br Methods The FDA adverse event reporting

The FDA adverse event reporting system (FAERS) was utilised to assess the association between the use of an entacapone-containing drug combination and the signal of death using a case/non-case method. All reports that were available in the FDA AERS database from January 2004 to December 2010 were accessed and downloaded from the FDA website ( However, in the dataset from 2004, there were some reports dated before 2004. FAERS is a spontaneous reporting system that contains data on adverse drug events and medication errors submitted to the FDA (Food and Drug Administration, 0000).
The FDA AERS contains either all or some of the information on the MedWatch reporting form that is usually sent by healthcare professionals as well as patients or insulin signaling from the United States (U.S.) or outside the U.S. In addition, this system includes reports sent from the manufacturers for serious adverse drug reactions in the U.S. or serious and unlabelled spontaneous reports from outside the U.S. It is worth noting that any report should include four elements to be considered a valid report prior to entry into the system: an identifiable patient, an identifiable reporter, the suspected drug and the adverse drug event. The reporter and suspected drug elements are available as free text while the adverse drug events are coded by the Medical Dictionary for Regulatory Activities (MedDRA). The MedDRA term level used to code the adverse drug event is the preferred term (PT) Food and Drug Administration, 0000; Poluzzi et al., 2009, 2010.
The main group of medications of interest was drugs that include entacapone for the treatment of Parkinson’s disease. Stalevo® is the only drug that contains entacapone (Food and Drug Administration, 2010a). Another group of medications was also included in this study, i.e. the combination of levodopa and carbidopa, which is marketed as Sinemet®. Entacapone is either used as a separate pill with levodopa and carbidopa or as a combination of the three drugs in one pill, as in the case of Stalevo® (Food and Drug Administration, 2010a). Both the trade and generic (chemical name) names were used to extract the reports that included entacapone-containing products as well as other drugs included in this study. The outcome of interest was death, and was searched using the term “death” in the PT field in the FAERS database.
A case/non-case method was used to analyse the association between the use of drugs of interest and the signal of death. Cases were the reports of the outcome of interest, which was “death”, and were extracted using the PT for any given drug, while the non-cases were all other reports related to the same drug (other than the reports of the outcome of interest, which was death). All death terms that were not related to the population of the study, for example “neonatal death” and “inter-uterine death”, were excluded. For both cases and non-cases, only reports that considered the drug of interest as the primary suspected drug were included in the analysis. The reporting odds ratio (ROR), as a measure of disproportionality, was used to assess the association between the drug of interest and death. The ratio of case/non-case reports for each group (the entacapone-containing drug combination group and the levodopa/carbidopa group) were compared to other medications. The ROR calculation is explained in detail elsewhere (Moore et al., 1997). All statistical analyses were performed using SAS® software (version 9.2) (SAS Institute Inc., Cary, North Carolina, USA).

The ROR of death associated with the entacapone-containing drug combination was statistically significant (1.86 [95% CI 1.50–2.31]). Conversely, the ROR of death associated with the combination of levodopa and carbidopa was not statistically significant (0.89 [95% CI 0.61–1.30)] (Table 1). Age was recorded in 48 cases of those who were using the entacapone-containing drug combination; the mean age was 75years with a minimum age of 50years and a maximum age of 93years. Only seven cases of patients who were using the combination of levodopa and carbidopa contained the age information; the mean age was 72, the minimum age was 40years and the maximum age was 87years. The majority of cases in both groups were males (entacapone group 64% and levodopa/carbidopa group 73%).