How to read the evidence · 3 of 4
Overall survival, progression-free survival and surrogate endpoints
Overall survival (OS) counts only death. Progression-free survival (PFS) stops the clock at progression or death, whichever comes first. Disease-free and event-free survival are used after treatment aimed at cure and stop the clock at a defined set of events. Because each trial defines its own events, the paper's definition is what counts.
Teaching example: one imaginary person, typical endpoint definitions.
- month 0: treatment starts
- month 8: Cancer progresses
- month 20: Death
| Endpoint | Clock stops at | Time recorded |
|---|---|---|
| OSOverall survival | Death | 20 months |
| PFSProgression-free survival | Cancer progresses | 8 months |
| DFSDisease-free survival | Cancer progressesCounts the cancer returning or death. Whether a second cancer counts is set by each trial. | 8 months |
| EFSEvent-free survival | Cancer progressesWhich events count is set by each trial; progression, relapse, a second cancer and death are common choices. | 8 months |
The same person contributes a different time to each endpoint. That is why a gain in progression-free survival does not automatically mean people live longer, and why papers must state exactly which events counted.
Surrogate endpoints
A surrogate endpoint is a stand-in measured earlier or more easily than the outcome that matters. FDA describes it as a marker thought to predict clinical benefit but not itself a measure of clinical benefit. In 1989 Prentice proposed a restrictive criterion for when an endpoint deserves the word: the surrogate must capture the relationship between the treatment and the true outcome. Whether progression-free survival, or tumour response, does so for overall survival differs by cancer and treatment, and has to be shown rather than assumed.
Sources and further reading
These pages explain general methods in plain language and were written for this site; the sources below are the references to read next. Some classic papers have no abstract online, so the explanations stay at textbook level.
Prentice RL. Surrogate endpoints in clinical trials: definition and operational criteria. Stat Med. 1989;8(4):431-40.
Fleming TR, DeMets DL. Surrogate end points in clinical trials: are we being misled?. Ann Intern Med. 1996;125(7):605-13.
US Food and Drug Administration. Accelerated Approval Program. fda.gov (content current as of 25 August 2026). Accessed 2026-10-20.