Protopathic bias arises when the initiation of a drug (exposure) occurs in response to a symptom of the (at this point undiagnosed) disease under study (outcome). For example, use of analgesics in response to pain caused by an undiagnosed tumour might lead to the erroneous conclusion that the analgesic caused the tumour. Protopathic bias thus reflects a reversal of cause and effect (Bias: Considerations for research practice. Am J Health Syst Pharm 2008;65:2159-68). This is particularly a problem in studies of drug-cancer associations and other outcomes with long latencies. It may be handled by including a time-lag, i.e. by disregarding all exposure during a specified period of time before the index date.
|Annex 1.||Guidance on conducting systematic revies and meta-analyses of completed comparative pharmacoepidemiological studies of safety outcomes|