Worldwide Research and Development BusinessTechnology, Pfizer, Inc., Groton, CT 06340, USA.
J Am Med Inform Assoc. 2013 Jun;20(e1):e162-8. doi: 10.1136/amiajnl-2012-001257. Epub 2013 Feb 28.
Ethical concerns about randomly assigning patients to suboptimal or placebo arms and the paucity of willing participants for randomization into control and experimental groups have renewed focus on the use of historical controls in clinical trials. Although databases of historical controls have been advocated, no published reports have described the technical and informatics issues involved in their creation.
To create a historical controls database by leveraging internal clinical trial data at Pfizer, focusing on patients who received only placebo in randomized controlled trials.
We transformed disparate clinical data sources by indexing, developing, and integrating clinical data within internal databases and archives. We focused primarily on trials mapped into a consistent standard and trials in the pain therapeutic area as a pilot.
Of the more than 20,000 internal Pfizer clinical trials, 2404 completed placebo controlled studies with a parallel design were identified. Due to challenges with informed consent and data standards used in older clinical trials, studies completed before 2000 were excluded, yielding 1134 studies from which placebo subjects and associated clinical data were extracted.
It is technically feasible to pool portions of placebo populations through a stratification and segmentation approach for a historical placebo group database. A sufficiently large placebo controls database would enable previous distribution calculations on representative populations to supplement, not eliminate, the placebo arm of future clinical trials. Creation of an industry-wide placebo controls database, utilizing a universal standard, beyond the borders of Pfizer would add significant efficiencies to the clinical trial and drug development process.
将患者随机分配到非最佳或安慰剂组的伦理问题，以及愿意随机分配到对照组和实验组的参与者稀缺，这使得人们重新关注在临床试验中使用历史对照。尽管已经提倡使用历史对照数据库，但没有发表的报告描述了创建这些数据库所涉及的技术和信息学问题。
利用辉瑞内部临床试验数据创建历史对照数据库，重点关注在随机对照试验中仅接受安慰剂的患者。
我们通过索引、开发和整合内部数据库和档案中的临床数据，对不同的临床数据源进行转换。我们主要关注映射到一致标准的试验和疼痛治疗领域的试验作为试点。
在超过 20,000 项辉瑞内部临床试验中，确定了 2404 项具有平行设计的完成安慰剂对照的研究。由于在较早期临床试验中存在知情同意和数据标准方面的挑战，我们排除了完成于 2000 年之前的研究，从而从 1134 项研究中提取了安慰剂受试者和相关临床数据。
通过分层和分段方法汇总部分安慰剂人群，从而为历史安慰剂组数据库汇集部分人群在技术上是可行的。一个足够大的安慰剂对照数据库将能够以前代表性人群的分布计算来补充，而不是消除，未来临床试验中的安慰剂组。利用通用标准，在辉瑞以外的范围内创建一个行业范围的安慰剂对照数据库，将为临床试验和药物开发过程带来显著的效率提升。
