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Effect of Lawyer-Submitted Reports on Signals of Disproportional Reporting in the Food and Drug Administration’s Adverse Event Reporting System

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Abstract

Introduction

Lawyer-submitted reports may have unintended consequences on safety signal detection in spontaneous adverse event reporting systems.

Objective

Our objective was to assess the impact of lawyer-submitted reports primarily for one adverse event (AE) on the ability to detect a signal of disproportional reporting for another AE for the same drug in the US FDA Adverse Event Reporting System (FAERS).

Methods

FAERS reports from January 2004 to September 2015 were used to estimate yearly cumulative proportional reporting ratios (PRRs) for three known drug–AE pairs—isotretinoin–birth defects, atorvastatin–rhabdomyolysis, and rosuvastatin–rhabdomyolysis—with and without lawyer-submitted reports. Isotretinoin and atorvastatin have been the subject of high-profile tort litigation regarding other AEs. A lower bound of the 95% confidence interval (CI) of one or more based on three or more reports defined a signal.

Results

Cumulative PRRs met signaling criteria in all analyses. For isotretinoin, lawyer-submitted reports increased PRRs for birth defects before 2008, with the largest increase in 2006 (2.9 [95% CI 2.4–3.5] to 3.3 [95% CI 2.8–3.9]); lawyer-submitted reports decreased PRRs for birth defects after 2011, with the largest decrease in 2013 (2.2 [95% CI 2.0–2.5] to 1.9 [95% CI 1.7–2.1]). For atorvastatin, lawyer-submitted reports reduced PRRs for rhabdomyolysis after 2013, with the largest decrease in 2015 (18.0 [95% CI 17.1–19.1] to 15.4 [95% CI 14.5–16.2]). Lawyer-submitted reports had little impact on PRRs for rosuvastatin and rhabdomyolysis.

Conclusions

Inclusion of lawyer-submitted reports in FAERS did not meaningfully distort known safety signals for two drugs subject to high-profile tort litigation for other AEs.

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Author notes

  1. James R. Rogers

    Present address: Department of Biomedical Informatics, Columbia University, New York, NY, USA

Authors and Affiliations

  1. Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA, 02120, USA

    James R. Rogers, Ameet Sarpatwari, Rishi J. Desai, Justin M. Bohn, Nazleen F. Khan, Aaron S. Kesselheim, Michael A. Fischer, Joshua J. Gagne & John G. Connolly

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  1. James R. Rogers
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  2. Ameet Sarpatwari
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  3. Rishi J. Desai
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  4. Justin M. Bohn
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  5. Nazleen F. Khan
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  6. Aaron S. Kesselheim
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  7. Michael A. Fischer
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Corresponding author

Correspondence to Joshua J. Gagne.

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Conflict of interest

James R. Rogers previously served as a paid consultant to Aetion, Inc., a software company, for unrelated work; he is currently a student at the Department of Biomedical Informatics, Columbia University, New York, New York, USA. Ameet Sarpatwari previously served as a paid consultant to Aetion, Inc., for unrelated work. Rishi J. Desai was the principal investigator of a research grant from Merck to Brigham & Women’s Hospital for unrelated work. Aaron S. Kesselheim has received prior research grants from the FDA Office of Generic Drugs and Division of Health Communication, for unrelated work. Joshua J. Gagne has received salary support from grants from Novartis Pharmaceutical Corporation and Eli Lilly and Company to Brigham and Women’s Hospital and is a consultant to Aetion, Inc. and to Optum, Inc., all for unrelated work. Justin M. Bohn, Nazleen F. Khan, Michael A. Fischer, and John G. Connolly have no conflicts of interest.

Funding

 Drs. Sarpatwari and Kesselheim's work was funded by the Laura and John Arnold Foundation, as well as the Harvard Program in Therapeutic Science and Engelberg Foundation.

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Rogers, J.R., Sarpatwari, A., Desai, R.J. et al. Effect of Lawyer-Submitted Reports on Signals of Disproportional Reporting in the Food and Drug Administration’s Adverse Event Reporting System. Drug Saf 42, 85–93 (2019). https://doi.org/10.1007/s40264-018-0703-x

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  • DOI: https://doi.org/10.1007/s40264-018-0703-x

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