The COVID‐19 pandemic has driven an unprecedented level of global activity in drug discovery and clinical development for effective therapeutics targeting the coronavirus disease. There are currently 744 therapeutics being tested in 2879 clinical trials globally. Almost 90% of these clinical trials are focused on monotherapies. Combination therapies are the mainstay of antiviral therapeutics to increase the potency of the individual compounds and to combat the rapid evolution of resistance, although combination therapies have inherently complex clinical and regulatory development challenges. Increased understanding of the SARS‐CoV‐2 lifecycle and COVID‐19 pathology provides a scientific rationale for evaluating the effectiveness of different combinations. In this paper, we provide an overview of the current clinical trial landscape for combination therapeutics targeting COVID‐19 through weekly scanning of national and international clinical trial registries. Our analysis delves specifically into dual combination therapies in what can be defined as “pivotal clinical trials” (active, randomised, controlled and at least phase II), with a focus on new and repurposed therapeutic candidates that have shown positive signals and/or been granted authorisation for emergency use based on positive efficacy and safety data.
This paper provides a longitudinal examination of local inequalities in health behaviours during a period of austerity, exploring the role of ‘place’ in explaining these inequalities. Data from the Stockton-on-Tees prospective cohort study of 836 individuals were analysed and followed over 18 months (37% follow-up). Generalised estimating equation models estimated the deprivation gap in health behaviours (smoking status, alcohol use, fruit and vegetable consumption and physical activity practices) between the 20% most- and least-deprived neighborhoods (LSOAs), explored any temporal changes during austerity, and examined the underpinning role of compositional and contextual determinants. All health behaviours, except for frequent physical activity, varied significantly by deprivation (p ≤ 0.001). Smoking was lower in the least-deprived areas (OR 0.21, CI 0.14 to 0.30), while alcohol use (OR 2.75, CI 1.98 to 3.82) and fruit and vegetable consumption (OR 2.55, CI 1.80 to 3.62) were higher in the least-deprived areas. The inequalities were relatively stable throughout the study period. Material factors (such as employment, education and housing tenure) were the most-important and environmental factors the least-important explanatory factors. This study suggests that material factors are the most important ‘place’ determinants of health behaviours. Health promotion activities should better reflect these drivers.
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