CMS introduces new guidance for real-world data studies in Medicare coverage decisions

The Centers for Medicare & Medicaid Services (CMS) is proposing a standardized real-world data (RWD) study protocol template, named HARPER+, designed to standardize protocols utilizing RWD to meet coverage with evidence development (CED) requirements.

In line with the broader trend towards the increased use of RWD and real-world evidence (RWE) in healthcare decision-making, CMS has unveiled new guidance aimed at streamlining the use of RWD in national coverage determinations (NCDs). The draft guidance represents a step by the agency towards what CMS describes as, "a more transparent and predictable evidence-generation framework to facilitate Medicare coverage."

NCDs describe the circumstances under which Medicare will provide coverage for particular medical services, procedures, or devices across the US. In some cases, many of these novel technologies may have limited evidence on effectiveness, health outcomes, safety, or cost-effectiveness for Medicare beneficiaries. The CED program allows CMS to provide conditional coverage of these technologies while additional evidence from clinical studies is collected to address uncertainties about effectiveness, safety, or cost-effectiveness. A notable example of an NCD requiring CED is the case of monoclonal antibodies directed against amyloid for the treatment of Alzheimer's disease (AD).

To address the need for a, “broader range of fit-for-purpose study designs for CED,” CMS has drafted guidance detailing its standards for studies using RWD. The guidance follows updated CED guidance released in August 2024, which expanded the range of acceptable study designs, including those leveraging RWD, to support Medicare coverage decisions for innovative technologies.

As part of this effort, CMS has proposed the HARPER+ template to standardize RWD study protocols developed by manufacturers or other sponsors. HARPER+ builds on the HARmonized Protocol Template to Enhance Reproducibility (HARPER) but includes additional elements tailored to meet Medicare coverage criteria and address CED requirements. Notably, it introduces a section titled ,"CMS-identified evidence gaps," which helps align research objectives with specific gaps identified by CMS. The template also incorporates protocol elements relevant to medical devices.

In developing HARPER+, CMS sought input from industry experts, government agencies, and academia to ensure consistency with existing guidance and best practices. HARPER+ aligns with other frameworks, including the FDA draft guidance for using RWD to support regulatory decision-making for medical devices and the National Evaluation System for health Technology Coordinating Center (NESTcc) Methods Framework. To assist stakeholders in understanding its requirements, CMS has provided an example protocol illustrating how information should be presented in specific sections.

CMS is now inviting public comment on the draft protocol template, with feedback requested by March 18, 2025.