Clinical Research: Phase 1 - Phase 4

Natural History vs. Registry Studies in Rare Disease

Patient registry and natural history studies are often thought of as interchangeable, but there are major differences in these approaches to clinical drug development. Understanding the role of each is important, as well as understanding the distinctions on how these study designs are used in pursuing treatments for rare diseases.

Patient Registries

A patient registry is an organized system for collecting, storing, analyzing, and disseminating information on people who have a disease, are predisposed to its occurrence, or who have been exposed to substances known or suspected to cause it. Patient registries are broad in scope and can be defined as needed across the drug development continuum.

A registry may be used to collect disease information, recruit patients for clinical trials, monitor patient care and outcomes, advance research hypotheses, observe patient behavior patterns, establish disease-specific standards of care, and support reimbursement discussions. As such, they often play a vital role in the design of natural history studies.

Natural History Studies

Natural history studies, by comparison, have a very specific goal: to track a disease’s course over time by identifying factors such as demographics, environmental conditions, and genetic variables that correlate to the disease and its outcomes. These produce greater understanding of how the condition develops and how it can most effectively be treated.

These studies document the disease’s course from the time immediately prior to inception, progressing from the presymptomatic phase through various clinical stages to the point where the patient is cured, becomes chronically disabled, or dies in the absence of clinical intervention.

A third type of study, reserved for special cases, is a natural history study used to represent a control population. These can be critically important in cases where very small patient numbers make use of a control or placebo population impractical. These involve intense and deliberate discussion with, and approval by, regulatory agencies and should be considered only in exceptional cases.