Creation and implementation of a historical controls database from randomized clinical trials.

ABSTRACT

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.