Breaking down the differences between observational studies and clinical studies for drug research.

What is an observational study?

In observational studies, researchers follow groups of people over a period of time. Depending on the study, those groups may include healthy people, people with a disease, or people who are at greater risk for developing a disease (because they have a family history, a gene, another associated condition, or an antibody that predisposes them to develop the disease).

An observational study is designed to ‘observe’ the daily lives of a person with a rare disease. 

They are called observational studies because a researcher “observes,” but does not “intervene.”  There is no drug administered or medicine given for the purpose of intervention, and the researchers are not changing the way the participants are normally treated.

In contrast, an interventional clinical study requires people to be assessed with a number of tests before they are approved to enter or start a study—all before medication is administered at a study site. Patients who are enrolled in a clinical study are then assessed periodically from the same study site, with a focus on a consistent set of assessment criteria. This allows the administrators to determine whether the medication caused any changes—either positive or negative. 

Observational studies are very important to researchers since they provide an opportunity to observe people with a rare disease in their normal everyday environment. Information typically collected in these studies includes the type and frequency of symptoms, what medications are being taken, what kind of tests are taken and what are the results of those tests over time, as well as how much and what kind of support is needed by the patients. With this information, researchers can learn:

• Common symptoms, and which symptoms lead to a diagnosis

• Which exposures or behaviors may increase the risk of triggering a rare condition 

• Clues that lead to new treatments

• Patterns and trends of diseases at different ages and among different types of people

• Everyday experiences and needs of people living with the disease in different environments

Types of observational studies

• Natural history studies look at the path of a rare disease, both observing the early signs or symptoms and assessing how it changes over time. Researchers often collect information about a person’s risk or predisposition towards developing a rare disease by checking their medical history, as well as collecting blood, saliva, and urine samples that may be studied to learn more about what may lead to the development of a rare disease. Data collecting from natural history studies may lead to a way to treat the disease or prevent it from progressing.

• Longitudinal studies involve an ongoing observation of a group of people over time, often to see whether those with different backgrounds, medical, or family history have different experiences of disease (for example, people with a family history of allergies who go on to develop an autoimmune disease).

In rare diseases, observational studies are especially important.

With most rare diseases, very little information exists that can provide a complete picture of all its symptoms, flares, tests, medications, and experiences that come from living with that rare disease over time.

Any or all of this information can be critical to help design a clinical trial for a study medication, as researchers need to take all these issues into account to help assure that the design of the study doesn’t negatively impact the patient in any way. 

Observational studies provide insights for clinical trials of potential new medications

The information gathered can be used by researchers who can then determine:

• What should be measured before, during, and after a clinical study?

• What medications are participants likely to take and need to continue taking?

• How long should a study last? 

• What kind of support may be needed during the study?

What participation in an observational study may require 

The requirements of a participant in an observational study may vary, based on the study and the disease. 

• Researchers will need participants’ medical history and access to medical records, as well as connection to the specialist who manages their disease. 

• Participants will continue to see their specialists and follow whatever advice or treatment is prescribed, and they may be asked to come into the study site for an in-person visit with the research team.  

• Some studies might ask for blood or urine samples so they can be tested for antibodies or other signs of disease, at the start of the study or during the course of the study. 

• At the visits with the study team, participants may be interviewed or asked questions about their condition and how it impacts their daily life and activities of daily living.  

Before becoming a participant in an observational study, just like in an interventional clinical study, the research team will review the study purpose, what patients can expect over the course of the study, and how it may affect their daily lives.

Once patients confirm that they understand what participation involves, they will be asked to sign a formal agreement of participation—an  Informed Consent Form.  Even after signing a form to accept participation, however, patients can withdraw their consent to participate, and discontinue their participation in the study at any point, without any penalty or trouble, if they change their mind.

Observational studies are a fundamental part of research into a disease. In the case of a rare disease, they may be a first step in the development of a new treatment. In fact, a guidance was recently published by the The Food and Drug Administration (FDA), titled “Rare Diseases: Natural History Studies for Drug Development.” In this report, the FDA recommends natural history studies as a means of collecting information about the natural course of a disease without intervening by adding a new experimental treatment. 

The guidance states: “Although knowledge of a disease's natural history can benefit drug development for many disorders and conditions, natural history information is usually not available or is incomplete for most rare diseases; therefore, natural history information is particularly needed for these diseases.”

To learn about opportunities to participate in observational studies for multifocal motor neuropathy (MMN), please click here.

To learn about opportunities to participate in observational studies for congenital myasthenic syndromes (CMS), please click here.

Sources:

https://www.cancer.gov/research/participate/what-are-observational-studies

https://www.mrcctu.ucl.ac.uk/patients-public/about-clinical-trials/what-is-an-observational-study/