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The US Food and Drug Administration (FDA) on Tuesday released new draft guidance clarifying how it plans to determine cases when real-world data may be sufficient for use in premarket and postmarket regulatory decisions, without changing the standards used to make those decisions.
The 21-page draft document, which is open for comment for the next 90 days, also explains how the agency plans to evaluate real-world data to determine whether it may be sufficiently relevant and reliable for various regulatory decisions. It also clarifies when an Investigational Device Exemption (IDE) may be needed to prospectively collect and use real-world data for the purposes of determining the safety and effectiveness of a device.
FDA makes clear that it believes real-world data, collected from sources outside of traditional clinical trials, can provide “powerful insight” into the benefits and risks of medical devices, including how they are used by health care providers and patients. The draft guidance gives generalized examples taken from actual uses of real-world data as valid scientific evidence for various regulatory decisions.
In seeking to outline the characteristics and sources of real-world data that may be sufficient for use in making regulatory decisions, the draft guidance explains how the quality (i.e., relevance and reliability) of such data can vary greatly across sources.
The agency also points to verifiable source documentation, which it says is the origin of real-world data elements, and can include, but is not limited to: paper or electronic inpatient and outpatient medical records and case histories, diagnostic laboratory and imaging data, patient-reported outcome measures, and medical device performance data that exists within the device such as self-diagnostics, error codes and patient diagnoses/treatments delivered (including the unique device identifier (UDI)).
Likewise, there are many types of regulatory decisions with varying levels of evidentiary needs, and though FDA says its evidentiary standards for regulatory decisionmaking are not changing, the agency notes that it will evaluate whether available real-world data is of sufficient relevance and reliability to address a specific regulatory decision.
“This draft guidance is a cornerstone of our strategic priority of creating a national evaluation system for medical devices,” FDA says. “That system would build on and leverage the vast amount of data and information collected during the treatment and management of patients.”
And though FDA does not endorse one type of real-world data over another, it says that sources of that data should be selected “based on the ability to address specific regulatory questions. Collection of [real-world data] should not dictate, interfere with or alter the normal clinical care of the patient, including choice of treatment.”
In addition to real-world data, FDA also defines “real-world evidence,” which it says may potentially be used to understand device performance at different points in its life cycle, including but not limited to:
And as real-world data methodology and infrastructure grow, FDA says real-world evidence may be well-suited to address issues identified by FDA; to reduce the time and cost of evidence generation to meet postmarket requirements; or to be used in lieu of submitting individual Medical Device Reports (MDRs) or to provide postmarket data in lieu of some premarket data under the Expedited Access Pathway (EAP) program.
The relevance and reliability of the source of the real-world data and its specific elements are highlighted by FDA as important factors that FDA will assess.
“The underlying data should be robust (i.e., provide meaningful information under a variety of conditions) for the purposes and analyses for which it was designed. These assessments will be used to determine whether the data source(s) and the proposed analysis generate evidence that is sufficiently robust to be used for a given regulatory purpose. That is, the threshold for whether RWD is sufficiently relevant and reliable for use will depend on the level of quality required and/or necessary to make a particular regulatory decision,” FDA notes.
FDA will assess the reliability of the data and the data sources by evaluating several factors including: “how the data were collected (data accrual); whether the data as collected are complete, accurate and adequate for answering the question at hand (data adequacy); and whether the people and processes in place during data collection and analysis provide adequate assurance that bias is minimized and data quality and integrity are sufficient (data assurance).”
FDA will also assess the relevance of real-world data and the source as a part of the evaluation of the regulatory issue being addressed.
“Relevance of [real-world data] for regulatory decision-making can be assessed either prior to a regulatory submission such as via the pre-submission process, or during the regulatory review process. Since data elements for existing RWD sources are determined in advance and are primarily chosen for non-regulatory purposes (e.g., quality assurance (QA) and quality improvement (QI) in the case of clinical care registries), FDA will assess whether the individual data elements contained within the existing RWD source are sufficient (i.e., complete, well-defined, and appropriate in scope and timing) to fulfill a regulatory purpose,” FDA says.
In terms of ensuring reliability, FDA says a “prospective protocol that pre-specifies the data elements to be collected, data element definitions (i.e., data dictionary to provide a common definitional framework), methods for data aggregation and documentation (e.g., common case report form, abstraction from verifiable sources), and the relevant time windows for data element utility and outcome assessments (i.e., common temporal framework) is essential.”
Key factors FDA will assess include:
FDA also offered the following examples from actual regulatory uses of real world evidence for regulatory decision making:
FDA is accepting comments on the draft guidance for the next 90 days.
Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices: FDA Draft Guidance for Industry and Staff
Tags: real-world data, device and real world evidence, device registries, FDA guidance on real world data