The use of historical controls and concurrent controls to assess the effects of sulphonamides, 1936–1945

Survival trial design and monitoring using historical controls

“…Despite of these facts, the HCTs has been widely applied in medical clinical research [7–13]. In randomized trials, factors such as age, race, and gender, that may be confounded with treatment effects are balanced with respect to their marginal or joint frequencies in the control and experimental groups through randomization.…”

When are randomised trials unnecessary? Picking signal from noise

“…These dramatic effects of sulphonamides were not observed in other conditions, however, and carefully controlled trials were required to distinguish confidently between moderate treatment effects and no material effects. 2 To help us think about the circumstances in which randomised trials are unnecessary, we sought help 3 in compiling a list of examples of treatments whose effects had been widely accepted on the basis of evidence from case series or non-randomised cohorts (box). We have considered three present day examples in more detail to help illustrate the basis for our conclusions:…”

Why the MRC therapeutic trials committee did not introduce controlled clinical trials

“…For example, several well-designed and analysed trials of sulphonamides were done by Snodgrass and Anderson at the Ruchill Hospital in Glasgow during the late 1930s. [31][32][33][34][35] The first of these (Snodgrass and Anderson 33 ) was reported by them as having been 'undertaken at the request of the Therapeutic Trials Committee of the Medical Research Council'. It employed alternate controls and included analyses using chi-square values and standard errors.…”