Real-World Data/Evidence Grew Under Covid: FDA
FDA’s adapting to the Covid-19 pandemic led to quicker and greater acceptance of real-world evidence, which has now led to the recognition that certain practices will be useful in this post-pandemic space. Speaking at the Food and Drug Law Institute’s annual meeting 5/20, CDER associate director for real-world evidence analytics John Concato said Covid-19 presented an opportunity to leverage real world data and evidence to inform clinical and regulatory decisions, while emphasizing the importance of maintaining scientific rigor.
Concato told the conference that importance of digital health technology both before and during the pandemic “cannot be overstated. The growing use of digital health technologies such as sensors and software applications is changing how clinical research is conducted, in particular decentralized clinical trials, which use technology to communicate with study participants and to collect data that can offer advantages, such as faster enrollment and sustained participation in trials, greater convenience for participants, the potential for less missing data and increased participant diversity,” he said.
Digital health technologies have increasingly been used in settings involving both traditional clinical trials and observational studies. An FDA-based example of digital technology is the Mystudies app, a Web-based configuration portal that can collect real-world data in a secure storage environment, according to Concato. The app has been deployed in both randomized trials and real-world data settings. MyStudies was developed by FDA and private sector partners and was released to the public in open source code so the app and patient data storage system can be reconfigured by organizations conducting clinical research, an agency notice says.
Another example of a digital health technology from FDA is the Cure ID App (https://cure.ncats.io), which collects real world data on novel uses of FDA approved drugs. Concato said it was originally developed for infections in developing parts of the world where infrastructure is not as advanced.
Due to Covid-19, the real-world evidence landscape has changed and new research approaches are being explored and adopted, including bringing their results to patients in ways that involve the collection and analysis of real-world data, Concato said. “In this context, sponsors can consider the appropriate use of real-world evidence, but only after assessing limitations related to data fitness-for-use, study design, and regulatory requirements, as well as importantly discussing your plans early with FDA, he said.
Joining the presentation was CDER senior regulatory counsel Stefanie Kraus, who shared lessons learned about real-world evidence over the past several years and highlighted some key points that stakeholders will want to consider. Data access is important and some real-world data sources, such as electronic health records and medical claims data, may be owned by parties other than the sponsor, she said. “Our evidentiary standards are the same, regardless of whether a study includes real-world data,” she added. “Data access is a critical aspect in determining whether data are fit-for-use and can meet those evidentiary standards. So sponsors should ensure that they can provide FDA with the data, including patient level data necessary to support decisions about safety and effectiveness.” Sponsors should also consider upfront data sharing agreements with real-world data holders to enable submission of data for FDA to review and agency access to source records as part of an inspection.
Kraus said sponsors should engage early with the agency when designing a study using real-world data. We’re mindful that sponsors may want to conduct feasibility evaluations to determine whether a data source can be fit-for-use in a particular clinical study design. However, with data access comes concerns that parties can run multiple analyses and cherry pick favorable results before finalizing the study protocol. So FDA will need to have confirmation that this didn't happen, including documenting for us steps taken during feasibility analyses, and you might want to think about audit trails in this process.”