On the assessment of adverse drug reactions from spontaneous reporting systems: the influence of under-reporting on odds ratios.

A well-known problem in spontaneous reporting systems (SRSs) for adverse drug reactions (ADRs) is under-reporting, that is, the problem that not all occurrences of ADRs are reported to the SRS. We look at the question of how to draw statistical conclusions from analyses of SRS data using reporting odds ratios. We will show that certain under-reporting problems play no role in assessing ADRs from SRSs: the results from the analyses turn out to be biased by some specific under-reporting problems, but not by others. SRS data can be particularly useful for the assessment of drug-drug interactions. If the assumption holds that there is an under-reporting problem for a first drug, and an under-reporting problem for a second drug, but that these two under-reporting problems do not influence each other, then reporting odds ratios estimated from SRSs are useful for signalling drug-drug interactions in the ADR-experiencing population. Similar results hold for covariate-drug interactions. We illustrate our results using two examples. Copyright 2002 John Wiley & Sons, Ltd.