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Abstract Purpose The establishment of recommended dosing regimens has always been a difficult aspect of drug development. This paper examines the extent to which postmarketing prescribing deviates from initially recommended dosing regimens. We used the World Health Organization's (WHO) periodically updated compilation of the ‘Defined Daily Dose’ (DDD) to reflect prevailing patterns of prescribing in national markets. The aim of this study was to evaluate DDD changes over time (1982–2000) and to identify possible determinants of these changes. Methods Data on DDD changes were obtained from the WHO's Oslo Collaborating Centre. We performed a case–control analysis in which we compared drugs with (cases) and without (controls) postmarketing changes in DDD on possible determinants associated with DDD change. Results We found 115 instances of a change of DDD in the period 1982–2000 (45 (39.1%) increases and 70 (60.9%) decreases). Antibiotics showed the greatest number of changes in DDD: predominantly increases in the 1980s, while the 1990s were dominated by decreases in DDD of mostly cardiovascular drugs. Conclusion Changes in DDD reflect the outcome of a melange of forces, including misconceptions of dose requirements during pre‐market development of drug and postmarketing changes in pharmacotherapeutic knowledge, clinical concepts, economic forces, and, in the case of anti‐infective agents, changing patterns of resistance/sensitivity of target microorganisms to the anti‐infective agent(s) in question. Copyright © 2002 John Wiley & Sons, Ltd.
Heerdink et al. (Mon,) studied this question.