Molecular Diagnostics and Liquid Biopsy Sample Prep: Development, Refinements and Opportunities
Hello. I'm Ann Nguyen, Senior Associate Conference Producer with Cambridge Healthtech Institute. Today, we have a podcast interview for The Liquid Biopsy Summit running this June 22-24 in San Francisco, California. We're chatting with Dr. Jamie Platt, Founder and Managing Director of BRIDGenomics, LLC.
Hi, Jamie. Nice to have you joining us today.
Hello. Thank you.
You have a prolific background in leading transitions of emerging NGS technologies into regulated molecular clinical diagnostics, and in shepherding molecular diagnostics assays from development to commercialization. How has that landscape changed, or not, over the last 15 years?
Yeah, well, the landscape has changed significantly, in my opinion, but some basic fundamentals in LDT, or laboratory developed tests, assay development has not changed. It can be very helpful to remain focused on these fundamentals as one embarks on entering this phase of molecular genomic test development, where it's so easy to get overwhelmed by the complexity of these systems and processes and the number of pieces that have to be brought together to build the test.
The fundamentals that have not changed are centered around an existing clinical need and the expected clinical utility for a specific test or assay, and the laboratories’ ability to produced that test in a way that ensures the most accurate and reliable result. These same fundamentals also apply to development of IVDs, or in vitro diagnostics, where this obligation would be on a manufacturer rather than on a clinical diagnostic lab.
Where we have seen major changes in the landscape of development and commercialization of molecular diagnostics is specifically in clinical diagnostic labs offering LDTs. Just as we would look at a panoramic view from a mountain peak and see three dimensions, there are three major areas of the clinical diagnostic landscape that have changed dramatically due to NGS technologies. Those are complexity, competition, and regulation.
First, the complexity has obviously increased, primarily in the breadth, depth, and types of variance that we can now interrogate. This complexity runs throughout specifications, design, development, optimization, validation, verification, and also in day-to-day operation of the assays. These pieces of the process that need to come together to build the assay system are greater and more complex, so from sample tracking, QC measures, sample preparation, library preparation, bioinformatics, clinical annotation, reporting, and data storage and management. In all of that complexity a clinical lab must figure out how to present the information to the clinician in a way that isn't simply a data dump, but provides information that the clinician can understand and utilize to provide the best in patient care.
After complexity, a second aspect of this very dynamic landscape is competition. The increasing competition in genomic or NGS-based clinical research in LDTs is making it difficult for smaller labs that can't optimize test costs through efficiencies of volume to compete with larger labs that have high volumes. Challenges with classic payer models and reimbursement levels have inspired some labs to create novel direct-to-clinician or direct-to-patient billing models that were seldom if ever seen the decade before NGS came to clinical diagnostics.
Finally, the third aspect is the professional guidelines and regulatory requirements that have been pushed to evolve more quickly to meet the needs of emerging technical capabilities and clinical demand. NGS in clinical diagnostics was a big part of driving PMI, or the Precision Medicine Initiative, and also FDA statements on the regulation of the development of LDTs. Professional guidelines around NGS assay development and utilization have been challenged with keeping pace with the rapidly expanding capabilities and projected uses.
These three areas, complexity, competition, and regulation, are the parts of the landscape I would say have changed the most dramatically.
You'll discuss key issues and opportunities for liquid biopsy sample prep during your presentation on June 23. Why do you want to highlight that particular process, and what's the main takeaway for your audience?
Primarily, it's so exciting how the increased capability of these detection systems, in other words, NGS platforms, have really been an incredible enabler of applications requiring the highest sensitivity. It's been really easy to focus on this sexy, cool technology and the detection, and lose sight of some of the fundamentals. In my mind, the primary and most critical component remains, regardless of the detection system, and that is you can't detect what you haven't sampled, or at least you really shouldn't be able to detect what you haven't sampled or there's big problem with your system. I really would like to highlight some of the commercially available options and also some of the gaps and maybe emerging opportunities for people to see where we could use new technology around sample prep. Whether it be in a high-throughput automated setting and being able to sample more specimen, or whether it be something where sampling from less specimen and still able to achieve the results we expect.
Looking even further into the future, what refinements in process and technology must still be made in the next decade before liquid biopsies can be used more regularly for broader routine applications?
Again, it goes back to sampling. Being able to sample the target, detect the target reliably in the specimen that's being tested; hopefully being able to do that in a way that's minimally invasive with regard to the patient; being able to produce those results in a timely manner, in an accurate manner; and having those results be clinically useful and valuable is going to be key. I think there's a lot of opportunities around sampling and sample prep in dealing with what the clinical validity and what that result actually means within a clinical context. It'll be really exciting to see the emerging clinical studies that come from this sensitive NGS technology using the appropriate sample prep methodologies.
Well, thank you, Jamie. There are so many more insights you can share here, but we're out of time. We'll look forward to learning more from you later at the conference.
Great. Thank you. I look forward to it.