When a randomised controlled trial is needed to assess drug safety. The case of paediatric ibuprofen.

Drugs are frequently made available for use before risks of rare but serious reactions have been identified and quantified. While this situation may be acceptable for drugs used to treat serious conditions, greater information on safety is needed for drugs used to treat less serious conditions, and particularly those medications available without prescription. Spontaneous reports and observational studies can provide useful data in most instances, but nonrandomised studies are inadequate in the presence of confounding by indication (i.e. when patients treated with a drug differ in their underlying risk of adverse outcome from patients given alternate treatments, independent of the effect of the drug). Such is the case in the US with regard to the use of paediatric ibuprofen as an antipyretic. In this setting, a rigorous and large randomised controlled trial is needed to provide valid and statistically stable risk estimates. A trial of this kind is a feasible way to develop clinically meaningful data on safety with respect to rare but serious adverse reactions.