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Background: Conducting clinical trials to assess experimental treatments for potentially pandemic infectious diseases is challenging. Since many outbreaks of infectious diseases last only six to eight weeks, there is a need for trial designs that can be implemented rapidly in the face of uncertainty. Outbreaks are sudden and unpredictable and so it is essential that as much planning as possible takes place in advance. Statistical aspects of such trial designs should be evaluated and discussed in readiness for implementation. Methodology/Principal findings: This paper proposes a generic ordinal sequential trial design (GOST) for a randomised clinical trial comparing an experimental treatment for an emerging infectious disease with standard care. The design is intended as an off-the-shelf, ready-to-use robust and flexible option. The primary endpoint is a categorisation of patient outcome according to an ordinal scale. A sequential approach is adopted, stopping as soon as it is clear that the experimental treatment has an advantage or that sufficient advantage is unlikely to be detected. The properties of the design are evaluated using large-sample theory and verified for moderate sized samples using simulation. The trial is powered to detect a generic clinically relevant difference: namely an odds ratio of 2 for better rather than worse outcomes. Total sample sizes (across both treatments) of between 150 and 300 patients prove to be adequate in many cases, but the precise value depends on both the magnitude of the treatment advantage and the nature of the ordinal scale. An advantage of the approach is that any erroneous assumptions made at the design stage about the proportion of patients falling into each outcome category have little effect on the error probabilities of the study, although they can lead to inaccurate forecasts of sample size. Conclusions/Significance: It is important and feasible to pre-determine many of the statistical aspects of an efficient trial design in advance of a disease outbreak. The design can then be tailored to the specific disease under study once its nature is better understood. [ABSTRACT FROM AUTHOR]

Thrombotic events caused by atherosclerosis are by far the most common cause of death in the world. Advances in treatment have prolonged the life of patients with atherosclerotic disease, but treating individuals with clinically manifest disease will not result in a cure, and will not prevent the majority of such events. This paper explores the possibility that early implementation of a drug-based approach to the prevention of atherosclerosis and atherothrombotic events could dramatically reduce the footprint of this disease. Specifically, we consider the potential impact on atherothrombotic events of a population-based, pharmacological approach to lowering serum LDL-cholesterol levels in asymptomatic adults aged 35-50 years. We also consider the feasibility and basic design considerations for a clinical trial to assess the validity of this public health and primary prevention approach. [ABSTRACT FROM AUTHOR]