MedTech industry seeks change in FDA’s draft RWE guidance

Medical device industry groups say the US Food and Drug Administration’s (FDA) draft guidance using real-world evidence (RWE) to support regulatory decision making for medical devices requires changes to make it workable, though some said the document was an improvement over the previous version.

The groups complained that the guidance is overly broad, should be better aligned with other efforts related to real-world data (RWD) and the agency’s guidance on RWD for pharmaceuticals, and that more information on data governance standards is needed.

The agency received 28 comments in response to the draft guidance.

The guidance was prompted by a Congressional mandate under the Food and Drug Omnibus Reform Act of 2022 (FDORA) that directed FDA to update its policy on using RWE for regulatory decisions. It also satisfied requirements under the Medical Device User Fee Amendments (MDUFA V) deal to update the 2017 guidance and provide more clarity on RWD and RWE.

Industry says draft is an improvement
Medial device trade groups, including the Advanced Medical Technology Association (AdvaMed) and the Medical Device Manufacturers Association (MDMA) said the draft is an improvement over the 2017 guidance on RWD.

“In general, the draft guidance builds on the FDA’s 2017 guidance, Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices and is a positive step forward in providing more clarity on the Agency’s expectations,” states AdvaMed.

The group further noted that the draft guidance “reflects more administrative aspects of the lessons learned over the last five years since the release of the original guidance.” The group states that the new guidance provides more information about how RWD should be organized in a submission, and that the definitions and explanations on data relevance and reliability provide more clarity on the information needed in a submission.

The Medical Device Manufacturers Association (MDMA) similarly said the draft is an improvement. “The 2023 draft guidance builds upon the 2017 version in a way that provides greater clarity regarding the agency’s expectations and provides industry with flexibility to use diverse types of RWD. MDMA is grateful that this draft guidance reflects FDA’s continued recognition that RWE can be the primary source of clinical evidence to support premarket applications for medical devices. We support FDA’s continued expansion of appropriate use of RWD/RWE.”

AdvaMed: Too broadly drafted
One of AdvaMed’s complaints is that the draft is overly broad. “The guidance appears to be broadly drafted to apply to a wide range of products, submission types, and applications of RWE. While the document is a positive step forward, the continued ambiguity for specific RWD sources and methods leaves significant room for interpretation. This increases the possibility of continued differences in expectations between sponsors and the Agency, but also continued differences between the various Office of Health Technologies (OHTs) and individual reviewers.”

AdvaMed further said the guidance does not provide enough information on the parameters and criteria that will be applied by the agency in evaluating the RWD. “Specifically, there are no substantive clarification on the criteria that will be used in the assessment of the data relevance and reliability. It still appears to be at the level of “we will know it when we see it.”

The group further noted that the guidance “does not address study methods which is an area where there remain significant challenges and misalignment of expectations between FDA and industry.”

Respondents urge adoption of other groups’ work on RWD
In other areas, AdvaMed also urged FDA to include more references to other groups’ work on using RWD and RWE and best practice guidelines regarding data quality, fit-for-purpose assessments, protocol development, and study design considerations.

The group states that “considerable work has been done in other organizations that describe protocol development and other relevant work. This will also increase harmonization in the approach.”

AdvaMed cites the work that has been done in this area by the National Evaluation System for Health Technology Coordinating Center (NESTcc) in its research methods and quality framework, the Duke Margolis Center for Health Policy’s Framework for Regulatory Use of Real World Evidence, and the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Real-World Evidence and Real-World data efforts.

The International Society for Pharmacoepidemiology (ISPE) concurred that the guidance should include more references to other sources of data to assess the quality of RWD studies.

“We recommend incorporating observational study checklists and data quality checklists. Potential observational study checklists such as The HARmonized Protocol Template (HARPER), Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement, and Good ReseArch for Comparative Effectiveness (GRACE), along with the National Evaluation System for health Technology Coordinating Center (NESTcc) Methods Framework, offer comprehensive tools to evaluate the quality of RWE studies,” ISPE said.

The group noted that “these additions would contribute to standardized and rigorous approaches in both observational studies as well as data quality standards within the regulatory framework.”

More alignment with other RWD guidance
Both Duke-Margolis and AdvaMed urged FDA to align this guidance with the guidance issued in August 2023 on RWE for drugs.

Duke-Margolis wrote that “though regulatory requirements differ for drugs and devices, we encourage the agency to continue to seek alignment on language/key terms and approaches for the use of RWD/E for medical product (medical devices, drugs, etc.) development.”

AdvaMed states that “FDA should ensure that the final guidance is complementary and not contradictory in relation to other RWD/RWE guidance FDA has issued such as FDA’s 2023 Guidance Considerations for the Use of Real-World Data and Real-World Evidence to Support Regulatory Decision-Making for Drug and Biological Products. FDA should also ensure that it is consistent with any related policy.”

PDA: Guidance needs to address data governance

The Parenteral Drug Association (PDA) recommended the guidance include a section on data governance.

The group states that “including data governance as a suggested discipline will guide users to adopt rules/standards, responsibilities, control strategies, and improvement mechanisms essential for enabling agile data management and data quality. Data governance also assures compliance by design by centralizing accountability and oversight for the implementation of policies and procedures to meet regulations and requirements for privacy, security, transparency, etc.”

MDMA objects to fit-for-purpose language
MDMA objected to the guidance’s new section on “fit for purpose” assessments, calling these assessments unduly burdensome.

“MDMA believes that the draft guidance does not provide for least burdensome expectations concerning the “Fit-for-Purpose of RWD,” as the draft guidance sets forth recommendations and requirements consistent with those of traditional clinical studies. The “Fit for-Purpose” assessment in 510(k) submission, premarket approval (PMA) applications, and de novo submissions is a new requirement for industry and MDMA is concerned regarding the level of detail that the draft guidance appears to contemplate, particularly with respect to low- to moderate-risk devices.” RAPS.org