An endpoint is the primary outcome that is being measured by a clinical trial. A cancer drug, for example, might use survival as an endpoint, comparing the five-year survival rate of patients using an experimental therapy against the five-year survival rate of patients using another treatment or a placebo.
A clinical trial might use a clinical endpoint or a surrogate endpoint. A clinical endpoint is an outcome that represents direct clinical benefit, such as survival, decreased pain, or the absense of disease. The most common and most meaninfgul clinical endpoint in cancer research is overall survival. A surrogate endpoint is a substitute for a clinical endpoint used in trials where the use of a clinical endpoint might not be possible or practical (if, for example, a drug’s direct benefits would take many years to measure). Unlike clinical endpoints, surrogate endpoints do not represent direct clinical benefit, but instead predict clinical benefit. For example, tumor shrinkage can be used as a surrogate endpoint for longer survival in clinical trials for drugs intended to treat some cancers. Some surrogates are said to be “established” or “validated,” meaning they have been proven to predict clinical benefit. Other surrogates have not been validated, but are “reasonably likely” to predict clinical benefit. This latter type of surrogate is the basis of the FDA’s accelerated approval pathway.
The specific endpoint chosen for a given study has to do with clinical trial design, the nature of the condition being treated, and the expected effect of the experimental therapy being tested. Here are a few common endpoints for clinical trials of cancer treatments:
- Disease Free Survival (DFS) – The length of time between treatment and relapse. This endpoint is generally used with treatments that leave patients without any detectable signs of disease, such as surgery.
- Progression Free Survival (PFS) – The length of time between treatment and measurable worsening of the disease. Generally used to study advanced diseases that are unlikely to be removed entirely.
- Response Rate (RR) – The percentage of patients whose cancer shrinks or disappears after treatment. Frequently used in single-arm trials, as it does not require direct comparison with a control.
- Overall Survival (OS) – The time between treatment and death. This measure includes death from any cause, including both the disease being treated and unrelated conditions. This means that OS, unlike some other endpoints, measures both the impact of a treatment after relapse and the survival impact of treatment side effects.
- Quality of Life (QoL) – A drug’s impact on pain or other symptoms related to a condition. Because many cancer treatments have negative side effects, drugs with the potential to improve Quality of Life can offer patients substantial benefits over existing treatments. This measure is often a Patient Reported Outcome, or PRO, meaning that it relies on patients’ accounts of a drug’s impact.