Real world data and FDA: Drugmakers seek more clarity on registry guidance
As the FDA crafts a new series of guidance documents on how biopharma companies can use real-world data, including patient registries, to help supplement their applications, pharma companies and industry group PhRMA are calling for more details and more consistency from the agency.
The push from industry around the use of real-world data has been supported by both the 21st Century Cures Act and industry-negotiated PDUFA VI (the next iteration of which is coming soon).
Industry group PhRMA explained in a comment posted last week that common elements from these coordinated RWD guidance documents from FDA “are not always aligned with the recommendations in this [registry] guidance, which may cause confusion. Similar approaches should be applicable across many RWD sources and the guidances should be aligned accordingly.”
Released in November, the draft guidance is intended to help sponsors and FDA with considerations when either proposing to design a registry or using an existing registry to support regulatory decision-making about a drug’s effectiveness or safety.
“In general, registries are better suited as a data source for regulatory purposes when sponsors aim to capture objective endpoints,” the FDA says in the draft, “such as death or hospitalization. Subjective endpoints, such as pain, can be collected in a registry, but additional challenges are involved to standardize such measurements.”
Incoming FDA chief Rob Califf has been a fan of RWD, particularly when randomized, and has worked on the topic in his previous role at Google’s parent company Alphabet. Life science companies, which previously sought more details on prior guidance docs, are again calling on the FDA to explain itself more.
McKesson, which operates an oncology real-world data and evidence business called Ontada, wrote, “At a minimum, FDA guidance should include content around the common types of registries (i.e., patient, specialty, provider, device, and population-level), and specifically, their unique characteristics should include specific data elements that make a registry ‘fit-for purpose’ for a particular scientific objective or use case.”
J&J’s Janssen also wants the FDA to go further in explaining how registries might factor into the agency’s benefit-risk assessments for new drugs:
For example, safety and efficacy endpoints derived from registry data can be designed with the same breadth and detail as those used in the context of a randomized controlled clinical trial. Registry endpoints have the advantage over some other types of data sources as duplications are more easily identified and addressed, and the study timeframes and units captured can be uniform. Registries also have the potential to measure severity of disease, not just disease occurrence and can allow the evaluation of benefits and risks in the real-world setting. To this end, Janssen requests that as the Draft Guidance is finalized, FDA include discussion on how registry data may inform the benefit-risk assessment.
Janssen’s chief data science officer Najat Khan wrote that the draft guidance “would be significantly strengthened if the FDA included discussion of challenges and potential solutions as well as advantages and limitations of secondary use of registry data.”
Amgen’s VP Brian Bradbury and SVP Mark Taisey called on the FDA to include a few examples of registries used for regulatory decision-making, including the use of an existing registry and the design of a new registry.
They also offer its own example of the Nordic Country Patient Registry for Romiplostim, which was originally established in 2009 as a post-authorization safety study to assess the long-term safety and outcomes in adult patients with chronic immune thrombocytopenia and was used to conduct a study of comparative effectiveness of romiplostim versus SOC with the goal of supporting an expansion of the romiplostim label.
“Additionally, the EXPECT pregnancy registry examined the occurrence of major congenital anomalies in pregnant women with severe asthma treated with omalizumab,” Bradbury and Taisey wrote.
Boehringer Ingelheim similarly calls for examples of use of real-world evidence, “specifically registries to support the approval of a new indication.” Boehringer offers the example of use of registry data from the US Scientific Registry of Transplant Recipients for an approval of a new indication of tacrolimus.
Amgen also calls on the FDA to expand its definition of RWE in this guidance and others, to include (addition in bold), “RWE is the clinical evidence about the usage and the potential benefits or risks of a medical product or about a disease state derived from analysis of RWD.”