Sometimes Less is More: FDA Issues White Paper on Selective Safety Data Collection

FDA recently released a CDER Center for Clinical Trial Innovation (C3TI) White Paper on Selective Safety Data Collection (SSDC), a subject about which there is little awareness. Selective Safety Data Collection (SSDC) describes the prospectively planned curtailment of safety data collection in studies where the safety profile of the drug has been well characterized. Although some information should always be collected from a clinical trial, e.g., serious adverse events, adverse dropouts, adverse events of special interest, other information may be unnecessary. Consider an approved drug, studied in 1200 subjects, with a table in Section 6 of labeling that lists nausea as an adverse reaction, e.g., 24% with drug and 13% with placebo. If subjects in the planned study are similar to those in registrational studies, how important would it be to query subjects about non-serious adverse events of nausea in a subsequent study? And given that routine laboratory data were collected and analyzed in these 1200 subjects, how important would it be to collect tens of thousands of additional laboratory values in the planned study? In this situation, FDA and other regulatory authorities recognize that such information would not add importantly to the safety knowledge about the drug. Collection of such data increases the burden of the study, first and foremost to participants, and also to investigators, sponsors, and regulatory authorities. Why worry about the burden? If clinical studies are less burdensome, more will be conducted, and more questions will be answered—the main goal of clinical research.

FDA expressed its willingness to adopt SSDC when it released its 2016 Guidance for Industry, “Determining the Extent of Safety Data Collection Needed in Late-Stage Premarket and Postapproval Clinical Investigations.” When I was an Office Director in CDER, we would encourage sponsors to use this approach in studies they were planning. Executives would smile and nod their heads in agreement, but no one took us up on the offer! Our thinking was that we needed international buy-in of this approach for it to be viable, given that these were multinational studies that involved regulators from around the world.

In 2016, I advanced SSDC as a topic for the International Council on Harmonisation (ICH). The matter was taken up as a topic by the ICH E19 Expert Working Group, and I was appointed as one of the FDA leads. In the working group, it became apparent that the resistance to SSDC was not so much from regulators outside the US, but rather from the companies, who felt like they needed to obtain every shred of information from their trials! They worried that a regulator—somewhere, sometime—would request the information, and thought that, rarely, the availability of comprehensive safety information might help explain the etiology of unusual serious adverse events. Moreover, such decisions could be driven by the most conservative member of leadership at each company!

ICH finalized the Guideline, “E19, A Selective Approach to Safety Data Collection in Specific Late-Stage Pre-Approval or Post-Approval Clinical Trials,” almost 3 years ago; however, the concept still draws little attention from industry. FDA is now increasing awareness of the concept with their new White Paper. The White Paper does an excellent job in explaining the concept of SSCD, its utility, past and present experience, and opportunities for future use, all with excellent examples. It is something we hope many of you will read.