Weatherby L B, Walker A M, Fife D, Vervaet P, Klausner M A
Ingenix Pharmaceutical Services, Epidemiology Division, One Newton Executive Park, Newton Lower Falls, MA 02462-1450, USA.
Pharmacoepidemiol Drug Saf. 2001 May;10(3):211-8. doi: 10.1002/pds.592.
'Dear Doctor' letters alert the prescribing community of drug labeling changes that contain new contraindications, warnings, adverse reactions, and precautions. There has been little assessment of the impact of these letters. We quantified the impact of two 'Dear Doctor' letters concerning interactions between cisapride and a series of drugs. A letter in 1995 described a risk of prolonged QT intervals and serious ventricular arrhythmia in patients who received macrolide antibiotics and imidazole antifungals in conjunction with cisapride. A June 1998 letter that expanded the list of contraindicated comedications had wider distribution than an earlier one, was accompanied by substantial Internet and media coverage, and was complemented by an effort to inform large pharmacy dispensing information organizations of the warnings against concurrent use of the named drugs.
Health plan members with one or more outpatient pharmacy claims for cisapride during the period 1 January 1995 through 31 May 1999 were identified among members of a large New England health insurer. A retrospective review of concurrent and nearly concurrent dispensings of cisapride and contraindicated comedications was undertaken in the automated pharmacy claims data using both graphical and statistical time-series analysis. We tabulated by month the fraction of cisapride dispensings that occurred in close temporal relation to dispensings of contraindicated comedications. Codispensings that occurred on the same day were taken as the most direct measure of prescriber responsiveness to the letters. Codispensings that occurred in windows of plus or minus 2 weeks (29 day window) and plus or minus 4 weeks (57 day window) were taken as measures of possible simultaneous consumption. Among overlapping dispensings, we counted the proportion dispensed by the same pharmacy. Time series regression analysis of secular, seasonal, and step-effects was conducted.
There was a steady decline in codispensing of cisapride and contraindicated medicines, and a pronounced seasonal effect, arising principally from the seasonal use of macrolide antibiotics. Against this background, the isolated Dear Doctor letter of October 1995 had no discernible effect on prescribing practices. The 1998 letter and surrounding activity, by contrast, were followed by a 66% decline in same-day dispensings and a smaller, but still pronounced decline in dispensings in the wider time windows. For most codispensings of contraindicated medications with cisapride, both medications came from the same pharmacy.
Publicity and direct intervention with dispensing pharmacies may be an important supplement to Dear Doctor letters when the goal is to eliminate the codispensing of drugs that should not be taken together.
“致医生函”会向处方医生群体通报药品标签变更情况，其中包含新的禁忌证、警示、不良反应和注意事项。目前对这些信函的影响评估较少。我们对两封关于西沙必利与一系列药物相互作用的“致医生函”的影响进行了量化。1995年的一封信函描述了接受大环内酯类抗生素和咪唑类抗真菌药联合西沙必利治疗的患者出现QT间期延长和严重室性心律失常的风险。1998年6月的一封信函扩大了禁忌合并用药清单，其分发范围比早期信函更广，同时伴有大量互联网和媒体报道，并通过向大型药房配药信息组织通报禁止同时使用指定药物的警告来加以补充。
在一家大型新英格兰健康保险公司的成员中，识别出在1995年1月1日至1999年5月31日期间有一次或多次西沙必利门诊药房配药记录的健康计划成员。利用图形和统计时间序列分析，对自动化药房配药数据中同时或几乎同时配给西沙必利和禁忌合并用药的情况进行回顾性审查。我们按月列出与禁忌合并用药配给时间密切相关的西沙必利配给比例。同一天发生的联合配药被视为处方医生对信函反应最直接的衡量指标。在正负2周（29天窗口）和正负4周（57天窗口）内发生的联合配药被视为可能同时用药的衡量指标。在重叠配药中，我们计算同一药房配给的比例。进行了长期、季节性和阶跃效应的时间序列回归分析。
西沙必利与禁忌药物的联合配药呈稳步下降趋势，且存在明显的季节性影响，主要源于大环内酯类抗生素的季节性使用。在此背景下，1995年10月单独发出的“致医生函”对处方行为没有明显影响。相比之下，1998年的信函及相关活动之后，同一天的配药量下降了66%，在更宽时间窗口内的配药量也有较小但仍很明显的下降。对于大多数西沙必利与禁忌药物的联合配药，两种药物都来自同一药房。
当目标是消除不应同时服用的药物的联合配药时，宣传和对配药药房的直接干预可能是“致医生函”的重要补充。
