FDA Developing Guidance on Real-World Data Quality Issues, Officials Say

As the US Food and Drug Administration (FDA) grapples with how to use real-world data for regulatory decisions, two FDA officials wrote in a perspective published last Friday in the Clinical Journal of the American Society of Nephrology that the agency is developing guidance on data quality issues unique to the real-world data setting and related study design considerations.

Aliza Thompson and Mary Ross Southworth of the Division of Cardiovascular and Renal Products within FDA’s Center for Drug Evaluation and Research (CDER) explain: “Although the FDA has experience using observational (noninterventional) study designs in the postmarket setting to evaluate product risks in broad populations, using nonrandomized methodologies to determine effectiveness can be problematic because of concerns about the ability to adequately control for confounding, selection bias, and the possibility of misclassification error.”

New data standards will need to be developed and FDA is “currently exploring,” they write, when the use of observational data “may be appropriate for evaluating effectiveness from a broad policy perspective and also, as individual drug manufacturers submit proposals for using real world data to support marketing applications.”

The draft guidance in development is not on CDER’s 2019 guidance agenda, but FDA did publish draft guidance in May on real-world evidence (RWE) submissions. Last December, the agency also released its framework for the use of RWE.

“There is widespread recognition that there will be a learning curve and that demonstration projects will play a critical role in defining how and when real world data and real world evidence can be used,” Thompson and Southworth add.

Kidney Disease

They also discuss how real-world data and RWE could provide a way to accelerate the development of therapies that improve the lives of patients with kidney disease.

“Many have noted the potential to integrate RCTs [randomized controlled trials] into the data-rich clinical care setting of patients on dialysis, and efforts are underway to understand and address current challenges to doing so,” they explain. “In RCTs of patients with common kidney diseases, such as diabetic kidney disease, real world data could be used to facilitate the identification and enrollment of patients into trials. Study methodologies aimed at capturing key efficacy outcomes using both traditional methods, and electronic health records or claims data could provide insight into the challenges and opportunities of using real world data to assess outcomes of interest by enabling a comparison between the two.”

But they warn that given the “size of the population with stage 4 and 5 CKD [chronic kidney disease] and fragmentation of health care among various US health care systems, successful use of such data will likely require collaboration among researchers and the aggregation of real world data from multiple sources. However, these novel approaches should not supplant larger efforts to include these populations in registration trials for drugs, where appropriate, or conduct dedicated RCTs in these populations.”

Clinical Journal of American Society of Nephrology