Martin Karin, Bégaud Bernard, Latry Philippe, Miremont-Salamé Ghada, Fourrier Annie, Moore Nicholas
Département de Pharmacologie, Université Victor Segalen, Bordeaux 2, Bordeaux, France.
Br J Clin Pharmacol. 2004 Jan;57(1):86-92. doi: 10.1046/j.1365-2125.2003.01953.x.
Clinical trials constitute the gold standard to assess the efficacy and safety of new medicines. However, because they are conducted in standardized conditions far from the real world of prescription and use, discrepancies in patient selection or treatment conditions may alter both the effectiveness and risks. On the basis of three examples, our objectives were to study the differences between the characteristics of treated populations and treatment patterns in clinical trials and in postmarketing settings and to discuss the potential consequences on actual efficacy and safety.
Treated populations were compared with patients included in premarketing clinical trials. Comparisons were made on the basis of demographic characteristics and treatment patterns.
Whatever the indicator and the drug studied, differences were observed: from 0.04% to 63% for tacrine, from 0% to 37% for celecoxib and from 6% to 52% for simvastatin, with possible consequences on the effectiveness and safety of the drug concerned. Our results confirm the under-representation of women and elderly patients in premarketing clinical trials, e.g. an M : F ratio of 4.6 in clinical trails of simvastatin vs 1.0 in the joint population. Moreover, the concomitant use of medicines was made extremely restrictive by the protocols of these trials while this was not the case in the postmarketing phase. This has possible consequences on the effectiveness and safety of the drug concerned.
These results plead for systematic ad hoc observational postmarketing studies for any novel and/or expensive medicine to assess the relevance of premarketing data.
临床试验是评估新药疗效和安全性的金标准。然而，由于它们是在远离实际处方和使用情况的标准化条件下进行的，患者选择或治疗条件的差异可能会改变疗效和风险。基于三个实例，我们的目标是研究临床试验和上市后环境中治疗人群特征和治疗模式的差异，并讨论对实际疗效和安全性的潜在影响。
将治疗人群与上市前临床试验中纳入的患者进行比较。根据人口统计学特征和治疗模式进行比较。
无论所研究的指标和药物如何，均观察到差异：他克林为0.04%至63%，塞来昔布为0%至37%，辛伐他汀为6%至52%，这可能会对相关药物的有效性和安全性产生影响。我们的结果证实了上市前临床试验中女性和老年患者的代表性不足，例如辛伐他汀临床试验中的男女比例为4.6，而联合人群中的比例为1.0。此外，这些试验的方案对药物的联合使用限制极大，而在上市后阶段并非如此。这可能会对相关药物的有效性和安全性产生影响。
这些结果呼吁对任何新型和/或昂贵药物进行系统的上市后特设观察性研究，以评估上市前数据的相关性。
