B. Begaud et al., FALSE-POSITIVES IN SPONTANEOUS REPORTING - SHOULD WE WORRY ABOUT THEM, British journal of clinical pharmacology, 38(5), 1994, pp. 401-404
1 Spontaneous reporting remains the most used and, undoubtedly, the mo
st cost-effective approach for the identification of adverse drug reac
tions (ADRs). Most of the limitations of this method are well recognis
ed but the possibility of receiving false-positive reports of coincide
ntal drug-event associations has received little attention. 2 In this
paper we propose a method based on the Poisson distribution for comput
ing the maximum number of reports of an ADR that could be expected to
be reported coincidentally. Three parameters are required: (i) the bac
kground risk of the event in the reference population, (ii) the total
number of patients treated with the drug considered and, (iii) the pro
portion of cases that have been reported to the pharmacovigilance syst
em. 3 For most empirical situations occurring in the post-marketing su
rveillance setting, the expected number remains low and only a maximum
of one to three cases could be accepted as possibly coincidental. 4 F
or rare adverse events such as agranulocytosis or toxic epidermal necr
olysis, coincidental associations are so unlikely that a number of rep
orts greater than three constitutes a strong warning and requires furt
her investigation. 5 These findings suggest that for rare events, repo
rts of coincidental drug-event associations are too unlikely to be con
sidered as an important limitation of spontaneous reporting.