Clinical Research: Phase 1 - Phase 4

Choices, Choices: Which Type of Natural History Study Meets Your Needs?

When you’re looking into conducting a natural history study, you’ve got two things to consider up front: the premise that underlies all of these studies, and which of several types suits your purpose. We tackled these and other topics in our last rare disease webinar.

Natural History vs. Registry Studies in Rare Disease considers a wide range of subjects, starting with why we perform natural history studies in the first place. These events focus on the disease, period, and not on any therapeutic being developed to treat it. Thus, the study must gather enough data to create a full understanding of the disease’s presentation and progression.

Well-designed natural history studies support development of multiple therapeutic options and are critical for identifying clinical development endpoints. Another vital attribute all share: dependence on high-quality data that results from rigorous planning and quality assurance.

With those established as essential common features, what specific type of natural history study makes sense for you? Here are some options:

Literature review. It’s the least expensive, least resource-intensive type of natural history study, but the scope is limited to what is reported in available literature. There is no access to patient records and no way to capture missing data. It’s difficult to standardize data collected from various articles, and these studies may not meet NHS objectives.

Retrospective chart review. Reviewing patient medical charts is relatively inexpensive and doesn’t commit extensive resources. However, you’re looking at clinical charts vs. research data, so some data may be missing. There is no way to correct or question the data, elements of which can vary over time and from site to site. You’ll also need patients’ informed consent.

Prospective cross-sectional study. Collecting data from a variety of patients at a moment in time has definite advantages: limited study duration, predefined data elements, and the prospect of gaining insight into general disease traits. But you don’t see patients’ experience over time, and there is scant insight on disease progression.

Prospective longitudinal study. Gathering patient data over a prospectively derived period provides predefined data elements and lets you assess disease progression. But these can take a long time to complete, making them potentially expensive, and you must plan for changes in measurements and standards of care over time.

Planning is really key here. Make sure to think ahead: What questions are you trying to answer? Are you linking phenotypic presentation of the disease back to specific genotypes? Maybe identifying a standard rate of progress? You need to consider these and many other questions before writing your protocol.