Postmarketing hepatic adverse event experience with PEGylated/non-PEGylated drugs: a disproportionality analysis

Hauben, M; Vegni, F; Reich, L; Younus, M; (2007) Postmarketing hepatic adverse event experience with PEGylated/non-PEGylated drugs: a disproportionality analysis. European journal of gastroenterology & hepatology, 19 (11). pp. 934-41. ISSN 0954-691X DOI:

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OBJECTIVE: To compare reporting frequencies of hepatic adverse events between PEGylated and non-PEGylated formulations of active medicinal compounds in spontaneous reporting systems using a data mining algorithm (DMA). METHODS: Statistical DMAs are being promoted as a means of identifying drug-event combinations that are disproportionately reported in large spontaneous reporting systems databases, a critical data source for pharmacovigilance. After a review of case reports of hepatotoxicity with PEGylated drugs possibly associated with the polyethylene glycol moiety, we carried out a retrospective disproportionality analysis of WHO's multinational drug safety database for events related to hepatic dysfunction comparing PEGylated versus non-PEGylated formulations of four active moieties. A threshold of posterior interval (PI) 95% lower limit >0 was used to define a signal of disproportionate reporting with a drug and an event and 90% PIs of the information component were compared to identify statistical differences between the two compounds. RESULTS: On the basis of a total of 18 477 cases containing at least one of the drug pairs, we found disproportionate reporting for hepatic-related events with both PEGylated and non-PEGylated formulations. Overlapping of 90% PIs of the information components, however, suggested that there was no statistically significant difference between the frequency of hepatic injury reported with PEGylated versus non-PEGylated drug formulations. CONCLUSION: We did not find significant indicators of differential reporting of hepatic injury between PEGylated and non-PEGylated drug formulations in this exploratory analysis using one DMA. The analysis also suggests that comparative disproportionality methodology although not in itself determinative, could be one useful component of a risk management plan for monitoring the postmarketing experience of drug delivery systems that uses multiple methods and data streams.

Item Type: Article
Keywords: Adverse Drug Reaction Reporting Systems/statistics & numerical data, *Algorithms, Bias (Epidemiology), *Databases, Factual, Drug Carriers/*adverse effects, Humans, Liver/*drug effects, Polyethylene Glycols/*adverse effects, Product Surveillance, Postmarketing/*methods, World Health Organization
Faculty and Department: Faculty of Public Health and Policy > Dept of Social and Environmental Health Research
PubMed ID: 18049161
Web of Science ID: 254356700005


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