Patient registries: EMA officials highlight opportunities in orphan drug development

Regulatory NewsRegulatory News | 25 August 2022 |  By 

Officials from the European Medicines Agency (EMA) tout the benefits of patient registries to support regulatory decision making for orphan medicinal products in a recent journal article in Frontiers in Pharmacology.
Citing the increasing use of real-world evidence (RWE), including patient registries, the officials say that such sources offer “useful evidence at different stages of orphan medicinal products lifecycle, including during the development phase by providing information on disease natural history, its prevalence and incidence to contextualise pre-authorisation clinical studies, to support orphan designation initial and maintenance applications by demonstrating significant benefit versus existing treatments, but also to generate post-authorisation long term data on their effectiveness and safety profiles.”
The article offers examples of registries that have been used during the evaluation of various orphan drugs, including multiple advanced therapy medicinal products (ATMPs), and provides insights on how those data sources facilitated the agency’s decision making. For instance, they note the Committee for Medicinal Products for Human Use (CHMP) has successfully used the Cystic Fibrosis Foundation Patient Registry to expand therapy for certain cystic fibrosis subpopulations with a certain genetic marker.
They also note that EMA has embarked on an ambitious project to harness RWE from a slew of registries through its Data Analytics and Real-World Interrogation Network (DARWIN EU). The regulators hope the network will support regulatory decision-making by “establishing and maintaining a catalog of known, relevant data holders, continually ensuring the discoverability and quality of data held by data holders in order to conduct scientific studies and analyses on behalf of the European Medicines Regulatory Network and EMA scientific committees.”
EMA’s joint Big Data Steering Group’s recently published a third workplan which lays out a timeline to develop DARWIN EU. According to the plan, by the end of this year, the research database will initiate four studies with the help of 10 research partners to gather real-world evidence (RWE). By the end of 2025, that is slated to grow exponentially, resulting in collection from 100 studies with the help of 40 partners. (RELATED: EMA, HMA outline evolution of DARWIN EU real-world database, Regulatory Focus 2 August 2022)
Eventually, the officials hope that DARWIN EU will help the Committee for Orphan Medicinal Products (COMP) with orphan designation requests and support other committees with drug utilization studies and post-market studies looking at the long-term safety and effectiveness of orphan drugs.
The authors acknowledge that it is often difficult to characterize the natural history of rare diseases due to small patient populations, geographically spread-out populations and the complexity of the diseases themselves. However, they argue that the growing number of patient registries capturing real-world data (RWD) may facilitate rare disease product development.
The officials recognize that there are multiple challenges gathering and analyzing data from patient registries that need to be considered.
“For example, in order to increase patient populations and statistical power of clinical studies on these medicines, data pooling from various registries and/or interoperability between these data sources are key,” the authors state. “This requires various registries collecting data on a particular disease of interest to capture the same information according to adopted standard coding terminologies and list of common data elements, during the development of an orphan medical product as well as post-marketing.”
They note that to address such challenges, additional steps may need to be taken to improve the completeness of registry data and its accuracy to ensure the data quality is sufficient to answer specific research questions. They also said it’s critical that issues such as data ownership, how to facilitate data collection, data access, data sharing and data linkage are addressed.
“All these aspects can be difficult to implement due to limited funding and resources available to registries, but also due to restrictions linked to national data protection requirements,” the authors said. “A clear sustainability plan laying down short and long term strategies on the development and maintenance of the registries is critical to ensuring their continuous viability, adaptability and suitability to support regulators’ decision making.”
The officials said there are opportunities to address these challenges, especially if drug sponsors and regulators engage each other throughout the product development lifecycle, such as business pipeline meetings, innovation task force briefing meetings, kick-off meetings for priority medicines (PRIME), dialogues during an orphan designation procedure, scientific advice procedures and pre-submission meetings. The article includes a graphic showing how such interactions can take place that may help sponsors visualize when in the regulatory timeline the various meetings can take place.
“Early engagement with registry holders is a key pre-requisite to understand the opportunities provided by registry data, but also their limitations when used to support demonstration of significant benefits of orphan medicinal products and their long-term monitoring postauthorisation,” the authors said.
With those challenges in mind, the officials are still optimistic the registries can successfully support orphan drug regulatory needs. They argue the registries can fill knowledge gaps by providing natural history data, information on standard of care, creating historical comparator cohort/external control arms in the frame of clinical trials and by providing long term safety and effectiveness data.
The authors caution that whether a registry is suitable for regulatory purpose needs to be assessed on a case-by-case basis, and by carefully balancing their opportunities against their limitations. Researchers will also need to consider factors such as what data elements are captured, the quality of that data and the governance of the data. With that in mind, the authors note researchers should read up on EMA’s guideline on registry-based studies which recommends performing feasibility and a quality management analysis.
“At an early-stage collaboration between pharmaceutical companies and registry holders will help to understand the suitability of the registry to answer a specific research question,” the officials said. “The multiple initiatives launched at European and international levels will provide frameworks to promote the values of registries from all stakeholders’ perspectives.
“Early and continuous dialogue facilitates sharing of experience and best practice to help further improve the quality of registries and allow their full exploitation in medicines research, development and monitoring for faster patients access to innovative treatments,” they added.
Frontiers in Pharmacology


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