Mathematical modelling of respiratory syncytial virus (RSV) in low- and middle-income countries: A systematic review.

BACKGROUND: Due to high burden of respiratory syncytial virus (RSV) in low- and middle-income countries (LMIC), international funding organizations have prioritized the development of RSV vaccines. Mathematical models of RSV will play an important role in assessing the relative value of these interventions. Our objectives were to provide an overview of the existing RSV modelling literature in LMIC and summarize available results on population-level effectiveness and cost-effectiveness. METHODS: We searched MEDLINE from 2000 to 2020 for English language publications that employed a mathematical model of RSV calibrated to LMIC. Qualitative data were extracted on study and model characteristics. Quantitative data were collected on key model input assumptions and base case effectiveness and cost-effectiveness estimates for various immunization strategies. FINDINGS: Of the 283 articles reviewed, 15 met inclusion criteria. Ten studies used modelling techniques to explore RSV transmission and/or natural history, while eight studies evaluated RSV vaccines and/or monoclonal antibodies, three of which included cost-effectiveness analyses. Six studies employed deterministic compartmental models, five studies employed individual transmission models, and four studies used different types of cohort models. Nearly every model was calibrated to at least one middle-income country, while four were calibrated to low-income countries. INTERPRETATION: The mathematical modelling literature in LMIC has demonstrated the potential effectiveness of RSV vaccines and monoclonal antibodies. This review has demonstrated the importance of accounting for seasonality, social contact rates, immunity from prior infection and maternal antibody transfer. Future models should consider incorporating individual-level risk factors, subtype-specific effects, long-term sequelae of RSV infections, and out-of-hospital mortality.

Incentivising innovation in antibiotic drug discovery and development: progress, challenges and next steps.

Political momentum and funding for combatting antimicrobial resistance (AMR) continues to build. Numerous major international and national initiatives aimed at financially incentivising the research and development (R&D) of antibiotics have been implemented. However, it remains unclear how to effectively strengthen the current set of incentive programmes to further accelerate antibiotic innovation. Based on a literature review and expert input, this study first identifies and assesses the major international, European Union, US and UK antibiotic R&D funding programmes. These programmes are then evaluated across market and public health criteria necessary for comprehensively improving the antibiotic market. The current set of incentive programmes are an important initial step to improving the economic feasibility of antibiotic development. However, there appears to be a lack of global coordination across all initiatives, which risks duplicating efforts, leaving funding gaps in the value chain and overlooking important AMR goals. This study finds that incentive programmes are overly committed to early-stage push funding of basic science and preclinical research, while there is limited late-stage push funding of clinical development. Moreover, there are almost no pull incentives to facilitate transition of antibiotic products from early clinical phases to commercialisation, focus developer concentration on the highest priority antibiotics and attract large pharmaceutical companies to invest in the market. Finally, it seems that antibiotic sustainability and patient access requirements are poorly integrated into the array of incentive mechanisms.

Crowdfunding our health: Economic risks and benefits.

Crowdfunding is an expanding form of alternative financing that is gaining traction in the health sector. This article presents a typology for crowdfunded health projects and a review of the main economic benefits and risks of crowdfunding in the health market. We use evidence from a literature review, complimented by expert interviews, to extend the fundamental principles and established theories of crowdfunding to a health market context. Crowdfunded health projects can be classified into four types according to the venture's purpose and funding method. These are projects covering health expenses, fundraising health initiatives, supporting health research, or financing commercial health innovation. Crowdfunding could economically benefit the health sector by expanding market participation, drawing money and awareness to neglected health issues, improving access to funding, and fostering project accountability and social engagement. However, the economic risks of health-related crowdfunding include inefficient priority setting, heightened financial risk, inconsistent regulatory policies, intellectual property rights concerns, and fraud. Theorized crowdfunding behaviours such as signalling and herding can be observed in the market for health-related crowdfunding. Broader threats of market failure stemming from adverse selection and moral hazard also apply. Many of the discussed economic benefits and risks of crowdfunding health campaigns are shared more broadly with those of crowdfunding projects in other sectors. Where crowdfunding health care appears to diverge from theory is the negative externality inefficient priority setting may have towards achieving broader public health goals. Therefore, the market for crowdfunding health care must be economically stable, as well as designed to optimally and equitably improve public health.

Structural equation model for estimating risk factors in type 2 diabetes mellitus in a Middle Eastern setting: evidence from the STEPS Qatar.

AIMS: Understanding type 2 diabetes mellitus is critical for designing effective diabetes prevention policies in Qatar and the Middle East. METHODS: Using the Qatar 2012 WHO STEPwise approach to surveillance survey, a subsample of 1224 Qatari participants aged 18-64 years was selected. Subjects had their fasting blood glucose levels tested, had not been diagnosed with or treated for diabetes, had a fasting time >12 hours and were not pregnant. We applied a hypothesized structural equation model (SEM) to assess sociodemographic, behavioral, anthropometric and metabolic variables affecting persons with type 2 diabetes mellitus. RESULTS: There is a direct effect of triglyceride levels (0.336) and body mass index (BMI) (0.164) on diabetes status. We also found that physical activity levels negatively affect BMI (-0.148) and positively affect high-density lipoprotein (HDL) (0.106); sociodemographic background negatively affects diet (-0.522) and BMI (-0.352); HDL positively affects total cholesterol (0.230) and has a negative effect on BMI (-0.108), triglycerides (-0.128) and waist circumference (-0.104). Diet has a positive effect on triglycerides (0.281) while family history of diabetes negatively affects total cholesterol (-0.104). BMI has a positive effect on waist circumference (0.788) and mediates the effects of physical activity over diabetes status (-0.028). BMI also mediates the effects that sociodemographic factors (-0.058) and physical activity (-0.024) have on diabetes status. BMI and HDL (-0.002) together mediate the effect of physical activity on diabetes status and similarly HDL and tryglycerides (-0.005) also mediate the effect of physical activity on diabetes status. Finally diet and tryglycerides mediate the effects that sociodemographic factors have on diabetes status (-0.049). CONCLUSIONS: This study's main finding is that triglyceride levels and BMI are the main variables directly affecting diabetes status in the Qatari population.

Postmarket policy considerations for biosimilar oncology drugs.

Oncology biological products are some of the most expensive drugs on the market and are a growing financial burden on patients and health-care systems. By 2020, numerous major biological cancer drugs will lose their patent protection allowing follow-on competitors, known as biosimilars, to enter the market. Clinical and regulatory considerations for biosimilars have begun to harmonise in Europe and the USA to help to define and streamline the pathway for biosimilar market authorisation. Yet, substantial international variation still exists in the pricing and market uptake of approved biosimilar oncology drugs. Differences in national postmarket policies for biosimilars might explain these disparities in pricing and uptake. In this Policy Review, policy approaches to competition between biosimilars and originators used by seven European countries--Belgium, France, Germany, Italy, the Netherlands, Norway, and the UK--and the USA are discussed, chosen because these countries represent a variety of postmarket policies and build on conclusions from previous work. We discuss these policies within the context of interchangeability, physician prescribing, substitutability, pharmacist dispensing, hospital financing and tendering, and pricing.

A systematic review and critical assessment of incentive strategies for discovery and development of novel antibiotics.

Despite the growing threat of antimicrobial resistance, pharmaceutical and biotechnology firms are reluctant to develop novel antibiotics because of a host of market failures. This problem is complicated by public health goals that demand antibiotic conservation and equitable patient access. Thus, an innovative incentive strategy is needed to encourage sustainable investment in antibiotics. This systematic review consolidates, classifies and critically assesses a total of 47 proposed incentives. Given the large number of possible strategies, a decision framework is presented to assist with the selection of incentives. This framework focuses on addressing market failures that result in limited investment, public health priorities regarding antibiotic stewardship and patient access, and implementation constraints and operational realities. The flexible nature of this framework allows policy makers to tailor an antibiotic incentive package that suits a country's health system structure and needs.

Targeting innovation in antibiotic drug discovery and development: the need for a One Health – One Europe – One World Framework

Antimicrobial resistance is a global crisis that threatens public health and modern medicine. The discovery and development of novel antibiotic products are critical components in combating it. Many international, European Union and national initiatives address the scientific, regulatory and economic barriers to antibiotic innovation. This study identifies, reviews and critically assesses these initiatives, and provides policy recommendations for improving the global and European agendas for research and development of antibiotics.