishing over time. There is an urgent need for better economic evidence from oncology drug trials and systematic processes to inform funding decisions. IMPLICATIONS FOR PRACTICE: High-cost oncology drugs may threaten the ability of health care systems to provide access to promising new drugs for patients. In order to make better drug-funding decisions and enable equitable access to breakthrough treatments, discussions in the oncology community should include economic evidence. This study summarizes the extra benefits and costs of newly approved drugs from pivotal trials during the postgenomic era of drug discovery. The reader will gain an appreciation of the need for economic evidence to make better drug-reimbursement decisions and the dynamics at play in todayâs oncology drug market
Economic impact of genomic diagnostics for intermediateârisk acute myeloid leukaemia
Acute Myeloid Leukaemia (AML) is a rare but serious group of diseases that require critical decisionâmaking for curative treatment. Over the past decade, scientific discovery has revealed dozens of prognostic gene mutations for AML while sequencing costs have plummeted. In this study, we compared the costâeffectiveness of multigene integrative analysis (genomic analysis) with the standard molecular testing currently used for diagnosis of intermediateârisk AML. We used a decision analytic model with data for costs and outcomes from British Columbia, Canada, to assess the longâterm (10âyear) economic impacts. Our results suggest that genomic analysis would result in a 26% increase in the use of firstâremission allogeneic stem cell transplantation. The resulting treatment decisions and downstream effects would come at an additional cost of 49Â 493 per qualityâadjusted lifeâyear gained. Costâeffectiveness was dependent on quality of life during the longâterm (5â10) years of survival, relapse rates following firstâremission chemotherapy and the upfront cost of transplantation. Nonârelapse mortality rates, shortâterm quality of life and the cost of genomic sequencing had only minor impacts. Further research on postâremission outcomes can lead to improvements in the costâeffectiveness of curative treatments for AML