The development of new medical treatments follows a well-known pathway from the assessment of safety to the evaluation of therapeutic efficacy, proceeding to pivotal trials to support market authorization decisions.1 Pivotal trials are most commonly designed as traditional randomized clinical trials, designed to maximize the chance of demonstrating safety and efficacy and often include restrictive inclusion and exclusion criteria. While such trials are well suited for that purpose, they can leave evidence gaps, including:
- How the therapy is most impactfully incorporated into clinical practice where there may be other available treatment options
- Real-world safety and effectiveness in the broader patient groups that may receive the treatment upon authorization but for whom limited information is available from the pivotal studies
As a result, regulatory approval of a new treatment is often followed by post-marketing evaluations aimed at addressing a variety of questions, including understanding the real-world setting of care, disease, safety, efficacy, or effectiveness of therapy.1 While there are a number of guidelines and articles that focus on details of the key content of a classic clinical trial protocol, few consider the nuances for protocol design when assessing pre- and post-marketing value in the real-world setting.