In this installment of Med Op-Ed: The concept of time toxicity is morphing from patient- to stakeholder-centric, clinical trial access remains a challenge, and why it’s time to revisit Response Evaluation Criteria in Solid Tumors (RECIST).

The Time Toxicity Problem

The concept of time toxicity was introduced 5 years ago to capture the time patients have been “quietly losing” during cancer care and to help minimize those burdens. But the term may now be used to promote pharmaceutical products and health system policies that promise convenience without necessarily delivering meaningful time savings for patients, according to Arjun Gupta, MD, and colleagues writing in the Journal of Clinical Oncology. Gupta and colleagues describe three examples in which the benefits to patients may be uncertain, modest, or absent, whereas benefits to stakeholders are more apparent.

The Context

• Drug reformulations: Subcutaneous formulations are often marketed as time-saving innovations for patients. But the convenience claim may overstate the benefit to patients. While some reformulations, such as daratumumab and amivantamab, offer meaningful time savings, a manufacturer-sponsored study of subcutaneous pembrolizumab found that the shorter administration time translated to only a 13% reduction in total in-clinic time.
• Home-based care: More than a third of patients and caregivers receiving formal home-based care considered it time-burdensome enough to count as contact days. While payers may reduce costs by moving care to lower-cost settings, hospital-at-home and home infusion programs can transfer complex tasks to patients and caregivers.
• Decoupled appointments: Some oncology practices separate lab work, clinician visits, and infusions across different days. Although this may be presented as a way to reduce patient wait times, separating appointments can help health systems increase infusion-chair throughput while requiring patients to make additional trips.

In Their Own Words

In each of the three cases above, the patient may be “presented as the beneficiary, while the bulk of the benefit accrues elsewhere,” and “the patient is left to absorb the residual time burden as a kind of off-target toxicity from the stated advance.”

Read it: Time Is Money, but for Whom? The Commodification of Time Toxicity in Oncology

The Clinical Trial Access Problem

Most adults who receive cancer treatment in the US do not participate in a clinical trial for a variety of reasons, including poor access. Expanding participation in cancer clinical trials requires shifting focus from patient factors to practice- and clinician-level barriers, concentrating resources where trials are available yet underused and building infrastructure where patients already receive care, according to Raymond U. Osarogiagbon, MBBS, in JAMA Network Open. 

The Context

• A recent study on clinical trial access found that only about 5% of adults with advanced/metastatic cancers treated at 107 US oncology practices where clinical trials were available received a clinical study drug from 2011 to 2024. More than 80% of enrollments came from a small proportion of physicians (23.4%) and practices (19.6%).
• Other research has found that among institutions with clinical trial infrastructure, only 20% of treated patients had an opportunity to participate in a trial; 60% did not participate because of structural factors (ie, no trial was available) and 20% because of clinical factors (ie, ineligibility for the trial).
• Interventions to improve clinical trial access should be tailored. Opening trials where target populations already receive care is one straightforward path to increasing diversity in enrollment by building and deploying trials infrastructure at those facilities, Osarogiagbon suggests.

In Their Own Words

“Dismantling barriers to clinical trials participation mandates good understanding of where these barriers are located and their relative scale across the multiple levels of origin and plausible intervention.”

Read it: The Keys to Opening Access to Clinical Trials

Moving Beyond RECIST

RECIST has served as the backbone of response assessment in oncology clinical trials, but it may not fully capture patient benefit in modern oncology, according to Chadi Nabhan, MD, MBA, and Vivek Subbiah, MD, in JAMA Oncology.

The Context

• RECIST’s appeal lies in its simplicity, but its thresholds — a decrease of at least 30% in target-lesion measurements for response and an increase of at least 20% from the smallest recorded measurement for progression — are “artificial” and “may not reflect disease biology,” the authors noted.
• In practice, clinicians want to understand whether a patient is benefiting from a therapy, but RECIST isn’t designed to answer that question; RECIST “standardizes measurements, but it does not capture meaning.”
• A modern framework would integrate anatomic, biological, and clinical signals, including continuous tumor-burden dynamics; functional imaging; molecular monitoring such as circulating tumor DNA; and clinical benefit, including patient-reported outcomes.

In Their Own Words

“RECIST remains valuable for standardization, but it should no longer be the primary arbiter of response.”

Read it: Beyond Tumor Size, Toward Meaningful Patient Outcomes—Resisting RECIST