Industry and Advocacy Groups Urge FDA to Allow More Real-World Data for Rare Disease Trials

FDA logo inside of magnifying glass

In January 2019, the U.S. Food and Drug Administration (FDA) updated a 2015 draft guidance on rare diseases. Although essentially agreeing with the changes, several organizations, both patient advocacy and industry groups, have called on the FDA to make additional changes.

In the 24-page draft guidance issued in January, there were changes to the natural history studies section, the inclusion of matters related to evaluating and validating biomarkers as surrogate endpoints, and other issues.

Scott Gottlieb, FDA commissioner, stated at the time, “The revised draft guidance issued today discusses select issues commonly encountered in rare disease drug development. While similar issues often also come up for common diseases, they’re frequently more difficult to address in the context of a rare disease for which there’s often limited medical and scientific knowledge.”

Since the draft guidance was issued, public comment was open. A number of organizations did so, including the National Organization for Rare Disorders (NORD), contract research organization (CRO) IQVIA, and biopharma companies Takeda Pharmaceutical and BioMarin Pharmaceutical.

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NORD, for example, indicated it supported the revised draft guidance and “particularly appreciates the additions and clarifications made to the natural history studies section.”

But, NORD also indicated it would like the FDA to revise its disease-specific drug development guidances to be more closely aligned with the draft guidance, “especially regarding its recommendations on natural history data registries, flexible clinical trial designs, inclusion criteria and expanded access protocols (EAPs),” reported the Regulatory Affairs Professionals Society.

In addition, NORD said it was still concerned the guidance might lead to “redundant registry efforts and restricted data ownership.” It also called on the agency to encourage the use of existing databases of real-world evidence (RWE) in clinical trials, such as NORD’s IAMRARE registry program.

In other comments, IQVIA, Takeda and BioMarin called for the agency to also address the use of real-world data (RWD) and RWE as possible external controls for natural history studies.

This is particularly relevant to clinical trials for rare diseases, where recruiting patients can be difficult. RWE and RWD would allow companies to utilize healthcare data and clinical trial data from outside the specific trial.

IQVIA asked the FDA to include guidelines about the use of patient registries.

“A registry may be used to recruit patients for clinical trials, monitor patient care and outcomes, advance research hypotheses, observe patient behavior patterns, provide external comparators, establish disease specific standards of care, and support reimbursement discussions. As such, registries often play a vital role in the design of natural history studies,” IQVIA wrote.

BioMarin specifically requested more information about how companies conducting clinical trials can modify existing biomarkers and other evaluation measures in situations where developing novel measures would be too time-consuming.

Another non-profit, Critical Path Institute (C-Path), believes the guidance could be improved by encouraging the use of Clinical Data Standards Consortium (CDISC) standards, as well as common data elements and global identifiers in natural history studies.

“In rare diseases, where many data collections are small, the value of standardization of data collection cannot be understated,” C-Path wrote. “In order to combine or compare data from different sources, such standardization is key.”

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