PURPOSE: This study aimed to develop an algorithm for uncovering associations masked by extreme reporting rates, characterize the occurrence of masking by influential outliers in two spontaneous reporting databases and evaluate the impact of outlier removal on disproportionality analysis. METHODS: We propose an algorithm that identifies influential outliers and carries out parallel analysis after their omission. It considers masking of drugs as well as of adverse drug reactions (ADRs), uses a direct measure of the masking effect and makes no assumptions regarding the number of outliers per drug or ADR. The occurrence of masking is characterized in the WHO Global Individual Case Safety Report database, VigiBase and a regional collection of reports from Shanghai, China. RESULTS: For WHO-ART critical terms such as myocardial infarction, rhabdomyolysis and hypoglycaemia outlier removal led to a 25-50% increase in the number of Statistics of Disproportionate Reporting (SDR) and gains in time to detection of 1-2 years, while keeping the rate of spurious SDRs from the parallel analysis at 1%. Twenty-three per cent of VigiBase and 18% of Shanghai SRS reports listed an influential outlier. Twenty-seven per cent of the ADRs and 5% of the drugs in VigiBase, and 2% of the ADRs and 3% of the drugs in Shanghai SRS were involved in an outlier. The overall increase in the number of SDRs for both datasets was 3%. CONCLUSION: Masking by outliers has substantial impact on specific ADRs including, in VigiBase, rhabdomyolysis, myocardial infarction and hypoglycaemia. It is a local phenomenon involving a fair number of reports but yielding a limited number of additional SDRs.
PURPOSE: This study aimed to develop an algorithm for uncovering associations masked by extreme reporting rates, characterize the occurrence of masking by influential outliers in two spontaneous reporting databases and evaluate the impact of outlier removal on disproportionality analysis. METHODS: We propose an algorithm that identifies influential outliers and carries out parallel analysis after their omission. It considers masking of drugs as well as of adverse drug reactions (ADRs), uses a direct measure of the masking effect and makes no assumptions regarding the number of outliers per drug or ADR. The occurrence of masking is characterized in the WHO Global Individual Case Safety Report database, VigiBase and a regional collection of reports from Shanghai, China. RESULTS: For WHO-ART critical terms such as myocardial infarction, rhabdomyolysis and hypoglycaemia outlier removal led to a 25-50% increase in the number of Statistics of Disproportionate Reporting (SDR) and gains in time to detection of 1-2 years, while keeping the rate of spurious SDRs from the parallel analysis at 1%. Twenty-three per cent of VigiBase and 18% of Shanghai SRS reports listed an influential outlier. Twenty-seven per cent of the ADRs and 5% of the drugs in VigiBase, and 2% of the ADRs and 3% of the drugs in Shanghai SRS were involved in an outlier. The overall increase in the number of SDRs for both datasets was 3%. CONCLUSION: Masking by outliers has substantial impact on specific ADRs including, in VigiBase, rhabdomyolysis, myocardial infarction and hypoglycaemia. It is a local phenomenon involving a fair number of reports but yielding a limited number of additional SDRs.
Authors: Mickael Arnaud; Francesco Salvo; Ismaïl Ahmed; Philip Robinson; Nicholas Moore; Bernard Bégaud; Pascale Tubert-Bitter; Antoine Pariente Journal: Drug Saf Date: 2016-03 Impact factor: 5.606
Authors: Joe-Elie Salem; Tao Yang; Javid J Moslehi; Xavier Waintraub; Estelle Gandjbakhch; Anne Bachelot; Francoise Hidden-Lucet; Jean-Sebastien Hulot; Bjorn C Knollmann; Benedicte Lebrun-Vignes; Christian Funck-Brentano; Andrew M Glazer; Dan M Roden Journal: Circulation Date: 2019-08-05 Impact factor: 29.690
Authors: Alana Cavadino; Lovisa Sandberg; Inger Öhman; Tomas Bergvall; Kristina Star; Helen Dolk; Maria Loane; Marie-Claude Addor; Ingeborg Barisic; Clara Cavero-Carbonell; Ester Garne; Miriam Gatt; Babak Khoshnood; Kari Klungsøyr; Anna Latos-Bielenska; Nathalie Lelong; Reneé Lutke; Anna Materna-Kiryluk; Vera Nelen; Amanda Nevill; Mary O'Mahony; Olatz Mokoroa; Anna Pierini; Hanitra Randrianaivo; Anke Rissmann; David Tucker; Awi Wiesel; Lyubov Yevtushok; Joan K Morris Journal: Drug Saf Date: 2021-05-09 Impact factor: 5.606
Authors: Richard D Boyce; Patrick B Ryan; G Niklas Norén; Martijn J Schuemie; Christian Reich; Jon Duke; Nicholas P Tatonetti; Gianluca Trifirò; Rave Harpaz; J Marc Overhage; Abraham G Hartzema; Mark Khayter; Erica A Voss; Christophe G Lambert; Vojtech Huser; Michel Dumontier Journal: Drug Saf Date: 2014-08 Impact factor: 5.606
Authors: S Cederholm; G Hill; A Asiimwe; A Bate; F Bhayat; G Persson Brobert; T Bergvall; D Ansell; K Star; G N Norén Journal: Drug Saf Date: 2015-01 Impact factor: 5.606
Authors: Antoni F Z Wisniewski; Andrew Bate; Cedric Bousquet; Andreas Brueckner; Gianmario Candore; Kristina Juhlin; Miguel A Macia-Martinez; Katrin Manlik; Naashika Quarcoo; Suzie Seabroke; Jim Slattery; Harry Southworth; Bharat Thakrar; Phil Tregunno; Lionel Van Holle; Michael Kayser; G Niklas Norén Journal: Drug Saf Date: 2016-06 Impact factor: 5.606