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BACKGROUND Early treatment may improve acute ischaemic stroke outcome. Gavestinel is a selective antagonist at the glycine site of the N-methyl-D-aspartate (NMDA) receptor, and is neuroprotective in animal models of ischaemic stroke. METHODS We did a randomised, double-blind, placebo-controlled trial to test whether gavestinel could improve functional(More)
Combinations of drugs are increasingly being used for a wide variety of diseases and conditions. A pre-clinical study may allow the investigation of the response at a large number of dose combinations. In determining the response to a drug combination, interest may lie in seeking evidence of 'synergism', in which the joint action is greater than the actions(More)
There is growing interest, especially for trials in stroke, in combining multiple endpoints in a single clinical evaluation of an experimental treatment. The endpoints might be repeated evaluations of the same characteristic or alternative measures of progress on different scales. Often they will be binary or ordinal, and those are the cases studied here.(More)
In a sequential clinical trial, the accumulating data are subjected to a series of interim analyses, each of which involves a comparison of the treatments under study in respect of the primary efficacy criterion. The trial is stopped as soon as it is evident that one treatment is superior to the other, or that no such difference is going to be found. The(More)
2 months ago, when the numbers known to have died from Ebola in west Africa could still be counted in hundreds, WHO made an important statement about investigational drugs and vaccines. This crisis is so acute, WHO declared, that it is ethical to offer interventions with potential benefits but unknown efficacy and side-effects, though every effort should be(More)
BACKGROUND Experimental treatments for Ebola virus disease (EVD) might reduce EVD mortality. There is uncertainty about the ability of different clinical trial designs to identify effective treatments, and about the feasibility of implementing individually randomised controlled trials during an Ebola epidemic. METHODS AND FINDINGS A treatment evaluation(More)
This paper considers the design and interpretation of clinical trials comparing treatments for conditions so rare that worldwide recruitment efforts are likely to yield total sample sizes of 50 or fewer, even when patients are recruited over several years. For such studies, the sample size needed to meet a conventional frequentist power requirement is(More)
When sequential clinical trials are conducted by plotting a statistic measuring treatment difference against another measuring information, power is guaranteed regardless of nuisance parameters. However, values need to be assigned to nuisance parameters in order to gain an impression of the sample size distribution. Each interim analysis provides an(More)
Phase II clinical trials are performed to investigate whether a novel treatment shows sufficient promise of efficacy to justify its evaluation in a subsequent definitive phase III trial, and they are often also used to select the dose to take forward. In this paper we discuss different design proposals for a phase II trial in which three active treatment(More)
In this paper, Bayesian decision procedures previously proposed for dose-escalation studies in healthy volunteers are reviewed and evaluated. Modifications are made to the expression of the prior distribution in order to make the procedure simpler to implement and a more relevant criterion for optimality is introduced. The results of an extensive simulation(More)