Joining the DoTS: new approach to classifying adverse drug reactions

Abstract

A new classification system for adverse drug reactions based on time course and susceptibility as well as dose responsiveness should improve drug development and management of adverse reactions The pharmacological classification of adverse drug reactions whose causality has been established currently rests on the perceived dose dependence and predictability of the adverse reaction. It is based on a proposal of Rawlins and Thompson, prefigured by others (see table A on bmj.com), to classify adverse drug reactions into two types1: type A reactions, dose dependent and predictable from the known pharmacology of the drug; and type B reactions, not dose dependent and unpredictable.2 This classification is simple; it helps drug regulation because prelicensing studies can reveal type A reactions,3 and it predicts that dose titration will reduce the risk of some reactions. However, it is sometimes difficult or impossible to assign a reaction to one type. For example, dose dependent (type A) nausea and vomiting due to erythromycin could also be classified as type B because it is not pharmacologically predictable. Furthermore, other types of adverse reactions are not comfortably classified by the system. For example, osteoporosis from corticosteroids depends not only on dose but also on duration of treatment. And some reactions, such as asthma from β adrenoceptor antagonists, do not occur in all patients. The classification has gradually been extended to other alphabetically labelled types (see table A on bmj.com), including type C (dose and time dependent (chronic) reactions), type D (delayed reactions), type E (withdrawal reactions), and type F (failure of therapy).4 These modifications have mitigated some of the difficulties of the classification system but have introduced others. The current classification is defined only by properties of the drug—its known pharmacology and the dose dependence of its effects. However, other criteria should be …