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Evaluating the potential for digital submission of expedited premarket safety reports to the FDA

Nature Reviews Drug Discovery volume 15, pages 670–671 (2016)Cite this article

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One of the primary mechanisms used by the FDA to protect human subjects participating in clinical trials is the requirement for mandatory safety reporting. Under the Code of Federal Regulations (21 CFR §312.32), sponsors of clinical trials conducted under an investigational new drug application (IND) must report serious and unexpected suspected adverse reactions (that is, adverse events for which there is a reasonable possibility that the drug caused the adverse event according to the sponsor's assessment) to participating investigators and the FDA in an expedited time frame (15 or 7 days depending on the type of event). The number of premarket safety reports submitted to the FDA's Office of Hematology and Oncology Products (OHOP) in an expedited basis has been steadily increasing in the past decade and, according to a recent analysis, most of the reports do not satisfy reporting criteria and are uninformative (Clin. Cancer Res. 9, 2111–2113; 2016). Distribution of uninformative safety reports can strain the resources of investigators, institutional review boards and the FDA, potentially creating a 'needle in a haystack' situation that can compromise detection of valid safety signals.

The FDA has been encouraging sponsors to devise mechanisms to reduce submission of uninformative expedited safety reports to improve consistency with the FDA's final rule on IND safety reporting requirements (see Further information), and several sponsors are exploring ways to improve reporting practices. For example, Merck & Co. recently communicated to the FDA that the company substantially reduced the number of reportable expedited safety reports in one of its clinical development programmes by implementing new procedures that focus on optimal utilization of qualified safety review physicians, establishment of consistent thresholds for causality assessment and identification of clinically relevant follow-up information.

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Figure 1: General workflow and technical configuration of the second stage of the FDA's premarket safety reports pilot programme.

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Authors and Affiliations

  1. Center for Drug Evaluation and Research, Food and Drug Administration, New Hampshire Avenue, Silver Spring, 20993, Maryland, USA

    Sean Khozin, Meredith Chuk, Tamy Kim, Geoffrey Kim & Richard Pazdur

  2. Office of Surveillance and Epidemiology, Food and Drug Administration, Silver Spring, 20993, Maryland, USA

    Suranjan De & Sanjay Sahoo

Authors
  1. Sean Khozin
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  2. Meredith Chuk
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  3. Tamy Kim
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  4. Suranjan De
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  5. Sanjay Sahoo
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  6. Geoffrey Kim
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  7. Richard Pazdur
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Corresponding author

Correspondence to Sean Khozin.

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The authors declare no competing financial interests.

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Khozin, S., Chuk, M., Kim, T. et al. Evaluating the potential for digital submission of expedited premarket safety reports to the FDA. Nat Rev Drug Discov 15, 670–671 (2016). https://doi.org/10.1038/nrd.2016.189

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