Time Well Spent: Lung Cancer Trials Offer Improved Survival Without Added Burden

Concerns about the time demands of clinical trials often deter cancer patients from enrolling. But a new study, published last month in JAMA Network Open, offers a reassuring counterpoint: For people with advanced non-small cell lung cancer (NSCLC), trial participation may not increase the time spent receiving care. It may even reduce hospitalizations.

A group of researchers, led by Timothy P. Hanna, M.D., Ph.D., at Queen’s University in Ontario, analyzed data from 250 patients who died between 2010 and 2019 after receiving systemic treatment for stage 3 or 4 NSCLC. Half participated in clinical trials; the others received the same drugs in routine care. The researchers then compared healthcare “contact days” among patients treated with the same systemic drugs. Contact days refer to any day with in-person medical encounters, such as appointments, treatments or hospitalizations.

The findings showed that people who participated in clinical trials lived longer: a median of 12.8 months compared with 10.5 months for those in routine care. Trial participants also had a slightly lower overall proportion of healthcare contact days (20.3%) versus those receiving routine care (21.2%).

During active treatment, the time difference was more striking. Trial participants had a median 18.4% of contact days, compared with 25.5% in routine care. Hospitalizations accounted for a much lower share of contact days in the trial group—18.5% versus 40%.

The researchers suggest that the structured monitoring in clinical trials may help detect complications early and avoid unplanned hospitalizations. Notably, participants in clinical trials did not experience delays in starting therapy and had more predictable outpatient schedules.

This study is the first known to directly compare time spent in care between clinical trial participants and routine care patients receiving the same treatments.

In an invited commentary, also published in JAMA Network Open, Erin Bange, M.D., of Memorial Sloan Kettering Cancer Center, and John Lin, M.D., of the University of Texas MD Anderson Cancer Center, said the study “equips oncologists with a better understanding of the current patient experience when counseling patients around decisions about trial enrollment.” The commenters described the findings as “reassuring” for both oncologists and patients considering clinical trial enrollment.

“These data are encouraging and suggest that clinical trials may not be as time-intensive as many patients and oncologists currently perceive,” Bange and Lin wrote.

The commentary also emphasized the need to reduce structural barriers that prevent trial access — especially for lower-income and rural patients — and highlighted innovations such as decentralized trial designs, remote monitoring and virtual visits to make participation more flexible and patient-centered.

The findings highlight how clinical trials may offer a more efficient model of care with fewer hospitalizations and better outcomes. With only about 6% of cancer patients enrolling in trials, this study may help ease those worries and support efforts to expand access.

The efficacy-effectiveness gap

As Hanna and his co-authors note, their study results fit into a growing body of evidence about “time toxicity,” which is the amount of time people with cancer spend receiving care for their disease. Studies across health systems and countries show patients treated in early-phase and later-phase trials — and in routine practice — have reported an approximately 20% to 33% rate of contact days, according to Hanna and colleagues.  They also point out that studies have shown that there is a clear “efficacy-effectiveness” gap when it comes to survival, with patients in routine practice often having inferior survival outcomes compared with those in trials. They say it is unknown whether the efficacy-effectiveness gap extends to time toxicity.

“Although patients in trials face protocol-mandated visits (and resultant planned contact days) over and above what would be expected in routine clinical care, patients in routine practice often have more comorbidities and less fitness and experience higher rates of physical toxic effects (and resultant unplanned contact days),” they wrote.

They said that evaluating the potential time toxicity efficacy-effectiveness gap is important “because it may allow for care improvement opportunities in both settings and clarify whether trial data could set expectations about time toxicity in routine practice.”