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Rare Disease Research: The Benefit of Registries

a doctor and her patient reviewing test results

The benefit of registries for real-world evidence generation in rare disease research

Linda Ross, senior director, peri- and post-approval operations, Evidera, discusses how registries can be an incredibly useful tool in research.

Advancements in gene therapy and transformative medicine have had a major impact on the development of treatments for rare diseases, resulting in a growing need for evidence of the safety, effectiveness and value of these treatments in the real world. Opportunities to improve health care, clinical outcomes and patient and caregiver quality of life are abundant, but for successful market access of novel treatments, robust—and frequently longitudinal—clinical and outcomes data from the usual care setting are necessary.

Registries can be an incredibly useful tool in gathering data on patient usual care, current treatment landscape(s) and long-term clinical outcomes to better understand the impact to the disease population and strategically plan for additional real-world patient research and treatment development. In observational, non-interventional registries or disease-specific registries (used to gather real-world evidence), identifying, engaging and enrolling as many of these rare disease patients as possible is vital to the success of the registry. One common challenge is convincing usual-care physicians of the benefit of participation in these observational registries since no experimental drug is provided. In these cases, it is imperative to convey the importance of every real-world patient experience to better understand the impact of treatments on patient outcomes outside of the clinical trial setting.

The success of a registry hinges largely on the study design, which can influence the operational aspects of the registry as well as patient engagement. The ability to operationalize the registry protocol is paramount—the best-written protocol cannot be successful if it is not feasible within sites and with site staff. The protocol must be flexible to adhere to standard of care procedures; it must allow for variability in data collection as each treating clinician may conduct standard of care visits and document clinical information differently; and, lastly, it must not influence standard of care treatment for the patient—it must adhere to the “real-world” treatment paradigm. Although these key principals for real-world data collection must apply, there still exist inherent challenges in enrolling patients into registries. How to best capture the patient data may depend on the protocol: disease-specific registries versus treatment-specific registries.

Treatment-specific registries are designed to enroll patients already receiving treatment, per physician intent, and all clinical data is associated to a specific product and focuses on treatment-specific clinical outcomes. This study design helps to understand:

  • Focused demographics of patients diagnosed with the rare disease and prescribed the specific treatment
    • Is there a difference in the demographics of the patients enrolled in the registry compared to the overall rare disease population as understood in published literature?
  • Clinical outcomes specific to the treatment
    • Are there clinical outcomes newly identified in the real world that were not identified during earlier clinical trials for the product?

The population reflected in the treatment registry would be a subset of the specific treatment population since not all patients may consent to participate in the registry, which of course is associated with potential selection bias.

Disease-specific registries are designed to enroll “all-comers” of a rare disease into a registry. A patient with a diagnosis can be eligible for enrollment and ongoing observation within the registry, without impacting standard of care treatment or schedules. This study design helps to understand:

  • Demographics of patients impacted by the rare disease, regardless of treatment
    • Are there trends in race/ethnicity?
    • Is there a specific age range for diagnosis?
    • Are there socio-economic influences in rare disease diagnosis and treatment?
  • Current treatment landscape—insight into all treatment options available to patients with a specific rare disease
    • Are there specific treatment protocols/guidelines already established?  Will new treatment approvals impact treatment protocols already in place?
    • Are there clinical outcomes associated with specific treatment regimens within the diseased population?
    • Are there complementary therapies that can enhance current treatments?

This also gives the sponsor flexibility in tracking their own product update versus other treatment options, all within the construct of the disease registry.

Registries provide an abundance of real-world insight into rare diseases, the populations who are afflicted by them, and the newly approved therapies that treat them. The data gathered through these studies can help to guide research objectives and direction, identify future real-world patient studies and help build the foundation for strong value story development to help optimize the chance of market access. While there are inherent challenges in designing and operationalizing any registry, those designed for rare diseases present additional challenges in patient identification, engagement and recruitment. Success comes with overcoming these challenges through a multi-faceted approach that uses proven best practices, innovative solutions and evolving resources.

For more information on registries, including patient engagement strategies, please read the full white paper.