Phase IV of Drug Development

Abstract

Not all Phase IV studies are post-marketing surveillance (PMS) studies but every PMS study is a phase IV study. Phase IV is also an important phase of drug development. In particular, the real world effectiveness of a drug as evaluated in an observational, non-interventional trial in a naturalistic setting which complements the efficacy data that emanates from a pre-marketing randomized controlled trial (RCT). No matter how many patients are studied pre-marketing in a controlled environment, the true safety profile of a drug is characterized only by continuing safety surveillance through a spontaneous adverse event monitoring system and a post-marketing surveillance/non-interventional study. Prevalent practice patterns can generate leads that could result in further evaluation of a new indication via the RCT route or even a signal that may necessitate regulatory action (change in labeling, risk management/minimization action plan). Disease registries are another option as are the large simple hybrid trials. Surveillance of spontaneously reported adverse events continues as long as a product is marketed. And so Phase IV in that sense never ends.

Keywords: Non-interventional/observational; effectiveness; generalizability; post-marketing safety surveillance; real world.