Patient registries and natural history studies are vital tools for orphan drug researchers, who often struggle with limited understanding of diseases and sparse data due to small patient numbers. In the second installment of the Premier Voices podcast with Angi Robinson, Vice President, Clinical Development Services, Rare Disease & Pediatrics, and Juliet Moritz, we look at what patient registries and natural history studies are, how they differ, and when each approach makes sense.
Fundamentally speaking, the initial steps toward approving a rare disease treatment are similar to those for treating more common afflictions. It starts with a foundational understanding of the disease, how the study drug works, and the projected preclinical and clinical study designs.
But when the target is a rare condition, data may be sketchy and dispersed, representing just a few patients and lacking any composite or aggregate numbers. There will be few tools for diagnosing some indications, and even those investigators considered key opinion leaders in specific indications may be working from limited information, often having no previous studies to draw on.
Patient registries and natural history studies can be invaluable in filling the holes left by this dearth of empirical knowledge.
Patient registries
A patient registry is an organized system for collecting, storing, and analyzing patient data. Registries are usually designed with some general objective related to data collection and the target data points, but there are few restrictions in their design and goals and the data sets they’re engineered to collect.
A registry can be set up for a limited time to answer very specific research questions, or it may collect data indefinitely to answer any variety of known or emerging research questions. It can even include direct communication between sponsor and patients. Registries can be applicable across the full continuum of the development pathway, influencing the early foundation of development; informing the design of natural history studies; and helping researchers achieve later objectives that include defining the study design, identifying documented health outcomes data, locating potential patients, supporting reimbursement discussions, and helping establish disease-specific standards of care.
Natural history studies
Natural history studies, by contrast, are very specific in their purpose: to track the course of diseases over time by identifying variables such as demographics, environmental factors, and genetics to understand how a disease develops — and, ultimately, how to treat it. It’s imperative that these studies be well-planned, thoughtfully executed, and closely monitored.
A literature review is probably the easiest way to begin clarifying the natural history of a condition, especially a rare disease. Literature reviews are generally inexpensive and require minimal resources but are limited by what exists in the available literature. Additionally, researchers have no access to patient records and no way to capture missing data.
Another popular natural history study is a retrospective chart review, which provides access to data from patients both living and deceased. Chart reviews are less costly than prospective trials but generally more expensive than literature reviews. On the minus side, researchers have no control over how the data is presented, and in all retrospective studies, it’s essential to define prospectively how you will handle missing data or data recorded in a way that differs from how you’re attempting to collect it.
It’s a complex and important topic, so check out the latest episode Premier Voices to hear straight from our clinical research experts.