Identifying and addressing safety signals in clinical trials.
Interventions for the prevention or treatment of disease that are based on our understanding of the pathobiologic features of the illness can provide benefit in how a patient feels or functions or in whether the patient survives. Such benefits are generally achieved through on-target biologic effects of the intervention. However, there are numerous recent cases in which it has been established or strongly suggested that off-target effects of such interventions have adversely altered their risk–benefit profile. For example, in patients with rheumatoid arthritis or osteoarthritis, the cyclooxygenase-2 (COX-2) inhibitors provide an analgesic benefit with a reduced risk of gastrointestinal side . . .