Confronting "Time Toxicity" In Global Oncology And Rare Disease Trials For Operational Excellence And Patient Retention

By Leila Cupersmith, CEO, Choice ClinOps

Consider the anecdotal story of Maria, a 42-year-old mother from São Paulo with breast cancer, enrolled in a Phase 2 trial and expecting monthly visits. The informed consent form promised exactly that. Reality proved different. Three weeks in, her 5-year-old son Miguel pressed his face against the window, counting cars—waiting for parents who'd spent 18 of the last 21 days traveling to the site, waiting in corridors, or recovering from treatments. Visits estimated at 2-3 hours stretched to 7—plus an 8-hour round-trip commute. Victor took unpaid leave from the fish market for each visit.

When Maria and Victor reviewed the ICF together—Miguel asleep between them, clutching his worn stuffed animal—the document listed visit frequencies but said nothing about actual hours consumed. They looked at each other, then at their son. Some decisions make themselves.

Maria's experience reflects reality for thousands worldwide. This is time toxicity — the hidden cost of clinical trial participation that quietly erodes both data quality and participants' remaining life. It's not just a participant experience issue; it's an operational and strategic risk affecting recruitment, retention, endpoint integrity, and sponsor reputation.

What Time Toxicity Means — And Why It Matters

Coined by Arjun Gupta, MD, et al. (2022), time toxicity quantifies the share of a patient's remaining life spent engaged with the healthcare system: travel, waiting, treatment, and recovery.¹ For oncology and rare disease trials, time toxicity can consume 20-30% of a participant's remaining life days.²⁻³

For executives planning 2026 budgets: Time toxicity is a measurable risk factor directly impacting your bottom line. Every percentage point increase correlates with 3-5% higher attrition rates and 15-20% increased monitoring costs.

The metric correlates with clinical outcomes: Participants experiencing high time toxicity have shorter progression-free and overall survival.³ When participants spend one in five days at trial sites, the system systematically selects for those with fewer burdens — biasing your survival analyses and undermining statistical power.

Where The Hours Go

Time toxicity accumulates across five critical touchpoints:

1. Screening and consent: Multi-step eligibility evaluations can mean month-long waits. Each postponement — missing tissue blocks, delayed reads, system delays — doubles travel time and participant waiting.

2. Treatment visits: Early-phase protocols are visit-dense. Australian data shows participants spent 29% of days in healthcare contact; this dropped to 14% only after visit compression.²

3. Travel and waiting: U.S. data shows "simple" outpatient visits consume three hours door-to-door in metropolitan centers.⁴ In Brazil's northern regions, travel often exceeds four hours each way.⁷

4. Unscheduled toxicity visits: Adverse-event follow-ups add unpredictable burdens, magnifying caregiver time costs and dropout risk.³

5. Caregiver time: Caregivers lose 10-14 work hours weekly, increasing as patients decline.⁹⁻¹⁰ Across Canada, Europe, and the U.S., unpaid caregiver labor is valued at $1.3 billion annually for oncology alone.⁹⁻¹¹ These invisible hours sustain the system yet rarely enter operational models.

The Global Picture: Regional Variations

Brazil/LATAM: Over half of Brazilian oncology patients travel outside their municipality; routes often exceed 150 kilometers.⁷ Unpaved roads and rainy season disruptions mean 150-kilometer journeys consume 5-6 hours each way. Economic disparities force choices between trial participation and immediate income needs. (Look for my next article on financial toxicity.)

Canada/U.S.: Rural patients face travel exceeding 60 minutes — a threshold correlating with lower enrollment and delayed therapy initiation.¹²⁻¹⁵ For rare disease trials, participants may require 4-6 hour drives or flights per visit, with costs (parking, lodging, meals, lost wages) exceeding $500 per visit — rarely sponsor-covered.

Europe: In France, longer travel time predicts poorer survival.¹⁶ The UK and Ireland set 45 minutes as the acceptable threshold; beyond this, uptake declines.¹⁷⁻¹⁹ Eastern European patients often travel across borders, adding visa complications and international travel costs.

APAC/Australia: Sydney data quantifies participants spending 29% of days in healthcare contact.² Sites cluster in major cities (Tokyo, Singapore, Seoul, and Mumbai) while patient populations live hours away. Japan's data shows travel time ≥120 minutes significantly reduces trial participation.²¹

Africa/Middle East: Centralized tertiary care combined with limited public transportation means patients often require multiple days away for single visits.²⁰ Many participants exhaust family resources on a single screening visit, creating impossible decisions about continued participation.

Behavioral And Operational Consequences

Scarcity and decision fatigue: Repeated long visits while managing medical care, appointments, and life responsibilities tax cognitive bandwidth, leading to missed ePRO entries, out-of-window visits, and early withdrawal.

Loss of control: Dense calendars and lack of timely communication erode engagement; patients prioritize personal time over protocol adherence or consider alternate trials with lower time commitments.

Caregiver capacity: Each added trip increases burnout and forecasts early withdrawal.

Collectively, these create selection bias: Participants most burdened drop out first, systematically skewing data toward healthier or more resource-advantaged individuals. The consequence? Millions in expenditures without adequate data to support marketing approval.

Building Your Time Toxicity Mitigation Strategy

1. Measure and model with DCT/hybrid strategy. Add contact day percentage and home days metrics to feasibility models. Target ≤15% contact days after Cycle 2. Add site-specific estimated visit duration to the ICF beside each visit and assessment requiring ≥1 hour.

2. Simplify protocols. Bundle assessments, widen windows (±3 days for labs; ±7 days for QoL), cut redundant imaging. Include cross-departmental team members early in feasibility discussions to eliminate assessments that are "nice to have" rather than endpoint-critical — especially if they increase participant toxicity.

3. Meet participants where they are. Partner with satellite centers, home healthcare, primary physicians, local labs, telehealth, or remote monitoring. When site travel is necessary, provide direct travel concierge services with sponsor-to-provider payment. (Financial toxicity alleviation discussed in my next article.)

4. Hybridize wisely. Use tele-toxicity checks, home nursing, ePROs, and local imaging with protocol-specific feedback loops to reduce in-person load while maintaining data integrity.²⁰

5. Engage caregivers. Include caregiver orientation, transparent calendars, feedback loops, and compensation. Plan for decreasing time and financial toxicity experienced by caregivers. Caregivers aren't specific to pediatric or cognitively impaired participants. If a participant depends on a caregiver, they're fundamental to quality of life and will directly impact enrollment, adherence, and retention. Navigate HIPAA complexities proactively: Caregivers don't automatically access PHI or become legally authorized representatives. Clarify roles at enrollment.

6. Track and mitigate: RBQM + Metrics + KPIs. Treat time burden as a monitored risk, metric, and KPI. Build automated trigger notifications and mitigation actions when participants exceed protocol-specific thresholds.

7. Budget realistically with a buffer. Allocate realistic funds for participant and caregiver logistics, support, and decentralized elements during initial study build — investments repaid through faster accrual and fewer deviations. Track spend monthly; don't wait until budget depletion forces change orders.

8. Collaboration with active listening: Site staff, patient advocacy groups, participants, and caregivers understand time toxicity better than operations staff not at sites. That knowledge is valuable. Proactively schedule, document, and report time toxicity and satisfaction measures from beginning through last follow-up. Add to project management plans, site management plans, monitoring plans, and CTMS. Ensure specific, measurable, accountable, realistic, time-bound execution plans with checks throughout the study duration.

Special Considerations: Rare Disease Trials

Rare disease studies often cluster expertise in single cities or countries, requiring international travel, visas, specialized transportation, or relocation for each visit. Sponsors can help by: consolidating screening into single extended visits; shipping home sample kits; partnering with advocacy groups and travel concierge services; optimizing DCT strategies, including telehealth, remote data capture (ePRO, wearables), and collaboration with local practitioners; and coupling DCT strategies with interoperable study systems. Here, time toxicity becomes literal geography — mitigating it defines feasibility itself.

From Compassion To Competitive Advantage

Reducing time toxicity isn't altruism; it's operations science. Sponsors who design to limit time toxicity see faster recruitment (lower perceived burden), higher retention (reduced caregiver fatigue), cleaner data (fewer out-of-window assessments), and lower total cost per participant.

In a marketplace where "patient centricity" has become cliché, measurable time efficiency differentiates credible sponsors from performative ones.

The Executive Question

As you plan 2026 global oncology and rare disease trials, ask: How many of your participants' remaining days will be consumed by your visit schedule rather than lived with their families? More importantly, what are you implementing this month to cut that number in half?

Time is the only currency that your participants can never earn back. Every hour of unnecessary time toxicity eliminated is an hour returned to someone counting their remaining months. That's not just ethical operations; it's the operational excellence differentiating sponsors who truly understand patient-centric trial design from those who simply claim to.

Time is the only truly finite resource in a clinical trial. Let's treat it that way — especially with participants and caregivers who volunteer their invaluable time to be our clinical trial partners.

About The Author: 

Leila Cupersmith is the founder, CEO, and principal clinical trial operations consultant of Choice ClinOps, LLC. Cupersmith helps small to midsize oncology and rare disease trial sponsors around the globe setup their studies for success, rescue at-risk studies, operationalize and execute streamlined clinical trial operations strategies during mergers and acquisitions, design and implement protocol and site specific patient pathways, develop and manage alliances, site engagement and management strategies, risk and change management, cost avoidance and audits. Leila is also the founder of the LinkedIn group Patient-Centric Oncology Clinical Trials, established in 2018 to bring patient inclusion and personal perspectives to the forefront of oncology clinical trial discussions, keeping the "why" of our work front and center.