ABSTRACT
<b>Objective</b>: It is very difficult to identify the frequency of rare adverse drug reactions (ADRs) precisely. A study was conducted to estimate the frequency of ADRs that were not observed in clinical studies by referring to the sales volume of the pharmaceuticals until the date when the ADR was first observed after a drug was marketed.<br><b>Methods and Subjects</b>: The study was conducted for the 17 pharmaceuticals to estimate the frequency of Hepatopathy. The date of report of the ADR to the Minister was obtained through information disclosure requests. The sales volume of the relevant pharmaceuticals was provided by IMS Japan. On the premise that all the ADRs were detectable, the probability (<i>P</i>) that an ADR was not detected right before drug administration in the first case of the ADR was estimated through Formula 1.<br>Formula 1 : <i>P</i>=1−{(<i>D</i><sub>0</sub><i>−S</i>)!÷(<i>D</i><sub>0</sub><i>−S−D<sub>N</sub></i>)!}/{<i>D</i><sub>0</sub>!÷(<i>D</i><sub>0</sub>−<i>D</i><i><sub>N</sub></i>)!} = 1−{(<i>D</i><sub>0</sub><i>−D</i><sub>0</sub>×<i>F</i>)!÷(<i>D</i><sub>0</sub><i>−D</i><sub>0</sub>×<i>F</i><i>−D<sub>N</sub></i>)!}/{<i>D</i><sub>0</sub>!÷(<i>D</i><sub>0</sub>−<i>D</i><i><sub>N</sub></i>)!}<br> <i>D</i><sub>0</sub> referred to the estimated person-days for all the patients subject to the drug therapy, <i>S</i> to the number of patients with ADR, <i>D</i><sub><i>N</i></sub> to the person-days until the date when the ADR was observed and <i>F</i> to the frequency of the ADR. <i>F</i> was estimated where the detection <i>P</i> was 0.95 or was close to 0.95.<br><b>Results and Discussion</b>: Among the pharmaceuticals investigated, the frequency was highest in product A (0.038%) and was lowest in product X (0.0000088%). In many cases, the package inserts describe the frequencies of rare ADRs as unknown. However, the frequency can be estimated relatively precisely through the method stated above using data, which may be kept by pharmaceutical manufacturers.
