Cancer Blood Tests Part 2: The clinical trial

How do you decide whether a clinical trial “worked”? In Part 2 of our Galleri series, we examine the landmark randomized trial of a blood test designed to detect more than 50 cancers. We explore why different outcome measures led to dramatically different headlines, discuss primary versus secondary outcomes, pre-registration, hierarchical testing, and post hoc analyses, and explain why mortality remains the outcome everyone is waiting for. Along the way, we uncover a statistical mystery involving dozens of missing cancers and discover how a little arithmetic can sometimes reveal more than a press release.

Statistical topics

cancer screeningexploratory analyseshierarchical testingmissing datamultiple testingoutcome measurespost hoc analysespre-registrationprimary and secondary outcomesrandomized clinical trialsscreening tests

Methodologic Morals

“When the simple numbers don't add up, pay attention. The arithmetic may be trying to tell you something.”“The first question should not be, did it work? It should be, what counts as success?”

References

Giridhar KV, et al. Safety and performance results from PATHFINDER 2, a registrational study of a multi-cancer early detection test in an intended-use population. Presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. May 2026.Hubbell E, Clarke CA, Aravanis AM, Berg CD. Modeled Reductions in Late-stage Cancer with a Multi-Cancer Early Detection Test. Cancer Epidemiol Biomarkers Prev. 2021;30(3):460-468. doi:10.1158/1055-9965.EPI-20-1134Neal RD, Johnson P, Clarke CA, et al. Cell-Free DNA-Based Multi-Cancer Early Detection Test in an Asymptomatic Screening Population (NHS-Galleri): Design of a Pragmatic, Prospective Randomised Controlled Trial. Cancers (Basel). 2022;14(19):4818. Published 2022 Oct 1. doi:10.3390/cancers14194818ASCO slides: https://grail.com/wp-content/uploads/2026/05/Swanton_ASCO-2026_NHS-Galleri_FINAL-Slides-05.26.2026.pdfUK registry protocol:  https://www.isrctn.com/ISRCTN91431511 Clinicaltrials.gov protocol: https://clinicaltrials.gov/study/NCT05611632

Common biases in cancer screening studies

Cancer screening studies are subject to several well-known biases that can make a screening test appear more effective than it actually is. Three of the most important are:

Lead-time bias: Screening advances the time of diagnosis, making survival from diagnosis appear longer even if the patient's lifespan is unchanged. For example, if a screening test detects a Stage II cancer