Heerdink Eibert R, Urquhart John, Leufkens Hubert G
Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences (UIPS), The Netherlands.
Pharmacoepidemiol Drug Saf. 2002 Sep;11(6):447-53. doi: 10.1002/pds.745.
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.
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.
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.
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.
确立推荐给药方案一直是药物研发中的一个难题。本文探讨了药品上市后处方与最初推荐给药方案的偏离程度。我们使用了世界卫生组织（WHO）定期更新的“限定日剂量”（DDD）汇编，以反映各国市场上普遍的处方模式。本研究的目的是评估1982年至2000年期间DDD的变化，并确定这些变化的可能决定因素。
关于DDD变化的数据来自WHO的奥斯陆合作中心。我们进行了一项病例对照分析，比较了DDD有上市后变化的药物（病例）和无变化的药物（对照）在与DDD变化相关的可能决定因素方面的情况。
我们发现在1982年至2000年期间有115例DDD变化的情况（45例（39.1%）增加，70例（60.9%）减少）。抗生素的DDD变化数量最多：在20世纪80年代主要是增加，而在20世纪90年代则主要是心血管药物的DDD减少。
DDD的变化反映了多种因素综合作用的结果，包括药物上市前研发期间对剂量需求的误解、上市后药物治疗知识、临床概念、经济因素的变化，以及就抗感染药物而言，目标微生物对相关抗感染药物的耐药/敏感模式的变化。
