Realist evaluators argue that evaluations need to ask not just what works but also what works for whom under what conditions. They argue interventions need to be evaluated in terms of the mechanisms they trigger and how these interact with context to generate different outcomes in different settings or populations. Hypotheses should be worded as context–mechanism–outcome configurations (CMOCs). Many realist evaluators argue that randomised trials are not a proper scientific design, do not encompass sufficient variation in contexts to test CMOCs and are inappropriately positivist in orientation. They argue that it is better to test CMOCs using observational designs which do not use randomisation. We welcome the focus on CMOCs but disagree with the view that trials cannot be used for realist evaluation. Trials are an appropriate scientific design when it is impossible for experimenters to control all the factors which have an influence on the result of an experiment. Trials can include sufficient variety of contexts to test CMOCs. Trials need not embody a positivist approach to the science of complex health interventions if they are oriented towards testing hypotheses, draw on theory which engages with deeper mechanisms of causation and use distinctly social science approaches such as qualitative research.

This chapter reflects on how evidence from realist trials and systematic reviews might be of value, not only in drawing conclusions about specific interventions and their theories of change but also in testing and refining the middle range theories which inform these and other interventions. While evaluation evidence should be of most immediate use in informing decisions about the implementation of the specific interventions being evaluated, a broader and more enduring use for evaluation could be in suggesting refinements to middle range theory. Such refinements might then be used to inform and influence the next generation of complex health interventions. In order to be useful in assessing the validity of middle range theory, evaluations will need to assess interventions informed by a limited number of middle range theories comprising a limited number of well-defined constructs. There may be value in conducting proof of principle studies separately from more pragmatic evaluations in order to test and refine middle range theory.

Chapter 2 outlines the history of DNA research and the key scientists who made the discoveries that enabled the manipulation of DNA. The scope, nature and ethos of science and the scientific method are described, with models for the scientific method and support for research. The importance of gathering and evaluating data in experimental science is outlined, and some of the key aspects and terminology are discussed.