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The ethical framework for human subject protection has its origins in the ancient Hippocratic Oath, which specified a prime duty of a physician to avoid harming the patient. -
In his encyclopedic ‘Canon of Medicine’, Avicenna suggests that in the clinical trial a remedy should be used in its natural state in disease without complications. He recommends that two cases of contrary types be studied and that study be made of the time of action and of the reproducibility of the effects. These rules suggest a contemporary approach for clinical trials. -
In 1537, he was responsible for treating the battlefield wounded soldiers. At that time, the conventional treatment to stop the bleeding was to pour boiling oil over the wound.
As the number of wounded was high and the supply of oil short, Ambroise had to resort to an unconventional treatment using a mixture of egg yolks, oil of roses, and turpentine. He found out that the alternative remedy positively affected wound healing, whereas the conventional treatment was ineffective. -
James Lind is considered the first physician to have conducted a controlled clinical trial of the modern era.
Lind’s trial involved twelve sailors with scurvy, who were who were accommodated in the same quarters, and had the same basic diet. His report illustrates his awareness of the need to guard against selection bias and shows how he tried to hold potential confounding factors constant – clinical condition, environment, and basic diet. -
The word "placebo" first appeared in medical literature in the early 1800s. However, it was only in 1863 that United States physician Austin Flint planned the first clinical study comparing a dummy remedy to an active treatment. He treated 13 patients suffering from rheumatism with an herbal extract which was advised instead of an established remedy. In 1886, Flint described the study in his book A Treatise on the Principles and Practice of Medicine.
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The Medical Research Council (MRC) UK carried out a trial in 1943-4 to investigate patulin treatment (an extract of Penicillium patulinum) for the common cold. This was the first double blind comparative trial with concurrent controls in the general population in recent times. It was one of the last trial with non-randomized or quasi-randomized allocation of subjects. The study was rigorously controlled by keeping the physician and the patient blinded to the treatment.
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The first randomized control trial of streptomycin in pulmonary tuberculosis was carried out in 1946 by the Medical Research Council MRC of the UK. Determination of whether a patient would be treated by streptomycin and bed-rest (S) or by bed-rest alone (C) was made by reference to a statistical series based on random sampling numbers drawn by Professor Bradford Hill. The trial quickly became a model of design and resulted, in the present universal use of randomized allocation in clinical trials
