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Snapshot: What is an Endpoint?

When scientists test a new treatment in a clinical trial, they need a reliable way to determine whether it is safe and effective. To do this, they rely on endpoints.

Endpoints are clearly defined outcomes that are measured during a trial to help determine the effects of an intervention. Clinical trials usually include several types of endpoints, each serving a different purpose. These endpoints are:

Primary endpoints

Secondary endpoints

Exploratory endpoints

The primary endpoint is the primary outcome that a trial is designed to assess. These endpoints relate to the main question that a trial is aiming to answer. For instance, in a Phase I clinical trial of a new drug for ataxia, the primary endpoint will relate to the drug’s safety (e.g., whether it causes any serious adverse effects). These endpoints are also called safety endpoints. In later-stage trials, the focus will shift toward the drug’s effectiveness (e.g., whether it reduces the severity of symptoms).

Secondary endpoints provide additional insights into a treatment’s effects, such as changes in walking, standing ability, or fatigue. These endpoints compliment primary endpoints by providing a better understanding of a treatment’s benefits and potential side effects.

Some studies also include exploratory endpoints, which allow scientists to assess other potential outcomes of an intervention, usually to help guide future studies.

Clinical vs. Surrogate Endpoints

Clinical endpoints directly measure clinical outcomes, like patient survival, function, and quality of life. Sometimes, clinical outcomes can be difficult or impractical to measure directly, like when a disease progresses slowly or a drug is expected to take a long time to have a clinical benefit. In these cases, scientists often use surrogate endpoints as substitutes for direct clinical measurements. For example, in a trial for a new drug for spinocerebellar ataxia (SCA), a clinical endpoint might be a change in score on the Scale for the Assessment and Rating of Ataxia (SARA). A surrogate endpoint in this trial might be lower levels of inflammation. In this case, reduced inflammation might be an early sign that the drug is working, long before scientists can detect changes in a patient’s symptoms. Surrogate endpoints are helpful because clinical improvements can take a long time to occur, so scientists can use these clues to see progress earlier.

Selecting and Analyzing Endpoints

All endpoints should be:

specific (clearly defined)
measurable (able to be consistently tracked)
scientifically appropriate (validated to accurately reflect a health outcome of interest)

Scientists must define endpoints before beginning a trial to prevent bias and ensure that their results are meaningful. Selecting endpoints is part of the larger process of developing a trial protocol, which often involves the research team, clinicians, patient partners, ethics boards, and regulatory agencies, such as the U.S. Food and Drug Administration (FDA) or Health Canada. After a trial is completed, scientists measure whether their pre-defined endpoints were met to see whether the trial was successful.

If you would like to learn more about endpoints and their importance in clinical trials, take a look at these resources from Mahalo and Health Tree Foundation.