The Promise of Liquid Biopsies

Cancer survival rates are heavily dependent on early diagnosis. For decades, population-scale cancer screening has been restricted to specific, organ-targeted tests, such as mammograms and colonoscopies. Multi-Cancer Early Detection (MCED) blood tests, or liquid biopsies, represent a paradigm shift. By utilising next-generation sequencing (NGS) and machine learning algorithms to detect cell-free DNA (cfDNA) methylation patterns in blood, MCED platforms aim to screen for over 50 types of cancer from a single draw, predicting the tissue of origin before symptoms appear.

As these screening platforms transition from laboratory development to population-scale clinical trials, the clinical validation and regulatory pathway are under intense global scrutiny. The landmark NHS-Galleri trial—enrolling 140,000 participants in England to evaluate GRAIL's Galleri test—serves as the primary global milestone for establishing the clinical utility of liquid biopsy screening.

Trial Milestones and the Clinical Reality

The final results of the three-year NHS-Galleri trial, presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in May 2026, provided critical data on the real-world performance of MCED tests:

• Primary Endpoint Outcome: The trial did not meet its primary endpoint of delivering a statistically significant reduction in combined Stage III and IV (late-stage) cancer diagnoses.

• Stage IV Downstaging: Despite missing the primary goal, the trial demonstrated a clinically meaningful 14% overall reduction in Stage IV cancer diagnoses in the screened group. This effect strengthened with repeated annual screening, reaching a 26% reduction by the third round.

• Early-Stage Detection: Annual MCED testing increased the detection of Stage I and II (early-stage) cancers by 16% compared to the standard of care, while reducing emergency presentation cancer diagnoses by 25%.

• Ongoing Follow-Up: While the active blood sampling phase completed in 2024, researchers are continuing to analyse long-term NHS health data to monitor survival outcomes over the coming years.

The Regulatory Path to Global Approvals

For diagnostics firms, securing regulatory approvals for MCED platforms is exceptionally complex. Unlike single-biomarker assays, MCED tests are high-risk, multiplex systems that combine advanced molecular biology with software algorithms.

To achieve FDA and EMA approvals, regulatory affairs teams must navigate three distinct areas:

• Class III / PMA Submission: As screening tests used in asymptomatic populations, MCED platforms are classified as Class III in vitro diagnostics (IVDs) by the FDA, requiring the most rigorous Premarket Approval (PMA) pathway. This demands extensive clinical utility data showing that the test improves patient outcomes without causing excessive false-positive interventions.

• Software as a Medical Device (SaMD): Because the tissue-of-origin prediction relies on machine learning classifiers, the software itself must be validated under SaMD guidelines, proving algorithm consistency, reproducibility, and security.

• IVDR Compliance in Europe: Under the EU's In Vitro Diagnostic Regulation (IVDR), MCED tests require independent validation by notified bodies, moving away from the previous self-certification models for laboratory-developed tests (LDTs).

Sourcing Regulatory Leaders for Advanced Diagnostics

Given these complex, multi-disciplinary requirements, diagnostics firms must structure their regulatory teams with leaders who understand both molecular assay validation and software algorithm regulation.

RSA prioritises several core competencies when placing regulatory leaders in the advanced diagnostics sector:

• NGS and IVD Regulatory Track Record: Direct experience leading successful FDA PMA submissions for next-generation sequencing assays and high-risk IVDs.

• SaMD and AI Validation Fluency: The capability to guide software engineering teams through FDA and EMA software validation requirements, documenting algorithm training and bias-mitigation protocols.

• Global Registrations Management: Experience coordinating parallel submissions across FDA (CDRH), European Notified Bodies (IVDR), and the UK’s MHRA, ensuring global launch alignment.

The clinical data from the NHS-Galleri trial has validated the science of liquid biopsies; the focus now shifts to the regulatory pathway. Securing regulatory directors who can navigate the interface of molecular biology, machine learning, and global device compliance is the primary requirement to transition MCED platforms from clinical trials to standard screening protocols.