The COVID-19 pandemic has led to an unprecedented response in terms of clinical research activity. An important part of this research has been focused on randomized controlled clinical trials to evaluate potential therapies for COVID-19. The results from this research need to be obtained as rapidly as possible. This presents a number of challenges associated with considerable uncertainty over the natural history of the disease and the number and characteristics of patients affected, and the emergence of new potential therapies. These challenges make adaptive designs for clinical trials a particularly attractive option. Such designs allow a trial to be modified on the basis of interim analysis data or stopped as soon as sufficiently strong evidence has been observed to answer the research question, without compromising the trial's scientific validity or integrity. In this article, we describe some of the adaptive design approaches that are available and discuss particular issues and challenges associated with their use in the pandemic setting. Our discussion is illustrated by details of four ongoing COVID-19 trials that have used adaptive designs.

Adaptive designs for clinical trials permit alterations to a study in response to accumulating data in order to make trials more flexible, ethical, and efficient. These benefits are achieved while preserving the integrity and validity of the trial, through the pre-specification and proper adjustment for the possible alterations during the course of the trial. Despite much research in the statistical literature highlighting the potential advantages of adaptive designs over traditional fixed designs, the uptake of such methods in clinical research has been slow. One major reason for this is that different adaptations to trial designs, as well as their advantages and limitations, remain unfamiliar to large parts of the clinical community. The aim of this paper is to clarify where adaptive designs can be used to address specific questions of scientific interest; we introduce the main features of adaptive designs and commonly used terminology, highlighting their utility and pitfalls, and illustrate their use through case studies of adaptive trials ranging from early-phase dose escalation to confirmatory phase III studies.

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That insect parasites regulate and, in the case of newly introduced species, sometimes reduce the average density of insect pests has led to an exmination of the properties of parasites in general. Consideration has been given to the manner in which parasites select hosts for oviposition and to the physiological and psychological basis of this selection. The distribution of parasite progeny among suitable hosts has been analysed in many cases, for the fewer the hostS that are superparasitized for any given number of parasite eggs laid the greater the efficiency of the parasite in reducing host density. It is obvious that before the factors of host selection and superparasitism become important in host-parasite interaction the parasite must find the host individuals. When the hosts are confined to a relatively small area the potential oviposition of the parasite, subject to discrimination among hosts and restraint in oviposition, often determines the level of parasitism. As distance between individuals of the host population becomes greater, however, it is necessary for the parasite to search the environment more extensively. Therefore, the ability of the parasite to find hosts is a factor of prime importance in determining its influence on the density of its host. The success with which a parasite discovers hosts in relation to host density is determined, of course, by several characteristics of the parasite species and by the modification of these characteristics through variations in the physical environment.

Initial densities and periods of infestation of adults of Trialeurodes vaporariorum and its chalcid parasite Encarsia formosa influence subsequent fluctuations in numbers of adults of both host and parasite.

Summary When Phytoseiulus persimilis was reared with Tetranychus urticae, infesting roses propagated in a greenhouse at controlled daily temperatures of 24°C (12 hrs) and 18°C (12 hrs), prey numbers fluctuated with peaks of increasing amplitude. Differential dispersal of prey and predator species was one factor contributing to the inability of the natural enemy to control the pest population.