vestigation was empirical, and in the early years the double blind controlled study was uncommon. In the 1950's when I was a resident in a large teaching hospital, I observed the use of investigational drugs under conditions which provided no useful information with regard to efficacy and in which the patients were protected from adverse results mainly by the fortunately benign nature of the drug and the condition being treated. This state of affairs was improved by the Kefauver-Harris Drug Amendments passed in 1962, as a result of the thalidomide experience, and effective since June 1963. As a passing note, it is of interest to observe that our present preclinical toxicity tests would not detect the teratogenicity of thalidomide, but it is probable that the better control and monitoring of clinical studies existing today would pick up the phocomelia at an early stage. In the 15 years since the amendments were passed by Congress, they have radically changed the way in which drug research is performed. While the initial impact was principally on clinical research, ever broader interpretations by the FDA of their powers and responsibilities under the law are affecting all aspects of ongoing pharmaceutical research, from chemical synthesis to marketing experience with approved drugs. Problems in Development of New Drugs Drug regulation, while not the only factor, has had a marked effect upon the time and costs required for the development of drugs in the United States. This is illustrated by the following: • In 1938 Parke, Davis & Co. submitted an application for Adrenalin in Oil (Epinephrine). The submission comprised a folder containing only 27 pages. The product is still in use after almost 40 years. • In 1948 an application was submitted for Benylin Expectorant. The submission consisted of a single bound volume of 73 pages. Nearly 30 years later it continues to be a major antitussive agent worldwide. • In 1958 an application was submitted for Povan Suspension (pryvinium pamoate). This required two volumes for a total of 439 pages. The product is still marketed in most countries, including the United States, as an effective treatment for pinworm infestation. • In 1962 an application was submitted for Norlestrin, now 12 370 pages in 31 volumes. Like the previous products, Norlestrin continues on the market as a safe and effective product. • Six years later, in 1968, an application was submitted for a new type
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