Cost-effectiveness thresholds: pros and cons Bertram, Melanie Y; Lauer, Jeremy A; De Joncheere, Kees ...
Bulletin of the World Health Organization,
12/2016, Letnik:
94, Številka:
12
Journal Article
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Cost-effectiveness analysis is used to compare the costs and outcomes of alternative policy options. Each resulting cost-effectiveness ratio represents the magnitude of additional health gained per ...additional unit of resources spent. Cost-effectiveness thresholds allow cost-effectiveness ratios that represent good or very good value for money to be identified. In 2001, the World Health Organization's Commission on Macroeconomics in Health suggested cost-effectiveness thresholds based on multiples of a country's per-capita gross domestic product (GDP). In some contexts, in choosing which health interventions to fund and which not to fund, these thresholds have been used as decision rules. However, experience with the use of such GDP-based thresholds in decision-making processes at country level shows them to lack country specificity and this - in addition to uncertainty in the modelled cost-effectiveness ratios - can lead to the wrong decision on how to spend health-care resources. Cost-effectiveness information should be used alongside other considerations - e.g. budget impact and feasibility considerations - in a transparent decision-making process, rather than in isolation based on a single threshold value. Although cost-effectiveness ratios are undoubtedly informative in assessing value for money, countries should be encouraged to develop a context-specific process for decision-making that is supported by legislation, has stakeholder buy-in, for example the involvement of civil society organizations and patient groups, and is transparent, consistent and fair.
Botulinum neurotoxins are diverse proteins. They are currently represented by at least seven serotypes and more than 40 subtypes. New clostridial strains that produce novel neurotoxin variants are ...being identified with increasing frequency, which presents challenges when organizing the nomenclature surrounding these neurotoxins. Worldwide, researchers are faced with the possibility that toxins having identical sequences may be given different designations or novel toxins having unique sequences may be given the same designations on publication. In order to minimize these problems, an ad hoc committee consisting of over 20 researchers in the field of botulinum neurotoxin research was convened to discuss the clarification of the issues involved in botulinum neurotoxin nomenclature. This publication presents a historical overview of the issues and provides guidelines for botulinum neurotoxin subtype nomenclature in the future.
Value-Based Pricing: L’Enfant Terrible? Garner, Sarah; Rintoul, Andrew; Hill, Suzanne R.
PharmacoEconomics,
01/2018, Letnik:
36, Številka:
1
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...an essential medicine might offer a large health benefit or high value (determined, for example, through cost-effectiveness analysis), but still might not be affordable (because of limited ...resources, high prices, or both)..." WHO supports its 194 Member States as they coordinate the efforts of multiple sectors of the government and partners-including bi- and multilaterals, funds and foundations, civil society organizations and private sector entities-to attain their health objectives and support their national health policies and strategies. ...there is no value in a medicine that is too expensive and sits on the shelf.
...it should be clear that any treatment recommendations8 integrated within the FRAX® tool have not been evaluated by WHO's Guidelines Review Committee and should not be construed as WHO-endorsed ...recommendations. Since 2008, recommendations issued by WHO are done so in strict compliance with the process described in the WHO Handbook for Guideline Development.9 Recommendations are based on systematic reviews of evidence, formal assessments of the certainty of the balance of benefits and harms of an intervention, and explicit consideration of factors such as feasibility, effect on equity, cost and the preferences of persons affected by the recommendations.
High costs and risks of research and development (R&D) have been used to justify the high prices of cancer drugs. However, what the return on R&D investment is, and by extension what a justifiable ...price might be, is unclear.
To compare incomes from the sales of cancer drugs with the estimated R&D costs.
This observational study used global pharmaceutical industry sales data to quantify the cumulative incomes generated from the sales of cancer drugs for companies that have held patents or marketing rights (originator companies). All cancer drugs approved by the US Food and Drug Administration from 1989 to 2017 were identified from the United States Food and Drug Administration's website and literature. Itemized product sales data were extracted from the originator companies' consolidated financial reports. For drugs with data missing in specific years, additional data was sought from other public sources, or where necessary, estimated values from known reported values. Drugs were excluded if there were missing data for half or more of the years since approval. Data analysis was conducted from May 2018 to October 2018.
Sales data were expressed in 2017 US dollars with adjustments for inflation. Cumulative incomes from the sales of these drugs were compared against the R&D costs estimated in the literature, which had been adjusted for the costs of capital and trial failure (risk adjusted).
Of the 156 US Food and Drug Administration-approved cancer drugs identified, 99 drugs (63.5%) had data for more than half of the years since approval and were included in the analysis. There was a median of 10 years (range, 1-28 years) of sales data with 1040 data points, 79 (7.6%) of which were estimated. Compared with the total risk-adjusted R&D cost of $794 million (range, $2827-$219 million) per medicine estimated in the literature, by the end of 2017, the median cumulative sales income was $14.50 (range, $3.30-$55.10) per dollar invested for R&D. Median time to fully recover the maximum possible risk-adjusted cost of R&D ($2827 million) was 5 years (range, 2-10 years; n = 56). Cancer drugs continued to generate billion-dollar returns for the originator companies after the end-of-market exclusivity, particularly for biologics.
Cancer drugs, through high prices, have generated returns for the originator companies far in excess of possible R&D costs. Lowering prices of cancer drugs and facilitating greater competition are essential for improving patient access, health system's financial sustainability, and future innovation.
Summary
Purpose: In low‐ and middle‐income countries (LMICs), a large proportion of people with epilepsy do not receive treatment. An analysis of the availability, price, and affordability of ...antiepileptic drugs (AEDs) was conducted to evaluate whether these factors contribute to the treatment gap.
Methods: Data for five AEDs (phenytoin, carbamazepine, valproic acid, phenobarbital, and diazepam) were obtained from facility‐based surveys conducted in 46 countries using the World Health Organization/Health Action International (WHO/HAI) methodology. Outcome measures were percentage availability, ratios of local prices to international reference prices, and number of days’ wages needed by the lowest‐paid unskilled government worker to purchase treatment. Prices were adjusted for inflation/deflation and purchasing power parity.
Key Findings: The average availability of generic AEDs in the public sector was <50% for all medicines except diazepam injection. Private sector availability of generic oral AEDs ranged from 42.2% for phenytoin to 69.6% for phenobarbital. Public sector patient prices for generic carbamazepine and phenytoin were 4.95 and 17.50 times higher than international reference prices, respectively, whereas private sector patient prices were 11.27 and 24.77 times higher, respectively. For both medicines, originator brand prices were about 30 times higher. The highest prices were observed in the lowest income countries. The lowest‐paid government worker would need wages from 1–2.6 days’ to purchase a month’s supply of phenytoin, whereas carbamazepine would cost 2.7–16.2 days’ wages. Despite its widespread use in LMICs, WHO/HAI survey data for phenobarbital was only available from a small number of countries.
Significance: In LMICs, availability and affordability of AEDs are poor and may be acting as a barrier to accessing treatment for epilepsy. Ensuring a consistent supply of AEDs at an affordable price should be a priority.
In a climate of economic uncertainty, cost effectiveness analysis is a potentially important tool for making choices about health care interventions. Methods for such analyses are well established, ...but the results need to be interpreted carefully and are subject to bias. Making decisions based on results of cost-effectiveness analyses can involve setting thresholds, but for individual patients, there needs to be disaggregation of benefits and harms included in a quality adjusted life year to ensure appropriate consideration of benefits and harms as well as personal preferences and circumstances.
The increasing emergence and spread of antimicrobial resistance is jeopardising the effectiveness of existing antibiotics.1 Since the golden age of antibiotic discovery in the 1950s and 1960s, few ...innovative antibiotics have been developed due to the scientific challenges and limited investment.2 Increasing antimicrobial resistance globally and inadequate development of new antibacterial treatments are threatening the achievement of universal health coverage (UHC) and the Sustainable Development Goals (SDGs).3 There have been intense discussions on these issues at the UN General Assembly, the World Health Assembly, the G7, the G20, the World Economic Forum, and other venues. ...as part of the blueprint, WHO is systematically drafting research and development roadmaps using a standardised methodology to identify critical research and product development needs. All these activities will form part of the future Global Development and Stewardship Framework to combat antimicrobial resistance that WHO, the Food and Agriculture Organization of the United Nations, and the World Organisation for Animal Health (OIE) are developing in line with the mandate provided by the UN High Level Declaration on Antimicrobial Resistance.12 This work will also inform work of the Ad-Hoc Interagency Coordination Group on Antimicrobial Resistance which will report back to the UN General Assembly in 2019 on how to ensure sustained effective global action to address antimicrobial resistance.
The phytohormone abscisic acid (ABA) regulates various physiological processes in plants. The molecular mechanisms by which this is achieved are not fully understood. Genetic approaches have ...characterized several downstream components of ABA signalling, but a receptor for ABA has remained elusive. Although studies indicate that several ABA response genes encode RNA-binding or RNA-processing proteins, none has been found to be functional in binding ABA. Here we show that FCA, an RNA-binding protein involved in flowering, binds ABA with high affinity in an interaction that is stereospecific and follows receptor kinetics. The interaction between FCA and ABA has molecular effects on downstream events in the autonomous floral pathway and, consequently, on the ability of the plant to undergo transition to flowering. We further show that ABA binding exerts a direct control on the FCA-mediated processing of precursor messenger RNA. Our results indicate that FCA is an ABA receptor involved in RNA metabolism and in controlling flowering time.
The duration and cost of cancer clinical trials could be reduced if a surrogate endpoint were used in place of survival. We did a meta-analysis to assess the extent to which two surrogates, tumour ...response and time to progression, are predictive of mortality in metastatic colorectal cancer and non-small-cell lung cancer.
Summary data (median time to progression, proportion of patients responding to treatment, and median overall survival) from randomised trials of first-line treatment in colorectal cancer (146 trials) and lung cancer (191 trials) were identified. Data were extracted and analysed by linear regression. We used prediction bands for trials with 250, 500, and 750 patients to identify the surrogate threshold effect that would predict a significant difference in survival.
Response to treatment and time to progression correlated with improvement in survival for both lung cancer (p<0·0001 and p=0·0003, respectively) and colorectal cancer (p<0·0001 for both). To predict a significant survival gain in colorectal cancer trials, an improvement of 20% in the number of patients responding to treatment was required in trials with 750 patients, increasing to 26% in trials with 500 patients and 38% in trials with 250 patients. In lung cancer trials, the same prediction required differences in response of 18% for 750 patients, 21% for 500 patients, and 30% for 250 patients. For time to progression for both cancer types, the incremental gain needed to predict a survival improvement was a median of 1·8 months for trials with 750 patients, 2·2 months for 500 patients, and 3·3 months for 250 patients.
Irrespective of trial size, large differences in tumour response rate are needed to predict a significant survival benefit. If surrogates are chosen as the primary endpoint in a clinical trial, time to progression is the preferred measure because more modest and achievable differences are needed for a significant survival benefit. Trials in metastatic lung cancer and colorectal cancer should measure survival as their primary outcome unless the surrogate outcome difference is anticipated to exceed the threshold effect size.
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