CMS Seeks Comments on Proposed Guidance Addressing Study Protocols That Use Real-World Data

On January 17, 2025, the Centers for Medicare & Medicaid Services (CMS) issued a proposed guidance document on study protocols that use real-world data (RWD). The proposed guidance focuses on studies with RWD sources in the context of Medicare National Coverage Determinations (NCDs) using CMS’s Coverage with Evidence Development (CED) paradigm. It presents a proposed standardized template for manufacturers or other sponsors to use when developing CED study protocols using RWD. The proposed guidance could also have broader implications with respect to RWD studies and coverage considerations. Comments on the proposed guidance are due by March 18, 2025.

CMS states that the proposed guidance’s “protocol template is primarily intended for studies that exclusively analyze RWD” in the context of NCDs with CED requirements. CMS states that the CED “may be part of the Parallel Review Program or the Transitional Coverage for Emerging Technologies (TCET) pathway.” For more information about the TCET pathway, which CMS finalized in 2024, see our prior alert.

CMS states that this proposed guidance “is part of a broader CMS modernization initiative to provide a more transparent and predictable evidence-generation framework to facilitate Medicare coverage.” For further discussion of that initiative, CMS refers readers to guidance documents issued last year addressing CED and National Coverage Analysis Evidence Reviews (also discussed in our prior alert).

According to CMS, the new proposed guidance “provides detailed and specific information about CMS standards for fit-for-purpose study designs using RWD to the public and potential study sponsors.” CMS states an intention for this guidance to “lead to more efficient approval of proposed CED studies by reducing the need for multiple rounds of review” and to “reinforce public confidence that CMS is applying rigorous standards to RWD studies.”

The proposed standardized RWD study protocol template is called the HARPER+. CMS states that the HARPER+ framework “is based on the HARmonized Protocol Template to Enhance Reproducibility (HARPER) but adapted for medical devices and Medicare coverage criteria.” CMS states that it solicited feedback from industry, government, and academia in developing the HARPER+. The proposed guidance discusses CMS’s methodology in developing this proposed RWD study protocol template, describes the proposed template’s components, and provides an appendix with the full proposed template. 

We encourage stakeholders to carefully review this proposed guidance and to consider providing input through public comments. In particular, there has been significant concern in the stakeholder community over the years that NCDs with CED requirements can improperly restrict coverage and access to items and services under Medicare. The RWD proposed guidance document should be evaluated with an eye toward those broader access considerations, concerns, and challenges in addition to the specific proposed protocol template for comment.