By Deborah Borfitz

July 14, 2008 | Cross-functional Safety Review Teams (SRTs) at GlaxoSmithKline are moving into full production with a clinical trials signal detection (CTSD) tool that is useful for evaluating data emerging from both ongoing and completed studies. In doing so, it is raising the standard for safety review while potentially reducing the cost of statistical programming support for its current study portfolio.

GSK’s pioneering efforts, which utilize the CTSD tool developed by Phase Forward’s Lincoln Safety Group, earned it top honors in the clinical trials category. (see Best Practices)

Phase Forward built the CTSD tool and, in connection with the services it provides to GSK, enhanced its functionality and usability to better match the working processes of SRTs, says Vlasta Pinkston, director of clinical safety and pharmacovigilance systems. “The enhancements developed for completed study review carried over seamlessly for instream review.”

For completed studies, signals are scored based on the strength of the statistical relationship between the adverse event and the investigational treatment versus the comparator treatment. For studies in progress, the software facilitates the identification of outliers in adverse events, laboratory data, vital signs, and ECG data. CTSD provides both graphical and tabular format displays that allow for drill down to the level of individual patients, says Sally Cassells, vice president of clinical systems and services at Phase Forward. For blinded studies in progress, where all subjects are treated as one arm, safety issues can be identified without the added guidance of a signal score.

Instream review is challenging on several fronts, not the least of which is getting statisticians, clinical development staff, and safety personnel on SRTs accustomed to some inevitable “gaps” in data availability while patients are enrolled in a study, says Pinkston. Due to logistics, data from disparate sources (the electronic data capture system and central lab providers) arrive at different times and have not been fully cleaned. The end game, after all, is earlier identification of safety signals.

For completed study review, the CTSD tool itself is best suited for late-phase parallel arm studies and doesn’t yet provide the signal scoring mechanism for complex study designs, says Pinkston. Use of the tool for early-phase study data is generally impractical due to the short length of these trials and the fact that subjects may be normal volunteers rather than patients with a targeted disease.

GSK rolled out CTSD for completed studies in 2007. Before moving into full production with instream review in April, GSK conducted three pilots over a period of nine months. “Other companies do instream review via outsourcing or as a special project using lots of resources and paper,” says Cassells. “GSK is the first to attempt to do routine instream review using an interactive, off-the-shelf software package.”

For completed study review, about 25% of SRTs representing over 100 users across GSK therapeutic areas are using the CTSD tool, says Pinkston. That figure is expected to grow considerably over the next one to two years.

Although it is too early to project resource savings attained by using CTSD for instream safety review, the figure is expected to be significant, says Pinkston. Evidence recently emerged showing GSK saved the cost of two SAS programmers for one project by using the CTSD tool rather than the old paper-intensive method of safety monitoring.

To date, GSK has loaded 10 ongoing studies into the tool for instream review,” says Pinkston. “GSK expects the number to grow rapidly over the next three to five years.” Of the first five studies where CTSD has been used for instream review, no major safety issues have been found by the tool. However, the more robust process and easy access to the data have significantly boosted the confidence of SRT members making safety determinations, says Pinkston. GSK is now conducting internal research to learn how much earlier known safety problems of an old, discontinued compound would have been detected using the CTSD tool.

GSK’s investment in CTSD to date has been approximately $300,000 in implementation and $200,000 in data conversion services over the past two years, says Pinkston. GSK expects to pay $900,000 for software licenses over a three-year period. 

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This article appeared in Bio-IT World Magazine.

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