TY - JOUR T1 - Rare adverse events in clinical trials: understanding the rule of three JF - BMJ Evidence-Based Medicine JO - BMJ EBM SP - 6 LP - 6 DO - 10.1136/ebmed-2017-110885 VL - 23 IS - 1 AU - Igho J Onakpoya Y1 - 2018/02/01 UR - http://ebm.bmj.com/content/23/1/6.abstract N2 - Investigators should report rare and very rare adverse events in clinical trials. Even though they may not give a signal in any single trial, a meta-analysis could reveal potentially important drug–adverse event associations that might require further verification. Data from a meta-analysis of such rare events can shorten the time to decision-making by regulatory agencies and/or drug manufacturers, especially in cases where the reported harms are severe.The benefit-harm profiles of new medicines are usually not fully known at the time of regulatory approval. … ER -