ABSTRACT
The salicylates, in whatever form – plant extracts or concoctions, tablets or other oral formulations, or topical preparations – have probably been extensively used throughout time for the treatment of pain, joint inflammation and fever in rheumatic and other painful conditions. Yet aside from the observations of the Reverend Edward Stone (1763) and the clinical observations in the nineteenth century (see Chapter 1), there were no formal clinical trials on the use of salicylates in treating rheumatic diseases until the introduction of corticosteroids in the late 1940s and 1950s, when studies were performed to compare the efficacy of these drugs to what was apparently a ‘recognised standard’, aspirin (Copeman, 1964; Roth, 1988a; Rainsford, 1999). Indeed it was not until the pioneering double-blind trials of aspirin compared with cortisone carried out by the Empire Rheumatism Council (1955; 1957) and the joint Medical Research Council/Nuffield Foundation (1954; 1955; 1957a; 1957b; 1959) and the Medical Research Council (1954; 1957) was there any real basis to the efficacy of aspirin in the treatment of rheumatic disease or the use of aspirin as a standard in clinical trials of these conditions. For the best part of three decades after these initial studies, aspirin was recognised as a standard for comparison in most clinical trials of the newer NSAIDs and other antirheumatic agents. These earlier studies of the effects of aspirin in rheumatic fever contrast to the paucity of reports of clinical trials with aspirin in osteoarthritis until the 1960s, when again it became a basis for comparison in trials with newer NSAIDs (Von Rechenberg, 1961; Lewis and Furst, 1987; 1994; Kean et al., 1999). It is only since the substantial numbers of clinical trials with ibuprofen during the 1980s and 1990s that this drug has supplanted aspirin as the accepted standard for comparison (Kean et al., 1999; Rainsford, 1999a).
