Analgesic Use, Agranulocytosis, and Aplastic Anemia

To the Editor.— I read with great interest the results of the International Agranulocytosis and Aplastic Anemia study. 1 This article gives rise, however, to some fundamental questions. First, was the method of calculation used appropriate to the study of a disease (agranulocytosis) that is largely drug induced? Second, what is the real meaning of the rate ratio estimate? Usually, a case-control study is concerned with a naturally occurring disease. The risk to the users of a particular drug is estimated by comparing the ratio of users and nonusers of the drug among cases (a/b) and controls (c/d). However, when patients with systemic diseases that can cause neutropenia are excluded, as was done in this study, the remaining cases of agranulocytosis are largely due to drugs. 2 If we focus on a particular drug, say X, then group b can be subdivided into patients with agranulocytosis due to drugs other