Purpose: Signals are used to alert clinicians of potential ADRs. Positive predictive values (PPVs) of antidote signals in ICUs are unknown. The primary purpose was to determine PPVs of six signals. The secondary objective was to determine the sensitivity of various ADR detection strategies including manual chart review, administrative data review, and voluntary reporting at identifying the same ADRs discovered using antidotes as a signal., Methods: Adult patients admitted to a medical ICU from July 1, 2005 to June 30, 2006 who were prescribed select signals were eligible. Evaluated antidote signals included injectable diphenhydramine, protamine, phytonadione, dextrose 50%, injectable methylprednisolone, and sodium polystyrene. For each signal, a random sample of 50 patients was evaluated for the presence of an ADR. ADR occurrences were determined using two objective causality instruments through retrospective chart review. Agreement between the instruments was required for ADR consideration. PPVs were determined for each signal., Results: Two hundred and twenty three patients (52% male) were evaluated, with a mean +/- SD age of 60 +/- 17 years, and a median simplified acute physiology score (SAPSII) of 48. PPVs were 0.64, 0.50, 0.38, 0.26, 0.24, and 0.02 for protamine, sodium polystyrene, dextrose 50%, diphenhydramine, phytonadione, and methylprednisolone, respectively. Sensitivity of other detection strategies from highest to lowest was chart review for explicit documentation, administrative database review, and voluntary reporting., Conclusions: Protamine and sodium polystyrene performed the best by detecting ADRs in at least one out of two evaluations. Detection strategies other than signals were not as sensitive at identifying the same ADRs as antidote signals., (Copyright (c) 2009 John Wiley & Sons, Ltd.)