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The development of resistance by organisms to antimicrobials is a natural phenomenon. Although it is increased by the use of antimicrobials, reduction in use of them will not necessarily reduce resistance, and there is a possibility that eventually most, if not all, antimicrobials will become largely ineffective. However, current estimates of the economic burden are modest – at anything from less than £5 to more than £20,000 in reported additional costs per patient per episode for hospital costs, and anything up to around £10 billion per year in societal costs, they are far lower than estimates of economic burden from other health problems, such as cancers, heart disease and mental disorders. The reason that current estimates of the cost of resistance are modest is that they are based loosely on the 'incremental' cost related to the extra treatment of resistant over susceptible primary infection. This masks the most critical economic burden, which is when resistance leads to the loss of many of the advantages in medical care that antimicrobials have enabled. For instance, advanced surgical procedures and cancer chemotherapy might become far more dangerous as rates of associated infection increase and cannot be treated. The effective 'removal' of antimicrobials could mean soaring rates of post-operative infection, mortality and morbidity from what are currently considered to be trivial infections, presenting an apocalyptic blow to health system development. The full economic burden of this is not only inestimable at present, but unimaginable. It is therefore urgent that a full system analysis of resistance is undertaken. Rather than continuing the focus solely on the additional cost of treating an infectious disease in the presence of resistance, what is needed now is to look at how health services more broadly might be affected if resistance becomes endemic, and the wider implications of this to society. Incentive mechanisms also need to be developed at a number of levels, and could require radical change, such as moving to more restrictive prescription (for example, through a hospital setting only, removing the ability to prescribe from primary and community care). Clearly the necessity of, and ability to implement, such radical change will need to be informed by the system analysis, and also supported by it when it comes to engaging the wider political and popular support that would be required. In needing to consider a system approach, resistance shares many of the characteristics of climate change. Both provide future significant threats to human well-being, both are subject to considerable uncertainty about their future extent and trajectory, both are global problems where the response differs across nations, and both have as an underlying cause the over-consumption of 'goods' that lead to short term benefit. Yet for both there is considerable inertia to major, radical, change because there is a focus on current burden and because the personal incentives seldom match those of society more generally. However, there appears to be increasing scientific consensus about the impact of global warming in a way that is perhaps less clear – or at least less coherent – for antimicrobial resistance. For global warming this has led to clear, simple and consistent messages from the scientific community, underpinning increasing acceptance of the desirability of action by a broader policy-making community including politicians, economists and philanthropists. For antimicrobial resistance there is a clear danger that waiting for the burden to become significant before taking action may mean waiting until it is too late to stop an apocalyptic scenario – the very drive behind the early environmental movement's advocacy of the 'precautionary principle'.

BACKGROUND: Food tax-subsidy policies are proposed to hold promise for helping to produce healthier patterns of food purchasing and consumption at population level. Evidence for their effects derives largely from simulation studies that explore the potential effects of untried policies using a mathematical modelling framework. This paper provides a critique first of the nature of the evidence derived from such simulation studies, and second of the challenges of cumulating that evidence to inform public health policy. DISCUSSION: Effects estimated by simulation studies of food taxes and subsidies can be expected to diverge in potentially important ways from those that would accrue in practice because these models are simplified, typically static, representations of complex adaptive systems. The level of confidence that can be placed in modelled estimates of effects is correspondingly low, and the level of associated uncertainty is high. Moreover, evidence from food tax-subsidy simulation studies cannot meaningfully be cumulated using currently available quantitative evidence synthesis methods, to reduce uncertainty about effects. Simulation studies are critical for the initial phases of an incremental research process, for drawing together diverse evidence and exploring potential longer-term effects. While simulation studies of food taxes and subsidies provide a valuable and necessary input to the formulation of public health policy in this area, they are unlikely to be sufficient, and policy makers should not place excessive reliance on evidence from such studies, either singly or cumulatively. To reflect known and unknown limitations of the models, results of such studies should be interpreted cautiously as tentative projections. Modelling studies should increasingly be integrated with more empirical studies of the effects of food tax and subsidy policies in practice.

This is the final version. Available on open access from Elsevier via the DOI in this record. ; We estimate the potential impact of COVID-19 on the United Kingdom economy, including direct disease effects, preventive public actions and associated policies. A sectoral, whole-economy macroeconomic model was linked to a population-wide epidemiological demographic model to assess the potential macroeconomic impact of COVID-19, together with policies to mitigate or suppress the pandemic by means of home quarantine, school closures, social distancing and accompanying business closures. Our simulations indicate that, assuming a clinical attack rate of 48% and a case fatality ratio of 1.5%, COVID-19 alone would impose a direct health-related economic burden of £39.6bn (1.73% of GDP) on the UK economy. Mitigation strategies imposed for 12 weeks reduce case fatalities by 29%, but the total cost to the economy is £308bn (13.5% of GDP); £66bn (2.9% of GDP) of which is attributable to labour lost from working parents during school closures, and £201bn (8.8% of GDP) of which is attributable to business closures. Suppressing the pandemic over a longer period of time may reduce deaths by 95%, but the total cost to the UK economy also increases to £668bn (29.2% of GDP), where £166bn (7.3% of GDP) is attributable to school closures and 502bn (21.9% of GDP) to business closures. Our analyses suggest Covid-19 has the potential to impose unprecedented economic costs on the UK economy, and whilst public actions are necessary to minimise mortality, the duration of school and business closures are key to determining the economic cost. The initial economic support package promised by the UK government may be proportionate to the costs of mitigating Covid-19, but without alternative measures to reduce the scale and duration of school and business closures, the economic support may be insufficient to compensate for longer term suppression of the pandemic which could generate an even greater health impact through major recession. ; EU Horizon 2020

This is the final version. Available on open access from National Academy of Sciences via the DOI in this record ; Policymaking during a pandemic can be extremely challenging. As COVID-19 is a new disease and its global impacts are unprecedented, decisions are taken in a highly uncertain, complex, and rapidly changing environment. In such a context, in which human lives and the economy are at stake, we argue that using ideas and constructs from modern decision theory, even informally, will make policymaking a more responsible and transparent process. ; Alfred P. Sloan Foundation ; Bocconi University ; European Union FP7 ; European Union Horizon 2020 ; Agence Nationale de la Recherche ; Foerder Institute at Tel-Aviv University ; Israel Science Foundation