Importance of proper conduct of clinical trials

Clinical trials provide the evidence that forms one of the cornerstones of modern evidence-based medicine, together with clinical judgement and patient values and preferences. 1 The US National Institutes of Health defines a clinical trial as, ‘a research study in which human subjects are prospectively assigned to one or more interventions (including placebo or control) to evaluate the effects of those interventions on health-related biomedical or behavioural outcomes’. 2 Clinical trials have a long history. Arguably, the first description of one can be found in the ‘Book of Daniel’ in The Bible. 3 In approximately 600 Before the Common Era, the Babylonian King Nebuchadnezzar ordered his people to eat meat and drink wine, which was a diet that he believed would keep them in good physical condition. Daniel of Judah and his friends (Shadrach, Meshach, and Abednego, who were convinced vegetarians) refused the royal diet and proposed to the royal steward the first recorded clinical trial protocol: ‘Test your servants for 10 days; let us be given vegetables to eat and water to drink. Then let our appearance and the appearance of the youths who eat the king's rich food be observed by you, and according to what you see deal with your servants'. Daniel and his youthful friends who ate a vegetarian diet and drank water were found in better physical condition than the ‘meat and wine group’, and so the king issued a new edict allowing his subjects to also eat legumes and drink water. This first open-label unblinded trial presented methodological issues that remain important in contemporary research: equipoise, selection bias, inadequate controlling for confounders and sample size, unclear outcomes definitions and assessment, but it did lead to an important change in routine practice (i.e. the diet as a form of preventive measure). Interestingly, the trial report was short and effective, even though it was only published 400 yr after study completion