The upper bound to the Relative Reporting Ratio—a measure of the impact of the violation of hidden assumptions underlying some disproportionality methods used in signal detection

Authors

  • Lionel Van Holle,

    Corresponding author
    1. Vaccine Safety Research Group, Vaccine Clinical Safety and Pharmacovigilance, GlaxoSmithKline Vaccines, Wavre, Belgium
    • Correspondence to: L. Van Holle, Vaccine Safety Research Group, Vaccine Clinical Safety and Pharmacovigilance, GlaxoSmithKline Vaccines, Parc de la Noire Epine, Avenue Fleming, 20, 1300—Wavre, Belgium. E-mail: lionel.f.van-holle@gsk.com

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  • Vincent Bauchau

    1. Vaccine Safety Research Group, Vaccine Clinical Safety and Pharmacovigilance, GlaxoSmithKline Vaccines, Wavre, Belgium
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  • Both authors state that the manuscript has not been published elsewhere.

ABSTRACT

Purpose

For disproportionality measures based on the Relative Reporting Ratio (RRR) such as the Information Component (IC) and the Empirical Bayesian Geometrical Mean (EBGM), each product and event is assumed to represent a negligible fraction of the spontaneous report database (SRD). Here, we provide the tools for allowing signal detection experts to assess the consequence of the violation of this assumption on their specific SRD.

Methods

For each product–event pair (P–E), a worst-case scenario associated all the reported events-of-interest with the product of interest. The values of the RRR under this scenario were measured for different sets of stratification factors using the GlaxoSmithKline vaccines SRD. These values represent the RRR upper bound that RRR cannot exceed whatever the true strength of association.

Results

Depending on the choice of stratification factors, the RRR could not exceed an upper bound of 2 for up to 2.4% of the P–Es. For Engerix™, 23.4% of all reports in the SDR, the RRR could not exceed an upper bound of 2 for up to 13.8% of pairs. For the P–E Rotarix™-Intussusception, the choice of stratification factors impacted the upper bound to RRR: from 52.5 for an unstratified RRR to 2.0 for a fully stratified RRR.

Conclusions

The quantification of the upper bound can indicate whether measures such as EBGM, IC, or RRR can be used for SRD for which products or events represent a non-negligible fraction of the entire SRD. In addition, at the level of the product or P–E, it can also highlight detrimental impact of overstratification. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

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