Over the past few years my field (hem/oncology) has witnessed an outstanding surge in popularity of a surrogate endpoint called POD24 (progression of disease within 2 years of chemoimmunotherapy) initially described in patients with follicular lymphoma. Follicular lymphoma is in most cases an indolent type of lymphoma, and patients commonly experience long remissions between relapses. Clinicians are interested in identifying a surrogate endpoint for overall survival (OS), hoping this might expedite clinical trials. Beyond risk prediction, they are also interested in “risk stratifying” patients to guide patient selection in clinical trials (e.g. test intervention only in high risk group).
This is the first paper describing POD24: https://www.ncbi.nlm.nih.gov/pubmed/26124482/
Since this original description, many have echoed that POD24 is indeed prognostic, and others have also used it in other types of lymphoma.
Here’s some criticisms and potential problems I foresee:
- While it makes perfect sense that a shorter time to progression might predict OS (I have a feeling that this might be the case not only in follicular lymphoma but in any type of cancer), I question that the survival risk magically increases at 24-months
- Massive loss of information: after dichotomizing time, one cannot make predictions on time anymore…
- POD24 prompts a landmark analysis from the time of first event, with all the associated issues inherent to landmarking (e.g. drops patients censored prior to landmark event). In other words, this creates unnecessary problems.
- Clinicians may be tempted to use POD24 for risk prediction, although we know dichotomization is particularly harmful for individual risk prediction
- Researchers have started looking at predicting modeling using POD24 as the outcome variable, using an arbitrary timepoint (why not POD 20 or 36?), and thereby losing the time-to-event information.
Aren’t there better solutions to improve risk prediction and to analyze trial data than the arbitrary dichotomization of an outcome variable?
If someone could direct me to an open-access database of lymphoma patients (including both relapse and survival data), I would be happy to make my case by running some simulations in R.
I’m posting this to hopefully spark an insightful discussion around the use of this surrogate endpoint.