Real-world evidence (RWE) refers to data regarding the use, effectiveness, and safety of medical products (such as drugs, biologics, and medical devices) that is derived from real-world sources, including electronic health records, claims data, patient registries, and other healthcare databases. Unlike data collected in controlled clinical trials, RWE is generated in routine clinical practice and reflects the diverse patient populations, clinical settings, and healthcare delivery systems encountered in real-world healthcare settings.

Importance of RWE: RWE is becoming increasingly important in regulatory submissions for medical devices. Traditionally, regulatory submissions have relied heavily on data from clinical trials conducted in controlled settings. However, RWE provides insights into how medical devices perform and are used in real-world clinical practice. Here are some impacts of RWE on medical device regulatory submissions:

1. Supplementing Clinical Trial Data
2. Expanded Indications
3. Post-Market Surveillance
4. Regulatory Decision Making
5. Reduced Regulatory Burden
6. Value-based Healthcare
7. Challenges and Considerations

Overall, the integration of RWE into regulatory submissions for medical devices represents a paradigm shift towards a more evidence-based, patient-centered approach to medical device regulation and healthcare decision-making.

Start to end regulatory submission process for medical device by using real world evidence

The use of RWE in regulatory submissions for medical devices involves several steps from the collection of data to its analysis and incorporation into the submission. Here’s a generalized start-to-end process:

1. Identifying Regulatory Requirements
2. Defining the Research Question
3. Data Source Selection
4. Data Collection
5. Data Management and Quality Assurance
6. Analysis and Interpretation
7. Evidence Synthesis
8. Regulatory Strategy Development
9. Submission Preparation
10. Regulatory Submission
11. Regulatory Review
12. Decision and Approval
13. Post-Market Surveillance
14. Lifecycle Management

Throughout this process, it’s essential to adhere to regulatory requirements, maintain data integrity and patient privacy, and communicate transparently with regulatory authorities regarding the use of real-world evidence in medical device submissions. Collaboration between medical device manufacturers, healthcare providers, regulators, and other stakeholders is critical to ensure the effective use of real-world evidence in regulatory decision-making

How Real World Evidence utilized in regulatory approval procedures for medical devices

United States

Submitting regulatory applications for medical devices that incorporate RWE in the United States typically follows a structured process outlined by the U.S. Food and Drug Administration (FDA). While the FDA has expressed interest in leveraging RWE to support regulatory decision-making, the specific procedures for submitting applications that rely on RWE may vary depending on the type of submission and the regulatory pathway chosen. Here’s a general overview of the procedure for regulatory submission using RWE in medical devices in the USA:

1. Pre-submission meeting (if applicable): Before submitting a regulatory application, it may be beneficial to request a pre-submission meeting with the FDA. During this meeting, the device sponsor can discuss the proposed use of RWE, the study design, data sources, and other relevant details with FDA representatives to receive feedback and guidance.
2. RWE study design: Design a study or studies that will generate RWE to support the regulatory submission. The study design should be carefully planned to address specific regulatory questions, such as safety, effectiveness, or performance of the medical device in real-world settings. Considerations include study objectives, patient population, data sources, study endpoints, statistical methods, and ethical considerations.
3. Data collection and analysis: Collect real-world data from various sources, such as electronic health records, registries, claims databases, patient-reported outcomes, and other relevant sources. Ensure that the data collected are of high quality, reliable, and relevant to the regulatory questions being addressed. Analyze the data using appropriate statistical methods to generate valid and reliable evidence.
4. Regulatory submission preparation: Prepare the regulatory submission package, including the RWE study protocol, study reports, statistical analysis plan, and any other relevant documents. Clearly describe the study design, data sources, analysis methods, results, and conclusions in the submission to demonstrate the validity, reliability, and relevance of the RWE generated.
5. Submission of regulatory application: Submit the regulatory application to the FDA through the appropriate pathway, such as a premarket submission (e.g., 510(k), PMA) or a request for De Novo classification. Include the RWE evidence as part of the submission package to support the safety, effectiveness, or performance of the medical device.
6. FDA review: The FDA will review the regulatory submission, including the RWE evidence, to assess the safety and effectiveness of the medical device. The review process may involve interactions between the FDA and the device sponsor to address any questions, concerns, or requests for additional information related to the RWE study design, data analysis, or interpretation.
7. Decision: Based on the review of the regulatory submission and the RWE evidence, the FDA will make a regulatory decision regarding the approval, clearance, or classification of the medical device. This decision may include labeling requirements, post-market surveillance commitments, or other conditions related to the use of RWE in regulatory submissions.

European Union

Primary pathway for regulatory approval of medical devices in the EU is through conformity assessment procedures, such as CE marking under the EU Medical Device Regulation (MDR), RWE can complement traditional clinical trial data and support various aspects of regulatory submissions. Here’s how RWE can be utilized in the context of regulatory approval procedures for medical devices in the EU:

1. Identifying Regulatory Requirements: Review the specific regulatory requirements outlined in the EU MDR and relevant guidance documents issued by the European Medicines Agency (EMA) and other regulatory authorities.
2. Evidence Generation Planning: Develop a strategic evidence generation plan that outlines how RWE will be collected, analyzed, and integrated into the regulatory submission. Define clear research questions, identify appropriate data sources, and plan study designs and analyses to generate robust RWE.
3. Data Source Selection: Identify suitable real-world data sources within the EU that can provide relevant information to support the safety, efficacy, or performance of the medical device. This may include electronic health records, medical registries, claims databases, patient registries, or other healthcare databases.
4. Data Collection and Management: Collect and manage the real-world data according to established protocols and data quality standards. Ensure compliance with data protection and privacy regulations, such as the General Data Protection Regulation (GDPR), and maintain the confidentiality and integrity of patient information.
5. Study Design and Analysis: Design observational studies or analyses to generate RWE that addresses specific research questions related to the medical device. Use appropriate statistical methods and epidemiological techniques to analyze the data and draw valid conclusions.
6. Risk Assessment and Benefit Evaluation: Conduct a comprehensive risk assessment and benefit evaluation based on the RWE generated. Assess the safety, effectiveness, and performance of the medical device in real-world clinical settings compared to traditional clinical trial data.
7. Regulatory Strategy Development: Develop a regulatory strategy that outlines how the RWE will be incorporated into the regulatory submission. Determine the most appropriate regulatory pathway (e.g., CE marking under MDR Annex IX or Annex XVI), prepare the submission documents, and address any regulatory considerations or challenges.
8. Submission Preparation: Prepare the regulatory submission documents, including the RWE analysis plan, study protocols, data summaries, statistical analyses, and any other supporting documentation required by the regulatory authority.
9. Regulatory Submission: Submit the regulatory application to the appropriate regulatory authority in the EU, such as a notified body or a competent authority. Include the RWE and supporting documentation as part of the submission package and clearly articulate how the RWE contributes to the overall assessment of the medical device.
10. Regulatory Review and Decision: The regulatory authority will review the submission, including the RWE, to assess the conformity of the medical device with regulatory requirements and determine whether market authorization should be granted. Be prepared to respond to any requests for additional information or clarification from the regulatory authority.
11. Post-Market Surveillance: Aftermarket authorization, continue to monitor the real-world performance of the medical device through post-market surveillance activities. Use ongoing RWE to support product lifecycle management, including label updates, post-market studies, and risk mitigation strategies.

Note: It’s important to engage with regulatory authorities early in the regulatory approval process to discuss the use of RWE and ensure alignment with regulatory expectations. Collaboration between medical device manufacturers, healthcare providers, regulators, and other stakeholders is essential to successfully leverage RWE for regulatory approval in the EU.