Joining the DoTS: new approach to classifying adverse drug reactions

Examples of immunological reactions that are clearly dose dependent include hay fever in response to high pollen counts 5 ; the immunogenic response to hepatitis B vaccine 6 ; desensitisation by the use of increasing doses of antigen (for example, cephalosporins) 7 ; and type IV hypersensitivity skin reactions. 8 It is therefore misleading to suggest that type B adverse drug reactions are not dose dependent. 2 In fact, it is clearer to divide adverse drug reactions into reactions that occur at supratherapeutic doses (toxic effects); reactions that occur at standard therapeutic doses (collateral effects); and reactions that occur at subtherapeutic doses in susceptible patients (hypersusceptibility reactions). Classification Criterion Dose related Time related Susceptibility related Allows classification on basis of clinical features No; dose dependency is not always clear from clinical observations and dose ranging studies are not always available Yes; the time course of a reaction can be directly observed in individual cases or populations Sometimes, depending on type of susceptibility Give insight into mechanism of reaction No; only implies the range of doses at which it occurs Yes; different mechanisms have different time courses Yes; mechanism and susceptibility are often linked Avoids assigning a reaction to more than one category No Yes No; an adverse drug reaction may be associated with multiple susceptibility factors Suggests how to monitor adverse reactions Yes Yes Yes Suggests population strategies for pharmacovigilance Yes Yes; also tells the patient when to be alert for an adverse reaction Yes (can identify patients at high risk or low risk) Helps in making decisions on treatment or avoiding adverse reactions Only some types Yes Only some types Guides drug development and regulation Yes; can help in defining the therapeutic dosage range Yes; suggests strategies for monitoring during drug development and after marketing Yes; defines subgroups at high risk or low risk Examples of DoTS (dose-time-susceptibility) classification Osteoporosis due to corticosteroids: