University of Rochester Medical Center, Dept. of Urology
Introduction: Before the advent of clinical trials and evidence-based medicine, physicians relied on anecdotal data and medical observations to determine the best treatments for their patients. The rich history of clinical trial design dates back to Biblical times and has been influenced significantly by the military. Throughout their dichotomous history, clinical trials have both allowed for the heroic development of life-saving therapeutics and served as an avenue for the shameful degradation of human rights. Methods: The literature was reviewed for historical descriptions of the scientific, ethical, and legal contributions to the development of clinical trials, particularly those by military. Results: The greatest Babylonian military leader King Nebuchadnezzar II (642-562 BCE) is credited with unintentionally conducting the first human study when he allowed several men to consume legumes and water rather than the standard diet of meat and wine. Centuries later, two military surgeons became pioneers in clinical trials. In 1537, when French army surgeon Ambroise Pare ran out of boiling oil to treat wounded soldiers, he tested an alternative (egg yolk, oil of roses, and turpentine) on a group of men, which proved to be more effective. During the War of the Austrian Succession in 1747, James Lind, a British Royal Navy surgeon conducted the first recorded prospective clinical trial when he tested citrus on sailors suffering from scurvy aboard the ship HMS Salisbury. Initial studies of modern chemotherapy can be traced to World Wars I and II. Mustard gas and sulfur mustards were observed to cause severe lymphoid hypoplasia and myelosuppression, which led to the eventual use of nitrogen mustard in Non-Hodgkin’s lymphoma. Contemporary codes of ethics and regulatory polices to protect trial subjects did not significantly evolve until more than two centuries after Lind’s work. While the horrific human medical experiments in the Japanese-occupied Far East conducted by the military during WWII were never widely publicized, the well-known Nazi military experiments led to the Nuremberg Code in 1947 and the Declaration of Helsinki in 1964. The majority of remaining modern advancements in trial design occurred in the last century with the adoption of Good Clinical Practice, including concepts such as blinding, randomization, and statistical criteria for drug testing and approval. Conclusions: The military greatly shaped the evolution of clinical trial design through efforts to ease human suffering with novel therapies as well as experimentation laden with deplorable human rights violations. SOURCE OF Funding: NA
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