Table 1.

Outcome measures of interest.

Variable	Role	Operational definition
Mean QA-PFS	Calculated outcome	Product of the PFS function, obtained by restricted mean survival estimation and the mean EQ-5D-5L index score prior to progression
TOX time, months	Partitioned survival variable	(Area under the Kaplan–Meier curve for days with AEs)/30.4375 days
TWiST time, months	Partitioned survival variable	(Area under the Kaplan–Meier curve for days to PFS event − area under the Kaplan–Meier curve for days with AEs)/30.4375 days
UTOX	Utility	Baseline: average EQ-5D-5L utilities collected during TOX state in the PRIMA trial; sensitivity analysis for the overall ITT population using a utility of 0.5
UTWiST	Utility	Assumed to be 1.0a
Mean Q-TWiST	Calculated outcome	Q-TWiST = UTWiST × TWiST + UTOX × TOX

^aTWiST was considered to have utility equal to 1.0, representing the best possible quality of life for a patient, and consistent with previous Q-TWiST analyses in oncology. ²⁹

AE, adverse event; EQ-5D-5L, European Quality of Life Five-Dimension, Five-Level questionnaire; ITT, intention-to-treat; PFS, progression-free survival; QA-PFS, quality-adjusted progression-free survival; Q-TWiST, quality-adjusted time without symptoms of disease or toxicity; TOX, time before PFS during which patients experienced grade ⩾2 AEs; TWiST, time without symptoms of disease or toxicity; UTOX, utility for TOX; UTWiST, utility for TWiST.