In late September 2021, the United States Food and Drug Administration (FDA) issued draft guidance, Real-World Data: Assessing Electronic Health Records and Medical Claims Data To Support Regulatory Decision-Making for Drug and Biological Products. The guidance is part of a series of guidance documents created to satisfy the Cures Act mandate and the PDUFA VI goal. It outlines recommendations on the use of real-world data (RWD) sourced from electronic health records (EHRs) and medical claims data to support regulatory decision-making for drugs and biologics.
The guidance focuses on three issues related to the use of RWD pulled from EHRs and claims data: the selection of data sources that appropriately address the study question; development and validation of definitions for study design elements; and data provenance and quality throughout the study lifecycle.
Selected Provisions of the Guidance
The FDA notes that sponsors who rely on RWD sourced from EHRs or medical claims data should submit study protocols and statistical analysis plans to FDA and request input from (or a meeting with) the relevant review division before starting the study. Those protocols and plans should identify all data sources that will be included in the study. Additionally, “each data source should be evaluated to determine whether the available information is appropriate for addressing a specific study hypothesis” and “it is important to understand … potential limitations” when EHR data is used to support regulatory submissions to the FDA.
The guidance also noted the importance of determining the relevance of a data source as “there are differences in the practice of medicine around the world and between health care systems that may affect the relevance of the data source to the study question. Patients in different types of commercial or government health care payment programs can differ in a range of characteristics, such as age, socioeconomic status, health conditions, risk factors, and other potential confounders.”
Additionally, the guidance recommends that sponsors state their reasoning for choosing a certain data source for a specific hypothesis, background information on the healthcare system and the methods of diagnosis and preferred treatments for the disease of interest, as well as a description of prescribing and use practices in the health system. If a sponsor uses foreign data sources, it will need to provide an explanation of how the above-named favors may affect the projection of the results to the United States population.
The guidance includes examples of potential limitations, such as when an EHR does not capture a patient’s entire care record if their treatment takes place across multiple health systems or networks. Additionally, the purpose of medical claims data is to support payment for care, and therefore, claims may not accurately reflect a particular disease, or a patient may have a disease or condition that is not reflected in claims data. Even if EHR systems are modified for the purpose of collecting additional data for prospective clinical studies, FDA cautions that “given the limited ability to add modules to collect extensive additional information, EHR-based data collection may still not be comprehensive.”
Complementary Guidance
The guidance supplements and complements the 2013 guidance from FDA, Best Practices for Conducting and Reporting Pharmacoepidemiologic Safety Studies Using Electronic Healthcare Data. However, the guidance does not address study design or type of statistical analysis, nor does it endorse any specific type of data source or study methodology, “For all study designs, it is important to ensure the reliability and relevance of the data used to help support a regulatory decision.”
Comment Period
Under the Federal Register notice, stakeholders can submit comments to the FDA by November 29, 2021.