Assessing the Overall Validity of Randomised Controlled Trials

ABSTRACT In the biomedical, behavioural and social sciences, the leading method used to estimate causal effects is commonly randomised controlled trials (RCTs) that are generally viewed as both the source and justification of the most valid evidence. In studying the foundation and theory behind RCTs, the existing literature analyses important single issues and biases in isolation that influence causal outcomes in trials (such as randomisation, statistical probabilities and placebos). The common account of biased causal inference is described in a general way in terms of probabilistic imbalances between trial groups. This paper expands the common account of causal bias by distinguishing between the range of biases arising between trial groups but also within one of the groups or across the entire sample during trial design, implementation and analysis. This is done by providing concrete examples from highly influential RCT studies. In going beyond the existing RCT literature, the paper provides a broader, practice-based account of causal bias that specifies the between-group, within-group and across-group biases that affect the estimated causal results of trials – impacting both the effect size and statistical significance. Within this expanded framework, we can better identify the range of different types of biases we face in practice and address the central question about the overall validity of the RCT method and its causal claims. A study can face several smaller biases (related simultaneously to a smaller sample, smaller estimated effect, greater unblinding etc.) that generally add up to greater aggregate bias. Though difficult to measure precisely, it is important to assess and provide information in studies on how much different sources of bias, combined, can explain the estimated causal effect. The RCT method is thereby often the best we have to inform our policy decisions – and the evidence is strengthened when combined with multiple studies and other methods. Yet there is room for continually improving trials and identifying ways to reduce biases they face and to increase their overall validity. Implications are discussed.