Although there are examples of controlled clinical trials as far back as biblical times (Book of Daniel 1:12-15), the modern scientific approach began in 1834, when Louis1 published his Essay on Clinical Instruction. In it, he laid down the principles that have remained largely unchanged, including the need for precise definition of the disease to be treated. Trials at the turn of the present century were largely in the preventive field of vaccination and immunization. It was after World War II, with the advent of antibiotics, that trials in the therapeutic field began to appear in large numbers.
The early therapeutic trials were simple in design: a therapeutic agent shown to be highly effective in vitro was tested in vivo against a known infective agent with sharp end points. The Medical Research Council2 trial of streptomycin in primary pulmonary tuberculosis in 1948 provides the classic example.
Marshall J. Controlled Clinical Trials in Cerebrovascular Disease: A Misused Tool. Arch Neurol. 1990;47(4):444–445. doi:10.1001/archneur.1990.00530040100024
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