FDA Releases Expectations for Using RWE in Support of New Drug Approvals
(Thursday, August 31, 2023)
Real World Data (RWD) collected from medical records and the Real World Evidence (RWE) generated from it can be used to seek market approval for new uses of FDA-approved products by the FDA. However, there are specific FDA requirements for the quality and integrity of the RWD before its acceptance by the FDA. A new FDA guidance document released this week outlined stringent guidelines for harnessing RWD to enable more comprehensive and realistic insights into a drug's performance that can be used to get FDA approval for label expansions and new indications.
RWD collection should be done via well-planned observational studies. Observational or non-interventional studies are where data is sourced from patient medical records from routine medical practice. There is no study-specific treatment; rather the patients are treated with available FDA-approved drugs per the standard of care, hence the name “non-interventional”. Unlike clinical trials, which adhere to research protocols and controlled conditions, medical records data reflects the actual usage of a marketed drug as prescribed by medical professionals based on patient-specific criteria. Some non-interventional studies go beyond routine RWD analysis and encompass additional activities like questionnaires, laboratory tests, and imaging studies.
Such studies do not require an Investigational New Drug (IND) application, but the FDA expects these studies to be approved by Independent Review Boards (IRBs) and has appropriate human subject protection (HSP) measures which may include getting informed consent from the patients whose records are being used for this study. Non-interventional studies can tap into diverse sources of RWD, including registries, electronic health records (EHRs), and medical claims.
FDA recommends that sponsors intending to use RWD/RWE for drug marketing applications pursue FDA feedback on study design, data sources, and research questions to facilitate the identification and resolution of potential challenges in study design, thereby enhancing the study's validity and reliability for the intended purpose. The best way to seek FDA meetings is through Type C meeting requests. Posting the study protocols on clinicaltrials.gov is also expected. Throughout the study lifecycle, meticulous monitoring should be conducted to ensure data accuracy, human subject protection, and data integrity. Deviations from the study protocol and procedures should be documented and promptly addressed, reflecting a risk-based quality management approach.
Sponsors must also embrace the concept of using subsets of larger real-world datasets to focus on specific research questions. For instance, if the aim is to support a labeling change for a drug's indication, there's no expectation to scour the entire dataset for every possible adverse event. However, any identified adverse events subject to post-marketing reporting must be reported as per regulations. Ultimately, sponsors bear the responsibility for the design, execution, and oversight of non-interventional studies. Selection of qualified researchers, adherence to protocols, maintenance of study records, and ensuring FDA access to relevant records all fall under their purview.
All the suggestions included in the new FDA guidance have been discussed earlier in various forms so should not come as a surprise to those following this field. The most important clarification is that these studies should be conducted outside INDs but still have written clinical protocols that are approved by the IRB and follow the same standards for data collection, monitoring, integrity, and data analysis as done for the clinical trials conducted under INDs.
Dr. Mukesh Kumar
Founder & CEO, FDAMap
Linkedin: Mukesh Kumar, PhD, RAC