What’s the difference? Endpoints versus outcomes in clinical trials
In biotech communications, we learn a lot on the job. That frequently involves picking up technical terms through context, without explicitly being told their exact meaning. We’ll often get to the point where we can use a word appropriately in a sentence, but still may not quite be able to define it with precision.
For that reason, the Ten Bridge team occasionally sits down to consider certain terms of our art and really understand them. We call these sessions “Words Have Meaning,” because, well, they do. Recently we took on the distinction between the words outcomes and endpoints in reference to clinical trials. To the uninitiated, these two concepts might sound like more or less the same thing – basically just how the trial turned out. And in fact some sources, such as this Wikipedia entry for clinical endpoint, basically say that clinical endpoints and clinical outcomes are both measures for assessing the goal in a clinical trial.
The Old Ballgame
But dig a little deeper, and you’ll find a distinction. In its Dictionary of Cancer Terms, the National Cancer Institute defines outcome as “a specific result or effect that can be measured.” Meanwhile, an endpoint is “an event or outcome that can be measured objectively to determine whether the intervention being studied is beneficial.” (Emphasis added).
The italicized part is key to distinguishing an outcome from an endpoint; it reveals that the endpoint is the thing you really want to know. An endpoint addresses the central reason for the trial, and is used in evaluations of its success. Outcomes, on the other hand, are the things you measure to inform your endpoints.
To put it in a more familiar perspective, suppose you go to the Red Sox game, and they win. That’s your endpoint. The outcome? That’s the final score.
FURTHER DISTINCTIONS
When people in our industry talk about outcomes and endpoints, they often use modifying words to classify them. Even the way we modify these words can give us some insight into their different meanings.
Outcomes are often categorized by how they are collected, or by whom; they are all about process and practice. They may be clinician-reported by a doctor performing a test, patient-reported through a symptom questionnaire or observer-reported by say, a parent reporting a child’s temperature. Often, they are performance-based, measuring, for example, how far a participant can walk in six minutes.
Endpoints, meanwhile, are more often classified by their purpose and significance. Primary endpoints are the make-or-break standards by which a trial’s success is measured, and often the factors that regulators will assess when deciding whether to approve a new therapy. Secondary endpoints provide supportive information that would not be sufficient to inform decision-making on its own, but they offer insights into questions such as how a treatment works or what effect it has on quality-of-life. Exploratory endpoints occur too infrequently to be of statistical value, or are too newly established to reliably inform efficacy or safety. But they are included either to offer useful insights or to help advance the science of clinical studies.
A SPECIAL CASE
There’s one more kind of endpoint that’s worth singling out. A surrogate endpoint is not directly related to clinical benefit itself, but has been shown to be predictive of the desired benefit. Cancer studies, for example, might use progression-free survival (time from treatment to either tumor regrowth or patient death) rather than overall survival to reach a conclusion more quickly. Alzheimer’s studies, which could easily take decades if they directly measured cognitive performance, have used reduction in amyloid beta plaques as a surrogate endpoint.
Surrogate endpoints are often used in an accelerated approval scenario, where an applicant is trying to get a new therapy approved for a population with urgent unmet need, but it might take years or decades to fully establish efficacy using a primary endpoint. In such cases regulators may allow earlier approval based on a surrogate endpoint, with follow-up studies required to confirm clinical benefit through a primary endpoint. This process has resulted in a small number of drug approvals that were later withdrawn because clinical benefit could not be confirmed, but it has also delivered efficacious treatments to many patients who otherwise would have been out of options.
Endpoints and outcomes can be complicated, and are only getting more so with the explosion of new modalities and measurement technologies coming into the clinic. Down the road, artificial intelligence and other advanced computational methods are likely to come into play. But the basic principles underlying these concepts will always be the same, and it pays to understand the terms we use to describe them.
