Measurement of progression-free survival, a widely used endpoint in cancer clinical trials, has methodological flaws that can lead to biased estimates.
Katherine Panageas, Dr.P.H., of Memorial Sloan-Kettering Cancer Center in New York, and colleagues examined the use of progression-free survival (PFS) as an endpoint measurement in clinical trials.
PFS is measured as the time from start of treatment to the first measurement of cancer growth. Disease progression is typically measured by radiologic tests, such as x-rays, at scheduled intervals. Most often, researchers do not know when progression actually occurs, so they can only estimate that it happened sometime between the test that showed progression and the previous one.
Methodological problems can arise when researchers define the date of progression as the date on which it was first detected, even though progression most likely occurred prior to that day. The researchers compared a variety of surveillance intervals using a simulated population to demonstrate how the evaluation schedule can affect the estimation of PFS.
The researchers found that the outcome of the trial can be heavily influenced by the surveillance interval and that comparing the PFS times of two studies with different evaluation schedules can lead to erroneous conclusions.
“The decision to use PFS as a primary endpoint should be considered carefully in the design phase of the trial. It is our intention to make researchers aware that estimates of PFS are highly dependent on when they look for progression. The clinical research community can address this concern by adopting consistent strategies for interval evaluations in the design phase,” the authors write.