ABSTRACT
This chapter begins with an exploration of safety issues across the lifespan of drug development: phases 1, 2, and 3. It introduces key considerations for developing a safety monitoring plan, collection of safety data, and statistical aspects. The development of a statistical plan for safety monitoring starts with a detailed discussion of the safety objectives. A variety of graphical approaches to safety monitoring are provided. However, unanticipated safety issues with mortality began to arise during the onset of the study, and after 434 subjects were randomized the study was halted due to increased mortality in the albumin-treated arm of the study. For example, several trials have tested drugs with known safety issues for use in other indications such as sirolimus in multiple system atrophy and pioglitazone and nilotinib in Parkinson's disease. Similar types of events may be coded as different preferred terms making it harder to detect safety issues, for example, Nausea/Vomiting/Dyspepsia or Skin reaction/Rash.
