The GeneXpert diagnostic platform from the US based company Cepheid is an automated molecular diagnostic device that performs sample preparation and pathogen detection within a single cartridge-based ...assay. GeneXpert devices can enable diagnosis at the district level without the need for fully equipped clinical laboratories, are simple to use, and offer rapid results. Due to these characteristics, the platform is now widely used in low- and middle-income countries for diagnosis of diseases such as TB and HIV. Assays for SARS-CoV-2 are also being rolled out. We aimed to quantify public sector investments in the development of the GeneXpert platform and Cepheid's suite of cartridge-based assays. Public funding data were collected from the proprietor company's financial filings, grant databases, review of historical literature concerning key laboratories and researchers, and contacting key public sector entities involved in the technology's development. The value of research and development (R&D) tax credits was estimated based on financial filings. Total public investments in the development of the GeneXpert technology were estimated to be $252 million, including >$11 million in funding for work in public laboratories leading to the first commercial product, $56 million in grants from the National Institutes of Health, $73 million from other U.S. government departments, $67 million in R&D tax credits, $38 million in funding from non-profit and philanthropic organizations, and $9.6 million in small business 'springboard' grants. The public sector has invested over $250 million in the development of both the underlying technologies and the GeneXpert diagnostic platform and assays, and has made additional investments in rolling out the technology in countries with high burdens of TB. The key role played by the public sector in R&D and roll-out stands in contrast to the lack of public sector ability to secure affordable pricing and maintenance agreements.
In 2012, bedaquiline became the first new treatment from a novel class to be approved for tuberculosis in nearly five decades and is now a core component of the standard of care for ...multidrug-resistant tuberculosis. In addition to the originator pharmaceutical company, Janssen, a range of governmental and non-profit entities have contributed to the development of bedaquiline. We identified various avenues of public investments in the development of bedaquiline: direct funding of clinical trials and a donation programme, tax credits and deductions, and revenues resulting from the priority review voucher (PRV) awarded to the originator. Data on investments were gathered through contact with study leads and/or funders; for non-responses, published average costs were substituted. The originator company's expenses were estimated by similar methods. Tax credits and deductions were calculated based on estimated originator trial costs and donation expenses. The value of the PRV was estimated by application of a published model. Public contributions through clinical trials funding were estimated at US$109-252 million, tax credits at US$22-36 million, tax deductions at US$8-27 million, administration of a donation programme at US$5 million, PRV revenues at US$300-400 million. Total public investments were US$455-747 million and originator investments were US$90-240 million (if capitalized and risk-adjusted, US$647-1,201 million and US$292-772 million, respectively). Estimating the investments in the development of a medicine can inform discussions regarding fair pricing and future drug development. We estimated that total public investments exceeded the originator's by a factor of 1.6-5.1.
Biologic drugs are notoriously expensive. Biosimilars, though priced lower, are also costly. Analysis of the cost of production of biologics suggests that the cost of manufacture is in many cases ...less than 10% of the price in high-income countries, and less than a third of the price of biosimilars in India. This in turn implies that the relatively high prices of biosimilars are largely due to the need to undertake laborious reverse-engineering and phase 3 trials to demonstrate clinical similarity. In this article, it is proposed that originators could be required to submit cell line stocks to regulators and disclose details of manufacturing processes. These would be shared with prospective non-originator manufacturers to greatly reduce the investments needed to bring a non-originator biologic to market. This system would allow far greater price reductions for biologics after the expiry of monopoly rights (e.g. patents), while maintaining the monopoly rights used to incentivize drug development.
Access to medicines is a global priority. Azerbaijan, Georgia, and Uzbekistan have different approaches to pricing policies for pharmaceuticals. The aim of this study was to analyze recent trends in ...the consumption and prices of non-communicable disease (NCD) medicines in Azerbaijan, Georgia, and Uzbekistan, in the outpatient setting.
We included medicines for asthma and COPD, cancer, cardiovascular disease, diabetes, epilepsy, and mental disorders. Sales data for pharmaceutical products in community pharmacies were extracted from a commercial database. Changes in consumption and prices were analyzed across all included NCD medicines, by disease category and pharmacological group.
Consumption of NCD medicines was highest in Georgia, at twice the levels in Azerbaijan, and four times levels in Uzbekistan. Average prices of NCD medicines, weighted by consumption, increased by 26% in Georgia, but decreased by 3% in Azerbaijan and by 0.1% in Uzbekistan. Prices increased for all disease groups in Georgia (from +13% for epilepsy medicines to +86% for cancer), varied by group in Uzbekistan (from -22% for epilepsy medicines to +47% for cancer), while changes in Azerbaijan were smaller in magnitude (from -4% for medicines for cardiovascular disease to +11% for cancer). Cancer medicines had markedly higher prices in Uzbekistan, and asthma and COPD medicines had markedly higher prices in Azerbaijan and Uzbekistan.
Georgia showed the highest outpatient consumption of NCD medicines, suggesting the broadest access to treatment. However, Georgia also saw marked price increases, greater than in the other countries. In Georgia, where there was no price regulation, widespread price increases and increases in consumption both contribute to increasing pharmaceutical expenditures. In Azerbaijan and Uzbekistan, increases in outpatient pharmaceutical expenditures were primarily driven by increases in consumption, rather than increases in price. Comparing trends in consumption and pricing can identify gaps in access and inform future policy approaches.
Higher plasma tenofovir concentrations are associated with higher risks of renal and bone adverse events. The pharmacokinetic boosters ritonavir (RTV) and cobicistat (COBI) significantly increase ...plasma area under the curve (AUC) concentrations of tenofovir disoproxil fumarate (TDF), by 25-37%. When combined with RTV or COBI, the dose of tenofovir alafenamide (TAF) is lowered from 25 mg to 10 mg daily, but the TDF dose is maintained at 300 mg daily.
To assess the differences in safety and efficacy between tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) in regimens with and without the pharmacokinetic boosters RTV and COBI.
A PubMed/Embase search inclusive of dates up to 17 July 2017 identified 11 randomised head-to-head trials (8111 patients) of TDF versus TAF. The Mantel-Haenszel method was used to calculate pooled risk differences and 95% confidence intervals using random-effects models. A pre-defined sub-group analysis compared TAF with TDF, either when boosted with RTV or COBI, or when unboosted.
Nine clinical trials compared TAF and TDF for treatment of HIV-1 and two were for hepatitis B treatment. The eleven clinical trials documented 4574 patients with boosting RTV or COBI in both arms, covering 7198 patient-years of follow-up. Some 3537 patients received unboosted regimens, totalling 3595 patient-years of follow-up. Boosted TDF-treated patients showed borderline lower HIV RNA suppression <50 copies/mL (
=0.05), more bone fractures (
=0.04), larger decreases in bone mineral density (
<0.001), and more discontinuations for bone (
=0.03) or renal (
=0.002) adverse events. By contrast, there were no significant differences in HIV RNA suppression rates or clinical safety endpoints between unboosted TAF and unboosted TDF.
TDF boosted with RTV or COBI was associated with higher risks of bone and renal adverse events, and lower HIV RNA suppression rates, compared with TAF. By contrast, when ritonavir and cobicistat were not used, there were no efficacy differences between TAF and TDF, and marginal differences in safety. The health economic value of TAF versus low-cost generic TDF may be limited when these drugs are used without cobicistat or ritonavir.
Seven years after the introduction of direct-acting antivirals (DAAs) for the treatment of hepatitis C, high prices remain a barrier for treatment programs worldwide. This study seeks to describe ...current prices for originator DAAs in 50 countries and evaluate the relationship between prices and GDP per capita.
Data on prices of sofosbuvir, daclatasvir, sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir were collected from national databases for 50 countries. Cost-based generic prices were estimated using an established algorithm, which accounts for costs of the active pharmaceutical ingredient (API), excipients, conversion costs of API to finished pharmaceutical product, taxes assuming manufacture in India, and a 10% profit margin. Correlation between current market prices and GDP per capita was assessed by Spearman rank-order correlation.
Median originator prices per standard course were US$40,502 for sofosbuvir, US$26,928 for daclatasvir, US$46,812 for sofosbuvir/ledipasvir, US$34,381 for sofosbuvir/velpatasvir, and US$30,710 for glecaprevir/pibrentasvir (G/P). The estimated cost-based generic prices for a 12-week course were US$28 for sofosbuvir, US$31 for ledipasvir, US$58 for velpatasvir, US$4 for daclatasvir. For fixed-dose combinations, estimated cost-based prices were US$58 for sofosbuvir/ledipasvir, US$85 for sofosbuvir/velpatasvir, and US$31 for sofosbuvir/daclatasvir (API cost data were insufficient to calculate an estimate for G/P). Cumulative originator sales of WHO-recommended DAAs reached US$82 billion by the end of 2019. Across the 50 countries, there was no correlation between GDP per capita and DAA price, nor between estimated viraemic population and DAA price. Sub-analyses within World Bank income groups found a significant negative correlation between price and GDP per capita for all DAAs within the high-income countries group.
Prices of DAAs vary widely across countries. The lack of correlation between DAA price and GDP per capita and viraemic population suggests that prices for DAAs are not adjusted based on country income level or potential patient population. Among high-income countries, DAA prices fall as income levels rise, possibly due to greater negotiating power of wealthier countries. DAA prices in most countries remain many times higher than estimated cost-based generic prices.
Universities undertake the majority of publicly funded research in Germany and hence bear a responsibility to contribute to global health efforts. So far, involvement and impact of German medical ...faculties in global health are unknown. Our aim was to systematically asses and evaluate German medical faculties' contribution to global health related research and education, as well as their policies and practices concerning open access publishing and equitable licensing.
We assessed the involvement in global health of all 36 publicly funded medical faculties in Germany during 2010-2014 in three areas: innovation, access and education, using the following indicators: research funding and publications focused on global health or poverty-related and neglected diseases; open access publishing and policies promoting access to medical innovations worldwide; provision of global health education. Data were gathered from public databases, university websites and questionnaires sent to individual universities for validation and triangulation.
There was a high level of variability between institutions and indicators. The proportion of research funding for poverty-related and neglected diseases research ranged between 0.0-1.1%. The top five institutions received nearly 85% of the total poverty-related and neglected diseases research funding. 20 of 36 universities had an institutional open access publishing policy, 19 had an open access publishing fund, 16 had neither. Only one university reported having used an equitable licensing policy. 22 of 36 faculties provided some global health education, but only one of them included global health in their core undergraduate medical curriculum as a compulsory course with more than just single lectures.
Obtained data indicate that global health and poverty-related and neglected diseases research at German medical faculties is highly concentrated in a few institutions, open-access publishing and equitable licensing policies are mostly absent, and only little global health education exists. Universities and government should address global health strategically in both research and education at medical faculties to reflect the country's economic and political weight and human resource potential.
BackgroundThe major shifts in the global burden of disease over the past decades are well documented, but how these shifts have affected global inequalities in health remains an underexplored topic. ...We applied comprehensive inequality measures to data from the Global Burden of Disease (GBD) study.MethodsBetween-country relative inequality was measured by the population-weighted Gini Index, between-country absolute inequality was calculated using the population-weighted Slope Inequality Index (SII). Both were applied to country-level GBD data on age-standardised disability-adjusted life years.FindingsAbsolute global health inequality measured by the SII fell notably between 1990 (0.68) and 2017 (0.42), mainly driven by a decrease of disease burden due to communicable, maternal, neonatal and nutritional diseases (CMNN). By contrast, relative inequality remained essentially unchanged from 0.21 to 0.19 (1990–2017), with a peak of 0.23 (2000–2008). The main driver for the increase of relative inequality 1990–2008 was the HIV epidemic in Sub-Saharan Africa. Relative inequality increased 1990–2017 within each of the three main cause groups: CMNNs; non-communicable diseases (NCDs); and injuries.ConclusionsDespite considerable reductions in disease burden in 1990–2017 and absolute health inequality between countries, absolute and relative international health inequality remain high. The limited reduction of relative inequality has been largely due to shifts in disease burden from CMNNs and injuries to NCDs. If progress in the reduction of health inequalities is to be sustained beyond the global epidemiological transition, the fight against CMNNs and injuries must be joined by increased efforts for NCDs.
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