The development of structural modifications of basic chemical compounds in an attempt to decrease toxicity or production of side effects or to increase therapeutic effectiveness has greatly expanded the list of available drugs of many types. Many new preparations deserve careful clinical evaluation to assess possible attainment of these goals. A comparative study which utilizes not only the drug to be tested but also an older or established medication with a similar action, which will serve as a standard of reference, and a placebo is usually helpful and often necessary. An illustration of this problem, and an approach to its study, is the case of the thiazide diuretics, of which there are approximately ten different preparations.
Chlorothiazide, the original form introduced in 1957, has frequently served as the standard with which the modified preparations are compared. A well-controlled, moderately long-term study comparing the antihypertensive properties of polythiazide, one of the