[Assessment of drug-related risk using expected/observed methods (standardized rate method): definition and application to pharmacovigilance].

Indirect standardisation or the standardised rate method, consists of a comparison of the number of observed and expected cases. This method could be applied in the field of pharmacovigilance in order to investigate the potential relationship between drug exposure and the occurrence of an adverse event. It consists of the calculation of an expected number of events obtained by multiplying the exposed population by the event rate in the reference population. The comparison is made by means of a standardised mortality or incidence ratio (SMR or SIR). Three examples of this method are presented. The first example concerns central nervous system demyelinating disorders and hepatitis B vaccine, where the SIR calculated from spontaneous reports was equal to 1.05 (95% CI [0.82-1.26]). In the second example, the SMR of cardiovascular deaths related to sildenafil was significantly different from 1 (0.69, [0.43-1.08]) using data from prescription-event monitoring. In the last example, a strong association between acute leukaemia and chemotherapy in breast cancer was found (SIR 28.5, [12.3-56.2]) using exhaustive data from cancer registries. This method allows a quick and cheap risk assessment, although the quality of available data may limit validity of results. In this case, the hypothesis need to be examined by further ad-hoc clinical and pharmacoepidemiological studies.