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Evaluation of Pre-marketing Factors to Predict Post-marketing Boxed Warnings and Safety Withdrawals

Author

Listed:
  • Andreas Schick

    (U.S. Food and Drug Administration)

  • Kathleen L. Miller

    (U.S. Food and Drug Administration)

  • Michael Lanthier

    (U.S. Food and Drug Administration)

  • Gerald Dal Pan

    (U.S. Food and Drug Administration)

  • Clark Nardinelli

    (U.S. Food and Drug Administration)

Abstract

Introduction An important goal in drug regulation is understanding serious safety issues with new drugs as soon as possible. Achieving this goal requires us to understand whether information provided during the Food and Drug Administration (FDA) drug review can predict serious safety issues that are usually identified after the product is approved. However, research on this topic remains understudied. In this paper, we examine whether any pre-marketing drug characteristics are associated with serious post-marketing safety actions. Methods We study this question using an internal FDA database containing every new small molecule drug submitted to the FDA’s Center for Drug Evaluation and Research (CDER) on or after November 21, 1997, and approved and commercially launched before December 31, 2009. Serious post-marketing safety actions include whether these drugs ever experienced either a post-marketing boxed warning or a withdrawal from the market due to safety concerns. A random effects logistic regression model was used to test whether any pre-marketing characteristics were associated with either post-marketing safety action. Results A total of 219 new molecular entities were analyzed. Among these drugs, 11 experienced a safety withdrawal and 30 received boxed warnings by July 31, 2016. Contrary to prevailing hypotheses, we find that neither clinical trial sample sizes nor review time windows are associated with the addition of a post-marketing boxed warning or safety withdrawal. However, we do find that new drugs approved with either a boxed warning or priority review are more likely to experience post-marketing boxed warnings. Furthermore, drugs approved with boxed warnings tend to receive post-marketing boxed warnings resulting from new safety information that are unrelated to the original warning. Drugs approved with a boxed warning are 3.88 times more likely to receive a post-marketing boxed warning, while drugs approved with a priority review are 3.51 times more likely to receive a post-marketing boxed warning. Conclusion Although drugs approved with a boxed warning or priority review are more likely to experience serious post-marketing safety events, other information provided during the FDA drug review that is easy to quantify is generally not associated with post-marketing safety events. It appears that these post-marketing events are not discernible during a pre-marketing review and therefore might not be avoidable using current review data.

Suggested Citation

  • Andreas Schick & Kathleen L. Miller & Michael Lanthier & Gerald Dal Pan & Clark Nardinelli, 2017. "Evaluation of Pre-marketing Factors to Predict Post-marketing Boxed Warnings and Safety Withdrawals," Drug Safety, Springer, vol. 40(6), pages 497-503, June.
  • Handle: RePEc:spr:drugsa:v:40:y:2017:i:6:d:10.1007_s40264-017-0526-1
    DOI: 10.1007/s40264-017-0526-1
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    References listed on IDEAS

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    1. Mary K. Olson, 2002. "Pharmaceutical Policy Change and the Safety of New Drugs," Journal of Law and Economics, University of Chicago Press, vol. 45(S2), pages 615-642.
    2. Olson, Mary K., 2008. "The risk we bear: The effects of review speed and industry user fees on new drug safety," Journal of Health Economics, Elsevier, vol. 27(2), pages 175-200, March.
    3. Olson, Mary K., 2004. "Are novel drugs more risky for patients than less novel drugs?," Journal of Health Economics, Elsevier, vol. 23(6), pages 1135-1158, November.
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