Natural history studies are a form of observational study that aim to help scientists gain comprehensive insights into a disease. In an observational study, data are gathered without offering a treatment or making any other attempt to affect the course of the disease. Many observational studies focus on specific aspects of a disease, such as tracking the presence of an individual biomarker, measuring a certain symptom, or studying cases in a particular population. A natural history study, on the other hand, is an effort to gather as much data about a disease in as wide a population as possible. 

These studies collect data about participants’ personal and medical histories, demographics, genetics, and more. They also follow participants over time, collecting “longitudinal” data that tracks the evolution of their condition.

Generally, natural history studies try to recruit participants who are representative of the entire population with the disease. Participants in these studies may be asked to contribute data remotely through surveys or by submitting medical records. They may also be asked to visit study sites to complete tests or undergo physical examinations. In some cases, researchers will ask for blood or tissue samples.

What kinds of data do natural history studies collect?

The goal is to collect as comprehensive data as possible about how the disease manifests and behaves over time. Unlike many smaller-scale observational studies, natural history studies do not necessarily aim to answer a specific question about the disease. Rather, their purpose is to generate large amounts of data that can fuel further research. These data are often organized into digital databases and/or repositories of biological samples, which are used as the basis for further studies.

Data from natural history studies can be utilized to understand things like:

  • What are the environmental and genetic conditions that contribute to the onset of the disease?
  • How does the disease develop over time?
  • What factors could affect its duration and severity?
  • Are there different subtypes of the disease? (Examples in ALS could include fast vs. slow progressors or limb vs. bulbar ALS)
  • Identifying potential biomarkers for diagnosing or measuring disease severity and/or progression.
  • Finding new drug targets and informing the development of potential treatments.
  • Lifestyle and environmental factors that could affect onset or symptoms.

Natural History Studies in ALS: The ALS Research Collaborative (ARC) Study

For a poorly understood condition like ALS, natural history studies are crucial for helping scientists understand the disease and informing the development of new treatments. The longest-running natural history study in the disease is the ALS Therapy Development Institute’s (ALS TDI) ALS Research Collaborative (ARC) Study. Through the ARC Study, ALS TDI researchers partner with people with ALS and asymptomatic carriers of ALS-related genetic mutations all over the world to gather comprehensive data about the disease.

Since 2014, more than 1,700 people have enrolled in the study, contributing trillions of data points about their personal history, genetics, disease progression, and more. Data collected by the ARC study include: 

  • Personal Background Information
    • Surveys on topics such as family history, geography, lifestyle, medical history, occupation, and ALS experience.
  • Blood Samples
    • Some ARC participants in the US and Canada contribute blood samples from home through monthly visits by an in-home phlebotomist.
  • Speech Tracking
    • Voice recordings made monthly over the phone provide insights into changes in speech over time.
  • Movement Tracking
    • Accelerometer devices measure movement and provide recordings of changes in ability over time.
  • Electronic Health Records
    • ARC participants may optionally integrate their Electronic Health Records (EHRs) into the ARC study. An EHR is an electronic version of a patient's history and care that is maintained by their medical provider over time.
  • ALSFRS-r Tracking
    • Monthly ALSFRS-r surveys help participants track their progression and provide a crucial point of comparison for other data collected through the study.
  • Whole Genome Sequencing
    • Certain ARC participants may be asked to submit samples for whole genome sequencing.

These data drive research at ALS TDI, helping us learn more about the disease, develop better measures for diagnosis and tracking progression, and accelerate the discovery of treatments. Data from the study is also made accessible to researchers worldwide through the ARC Data Commons, an innovative data-sharing platform powered by Google Cloud and Google’s Looker application. This has been made possible by the generous participation of thousands of people living with ALS and asymptomatic carriers of ALS-related genetic mutations over the past decade, including hundreds of participants who continue to contribute data every month. 

Other Natural History Studies in ALS

In addition to the ARC Study, there are several other natural history studies concurrently working to gather data about the disease. While many of these studies may collect similar data, there are key differences that make the existence of multiple natural history studies a positive factor in ALS research. Some studies, like ARC, are completely or primarily remote, while some require in-person participation. Some may collect biological samples, some clinical data and surveys, and others both. Some are ongoing indefinitely, while others seek to collect (or have already collected) data over a specified period of time. 

Additional natural history studies, datasets, and biorepositories in ALS include:

In science, it is essential to be able to replicate the results of any study to make sure the results are accurate. Even where these studies and datasets overlap, it can be important to have multiple sources of similar data available to researchers to replicate results. When concluding an analysis of a large dataset, researchers can then try to run a similar analysis using a different data source—and be even more confident in their conclusions if they achieve the same result.

To learn more about ALS TDI’s ARC Natural History Study, click here.

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