When More Is Less: An Exploratory Study of the Precautionary Reporting Bias and Its Impact on Safety Signal Detection

TY - JOUR

T1 - When More Is Less

T2 - An Exploratory Study of the Precautionary Reporting Bias and Its Impact on Safety Signal Detection

AU - Klein, Kevin

AU - Scholl, Joep H G

AU - De Bruin, Marie L

AU - van Puijenbroek, Eugène P

AU - Leufkens, Hubert G M

AU - Stolk, Pieter

N1 - © 2017 American Society for Clinical Pharmacology and Therapeutics.

PY - 2018/2

Y1 - 2018/2

N2 - Concerns have been expressed that large numbers of nonvalue-added reports have been accumulating in adverse drug reaction (ADR) databases, for example, via patient support programs. We performed an assessment of the impact of such reports, which we refer to as "precautionary reports," on safety signal detection in the Netherlands. The case narratives of ADR reports of three case products were screened with text-mining algorithms to identify those reports that lack a causal relationship with the suspected medicinal product. We demonstrate that precautionary reports impede the optimal use of the pharmacovigilance system by, on the one hand, masking safety signals and, on the other hand, creating spurious signals. The precautionary reporting bias and its suppressing effect on statistical signal detection results in an altered adverse event safety profile. The findings from this study highlight the need for a better alignment between regulatory authorities and marketing authorization holders regarding pharmacovigilance guidelines.

AB - Concerns have been expressed that large numbers of nonvalue-added reports have been accumulating in adverse drug reaction (ADR) databases, for example, via patient support programs. We performed an assessment of the impact of such reports, which we refer to as "precautionary reports," on safety signal detection in the Netherlands. The case narratives of ADR reports of three case products were screened with text-mining algorithms to identify those reports that lack a causal relationship with the suspected medicinal product. We demonstrate that precautionary reports impede the optimal use of the pharmacovigilance system by, on the one hand, masking safety signals and, on the other hand, creating spurious signals. The precautionary reporting bias and its suppressing effect on statistical signal detection results in an altered adverse event safety profile. The findings from this study highlight the need for a better alignment between regulatory authorities and marketing authorization holders regarding pharmacovigilance guidelines.

KW - Journal Article

U2 - 10.1002/cpt.879

DO - 10.1002/cpt.879

M3 - Journal article

C2 - 28913827

SN - 0009-9236

VL - 103

SP - 296

EP - 303

JO - Clinical Pharmacology and Therapeutics

JF - Clinical Pharmacology and Therapeutics

ER -