What Are Observational Studies?

Observational studies and clinical trials are the two main types of clinical research. Clinical trials generally aim to test new treatments, while observational studies help answer questions about ALS based on "real-world evidence.” The researchers don’t intervene to try to change outcomes like disease progression or survival, instead they collect information and make observations about people’s ALS journey, health and the care they receive.

During an observational study, researchers might follow a group of people living with ALS over time to see how their disease progresses or use a wide range of samples and clinical information to investigate genetic causes of ALS or potential biomarkers. Observational studies can also be used to explore the role of environmental factors, such as toxins, in ALS development. These are often cohort studies – a type of observational study that looks at a group of people with something in common, such as where they live or the same profession (like serving in the military or playing professional sports).

Other Differences from Clinical Trials

Because clinical trials need to produce reliable data to support FDA approval, people with ALS must have very specific characteristics to participate. Observational studies also require interested individuals to meet specific eligibility criteria; however, more people living with ALS usually are able to participate.

Compared with clinical trials, observational studies also tend to be less time-consuming for participants. A person with ALS might be asked to complete a detailed questionnaire, undergo some basic tests and/or provide blood, urine or cerebral spinal fluid (CSF) samples.

Most notably, people with ALS who participate in observational studies are not assigned to a treatment or intervention like participants in clinical trials. Although observational studies are not directly testing an intervention, this type of research is still vital for finding new treatments and cures. Successful drug development requires a thorough understanding of what causes the disease, who is at risk of developing it, the symptoms it produces and how it progresses – information gathered through observational research.

Natural History Studies

One of the most common types of observational studies researchers use to learn more about ALS is called a natural history study. This type of study looks at how ALS progresses over time. Because ALS affects people so differently, understanding what happens from the time immediately before the disease develops through its clinical stages is exceedingly important.

During a natural history study, researchers gather information from each participant. This can include the person's gender, age of symptom onset, site of onset, genetic testing results (if known), examination data, ALSFRS-R scores, clinical milestone data (such as time to feeding tube placement or time to non-invasive ventilation) and many other items.

This information can then be used by researchers at academic ALS centers and/or pharmaceutical companies to better under ALS and its progression, inform better clinical trial design and build the scientific foundation of drug development programs. These studies also help inform patient care, best practices and research priorities.

Registry Studies

Some observational studies don’t recruit participants directly. Instead, they answer specific research questions using information people with ALS have voluntarily submitted to a special database called a registry. This information may include age, race, sex, risk factors, treatment undergone and disease progression. Researchers can also use the data collected by registries to identify trends over time, monitor outcomes and study standard of care or best practices.

Some registries, like the National ALS Registry, were developed for a specific purpose. The National ALS Registry was established by Congress in 2008 to collect information that can be used to estimate the number of new cases of ALS that will be found each year in the United States. Information collected by the National ALS Registry is also being used to better understand who gets ALS and what factors affect the disease.

To get the most accurate picture of the disease, it is important to include as many people living with ALS as possible in registry databases. Learn more about enrolling in the National ALS Registry.

Studies for Family Members

There are several ongoing opportunities for healthy people with a family history of ALS to participate in observational research.

The ALS Families Project is helping researchers learn more about why motor neuron degeneration begins and how or why it progresses. This study provides genetic testing and counseling to help participants decide if they want to learn their genetic status and understand and manage their risk. 

The DIALS (Dominant Inherited ALS) Network is recruiting first-degree relatives of people with ALS linked to C9orf72 or SOD1 gene mutations who do not have symptoms of the disease themselves. The researchers plan to follow participants for five years to identify early diagnostic signs and characterize biomarkers at the time any symptoms may develop.

The Pre-symptomatic Familial ALS (Pre-fALS) study is recruiting healthy individuals with a family history of ALS to learn more about the genetic and environmental factors that put people at risk for developing the disease. The researchers also are looking to uncover what happens before ALS symptoms develop, as well as the onset and progression of the disease in individuals who are later diagnosed with ALS.  

More research opportunities for family members of people with ALS can be found on ClinicalTrials.gov. To start your search, enter “ALS \(Amyotrophic Lateral Sclerosis\)” in the box for “Condition or disease”. You can then refine your search by adding words like “presymptomatic” or “family” in the “Other terms” box.

ALS Association Support

Thanks to the outpouring of support from the ALS Ice Bucket Challenge in 2014, we have been able to fund many valuable observational studies taking place around the world. This work has helped scientists better understand the disease, identify new drug targets and biomarkers for diagnosis, expedite clinical trials, and make DNA sequencing data available to the entire ALS research community. Since 2014, more than 20 genes associated with ALS development have been discovered, doubling the number of known ALS-linked genes and providing critical insight into the proteins and pathways involved in disease development and progression.