Cancer Diagnostic Delay Rates Associated With a Population-Based Screening Trial Evaluating a Cell-Free DNA...

Clinical trials evaluating population-based screening tests or other interventions likely to affect care delivery in real-world settings often do not consider spillover effects, such as whether the intervention rollout affects access to limited health care services.

To examine whether regional participation in a population-based screening trial (NHS-Galleri) of a cell-free DNA-based multicancer early detection (MCED) test was associated with changes in cancer diagnostic delay rates.

Cross-sectional study of all 21 cancer alliance regions in England, 8 of which participated in the population-based MCED screening trial. An event study using difference-in-differences design evaluated changes from 6 months before (April 2021) to 3 years after trial start (September 2024).

Regional participation in the population-based MCED screening trial.

The primary outcome was diagnostic delay rates (percentage of patients referred for suspected cancer evaluation taking longer than 28 days to reach diagnostic resolution), a surrogate measure for system-level spillover effects; the secondary outcome was patient referral rates. Analysis focused on a primary group of 3 cancer types (head and neck, lung, and upper gastrointestinal) that were identified in the trial protocol and were not subject to routine screening.

Overall, 1 875 236 patient referrals for suspected head and neck, lung, or upper gastrointestinal cancers were recorded across all 21 regions. In the first 6 months of the population-based screening trial, diagnostic delay rates increased in participating regions (28.6% before trial start and 29.6% after) and decreased in nonparticipating regions (28.9% to 26.3%), an adjusted difference-in-differences estimate of 3.4 percentage points (95% CI, 1.9-5.0; P < .001). This increase persisted during the second 6-month period (adjusted difference-in-differences estimate of 4.8 percentage points [95% CI, 1.9-7.7; P = .003]) and was no longer statistically significant thereafter. Patient referral rates for suspected head and neck, lung, and upper gastrointestinal cancers were also higher in participating regions in the first 6 months (adjusted difference-in-differences estimate of 23.8 per 100 000 population [95% CI, 0.9-46.8; P = .04]).

Regional participation in a population-based MCED screening trial was associated with a modest increase in diagnostic delay rates for patients referred for suspected head and neck, lung, and upper gastrointestinal cancers. This increase is unlikely to have materially affected interpretation of the MCED screening trial primary findings. Future trials of population-based screening interventions likely to affect demand for limited health care resources should consider monitoring for system-level spillover effects.