The history of clinical trials before 1750 is brief.
The concepts behind clinical trials, however, are ancient. The Book of Daniel chapter 1, verses 12 through 15, for instance, describes a planned experiment with both baseline and follow-up observations of two groups who either partook of, or did not partake of, "the King's meat" over a trial period of ten days. Persian physician and philosopher, Avicenna, gave such inquiries a more formal structure. In The Canon of Medicine in 1025 CE, he laid down rules for the experimental use and testing of drugs and wrote a precise guide for practical experimentation in the process of discovering and proving the effectiveness of medical drugs and substances. He laid out the following rules and principles for testing the effectiveness of new drugs and medications:
- The drug must be free from any extraneous accidental quality.
- It must be used on a simple, not a composite, disease.
- The drug must be tested with two contrary types of diseases, because sometimes a drug cures one disease by its essential qualities and another by its accidental ones.
- The quality of the drug must correspond to the strength of the disease. For example, there are some drugs whose heat is less than the coldness of certain diseases, so that they would have no effect on them.
- The time of action must be observed, so that essence and accident are not confused.
- The effect of the drug must be seen to occur constantly or in many cases, for if this did not happen, it was an accidental effect.
- The experimentation must be done with the human body, for testing a drug on a lion or a horse might not prove anything about its effect on man.
One of the most famous clinical trials was James Lind's demonstration in 1747 that citrus fruits cure scurvy. He compared the effects of various acidic substances, ranging from vinegar to cider, on groups of afflicted sailors, and found the group who were given oranges and lemons had largely recovered from scurvy after six days.
Frederick Akbar Mahomed (d. 1884), who worked at Guy's Hospital in London, made substantial contributions to the process of clinical trials during his detailed clinical studies, where "he separated chronic nephritis with secondary hypertension from what we now term essential hypertension." He also founded "the Collective Investigation Record for the British Medical Association; this organization collected data from physicians practicing outside the hospital setting and was the precursor of modern collaborative clinical trials and t123."
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