Postmarket Drug Surveillance Without Trial Costs: Discovery of Adverse Drug Reactions Through Large-Scale Analysis of Web Search Queries

Elad Yom-Tov,Evgeniy Gabrilovich

doi:10.2196/jmir.2614

Abstract

BackgroundPostmarket drug safety surveillance largely depends on spontaneous reports by patients and health care providers; hence, less common adverse drug reactions—especially those caused by long-term exposure, multidrug treatments, or those specific to special populations—often elude discovery.ObjectiveHere we propose a low cost, fully automated method for continuous monitoring of adverse drug reactions in single drugs and in combinations thereof, and demonstrate the discovery of heretofore-unknown ones.MethodsWe used aggregated search data of large populations of Internet users to extract information related to drugs and adverse reactions to them, and correlated these data over time. We further extended our method to identify adverse reactions to combinations of drugs.ResultsWe validated our method by showing high correlations of our findings with known adverse drug reactions (ADRs). However, although acute early-onset drug reactions are more likely to be reported to regulatory agencies, we show that less acute later-onset ones are better captured in Web search queries.ConclusionsOur method is advantageous in identifying previously unknown adverse drug reactions. These ADRs should be considered as candidates for further scrutiny by medical regulatory authorities, for example, through phase 4 trials.

Highlights

Existing mechanisms for postmarket drug surveillance work well in many cases, but failures resulting in harm to patients and even fatalities are widely documented [1], including the withdrawal of thalidomide in the 1960s [2], and more recently of cerivastatin [3], troglitazone [4], and rofecoxib [5]
Our method is advantageous in identifying previously unknown adverse drug reactions. These ADRs should be considered as candidates for further scrutiny by medical regulatory authorities, for example, through phase 4 trials. (J Med Internet Res 2013;15(6):e124) doi:10.2196/jmir
One kind is run by regulatory agencies, such as MedWatch by the US Food and Drug Administration (FDA) and the Vaccine Adverse Event Reporting System (VAERS) by the FDA and the Centers for Disease Control and Prevention (CDC) in the United States, the Yellow Card Scheme by the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom, and the International Drug Monitoring Programme by the World Health Organization (WHO)

Summary

Introduction

Existing mechanisms for postmarket drug surveillance work well in many cases, but failures resulting in harm to patients and even fatalities are widely documented [1], including the withdrawal of thalidomide in the 1960s [2], and more recently of cerivastatin [3], troglitazone [4], and rofecoxib [5]. One kind is run by regulatory agencies, such as MedWatch by the US Food and Drug Administration (FDA) and the Vaccine Adverse Event Reporting System (VAERS) by the FDA and the Centers for Disease Control and Prevention (CDC) in the United States, the Yellow Card Scheme by the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom, and the International Drug Monitoring Programme by the World Health Organization (WHO) These are supplemented by public (or public-private cooperation) initiatives, such as Research on Adverse Drug Events and Reports (RADAR), and Web sites, such as eHealthMe.com, which collect patient-reported information on drug outcomes. Postmarket drug safety surveillance largely depends on spontaneous reports by patients and health care providers; less common adverse drug reactions—especially those caused by long-term exposure, multidrug treatments, or those specific to special populations—often elude discovery

Methods

Results

Discussion

Conclusion