Summary Recent years have seen substantial improvements in life expectancy and access to antimicrobials, especially in low-income and lower-middle-income countries, but increasing pathogen resistance ...to antimicrobials threatens to roll back this progress. Resistant organisms in health-care and community settings pose a threat to survival rates from serious infections, including neonatal sepsis and health-care-associated infections, and limit the potential health benefits from surgeries, transplants, and cancer treatment. The challenge of simultaneously expanding appropriate access to antimicrobials, while restricting inappropriate access, particularly to expensive, newer generation antimicrobials, is unique in global health and requires new approaches to financing and delivering health care and a one-health perspective on the connections between pathogen transmission in animals and humans. Here, we describe the importance of effective antimicrobials. We assess the disease burden caused by limited access to antimicrobials, attributable to resistance to antimicrobials, and the potential effect of vaccines in restricting the need for antibiotics.
Abstract Quasi-experimental studies are increasingly used to establish causal relationships in epidemiology and health systems research. Quasi-experimental studies offer important opportunities to ...increase and improve evidence on causal effects: (i) they can generate causal evidence when randomized controlled trials are impossible; (ii) they typically generate causal evidence with a high degree of external validity; (iii) they avoid the threats to internal validity that arise when participants in non-blinded experiments change their behavior in response to the experimental assignment to either intervention or control arm (such as compensatory rivalry or resentful demoralization); (iv) they are often well-suited to generate causal evidence on long-term health outcomes of an intervention, as well as non-health outcomes such as economic and social consequences; and (v) they can often generate evidence faster and at lower cost than experiments and other intervention studies.
The objective of this study was to contrast the historical development of experiments and quasi-experiments and provide the motivation for a journal series on quasi-experimental designs in health ...research.
A short historical narrative, with concrete examples, and arguments based on an understanding of the practice of health research and evidence synthesis.
Health research has played a key role in developing today's gold standard for causal inference—the randomized controlled multiply blinded trial. Historically, allocation approaches developed from convenience and purposive allocation to alternate and, finally, to random allocation. This development was motivated both by concerns for manipulation in allocation as well as statistical and theoretical developments demonstrating the power of randomization in creating counterfactuals for causal inference. In contrast to the sequential development of experiments, quasi-experiments originated at very different points in time, from very different scientific perspectives, and with frequent and long interruptions in their methodological development. Health researchers have only recently started to recognize the value of quasi-experiments for generating novel insights on causal relationships.
While quasi-experiments are unlikely to replace experiments in generating the efficacy and safety evidence required for clinical guidelines and regulatory approval of medical technologies, quasi-experiments can play an important role in establishing the effectiveness of health care practice, programs, and policies. The papers in this series describe and discuss a range of important issues in utilizing quasi-experimental designs for primary research and quasi-experimental results for evidence synthesis.
Summary Diagnostics are crucial in mitigating the effect of disease outbreaks. Because diagnostic development and validation are time consuming, they should be carried out in anticipation of ...epidemics rather than in response to them. The diagnostic response to the 2014–15 Ebola epidemic, although ultimately effective, was slow and expensive. If a focused mechanism had existed with the technical and financial resources to drive its development ahead of the outbreak, point-of-care Ebola tests supporting a less costly and more mobile response could have been available early on in the diagnosis process. A new partnering model could drive rapid development of tests and surveillance strategies for novel pathogens that emerge in future outbreaks. We look at lessons learned from the Ebola outbreak and propose specific solutions to improve the speed of new assay development and ensure their effective deployment.
New Vaccines against Epidemic Infectious Diseases Røttingen, John-Arne; Gouglas, Dimitrios; Feinberg, Mark ...
The New England journal of medicine,
2017-Feb-16, Letnik:
376, Številka:
7
Journal Article
The need to align investments in health research and development (R&D) with public health demands is one of the most pressing global public health challenges. We aim to provide a comprehensive ...description of available data sources, propose a set of indicators for monitoring the global landscape of health R&D, and present a sample of country indicators on research inputs (investments), processes (clinical trials), and outputs (publications), based on data from international databases. Total global investments in health R&D (both public and private sector) in 2009 reached US$240 billion. Of the US$214 billion invested in high-income countries, 60% of health R&D investments came from the business sector, 30% from the public sector, and about 10% from other sources (including private non-profit organisations). Only about 1% of all health R&D investments were allocated to neglected diseases in 2010. Diseases of relevance to high-income countries were investigated in clinical trials seven-to-eight-times more often than were diseases whose burden lies mainly in low-income and middle-income countries. This report confirms that substantial gaps in the global landscape of health R&D remain, especially for and in low-income and middle-income countries. Too few investments are targeted towards the health needs of these countries. Better data are needed to improve priority setting and coordination for health R&D, ultimately to ensure that resources are allocated to diseases and regions where they are needed the most. The establishment of a global observatory on health R&D, which is being discussed at WHO, could address the absence of a comprehensive and sustainable mechanism for regular global monitoring of health R&D.
The Coalition for Epidemic Preparedness Innovations was established in 2016, to develop vaccines that can contribute to preparedness for outbreaks of epidemic infectious diseases. Evidence on vaccine ...development costs for such diseases is scarce. Our goal was to estimate the minimum cost for achieving vaccine research and development preparedness targets in a portfolio of 11 epidemic infectious diseases, accounting for vaccine pipeline constraints and uncertainty in research and development preparedness outcomes.
We assembled a pipeline of 224 vaccine candidates from preclinical through to phase 2 for 11 priority epidemic infectious diseases. We used a linear regression model to identify drivers of development costs from preclinical through to end of phase 2a. Drawing from published estimates of vaccine research and development probabilities of success, we simulated costs for advancing these 224 vaccine candidates through to the end of phase 2a. We combined these findings to determine minimum costs for progressing at least one vaccine through to the end of phase 2a per epidemic infectious disease by means of a stochastic optimisation model.
The cost of developing a single epidemic infectious disease vaccine from preclinical trials through to end of phase 2a is US$31–68 million (US$14–159 million range), assuming no risk of failure. We found that previous licensure experience and indirect costs are upward drivers of research and development costs. Accounting for probability of success, the average cost of successfully advancing at least one epidemic infectious disease vaccine through to the end of phase 2a can vary from US$84–112 million ($23 million–$295 million range) starting from phase 2 to $319–469 million ($137 million–$1·1 billion range) starting from preclinical. This cost includes the cumulative cost of failed vaccine candidates through the research and development process. Assuming these candidates and funding were made available, progressing at least one vaccine through to the end of phase 2a for each of the 11 epidemic infectious diseases would cost a minimum of $2·8–3·7 billion ($1·2 billion–$8·4 billion range).
Our analysis provides new evidence on vaccine research and development pipelines and associated costs for 11 epidemic infectious diseases, highlighting both funding needs and research and development gaps for achieving vaccine research and development preparedness targets.
This work was partly supported by the Research Council of Norway through the Global Health and Vaccination Programme GLOBVAC.
Summary Access to quality-assured antimicrobials is regarded as part of the human right to health, yet universal access is often undermined in low-income and middle-income countries. Lack of access ...to the instruments necessary to make the correct diagnosis and prescribe antimicrobials appropriately, in addition to weak health systems, heightens the challenge faced by prescribers. Evidence-based interventions in community and health-care settings can increase access to appropriately prescribed antimicrobials. The key global enablers of sustainable financing, governance, and leadership will be necessary to achieve access while preventing excess antimicrobial use.
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