Knowing the course of a given disease over time provides important information to drug developers on how the disease progresses in the absence of intervention, providing clues on how best to treat it. This information is obtained through what is known as a natural history study: an observational study that follows a group of people over time who have, or are at risk of developing, a specific medical condition or disease. These studies identify demographic, genetic, environmental and other variables that correlate with the disease’s development and outcomes.

Information obtained from a natural history study plays an essential role at every stage of product development, such as identifying the patient population and identifying or developing clinical outcome assessments and biomarkers.

Natural history studies are often part of disease registries, which significantly benefit research efforts by: providing a centralized repository of patient data, supporting natural history studies and treatment evaluations, fostering collaborative research and biomarker identification, and raising disease awareness. Registries like AADCAware, for example, promote data sharing and standardization of research practices across institutions and countries for the rare disease aromatic l-amino acid decarboxylase (AADC) deficiency. Another example is the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS), which is the largest prospective natural history study performed in DMD to date.

Learn more about natural history studies and their importance – especially for the rare disease community – below.

Why are natural history studies conducted?

Natural history studies have many purposes, chief among them the ability to provide information to help researchers and clinicians understand the disease course over time. Other important reasons they are conducted include the opportunities to:

  • Better characterize the disease
  • Characterize the patient population and identifying subgroups within the population
  • Understand the day-to-day effects of the disease on the lives of patients and their families from their perspective
  • Highlight areas of unmet medical need
  • Inform research priorities from patient and clinical perspectives
  • Establish diagnostic criteria
  • Develop clinical care guidelines
  • Identify biomarkers
  • Collect patient-reported outcomes and other clinical outcomes, which can be used to identify outcome measures to be used in clinical trials
  • Increase patient participation and retention in clinical trials
  • Compile data from the patient perspective that can be used by the FDA as part of their marketing review process
  • Amass data to advocate for expanded insurance coverage for therapies and services

Why participate in a natural history study?

Due to the small numbers of people affected by rare diseases, many rare diseases have incomplete natural history data. Therefore, there are unique challenges in understanding the disease and drug development for these conditions. Participating in a natural history study can be very beneficial to the community for many reasons:

  • The data from a natural history study can:
    • be used in FDA review of new therapies for rare disease, resulting in regulatory approval and making the therapy accessible to those with the rare disease
    • be used as evidence with government policy makers when expressing the needs of people with rare diseases
  • Helps with the development of clear diagnostic criteria or clinical management guidelines by considering patient/caregiver burden
  • Supports the development of clinical trials by helping to design better study criteria
  • Raises awareness of disease in medical, academic and pharmaceutical communities
  • Provides your patient community with a sense of momentum and increase interest in participation in research
  • It can lead to the development of more effective, safe treatments or potentially a cure for the disease

All of this information can also be found in our Insightful Moments™ clinical trials roadmap

If you have questions or want to learn more, please call 1-833-PTC-HOPE (1-833-782-4673) or email us at