MCED - Big News for Cancer Screening and Early Detection
Following President Trump’s signature, the Nancy Gardner Sewell Medicare Multi-Cancer Early Detection (MCED) Screening Coverage Act is now law, establishing a new Medicare benefit category for MCED tests and creating a clear pathway to meaningful coverage once MCED tests are FDA approved (Link).
This is a major milestone, and I want to highlight a few reflections:
1) A remarkable achievement by Grail and MCED supporters
MCED is one of the most exciting frontiers in precision medicine. The ability to detect cancer signals through blood-based screening represents years of innovation in genomics, bioinformatics, and translational science, and tremendous collaboration across academia, industry, and clinical research.
2) A win for patients, especially where screening options do not exist
Roughly two-thirds of cancers still have no standard-of-care (SOC) screening. That gap costs lives. MCED has the potential to expand access to early detection for cancers that are often found too late.
3) FDA review remains essential and key scientific questions remain
Coverage policy is a huge step forward, but clinical performance and real-world use cases still need to be validated and refined. Some important questions the scientific and clinical community may need to help address include:
• For cancers with existing SOC screening, should MCED be used as an initial screen, or as a complementary test (e.g., SOC first, MCED as an add-on)?
• Since sensitivity for certain SOC-screened cancers may be lower than SOC, how do we ensure MCED does not unintentionally reduce detection by replacing established screening?
• With tissue-of-origin prediction not perfect (even at ~90% accuracy), what is the best clinical pathway when a cancer signal is detected but follow-up workup at the predicted site is negative?
These are not reasons to slow down. They are exactly the kind of questions that will strengthen the field and make implementation safer and more effective.
4) Reimbursement will accelerate innovation and ultimately benefit patients
A predictable reimbursement pathway will spur more developers to invest, more studies to be conducted, and more evidence to be generated. The science will improve, the tests will get better, and most importantly, patients will benefit from broader adoption of early detection.
This is an exciting moment for cancer screening. The work continues, but today is worth celebrating.
FDA Draft Guidance on MRD Endpoints in Multiple Myeloma: What It Means for Drug Developers and IVD Innovators
Today, FDA released a draft guidance titled “Minimal Residual Disease and Complete Response in Multiple Myeloma: Use as Endpoints to Support Accelerated Approval.” While nonbinding, the document represents a significant regulatory signal: minimal residual disease (MRD) negativity is now explicitly recognized as an acceptable primary endpoint to support accelerated approval in multiple myeloma (MM).
Beyond its implications for oncology drug development, this guidance marks a pivotal inflection point for IVD and companion diagnostic (CDx) developers, particularly those working on NGS-based MRD assays and next-generation flow (NGF). At the same time, it surfaces unresolved challenges around assay harmonization, regulatory alignment, and global clinical trial execution, especially in the context of multiregional clinical trials (MRCTs).
1. Why MRD Matters More Than Ever for Drug Development and Approval
Historically, accelerated approval in MM relied on endpoints such as overall response rate (ORR). However, as therapeutic efficacy has improved with response rates exceeding 90% in some settings, traditional endpoints are becoming less discriminating and require increasingly large trials.
The FDA guidance acknowledges this reality and positions MRD negativity as a more sensitive, biologically meaningful measure of treatment effect. FDA explicitly recognizes MRD as:
A prognostic biomarker associated with improved progression-free and overall survival;
An endpoint capable of supporting accelerated approval in both single-arm and randomized trials;
A bridge that allows earlier regulatory decisions, while confirmatory trials continue to mature.
From a drug development standpoint, this creates a pathway to:
Shorter development timelines;
More efficient trial designs;
Earlier patient access to transformative therapies.
Critically, the guidance also reinforces FDA’s expectation that MRD-based accelerated approvals must be followed by timely confirmation of clinical benefit, underscoring that MRD is not a shortcut, but a scientifically grounded surrogate.
2. A Strategic Opportunity for IVD and CDx Developers
For IVD companies, this draft guidance is more than regulatory housekeeping, it is a market-shaping signal.
FDA clearly states that MRD assays used to support regulatory decisions must be appropriately validated, and it explicitly references both:
Sequencing-based methods (e.g., NGS), and
Flow cytometry–based approaches, including next-generation flow (NGF).
This creates several concrete opportunities:
Expansion of regulated MRD testing beyond exploratory or academic use into registrational drug trials;
Increased demand for fit-for-purpose, analytically validated assays with defined sensitivity (≥10⁻⁵) and robust performance;
Earlier and deeper drug–diagnostic co-development discussions, even when assays are not formally labeled as CDx at approval.
NGS developers can leverage strengths in sensitivity, clonotype tracking, and scalability, while flow/NGF providers can emphasize speed, cost efficiency, and broad clinical familiarity. Importantly, FDA does not mandate a single technology, which opens space for innovation, differentiation, and competition.
3. The Hard Part: Harmonization Across Technologies, Assays, and Regions
While FDA’s openness is welcome, it also exposes a major unresolved issue: harmonization.
The guidance allows multiple MRD technologies, thresholds, and analytical approaches, but in practice, this flexibility creates challenges:
NGS vs. Flow / NGF
Differences in analytical sensitivity, precision near cutoff, baseline calibration failures, and sample requirements complicate cross-trial and cross-platform comparisons.
FDA appropriately emphasizes assay validation and context of use, but stops short of defining equivalency or interchangeability standards.
LDTs vs. IVDs
Many MRD assays used today are laboratory-developed tests (LDTs).
When these assays are used as primary endpoints supporting drug approval, questions arise:
When does an LDT become an investigational device?
When is an IDE required under 21 CFR Part 812?
How should sponsors manage transitions from LDTs to commercial IVDs?
MRCT and Global Regulatory Friction
For global development programs, the complexity multiplies:
EU IVDR imposes stricter controls on IVD performance, clinical evidence, and intended use;
China’s HGRAC framework adds constraints on sample export and genetic data use;
Divergent expectations across regions risk fragmented assay strategies, duplicated validation efforts, and operational inefficiencies.
Without proactive alignment, MRD risks becoming a regulatory bottleneck rather than an enabler of global drug development.
4. This Is a Draft so Stakeholder Input Is Essential
FDA is explicit that this document is draft guidance, issued for comment only, and that the Agency expects ongoing dialogue with sponsors, diagnostic developers, and other stakeholders
This is a critical window for:
IVD and CDx companies to advocate for practical, globally harmonizable assay expectations;
Drug sponsors to highlight real-world operational challenges in MRCTs;
Regulators and standards bodies to move toward greater cross-platform and cross-region convergence.
Thoughtful public comments can meaningfully shape the final guidance, especially in areas such as assay comparability, validation expectations, and coordination between drug and device regulatory pathways.
Closing Thought
FDA’s draft guidance sends a clear message: MRD is no longer just a biomarker; it is becoming regulatory infrastructure. For drug developers, it offers a faster path to patients. For IVD innovators, it opens a new frontier of clinical and regulatory relevance. But realizing this promise will require coordination, harmonization, and engagement now; before the guidance is finalized.
Stakeholders across the ecosystem should take FDA up on its invitation to comment. The future of MRD-guided drug development is being written in real time.
YDX Group: Helping Diagnostics Innovators Move Faster With Confidence
Former FDA leaders share why they founded YDX Group — to help diagnostics and precision medicine innovators navigate regulatory complexity with clarity, confidence, and trusted judgment.
Passion. Experience. Diligence.
These words have guided our careers for decades ─ and they are the reason we founded The YDX Group.
We started YDX because we believe that transformative diagnostics and medical technologies deserve more than good science. They deserve a regulatory strategy that is just as rigorous, just as thoughtful, and just as committed to improving lives.
Today, teams are pushing the boundaries of precision medicine: molecular diagnostics, liquid biopsy, cancer screening, companion diagnostics, digital pathology, and AI-enabled technologies are evolving at extraordinary speed. At the same time, regulatory expectations are evolving too ─ sometimes quickly, sometimes unevenly, and often with high stakes.
We’ve lived that evolution firsthand. And we founded YDX to help innovators navigate it with clarity, confidence, and credibility.
Our Genesis: Three FDA Leaders, One Shared Purpose
The YDX Group was founded by Dr. Yun-Fu Hu, Dr. Donna Roscoe, and Dr. Xueying (Sharon) Liang. We met while working at the Division of Molecular Genetics and Pathology (DMGP) at FDA ─ the group entrusted to regulate IVDs and LDTs across a wide spectrum of technologies, including:
Genetic testing
Molecular cancer diagnostics (e.g., liquid biopsy, cancer screening, monitoring, minimal residual disease)
Companion / complementary diagnostics
Digital pathology
Artificial intelligence devices
For more than a decade, we worked together through major shifts in the regulatory landscape. We served in senior leadership roles and participated in the real work behind regulatory decisions: evaluating evidence, shaping policy, and asking the questions that determine whether a technology is ready for patients.
The Moment We Knew YDX Needed to Exist
Over the years, we saw the same pattern again and again.
We saw promising technologies slowed down not by lack of innovation, but by lack of regulatory clarity early enough to make the right development choices. We saw teams invest heavily in studies that didn’t answer the questions regulators would ask. We saw brilliant scientists struggle to translate complex evidence into a clear and defensible story. And we saw timelines slip because communication with regulators wasn’t structured for success.
Those moments stayed with us.
They helped shape our belief that successful regulatory strategy is built on sound science, transparent communication, and trusted relationships ─ and that every team deserves direct access to experienced experts who can help them make the right high-stakes decisions at the right time.
That’s why we founded YDX.
What YDX Stands For
The name YDX reflects the first names of our three founders: Yun-Fu, Donna, and Xueying (Sharon).
But the name also represents our mission:
To empower innovation, mitigate risks, optimize resources, and deliver tailored solutions that address unmet medical needs ─ so that breakthrough technologies can reach the people who need them.
Or, in the words of one of our favorite lines:
YDX ─ Your Development eXpedited.
What We Do: Regulatory Strategy That Moves Development Forward
At YDX, we provide high-quality regulatory consulting from former FDA leaders, helping innovators accelerate the development and approval of diagnostics, medical devices, and precision medicine solutions.
Headquartered in Bethesda, Maryland, we specialize in global in vitro diagnostics device regulations ─ supporting everything from design controls to test validations, and from FDA to EU and China. We guide clients through the complexities of R&D, manufacturing, clinical trials, and regulatory compliance with strategic insight and practical execution.
Who We Help
We work with organizations across the diagnostic and precision medicine ecosystem, including:
Diagnostics and medtech startups building their first regulatory strategy
Pharmaceutical and biotech teams developing companion diagnostics and biomarker programs
Digital health and AI innovators navigating evolving policy expectations
Established companies expanding globally across FDA, EU IVDR, and China pathways
Investors and boards seeking independent regulatory risk assessment for high-stakes decisions
Whether you’re early-stage or approaching submission, our role is the same: help you build a plan that stands up to scrutiny and supports success.
How We Help: Six Ways We Support Innovation
We structure support based on what our clients need most ─ whether that’s early strategy, FDA interaction, submission planning, or evidence gap resolution.
Our core service areas include:
1) Regulatory Pathway Assessment & Strategic Planning
We help teams identify the most efficient, evidence-based pathway tailored to their product, risk profile, and development stage—and create a clear, defensible plan aligned with FDA expectations.
2) FDA Engagement, Submission Planning & Review Support
From Q-Sub strategy to briefing packages, mock Q&A, and interactive review response cycles, we help teams communicate effectively with FDA and anticipate reviewer expectations.
3) Companion Diagnostics Strategy & Co-Development Guidance
We help teams align diagnostic and therapeutic development ─ from biomarker strategy through analytical/clinical validation planning and global regulatory alignment.
4) AI/ML & Digital Health Regulatory Support
We help innovators interpret evolving policy, structure evidence, and prepare for expectations around transparency, performance, and lifecycle management.
5) Evidence Evaluation & Scientific Advisory
We bring experience reviewing hundreds of diagnostics and devices to help teams strengthen their evidence packages ─ analytical, clinical, statistical, and risk-benefit.
6) Regulatory Risk Assessment for Investors & Boards
We provide independent, FDA-informed risk and pathway assessments to support investment, acquisition, and portfolio decisions.
How We Work: Direct, Transparent, and Hands-On
At YDX, you work directly with seasoned regulatory leaders ─ not a layered consulting structure.
We structure our support to fit each client’s needs ─ from early concept discussions to submission planning and FDA interaction. Our engagements are:
Collaborative and hands-on
Focused on clear, actionable recommendations
Tailored for diagnostics, devices, and digital health innovation
Confidential and trusted, especially for high-stakes regulatory decisions