Drug development prior to 1800 was based almost completely on observational trial and error. The earliest known exception was a controlled drug trial conducted by James Lind in 1747 on an English ship to show the effectiveness of citrus fruit in the treatment of scurvy. Clinical tests, but not concurrent comparative trials, were conducted by Charles Maitland in 1722 in London to show the effectiveness of variolation in preventing smallpox, and a controlled drug trial was conducted by Edward Jenner in London in 1796 to show the effectiveness of material taken from cowpox sores of young milkmaids (later called smallpox vaccine) in preventing smallpox. In 1775, William Withering learned from an elderly woman herbalist in Shropshire, England about her use of the Foxglove plant (whose active ingredient Withering later determined to be digitalis) in treating heart disease, and in 1785 published the results of his treatment of 158 patients with the drug, but he did not conduct a controlled study.

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美国联邦人用药物监管的演变：历史论文

1800 年之前的药物开发几乎完全基于观察性试验和错误。已知最早的例外是詹姆斯·林德（James Lind）于 1747 年在一艘英国船上进行的一项对照药物试验，以显示柑橘类水果治疗坏血病的有效性。Charles Maitland 于 1722 年在伦敦进行了临床试验，但没有同时进行比较试验，以证明天花预防天花的有效性，而 Edward Jenner 于 1796 年在伦敦进行了一项对照药物试验，以显示取自预防天花的年轻挤奶女工的牛痘疮（后来称为天花疫苗）。1775 年，威廉·威瑟林从什罗普郡的一位老妇草药师那里得知，