White Paper

Executive Summary

MRD / monitoring is growing rapidly, especially in the U.S., with increasing trial launches and readouts, expanding coverages and reimbursement, growing test volumes, and even slow inclusion into the NCCN guidelines. However, there remains a large gap in regard to standardizing the crowded space – there are many different assays, multiple approaches, and data that may not be directly comparable to each other. Understanding how to interpret data points and assay characteristics (e.g., tumor-informed vs. tumor-agnostic, number of loci tracked, PCR vs. NGS, baseline sequencing breadth) are all critical for making informed decisions on the trade-offs that exist.

Sensitivity currently is the key lever by which many assays are compared or marketed, but is primarily evaluated via the assay’s limit of detection (LoD) in lieu of clinical sensitivity data or as a universal measure across settings or cancer types. However, both analytical sensitivity and clinical sensitivity have variables that can confound comparisons if not standardized. For example, analytical sensitivity, or the LoD, is impacted by considerations such as the type of sample (e.g., contrived vs. clinical) and input amount. The clinical sensitivity is impacted by considerations such as the cancer type and stage, patient demographic, test timing, and test frequency.

Standardizing these not only allows informed decision-making around test use but also allows us to build together to a future where MRD / monitoring is more easily accessible and actionable for patients. As clinical data grows, we may better understand the actionability of MRD / monitoring results in different clinical use cases and settings and thereby better understand where the threshold of analytical sensitivity should be (perhaps even on a case-by-case basis).