NEW YORK (GenomeWeb) – The clinical lab market is a symbiosis between laboratorians and industry. Companies develop products in intimate collaboration with clinical researchers in the trenches, and the ever-important validation of assays and platforms demands lab directors be willing to undertake experiments for the greater good of the field and their patients.
In this ecosystem — with clinical lab directors acting as "key opinion leaders," participating in scientific advisory boards, requesting investigator-initiated grants to test products, and performing extensive beta testing outside of industry — labs are not simply customers who purchase ready-made platforms and assays off the shelf, but rather integral to development and testing, and potentially impactful to sales and marketing.
In this fluid milieu, the boundaries between academia and industry may be somewhat different than in other scientific domains. With over four decades of lab experience, Christine Ginocchio recently shifted more to the industry side, becoming vice president of global microbiology affairs at BioMérieux in February of 2014. However, she has also maintained some of her academic affiliations.
At the Clinical Virology Symposium this week in Daytona Beach, Fla., Ginocchio sat down with GenomeWeb to talk about her recent career transition, and to discuss the trends she sees in the clinical lab space and a few of the products in development at BioMérieux subsidiary BioFire Diagnostics. Below is a transcript of the interview edited for clarity.
What are your current academic affiliations?
I officially retired a year ago from North Shore-LIJ Health System Laboratories, NY, but I have retained my faculty position, so I am still a professor of medicine in the Hofstra North Shore-LIJ School of Medicine, which is nice, because I really enjoy teaching the medical students. With the faculty appointment I can also keep my editor-in-chief position for the Journal of Clinical Virology.
Have you perceived any barriers in moving between academia and industry?
There were no barriers for the transition, but there are some things you have to give up. You do not have your own lab; you are not doing independent research. However, I do a lot of work with BioFire, and they are very active in pursuing external funding through various grant agencies such as the National Institutes of Health and Department of Defense. From the academic standpoint, I still have my teaching, and I'm still writing grants and research protocols with collaborators.
I do a variety of different types of presentations, including strict, balanced scientific presentations at national and international conferences. I may also do commercial presentations, but they are for a company workshop, symposium, or a requested customer presentation.
Did you consider other companies besides BioMérieux?
Yes. I had consulted for several companies for many years, and when they knew I was going to be retiring, other companies made me some nice offers also.
However, I had also worked with BioMérieux as both a consultant and an investigator for 20 years or so. We did a lot of collaborative R&D when it was Organon Teknika in the Netherlands, working on assay development and early pilot testing of what they had designed. They were bought by BioMérieux, so I knew a lot of the people in the company from both Organon Teknika and BioMérieux. I felt very comfortable there. Not that I didn't with the other companies, because I knew a lot of exceptional people there too.
I think the deciding factor — because the decision was hard — was when they bought BioFire, because molecular diagnostics and assay development was always such a strong part of what I did in my clinical and research laboratories.
What is the relationship like between clinical lab directors and industry, from your perspective — is it like customer and vendor?
To some degree yes, it is a customer-vendor relationship. However the relationships can expand to include clinical and research collaborations and the depth of the relationships can vary dramatically.
There has been a very positive change in these relationships over the last 15 years.
Previously, companies would design and develop an assay or a platform, they would bring it through the US Food and Drug Administration, and then bring it to a customer, who would realize that the platform or test didn't make any sense or was not optimal for laboratory workflow. Companies realized that if they were going to make all this investment, they should really talk to the people who would be using the test, both the laboratorians and the healthcare providers. Now, most companies realize the high value of scientific advisory boards and really speaking with the customer.
I think BioMérieux and BioFire benefit from having a number of people like myself that came from actual clinical labs. I worked in clinical infectious disease labs for 40 years. I know that people can sometimes have great ideas, but we can look and quickly assess whether it will work in the lab. If you're spending a lot of money, especially bringing tests through the FDA, getting the advice of laboratorians is what companies need to do early in the design process.
Clinical sites also do a lot of the preliminary testing, and can look at how the instrument performs, before it gets to the point where it's too far gone to make changes.
Are there any trends in molecular diagnostics you can see from your vantage point that your colleagues here at CVS might not yet be aware of?
To be honest, I really thought that basic PCR would have gone away a lot sooner. It's still going to be here for quite a while, but it's all about faster and more portable. This year the FDA approved the first point-of-care CLIA-waived molecular test. In many instances you want the testing to be performed near the patient, because we know the faster and easier it is to get the data, the larger the clinical and financial impact.
There's been a lot of cool technology in the last ten years, but I think in the last three years, the field has exploded with nanotechnologies, handheld devices, microfluidics, non-PCR based amplification technologies, and extreme PCR. I think traditional PCR assays will get better, faster, their boxes will get smaller, and you'll start to see a lot more point-of-care approved tests.
The other revolution that will come will be NGS. In terms of development, it is where mass spectrometry was maybe five or ten years ago. It's a fabulous application, you can do a lot with it, but for it to be used daily in a clinical lab, it has to be a black box like today’s MALDI-TOF mass spectrometry systems have become. For routine use, we are moving to more rapid results — if possible we would prefer not to use a system that's going to take eight or 10 hours for a few samples. This is certainly fine for exceptions and specific cases. The bioinformatics have to be easy, and technically not complex, it has to be sample in, result out to the point where you can place these types of systems in any lab.
There seems to be a buzz about pricing and reimbursement for multiplex tests here at CVS, can you comment on that from the perspective of BioFire panels?
The CPT coding for multiplex molecular tests is tiered now for respiratory and gastrointestinal panels. The first tier is three to five targets, the next is six to 11, and then 12 to 25, and there are set reimbursement prices.
The top tier reimbursement is around $550, however whether or not a test is reimbursed varies, and if so, the amount can be highly variable.
The tiered structure of syndromic screening makes a lot of sense from a clinical and financial standpoint. For example, if there are 22 pathogens, and the reimbursement is $47.50 per target, technically the test could be billed for more than $1,000. The commercially available highly multiplex tests range in cost from approximately $100 to $250. Therefore the top tiered reimbursement is very appropriate in relation to the cost per test, and does not result in the excessive billing that individual analyte coding would allow. However, reimbursement is always a big black hole and depends on the insurance company, Centers for Medicare and Medicaid Services, inpatient or outpatient, etc. It is really very complicated.
So, a panel can test all of the targets, but only report some of them?
You test for all targets in the current assays, and results are reported for all targets. If laboratories choose to not report certain results that is their decision.
However, this can create a bit of a dilemma — what do you do with a positive result for a target that you did not intend to report, if that result may be significant?
Some laboratories may select to suppress certain results if that is an option. However, most current systems do not provide that option. In my health system the medical board decided that the complete panel would be the standard of care with all results reported. You could not order just the flu PCR, or just the [respiratory syncytial virus].
There are many reasons why the complete panel should be run aside from making a diagnosis, including the detection of mixed infections, identifying a pathogen not suspected in the initial diagnosis, and for infection control issues.
If panels require more interpretation in the context of the clinical picture, how do you communicate that to physicians?
We spent a lot of time on education, doing grand rounds, and explaining the tests when we brought them on. It's our responsibility as lab directors to make sure we educate physicians and other healthcare providers so they understand what the results are and what they mean.
But do you want companies to market directly to physicians?
Having been a lab director, I can tell you that we highly prefer if companies speak first with the laboratory director. Companies should definitely engage other healthcare providers and administrators in collaboration with laboratory directors. The laboratory is our territory, this is our job, we are the experts, and we will certainly involve our clinicians and administrators in the selection of new tests and the management of their appropriate use. We certainly are open to requests from our clinicians also.
In a previous Q&A with GenomeWeb you advocated for more syndromic screening, is that still the case?
Yes, and there's more to syndromic screening than just the diagnosis. There's effect on treatment, infection control, patient management, epidemiology, and surveillance.
What we're learning with comprehensive GI panels now is similar to what we learned a few years ago with the big respiratory panels. Standard diagnostics missed many infections and there is a lot of asymptomatic carriage that we never knew about before.
There are also a lot of questions, but we now have the tools to provide the answers. For example, we used to think rhinovirus was just the cause of the common cold, and nobody really looked for rhinovirus. Now that we can easily detect rhinovirus in the panels, we have identified certain patient populations, such young children, dying of severe rhinovirus infections.
Years ago when I started doing respiratory panels, some of my colleagues said, "Why are you testing for all those pathogens; nobody knows what it means, and we can't treat them." I think over the last 10 years our knowledge of what these infections mean has increased tremendously and we now understand the diseases caused by these pathogens. If we never look for them, how are we going to understand them? I think we're going to go through that same stage with the stool pathogens, and that's OK.
Shifting gears a little, you've written in the past about H1N1 influenza tests that received Emergency Use Authorization — do you think EUA is a path to commercialization, and why did BioFire choose to submit an assay for Ebola?
H1N1 hit so hard and so fast, and it was the first time I can remember in my career that the FDA invoked EUA. Having that mechanism in place is for the good of the community. When a company makes these tests, they still have to go through extensive analytical performance testing to even get a FDA EUA.
An EUA for Ebola is not about making money, at the end of the day. Fortunately, in the US we never had many cases. It's more about an obligation to do a public service and provide a means to deal with what could have been a global catastrophe. Personally, I hope it sits on a shelf and we never have to use it, but you never know, and we are now prepared.
Could you forsee an EUA being issued in the future if an emerging infection, like Chikungunya for example, suddenly takes off and there is an outbreak?
Currently, I question if Chikungunya would qualify as an EUA. Ebola qualified because it became a potential global catastrophe overnight. H1N1 hit and we had no warning. But we know Chikungunya and Dengue are coming; it's no mystery. We know the viruses are in Florida now, and we need to have assays going through FDA trials now, in preparation for increased spread of these diseases. Unless we have a sudden major outbreak situation in the US, in my opinion it is not an emergency use in the classical sense.
Recent CDC and WHO meetings regarding Middle East Respiratory Syndrome coronavirus have highlighted the need for clinical diagnostic tests, and agencies are encouraging manufacturers to develop MERS assays. Tests need to be developed now so we are prepared in the event of an outbreak.
Can you describe any other panels BioFire has in development?
The focus of our interests is syndromic panels. There are many syndromes that would be applicable to highly multiplexed panels.
We currently have a meningitis/encephalitis panel in review by the FDA. The panel detects the most prevalent eight viral pathogens, six bacterial pathogens, as well as Cryptococcus neoformans/gattii.
Other syndromes of interest are direct sepsis detection, lower respiratory tract infections, and undifferentiated febrile illnesses.
Imagine a traveler from South America comes into an [emergency department] with a fever — it could be Chikungunya, Dengue, Yellow fever, malaria, or perhaps Lepotspirosis — this is a highly needed panel, especially with the ease of global travel.