Changes in prescribed drug doses after market introduction.
OBJECTIVE
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.


CONCLUSIONS
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.
Heerdink
Eibert R
ER
Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences (UIPS), The Netherlands. E.R.Heerdink@pharm.uu.nl
Urquhart
John
J
Leufkens
Hubert G
HG
D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D002317:Cardiovascular Agents / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000706:statistics & numerical data; D017723:Drug Utilization Review / Q000191:economics / Q000592:standards* / Q000706:statistics & numerical data; D006801:Humans; D011358:Product Surveillance, Postmarketing / Q000191:economics / Q000706:statistics & numerical data*; D014944:World Health Organization
D000900:Anti-Bacterial Agents; D002317:Cardiovascular Agents