Should methods of correction for multiple comparisons be applied in pharmacovigilance? Reasoning around an investigation on safety of oral antidiabetic drugs

Lorenza Scotti, Silvana Romio, Arianna Ghirardi, Andrea Arfè, Manuela Casula, Lorna Hazell, Francesco Lapi, Alberico Catapano, Miriam Sturkenboom, Giovanni Corrao

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: In pharmacovigilance, spontaneous reporting databases are devoted to the early detection of adverse event ‘signals’ of marketed drugs. A common limitation of these systems is the wide number of concurrently investigated associations, implying a high probability of generating positive signals simply by chance. However it is not clear if the application of methods aimed to adjust for the multiple testing problems are needed when at least some of the drug-outcome relationship under study are known. To this aim we applied a robust estimation method for the FDR (rFDR) particularly suitable in the pharmacovigilance context. METHODS: We exploited the data available for the SAFEGUARD project to apply the rFDR estimation methods to detect potential false positive signals of adverse reactions attributable to the use of noninsulin blood glucose lowering drugs. Specifically, the number of signals generated from the conventional disproportionality measures and after the application of the rFDR adjustment method was compared. RESULTS: Among the 311 evaluable pairs (i.e., drug-event pairs with at least one adverse event report), 106 (34%) signals were considered as significant from the conventional analysis. Among them 1 resulted in false positive signals according to rFDR method. CONCLUSION: The results of this study seem to suggest that when a restricted number of drug-outcome pairs is considered and warnings about some of them are known, multiple comparisons methods for recognizing false positive signals are not so useful as suggested by theoretical considerations.

Original languageEnglish
Article numbere11654
JournalEpidemiology Biostatistics and Public Health
Volume12
Issue number4
DOIs
Publication statusPublished - 2015

Keywords

  • Bladder safety
  • Cardiovascular safety
  • False discovery rate
  • Noninsulin blood glucose lowering drugs
  • Pancreatic safety
  • Pharmacovigilance
  • Spontaneous report database

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Public Health, Environmental and Occupational Health
  • Community and Home Care

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