Clinical trials

The transition from laboratory testing to evaluation in humans marks an important stage in vaccine development. Concerns about safety and benefit to the patient and to the community may raise complex ethical issues, whereas the inherent variability of human responses must be taken into account to obtain valid estimates of vaccine effect. This latter requirement explains why a coherent statistical framework for the design, analysis, and interpretation of clinical trials is regarded as essential today. A vast body of experience and methodology has been developed since the 1940s, when the scientific method was first applied systematically to the evaluation of vaccines. One striking feature of clinical trial research is its broad collaborative nature, involving laboratory, epidemiological, clinical, and statistical skills. As a result, rather than attempt to describe in detail the planning and conduct of clinical trials, this chapter will review the broad principles and stages involved in evaluating vaccines in humans, using examples from the literature. Details of methodological and other issues of particular relevance to vaccine evaluation are provided in Subheading 3. In the UK and elsewhere, the Clinical Trials Directive 2001/20/EU will be implemented by May 2004 to provide legislation that will standardize clinical trials throuhgout the European community