The 21st Century Cures Act (Cures Act),1 which became law in the United States December 13, 2016, has highlighted the need for robust real-world data to demonstrate effectiveness and safety of healthcare innovations that meet the requirements of regulators and payers alike. Included in the Act is an agreement to fund and accelerate cancer research and overall medical product development and delivery, as well as increase choice in, access to, and quality of American healthcare. One result of the Act has been to increase interest from both industry and regulatory authorities, such as the US Food and Drug Administration (FDA), in pragmatic randomized trials (PRTs). In December 2018, the FDA’s Framework for Real-World Evidence Program2 was published, which “created a framework for evaluating the potential use of real-world evidence (RWE) to help support the approval of a new indication for a drug already approved under section 505(c) of the FD&C Act or to help support or satisfy drug post-approval study requirements.”
The industry has yet to feel the impact of this paradigm shift, not least because the traditional explanatory randomized controlled trial (RCT) utilizing surrogate endpoints to establish efficacy and safety in a highly selected population under optimal conditions has been the gold standard for researchers and regulators alike for many decades. These trials, which generate high-quality robust data with high intrinsic validity upon which to base conclusions about causal relationships, answer the explanatory question “is the intervention efficacious and safe in tightly controlled, artificial conditions?” However, they ignore the more pragmatic question “is this an effective and safe option for my patient?” The pragmatic trial design was developed to answer the latter, which is a key question that can inform potentially life-altering decisions required by payers, clinicians, and even patients themselves.policy process.