• Concomitant medications, unless they are likely to interact with the drug being given, have an antitumor effect, or meet a specific objective of the trial (e.g., are integral to a health economics/costing study).

The analysis also indicated that a subsample of about 400 patients provided adequate probability of detecting adverse events with at least a 3 percent excess toxicity. The authors suggested that the FDA should put forth a detailed guidance document with clear directives on data collection requirements for concomitant medications and adverse events for trials of supplementary drug indications.

The FDA responded by issuing a new draft guidance in February 2012 stating that targeted safety data collection akin to what was done in the ASCO study may be appropriate when the safety profile of the drug is already well characterized from prior studies, with adverse event type and frequency being similar across multiple studies, and when the expected adverse event rates in study population are likely to be similar to what was found in previous studies. In addition, the FDA specified that targeted safety data collection may be appropriate for postmarketing studies for new indications, studies required to meet postmarketing requirements, and large outcome studies.

“We’re making great progress here. We have strong data that supports the notion that for supplemental applications there can be substantial reduction in the amounts of safety data collected without missing any important safety signals. I think that’s been acknowledged in the recent FDA draft guidance on this topic,” said Schilsky.

Sherman, of the FDA, pointed out during her presentation that the purpose of the draft FDA guidance is to help clinical trial sponsors determine the amount and types of safety data that should be collected during late-stage premarket and post-approval clinical investigations. She said this draft guidance makes clear that sponsors can use a variety of approaches to fulfill their monitoring responsibilities, and that sponsors may request different reporting formats or frequencies for adverse event reporting either by describing the method in the protocol or by requesting a waiver. Either way, Sherman stressed, alternative reporting must be agreed to by the FDA in advance of the trial launch. “Before your plan is put into place, come talk to us and make sure that everyone is happy,” she said.

Roychowdhury was more cautious about modifying adverse event



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