Estimating causal effects on quality of life under treatment discontinuation: the ALTA-1L trial

This study bridges the ICH E9(R1) estimand framework with causal inference methods for time-to-event HRQoL analysis when discontinuation precludes observation. By quantifying bias from standard approaches, we provide methodological clarity for applied researchers. To facilitate practical implementation, we translate these insights into a decision flowchart for estimand specification and method selection when intercurrent events (ICEs) act as competing events. Future trials should prespecify ICE-handling strategies and consider data collection beyond ICEs to support treatment policy estimation.