Published protocols provide industry-wide framework for validating tumor-informed ctDNA assays that detect molecular residual disease.
The Blood Profiling Atlas in Cancer (BLOODPAC) Consortium has published new analytical validation standards for liquid biopsy tests that monitor cancer recurrence, providing test developers with standardized protocols for molecular residual disease (MRD) assays.
The consensus document, published in JCO Precision Oncology, establishes generic protocols for the analytical validation of tumor-informed circulating tumor DNA (ctDNA) assays. These MRD tests identify molecular signatures of cancer associated with remnant or recurrent disease following treatment and can help monitor patient response to treatments in real time.
“These protocols reflect a deep collaborative effort and a shared commitment to advancing high-quality, reproducible MRD testing,” says Lauren Leiman, executive director of BLOODPAC, in a release. “By providing a unified framework for analytical validation, BLOODPAC is helping to accelerate the development of trustworthy ctDNA MRD assays that will benefit patients.”
Technology-Agnostic Approach
The protocols can be adapted to any tumor-informed MRD assay regardless of technology platform, including next-generation sequencing (NGS) or digital PCR (dPCR), panel design algorithm, or workflow component. This technology-agnostic approach addresses current variability in how analytical validation studies are designed and conducted, which creates challenges for both developers and regulators.
The BLOODPAC protocols aim to address challenges by:
- Providing guidance for determining key analytical performance characteristics, including limit of blank, limit of detection, accuracy, and precision.
- Addressing additional factors that influence assay performance, such as guard banding, to establish assay robustness, specimen stability during preparation and shipping, and assessment of interfering substances that may impact accuracy.
- Recommending methods for evaluating contrived and clinical sample comparability, ensuring that reference materials used in assay validation perform the same as patient-derived cfDNA samples.
The BLOODPAC MRD Analytical Validation Working Group, which developed the manuscript, represents experts across biotech and pharmaceutical industries, academia, and regulatory sectors. Contributors include specialists in molecular diagnostics, bioinformatics, oncology, and regulatory science.
“MRD is being established as a relevant biomarker across multiple solid tumor malignancies. Developing a unified framework of analytical standards is essential to ensure these assays are validated quickly, deliver robust and reproducible results, and can be confidently adopted in clinical practice,” says Jonathan Baden, executive director and head of precision medicine of Bristol Myers Squibb, in a release.
Building on Previous Standards Work
The new protocols build on BLOODPAC’s ongoing efforts to establish industry-wide standards for test validation. The consortium recently published recommendations in the Journal of Molecular Diagnostics outlining key considerations for analytical validation of blood-based tumor mutational burden (bTMB) assays, which show promise for predicting immunotherapy response in patients with advanced and metastatic solid tumors.
BLOODPAC previously published generic analytical protocols in Clinical Chemistry that helped define industry standards for developing next-generation sequencing-based ctDNA liquid biopsy tests.
“BLOODPAC’s goal is to give developers a clear foundation for demonstrating the analytical performance of ctDNA MRD assays—no matter the technology—so that the focus can shift more quickly to what matters most: delivering reliable tests that inform patient care,” says Leiman in a release.
The consortium is managed by the Center for Computational Science Research Inc, an Illinois-based 501(c)(3) nonprofit corporation focused on accelerating the development, validation, and accessibility of liquid biopsy assays to improve cancer patient outcomes.
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