Use of Real-World Data and Real-World Evidence to Support Medical Device Regulatory Decision-Making (DRAFT)

This is a draft guidance. Not for implementation.

What You Need to Know? 👇

What types of real-world data sources can be used to support medical device regulatory submissions?

RWD sources include registries, electronic health records, administrative claims data, patient-generated data from digital health technologies, device-generated data, public health surveillance data, clinically annotated biobanks, and medical device data repositories. FDA doesn’t endorse one type over another.

When is an IDE required for collecting real-world data for medical device studies?

An IDE is typically not required if the device is used in normal medical practice and data collection doesn’t impact device administration. However, if data gathering influences treatment decisions or physicians are instructed to treat patients in prescribed ways for research purposes, an IDE may be required.

How does FDA assess whether real-world data is “fit-for-purpose” for regulatory decision-making?

FDA evaluates RWD relevance (data availability, timeliness, generalizability) and reliability (data accrual methods, quality controls, integrity). The assessment considers whether data can credibly address the study question and support the specific regulatory decision being made.

What documentation should sponsors include when submitting RWE in regulatory applications?

Sponsors should include a fit-for-purpose assessment, study protocol with operational definitions, study report, and cover letter identifying RWD sources. Documentation must demonstrate data relevance, reliability, and how RWE fits into the totality of clinical evidence submitted.

Can real-world evidence from EUA-authorized devices be used in subsequent regulatory submissions?

Yes, clinical data from devices authorized under Emergency Use Authorization may be considered RWD if determined fit-for-purpose. The routine clinical use of EUA devices isn’t considered clinical investigation, and this data can support future premarket submissions following proper assessment.

What are the key considerations for defining study populations and endpoints when using real-world data?

Sponsors must develop both conceptual and operational definitions for all data elements before study initiation. This includes defining study timeframes relative to index dates, ensuring data elements capture intended concepts, and minimizing misclassification through validation studies when appropriate.

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What You Need to Do 👇

Recommended Actions

1. Conduct fit-for-purpose assessment of RWD relevance and reliability
2. Document and provide in FDA submission:
   • Purpose of using RWE
   • Description of RWD sources
   • Study protocol and analysis plan
   • Data management and quality control plans
   • Human subject protections
   • Validation/adjudication results if conducted
3. Ensure adequate documentation of:
   • Data collection procedures
   • Quality control processes
   • Data linkage methodologies
   • Changes in clinical practice
   • Missing data assessment
4. Prepare regulatory submission including:
   • Cover letter identifying RWD/RWE components
   • Fit-for-purpose assessment
   • Protocol
   • Study report
   • Additional required documentation
5. Consider early engagement with FDA through Q-submission program to discuss RWE approach

Key Considerations

Clinical testing

• Clinical evidence can be generated from RWD alone or combined with traditional clinical studies
• Studies using RWD should be carefully designed to mitigate potential bias
• Protocol and analysis plan should be created prior to analyzing RWD
• Sample size should be adequate to detect clinically meaningful differences

Safety

• Safety assessment should be based on comparison of serious device-related adverse event rates
• Adverse event reporting plans must be included
• Safety endpoints and outcomes should be clearly defined

Other considerations

• RWD must be relevant and reliable for generating RWE
• Data quality and integrity must be demonstrated
• Appropriate data management practices must be in place
• Patient privacy protections must be established
• Study protocols must be documented and followed
• Changes in clinical practice over time must be considered
• Data linkages across sources must use predefined methodologies
• Statistical analysis plans must be pre-specified
• Documentation of previous use of RWD source should be provided

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Relevant Guidances 🔗

• Use of Real-World Data to Generate Evidence for Medical Device Regulatory Decisions
• Q-Submission Program: Strategic Framework for FDA Interactions in Medical Device Development

Related references and norms 📂

• ICD-10-CM: International Classification of Diseases, Tenth Revision, Clinical Modification
• LOINC: Logical Observation Identifiers, Names, and Codes
• SNOMED CT: Systematized Nomenclature of Medicine Clinical Terms
• CPT: Current Procedural Terminology

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Original guidance

• Use of Real-World Data and Real-World Evidence to Support Medical Device Regulatory Decision-Making
• HTML / PDF
• Issue date: 2023-12-14
• Last changed date: 2024-02-07
• Status: DRAFT
• Official FDA topics: Radiation-Emitting Products, Real World Data / Real World Evidence (RWD/RWE), Medical Devices, Postmarket, Premarket
• ReguVirta ID: e27dd4ae6000d19be8c0d4480b326bc9