comes to the characterization of safety in that subgroup because it simply cannot be shown.”

Less Burdensome Reporting

Many clinical trials conducted by the NCTN assess secondary indications for approved drugs. Schilsky reported that a retrospective study conducted by ASCO in collaboration with industry used cancer clinical trial data to assess whether much of the collection and reporting of adverse events for drugs being tested for supplemental indications is necessary. A recent draft guidance from FDA (2012c) may help improve the efficiency of such trials by explicitly encouraging new and less burdensome ways of gathering and reporting adverse events and concomitant medications.

“Sometimes important safety signals can be obscured by all the additional information we’re required to report that oftentimes is not terribly informative,” Schilsky said. “We want to reduce the data collection burden on the clinical trials system so we can enhance physician participation, because one of the big obstacles we hear from doctors all the time is that there is so much paperwork involved in doing clinical trials that it’s just not worth the trouble,” Schilsky added.

The ASCO study reanalyzed multiple clinical trial toxicity databases and examined various sampling methods to determine if a more streamlined and “optimized” approach to data collection would provide sufficient safety data to support supplemental applications. This study found that capturing excess Grade 1 or 2 adverse events did not appear to add to the known safety profile, and that the probability of missing a previously unrecognized, clinically significant Grade 3 or 4 adverse event was low when the optimized data collection approach was used. In addition, review of concomitant medication databases from six trials demonstrated that no new information was gained from the summary tabulations required to be listed in the application for a supplementary new drug or biologic indication.

The resultant white paper (Abrams et al., 2009) recommended that for future supplemental trials with the appropriate qualifications, researchers need not collect

• Grade 1 or 2 adverse events (AEs) (already known);

• Grade 3 or 4 AEs in all patients;

• Stop/start dates for AEs except by cycle; or



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