Characterizing Time Toxicity in Lung Cancer Clinical Trials: Development and Application of a Novel Time Burden Metric

Vollständiger Abstract

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PURPOSE Participation in clinical trials imposes additional time commitments beyond routine care; however, trial-associated time toxicity (TT) remains underinvestigated and poorly characterized. The purpose of this study was to develop a scalable, procedure-based metric to quantify total time required for trial participation using the protocol schedule of events. We applied this framework to lung cancer clinical trials to estimate trial-associated burden and explore changes in TT over time. MATERIALS AND METHODS Protocols for clinical trials associated with United States (US) Food and Drug Administration (FDA) approvals of oral lung cancer therapies were obtained from public sources. Using each protocol's schedule of events, study-mandated procedures were assigned time toxicity units (TTUs) based on standardized time estimates. TTUs for each procedure were multiplied by their frequency and summed for screening through cycle 5 to determine a trial's total time toxicity (TTT). Days with health care contact (DHC) were summed over the same period to determine total DHC (TDHC). Median (m) TTT and TDHC were compared between studies published in 2005-2014 and 2015-2024 to assess temporal trends. Two-sample Mann-Whitney U tests were used for nonparametric comparisons. RESULTS Thirty-two phase-specific protocols from trials published between 2005 and 2024 were included. Among studies published in 2005-2014 (n = 7), the median TTT (mTTT) was 63.8 (41.8-109.3) versus 82 (50.3-139.5) in 2015-2024 (n = 25) ( P = .042). Corresponding median TDHC values were 14 (10-21) versus 15 (11-44), respectively ( P = .16). CONCLUSION More contemporary studies demonstrated higher TTT, with significantly greater mTTT observed in studies published in 2015-2024 versus 2005-2014. TDHC demonstrated less sensitivity in capturing differences in time burden. These findings demonstrate the feasibility and practical applicability of the proposed TT framework for characterizing protocol-associated time burden. Prospective validation and broader implementation may help inform patients and encourage streamlined protocol development.