Real-World Evidence (RWE)

Key facts

Statutory basis

FD&C Act Section 505F, added by the 21st Century Cures Act (2016)

FDA framework

Framework for FDA Real-World Evidence Program, December 2018

Regulatory uses

Safety surveillance, new indications, postapproval study requirements

What is real-world evidence?

FDA defines real-world evidence as the clinical evidence regarding the usage and potential benefits or risks of a medical product derived from analysis of real-world data (RWD). RWE is the output of a study; RWD is the input.

The 21st Century Cures Act of 2016 added Section 505F to the Federal Food, Drug, and Cosmetic Act, directing FDA to create a program to evaluate the potential use of RWE to support approval of new indications for approved drugs and to help satisfy postapproval study requirements. FDA published its framework for that program in 2018 and has since issued guidance on data sources and study design.

How real-world evidence is generated

RWE can come from several study designs:

• Retrospective observational studies using existing claims, electronic health record or registry data.
• Prospective observational studies and registries that follow patients in routine care.
• External control arms, which compare a single-arm trial with similar patients drawn from RWD.
• Pragmatic randomized trials that randomize patients but collect outcomes through routine care data.

Why real-world evidence matters

For regulators, RWE supports safety monitoring and, in selected cases, labeling changes and new indications. For payers and health technology assessment bodies, it shows whether trial results hold up in routine practice, which informs coverage, outcomes-based contracts and value assessments.

Manufacturers use RWE to compare products that were never tested head to head, to understand adherence and treatment patterns, and to plan launches and lifecycle strategy. Health economics and outcomes research (HEOR) and medical affairs teams are its main producers inside companies.

RWE vs randomized trial evidence

Observational RWE is vulnerable to confounding, because patients who receive a treatment in routine care often differ from those who do not. Methods such as propensity score matching reduce that bias but cannot remove it. FDA evaluates RWE case by case, looking at data reliability, relevance and study design, so RWE generally complements randomized controlled trials rather than replacing them.