Moore N, Noblet C, Kreft-Jais C, Lagier G, Ollagnier M, Imbs J L
Centre Régional de Pharmacovigilance de Rouen, CHU de Rouen, France.
Therapie. 1995 Nov-Dec;50(6):557-62.
The French drug surveillance (pharmacovigilance) system is based on a network of 31 regional centres which receive adverse drug reaction (ADR) reports from health professionals and are drug information centers. Cases are entered into a common database, with causality scores. This database contains large amounts of data, which may be used for pharmaco-epidemiological studies. As an example, all cases in which an antihypertensive drug, suspect or not, was cited were identified. ACE-inhibitor cough was also explored.
Since 1985, > 70,000 case reports have been entered into the database. 63 per cent were reported by specialists, 20 per cent by GPs. 54 per cent came from University Hospitals, 21 per cent from private practice. The most numerous age group was 60 to 69. The overall sex ratio (F/M) was 1.28, the female preponderance being most marked at < 39 and > 70 years of age. 43 per cent took only one drug, 20 per cent two drugs, 13.4 per cent three, and 24 per cent > three drugs. The most frequently reported effects concerned the skin and appendages (15 per cent), general status and central nervous system (9.5 per cent each), platelets, liver, and GI systems (6 per cent each). Outcome was favourable in 74 per cent. Dechallenge was positive in 71 per cent, rechallence in 6 per cent. 3.4 per cent of the patients died; in 2.2 per cent death was related to a reaction. Causality assessment indicated close temporal relationship (C2 or C3) in 69 per cent of cases; in 51 per cent of cases, no other obvious cause was found. 66 per cent of the reactions were labelled when reported. The database could also be used to explore drug utilisation: as an example, we studied the age and sex distribution of reports containing antihypertensive drugs, irrespective of their possible causal role in the reaction. Antihypertensives were mentioned in 14 per cent of the reports. The age distribution was skewed towards greater age, with a maximum of 70 years. F/M was 1.57, with more M use < 20 and 30-59, whereas F were more common between 20-29 and 60 years. beta-blockers were more often associated with patients under 70, whereas above 70 diuretics and centrally acting antihypertensive drugs were more often reported. This could be related to greater use or worse tolerance of these drugs. As an example of the exploration of a specific drug-reaction relationship, we explored the relationship between the use of ACE inhibitors (ACEI) and cough. ACE inhibitors were present in 6 per cent of cases, but in 75 per cent of reports of cough. F/M was 1.29 (NS) for all reports concerning ACEI, 1.28 for cough unrelated to ACEI, 2.1 for cough with ACEI (P < 0.05). Cough was present in 12 per cent of all reports concerning ACEI. There was no clear difference between ACEI for cough or sex ratio; women cough more with ACEI. This does not seem related to greater ACEI use by women or to greater sensitivity of women to cough. The reason for this sex difference remains to be explained. There are large amounts of essentially underutilized data in drug surveillance databases. How they can or should be used remains to be validated.
法国药品监测（药物警戒）系统基于一个由31个区域中心组成的网络，这些中心接收来自卫生专业人员的药品不良反应（ADR）报告，并且是药品信息中心。病例被录入一个带有因果关系评分的通用数据库。该数据库包含大量数据，可用于药物流行病学研究。例如，识别出所有提及抗高血压药物（无论是否可疑）的病例。还对血管紧张素转换酶抑制剂（ACEI）引起的咳嗽进行了研究。
自1985年以来，已有超过70,000份病例报告录入该数据库。63%由专科医生报告，20%由全科医生报告。54%来自大学医院，21%来自私人诊所。人数最多的年龄组为60至69岁。总体性别比（女/男）为1.28，女性优势在年龄小于39岁和大于70岁时最为明显。43%的患者仅服用一种药物，20%服用两种药物，13.4%服用三种药物，24%服用三种以上药物。报告最多的不良反应涉及皮肤及附属器（15%）、一般状况和中枢神经系统（各9.5%）、血小板、肝脏和胃肠道系统（各6%）。74%的患者预后良好。撤药反应阳性率为71%，再激发阳性率为6%。3.4%的患者死亡；2.2%的死亡与不良反应有关。因果关系评估显示69%的病例存在密切的时间关系（C2或C3）；51%的病例未发现其他明显病因。66%的不良反应在报告时被标注。该数据库还可用于探索药物利用情况：例如，我们研究了包含抗高血压药物的报告的年龄和性别分布，而不考虑其在不良反应中可能的因果作用。14%的报告提及了抗高血压药物。年龄分布偏向老年，最高年龄为70岁。女/男比例为1.57，男性在年龄小于20岁和30至59岁时使用较多，而女性在20至29岁和60岁之间更为常见。β受体阻滞剂与70岁以下患者的关联更为常见，而70岁以上患者中利尿剂和中枢性抗高血压药物的报告更为频繁。这可能与这些药物的使用更多或耐受性更差有关。作为探索特定药物-不良反应关系的一个例子，我们研究了ACE抑制剂（ACEI）与咳嗽之间的关系。ACEI在6%的病例中出现，但在75%的咳嗽报告中出现。所有关于ACEI的报告的女/男比例为1.29（无统计学差异），与ACEI无关的咳嗽的女/男比例为1.28，ACEI引起咳嗽的女/男比例为2.1（P<0.05）。在所有关于ACEI的报告中，12%出现了咳嗽。ACEI引起咳嗽或性别比方面没有明显差异；女性使用ACEI时咳嗽更多。这似乎与女性更多使用ACEI或女性对咳嗽更敏感无关。这种性别差异的原因仍有待解释。药物监测数据库中有大量基本未被充分利用的数据。如何或是否应该利用这些数据仍有待验证。
