Today’s medical community recognizes and appreciates the importance of carefully controlled medical trials, but it took centuries of progress to achieve. Beginning with James Lind’s landmark clinical trial of scurvy in 1747 and continuing through essential research milestones, the clinical trials performed today exhibit the culmination of meticulous design and precise implementation.
1747: The Very First Clinical Trial Studies Scurvy
Though humans experimented with the concept of clinical research before the 18th century, James Lind is the first physician credited with conducting a controlled clinical trial in the modern era. Dr. Lind, a Scottish surgeon working on a ship in 1747, observed the high mortality rate of sailors as a result of scurvy.
Lind took matters into his own hands by performing a comparative clinical trial of the most promising cure for scurvy at the time. As he explained in his trial notes, “On the 20th of May 1747, I selected twelve patients in the scurvy, on board the Salisbury at sea. Their cases were as similar as I could have them. They all in general had putrid gums, the spots and lassitude with weakness in the knees.”
Lind went on to explain that the clinical trial patients remained in quarantine away from other sailors and ate the same meals each day. The only factor that changed between the patients was the treatment they received for scurvy:
“Two were ordered each a quart of cyder a day. Two others took twenty-five drops of elixir vitriol three times a day … Two others took two spoonfuls of vinegar three times a day … Two of the worst patients were put on a course of sea-water .. Two others had each two oranges and one lemon given them every day … The two remaining patients, took … an electuary recommended by a hospital surgeon.”
Lind noticed that the treatment of oranges and lemons offered the most dramatic results, with the sailors recovering after only six days. Not only did this original clinical trial achieve a systematic review of scurvy and effective treatment recommendations, but it lay the foundation for clinical trial methods of the future.
1863: The First Clinical Trial to Use a Placebo
More than 100 years after Lind’s landmark study, U.S physician Austin Flint led the first clinical study comparing a dummy remedy, called a placebo, to an active treatment. Flint treated 13 rheumatic fever patients with a dummy “placebic remedy”, then compared his results to the well-established results of the most common active treatment at the time.
As Flint explained, “… to secure the moral effect of a remedy given specifically for the disease, the patients were placed on the use of a placebo which consisted, in nearly all of the cases, of the tincture of quassia, very largely diluted. This was given regularly, and became well known in my wards as the placebic remedy for rheumatism.” There was no significant difference between the results achieved by the placebo and the standard active treatment, demonstrating the power of perception and the placebo.
1943: The First Double Blind Controlled Trial
Nearly one century after Flint underscored the role of the placebo, the Medical Research Council (MRC) of the United Kingdom completed a trial to explore the treatment of patulin for the common cold. This trial proved to be the very first double blind comparative trial with concurrent controls.
In other words, the study was carefully controlled by ensuring neither the physician nor the patient knew who received the patulin treatment and who received the placebo. More than 1,000 British office and factory workers suffering from colds volunteered for this study, which was quite an accomplishment during the height of World War II in Europe.
Though this clinical trial was unable to show any protective effect of patulin, it did pave the way for the type of double blind control that is now considered essential for reliable clinical research.
These three famous clinical trials laid the foundation for every clinical trial to come.