Health care contact days and outcomes in clinical trials vs routine care among patients with non-small cell lung cancer

Importance — Although patients enrolled in trials have superior survival outcomes compared with those in routine practice, it is unknown whether such differences extend to contact days, a measure of time toxicity.

Objective — To evaluate differences in contact days for patients with advanced stage non-small cell lung cancer (NSCLC) receiving care in trials or routine practice.

Design, setting, and participants — This population-based, retrospective, matched cohort study assessed adults from Ontario, Canada, who were diagnosed with advanced-stage NSCLC between January 1, 2010, and December 31, 2017, and who died between January 1, 2010, and December 31, 2019. The maximum follow-up time from diagnosis was 2 years. Data analysis was performed from May 5, 2024, to October 22, 2024.

Exposure — Patients receiving specific, systemic, palliative-intent, cancer-directed drug(s) as part of a trial were matched 1:1 with patients who received the same drug(s) after approval in routine practice in the same line of treatment.

Main outcomes and measures — Contact days (days with in-person health care contact) were identified through administrative claims data. Models were fitted with cubic splines to describe trajectories of weekly percentage of contact days.

Results — Of the 250 patients (mean [SD] age, 63.6 [9.2] years; 140 [56.0%] male), 125 were trial participants and 125 were receiving care in routine practice. Trial participants were younger (median [IQR] age, 63 [56-69] years vs 64 [58-70] years in routine care patients; standardized difference, 0.21) and had fewer comorbidities (eg, hypertension [45 (36.0%) vs 59 (47.2%); standardized difference, 0.23]). Median (IQR) contact days from diagnosis to death were higher for trial participants compared with those in routine practice (79 [62-104] vs 68 [46-98] days; standardized difference, 0.26). However, trial participants had a longer median (IQR) overall survival (eg, 12.8 [8.7-18.0] vs 10.5 [5.2-14.7] months; standardized difference, 0.46) and a slightly lower median percentage of contact days after adjusting for survival (20.3% [95% CI, 18.1%-21.7%] vs 21.2% [95% CI, 19.3%-25.7%]). During treatment, trial participants experienced a lower median percentage of contact days (18.4% [95% CI, 16.3%-20.8%] vs 25.5% [95% CI, 20.7%-30.3%]); inpatient care accounted for 18.5% (95% CI, 11.1%-29.6%) of on-treatment contact days for trial participants vs 40.0% (95% CI, 30.0%-47.6%) in routine practice. Normalized contact-day trajectories were U-shaped for all groups, with lower peaks and troughs among trial participants.

Conclusions and relevance — In this population-based cohort study, patients receiving systemic therapy as part of trials experienced a lower percentage of contact days, accounted for by greater hospitalization rates in routine practice. Addressing the predominantly outpatient, protocol-mandated visits may represent opportunities to decrease trial-related time toxicity.