The survival-incorporated median versus the median in the survivors or in the always-survivors: What are we measuring? And why?

TL;DR

This paper introduces the survival-incorporated median as a new way to summarize clinical outcomes in studies with death as a competing event, providing clearer insights into treatment effects.

Contribution

It proposes the survival-incorporated median as an alternative to traditional methods, integrating survival status into outcome summaries for better clinical interpretation.

Findings

Survival-incorporated median accounts for survival status in outcome measures.

Traditional medians can mislead by ignoring death as part of the outcome.

Application to prostate cancer study demonstrates its practical usefulness.

Abstract

Many clinical studies evaluate the benefit of a treatment based on both survival and other continuous/ordinal clinical outcomes, such as Quality of Life scores. In these studies, when subjects die before the follow-up assessment, the clinical outcomes become undefined and are truncated by death. Treating outcomes as "missing" or "censored" due to death can be misleading for treatment effect evaluation. We show that if we use the median in the survivors or in the always-survivors as estimands to summarize clinical outcomes, we may conclude that a trade-off exists between the probability of survival and good clinical outcomes, even in settings where both the probability of survival and the probability of any good clinical outcome are better for one treatment. Therefore, we advocate not always treating death as a mechanism through which clinical outcomes are missing, but rather as part of the outcome measure. To account for the survival status, we describe the survival-incorporated median as an alternative summary measure for outcomes in the presence of death. The survival-incorporated median is the threshold such that 50% of the population is alive with an outcome above that threshold. Through conceptual examples and an application to a prostate cancer treatment study, we show that the survival-incorporated median provides a simple and useful summary measure to inform clinical practice.