The Digital Pathology Association’s FDA Task Force prepared four questions for the Regulatory Panel session held at the Pathology Visions conference last week. The third, two part question was:

• Does WSI fit within the paradigm of a Laboratory Developed Test?
• What would be required for Self- Validation?

The regulatory panel consisted of representatives from the FDA, CAP, and CMS/CLIA and was moderated by Dr. Stephen Hewitt of NCI. The questions above are very important but the answers have different implications on the audience.  Digital pathology manufacturers are overseen by the FDA, and laboratories are overseen by CMS and CLIA guidelines.  However, the only clear answer given to these questions was by FDA representative Tremel Faison.  She announced,

WSI are systems and are not considered, by definition, as Laboratory Developed Tests (LDT).

To date, the FDA’s oversight of LDTs has been very limited and LDTs have been enforced at the discretion of the Centers for Medicare and Medicaid Services (CMS) which governs CLIA.  Although it is very clear the FDA plans to play a bigger role in the oversight of LDTs based on the public hearing held in July of 2010, and the fact that they tabled their final guideline on IVDMIAs to address the broader issue of  LDT oversight.  Dr. Bruce Friedman discusses this further and provides a very good background in his blog post, “FDA Shelves IVDMIA Regulatory Initiative; Will Focus on Laboratory Developed Tests” at Labsoftnews.com.

Also present at the regulatory panel last week was CLIA/CMS representative Debra Sydnor and Dr. Walter Hendricks who represented CAP as a CMS approved accreditation organization under CLIA.  These two presentations were very important to pathologists and laboratories professionals and they should have provided a clear understanding of what is or is not available to them for clinical use of digital pathology for patient care.

Dr. Hendricks provided an overview of what CAP initiatives are currently underway to assist pathologists and laboratories with validation of digital pathology.  For example, he discussed the soon to be issued CAP guidelines for Validation of WSI and Dr. Anil Parwani gave a presentation earlier in the week about the guidelines. The guidelines were created by the CAP Center Working Group as,

13 STATEMENTS developed to assist the pathology community with validating WSI for clinical diagnostic use.

based on an:

• Increasing interest in using whole slide imaging(WSI) for diagnostic purposes in pathology.
• Increasing questions about what needs to be done to ‘validate’ a WSI system for clinical service and if validation is necessary.
• Lack of current standardized guidelines regarding validation of WSI for diagnostic use.

Down the road (although no plan is currently in place) some of these guidelines may become a CAP Checklist Requirement.  However currently there are several CAP Checklists items that are applicable today to digital pathology.  Dr. Hendricks outlined all of these in his other Visions CAP presentation titled “The CAP Laboratory Accreditation Program Practical World View on Digital Pathology from a CLIA Accreditation Provider.”  Based on all of this it would be easy for pathologists and laboratories to assume that CAP is trying to provide guidance on self-validation of digital pathology/WSI systems.

What does CMS/CLIA have to say about all this?  Honestly, I’m not too sure. I found the regulatory panel presentation by Ms. Sydnor to be very confusing.  I reviewed my notes and her presentation again this morning but could not make any more sense of it.  It appears by her powerpoint that she gave some background on CLIA and then highlighted CLIA requirements that are applicable to digital pathology.  Ms. Sydnor never said that WSI was not an LDT like the FDA, but in an attempt to answer a question about the components of a digital pathology system she stated,

CLIA supports the FDA.

But was this statement made based on her (or CMS/CLIA’s) unfamiliarity with digital pathology? I did not come away with any confidence that CMS/CLIA have any real understanding of what laboratories currently face regarding digital pathology.

NOW WHAT? That’s really the big question for laboratories to try and answer.  My best advice is to proceed with caution but PROCEED! There are a lot of ways to use digital pathology that will not impact compliancy with CLIA; remember the only major intended use up for debate right now is primary diagnosis.  Examples include tumor boards, consultations, intra-operative, education, archival, decision support, peer review, quality assurance, and manual or automated image analysis.  In a previous post on my blog about the regulation of digital pathology I stated,

Are you even ready for primary diagnosis with digital pathology?  There are a TON of other areas that need to be addressed to make primary diagnosis with digital pathology work. Barcodes, laboratory workflow (before and after the scanner), data storage and management, and integration with your LIS, PACS, and EMR. Just to name a few.

If you are serious about our digital pathology future then stop worrying about what the FDA is saying (or not saying) and get to work! Prepare the labs for change and start using digital pathology for all those applications you are sick of hearing about.

If you are one of those rare labs that has everything worked out and are ready for primary diagnosis, then set up a clinical trial collaboration with a manufacturer or use your own discretion on self-validation of digital pathology.  As discussed above several resources are available for self validation of digital pathology.   Use the CAP guidelines, CAP accreditation checklists, applicable CLIA requirements, and the newly release DPA white paper on validation to guide you.  Ultimately the decision is up to you and what you are comfortable with.

The second most popular question people ask me as a consultant in digital pathology is,

Have there been any updates to the FDA’s position on Digital Pathology?

No, but there are safe and effective ways to use digital pathology in a clinical setting today.   The FDA regulates what digital pathology manufacturers can claim or say their technology is used for, not what a pathologist or a hospital does with digital pathology. Safe and effective uses of digital pathology are available today that can benefit hospitals, labs, pathologists, medical students, residents, patients and more.  Examples include tumor boards, consultations, intra-operative, education, archival, decision support, peer review, quality assurance, and manual or automated image analysis.

You are thinking…

Blah, blah, blah, blah.. and blah. I’ve heard all of this before!  Tell me when will this be ready and safe for primary diagnosis?

Okay, but let me warn you… you asked for it! CLIA is who regulates laboratory use of digital pathology.  So, let’s see what CLIA says:

Sec. 493.1253  Standard: Establishment and verification of performance
specifications

    (a) Applicability. Laboratories are not required to verify or
establish performance specifications for any test system used by the
laboratory before April 24, 2003.
    (b)(1) Verification of performance specifications. Each laboratory
that introduces an unmodified, FDA-cleared or approved test system must
do the following before reporting patient test results:
    (i) Demonstrate that it can obtain performance specifications
comparable to those established by the manufacturer for the following
performance characteristics:
    (A) Accuracy.
    (B) Precision.
    (C) Reportable range of test results for the test system.
    (ii) Verify that the manufacturer's reference intervals (normal
values) are appropriate for the laboratory's patient population.
    (2) Establishment of performance specifications. Each laboratory
that modifies an FDA-cleared or approved test system, or introduces a
test system not subject to FDA clearance or approval (including methods
developed in-house and standardized methods such as text book
procedures, Gram stain, or potassium hydroxide preparations), or uses a
test system in which performance specifications are not provided by the
manufacturer must, before reporting patient test results, establish for
each test system the performance specifications for the following
performance characteristics, as applicable:
    (i) Accuracy.
    (ii) Precision.
    (iii) Analytical sensitivity.
    (iv) Analytical specificity to include interfering substances.
    (v) Reportable range of test results for the test system.
    (vi) Reference intervals (normal values).
    (vii) Any other performance characteristic required for test
performance.
    (3) Determination of calibration and control procedures. The
laboratory must determine the test system's calibration procedures and
control procedures based upon the performance specifications verified
or established under paragraph (b)(1) or (b)(2) of this section.
    (c) Documentation. The laboratory must document all activities
specified in this section.

The sentence highlight above “… or introduces a test system not subject to FDA clearance or approval” means that a laboratory should be able to validate a digital pathology solution on their own for clinical use.  And although the FDA has not formally stated whether scanners will be “subject to FDA approval” it seems clear through they will.  The background briefing document about the Advisory Panel Meeting held in October 2009 stated,

FDA hopes to gather information about how to evaluate and compare the performance characteristics of both the light microscope- the reference method- and the digital WSI method-…FDA follows the Code of Federal Regulation 21 CFR 860.7 for ensuring the safety and effectiveness of regulated medical devices…FDA believes the first requirement for adoption of digital whole slide imaging will be the maintenance of the diagnostic accuracy and reproducibility of current surgical pathology diagnostic performance using the conventional light microscope- the current reference method for the diagnosis of cancer and other histopathological entities.

At the Advisory Panel Meeting, Tremel Faison the Scientific Reviewer in the Office of In Vitro Diagnostic Device Evaluation and Safety, stated:

“…everything here at the FDA starts with an intended use. Intended use shapes how the device will be regulated, in what population and ultimately the study design.  For the scope of this Panel meeting, the intended use is defined as the use of whole slide imaging for primary diagnosis of surgical pathology microscope slides in lieu of a microscope. This is not an adjunctive intended use, and for our purposes, we will be considering the use of whole slide imaging for all surgical pathology specimens. It will not be organ or disease specific…

We recognize that the technological advances associated with whole slide imaging make its use a reality. Whole slide imaging systems are not Class I exempt and are therefore subject to premarket requirements.

As I said above, although the FDA has not formally stated whether scanners will be subject to FDA approval it seems clear they will.  So, now what? You could try and go through CLIA for approval of your scanner within the lab or wait for direction from the FDA.  Neither seems like that great of an option.

I started this post with the second most popular question asked of me and here is my response:

What does it matter!  Are you even ready for primary diagnosis with digital pathology?

There are a TON of other areas that need to be addressed to make primary diagnosis with digital pathology work.  Barcodes, laboratory workflow (before and after the scanner), data storage and management, and integration with your LIS, PACS, and EMR.   Just to name a few.

If you are serious about our digital pathology future then stop worrying about what the FDA is saying (or not saying) and get to work! Prepare the labs for change  and start using digital pathology for all those applications you are sick of hearing about.

In post USCAP Part 1: The BIG Players In Digital Pathology I said, “A shift in the mindset of pathologists could be felt throughout the meeting and left the digital pathology industry energized about what 2011 will bring. No more just looking and talking about digital pathology, pathologists were truly starting to plan and think about how to adapt to their digital future.”   This is a big step toward the “tipping point” of digital pathology, however, we still have several barriers to work through including cost, regulatory, technical, and psychological.

COST

Cost justification is difficult in digital pathology, however, there are several options to help deal with this barrier.   At USCAP two companies, MikroScan and Motic, showcased small, affordable, high-quality scanners for only $35,000.

Mikroscan's D2 Desktop Scanner

Mikroscan’s Victor Casas said “we are here to disrupt the workflow” by creating an affordable system that is outside the lab and on the pathologists desk.  Mikroscan believes that they do not compete against the high-throughput systems created by other manufacturers, instead their systems are positioned to work with them.  Mikroscan wants to focus on intra-operative/frozen section scanning; small, remote labs in rural areas; and the personal scanning needs of pathologists.  The D2 scanner’s has a very nice “desktop” look and  the paddle (aka slide holder) can load four 1×3 slides, two 2×3 slides, or one 2×3 and two 1×3 slides.  Objectives include a 2.5x for the macro scan, 20x, and 40x for high resolution scanning.

Motic’s microscope based system can be configured for 1 or 25 slides, and offers microscope-like flexibility with slide acquisition up to 100x and of the z-axis.  Scans average around 4 minutes for a 15 mm2 area (scan time only).  Their system supports a server software and viewer, and has the capability for real-time remote telepathlogy of the microscope.

However, if your digital pathology needs include mid or high-throughput scanning the cost barrier will not be overcome simply with low cost equipment.  Instead you need a business plan and strategy.  My company, Digital Pathology Consultants, helps organizations of all sizes create a business plan that will  ”cost justify” digital pathology and set you up for digital success now and in the future.  Our 5WH program provides clients with a cost-effective, unbiased business case for digital pathology.  The 5WH program is based on a common methodology for information gathering and the goal is simply to answer the who, what, where, when, why and how of digital pathology.  Although the methodology is simple, discovering the best answers to these questions is not easy and that is why you need help.

REGULATORY

Some day (hopefully within the next 10 years…) I’ll be able to blog about the FDA’s plan on how to regulate digital pathology manufacturers.  Until that day comes pathologists, and their labs, must determine ways to safe guard themselves but still move forward with the use of digital pathology.  Remember the FDA regulates what digital pathology manufacturers can claim or say their technology is used for, not what a pathologist or a hospital does with digital pathology.   CLIA is who regulates laboratory use of digital pathology.  At USCAP, CAP announced that the Pathology and Laboratory Quality Center were developing guidelines for digital pathology titled “CAP Validation Principles for Whole Slide Imaging in Digital Pathology.”  The goal of this document is to develop principles to assist pathologists in properly validation WSI digital imaging systems. The draft recommendations will be available for public review in Sring 2011.

TECHNICAL

In post USCAP Part 2: Innovation Trends in Digital Pathology I discussed technology trends and how these are helping to address technical barriers of adoption.  However, our biggest initiative must be to educate others in the HIT world and share what we learn, and to not shy away from this very real component of digital pathology.  Two white papers were published by the Digital Pathology Association in 2010 and are good examples of what we must do to prepare for the  data wave and the level of integration necessary to ensure pathology departments are successful with digital pathology now and in the future.

PSYCHOLOGICAL

Psychological barriers is a “hot topic” for me.  I firmly believe this is an area the digital pathology industry must have a plan to address or adoption may never truly succeed.   At Digital Pathology Consultants we have developed a coaching program to help departments or individual pathologists overcome the psychological impacts of digital pathology.  I also know this is a point of interest for Aperio, and their CMO Jared Schwartz, MD PhD.  Dr. Schwartz recently did a webinar on the Psychological Barriers and how Aperio is working to address them.

Overall, USCAP 2011 was an amazing meeting with lots to see and discuss about digital pathology.  What do you think- take the poll below:

You literally walked right into the world of digital pathology, sandwiched between Aperio and Ventana, when you entered the exhibit hall at USCAP 2011 in San Antonio last week.  A shift in the mindset of pathologists could be felt throughout the meeting and left the digital pathology industry energized about what 2011 will bring. No more just looking and talking about digital pathology, pathologists were truly starting to plan and think about how to adapt to their digital future.

The amount of information I gained last week, specifically about digital pathology (and LEAN too), still has my head spinning.  If you missed the meeting or did not get as much time as you would have liked in the exhibit hall, then read on and follow my three part series on digital pathology at USCAP 2011.

Part 1: The BIG Players in Digital Pathology

When I say BIG- literally, I mean BIG!  To qualify as a BIG player in digital pathology you must have BIG (and very deep) wallets, BIG exhibit booths, BIG scanners, and BIG plans for the future of digital pathology!  The BIG players are (in no particular order):

Aperio

You could not miss Aperio, or their giant projector ball! They were one of the first booths you saw when you entered the exhibit hall.   Their two big initiatives were the NEW ScanScope AT and Spectrum Healthcare. The ScanScope AT is similar to the XT, but with a 400 slide carousel and a new flat loading method that “pushes and pulls” the glass slide on to the stage.  Aperio says the AT has a 25% improvement in scan time with a throughput of 30 slides an hour at 20x.

In addition to the AT, Aperio was showing a sneak preview of their new workflow solution Spectrum Healthcare to a select few. These demonstrations were to gain feedback and impressions of this new product (not yet released). I was fortunate to be one of the select few (Thanks Ole!) to see it. Spectrum Healthcare has a nice clean look, and is designed to provide an intuitive user experience based on the workflow of key clinical applications.

Ventana

“Ventana Digital Pathology Powered by Bioimagene” is the new tag line for the duo.  Although the well known Bioimagene brand was not present in the Ventana booth, their iScan Coreo Au scanner, Virtuoso data management software, and whole slide images were.  A great example of integration of the two brands were large touch screen displays throughout the booth that showcased whole slide images of new antibodys, like ERG for prostate.  It is clear that Ventana has a plan and strategy for digital pathology, and is working hard to fully integrate the Bioimagene team and products into their portfolio.

Omnyx

There were lots of familiar and new faces in the Omnyx booth! Omnyx has been hiring (and is still hiring) a lot of people to support the launch of their digital pathology solutions, currently for research use only.  Omnyx showcased new technology with their VL120 scanner and a new web-enabled viewer for mobile devices (think iPad and laptops) for remote access to their pathologist workstation solution.  The VL120 has the same components as the VL4 but with a flat-bed load and scan system.  There are six stackable trays that each hold 20 slides and can be placed in the VL120.  The VL120 will not be available until Q4 2011.

Olympus

Olympus had an very impressive booth fully equipped with a surgical suite, new microscopes, consumer cameras, and their full digital pathology product line.  The goal was to make pathologists aware that they are more than a microscope provider, they are a healthcare company.  I imagine it worked! You couldn’t help but be curious about the surgical suite and the large array of products on display.  Their DP product line included the VS110 with fluor and 100 slide autoloader; The NanoZoomer RS 2.0 with new fluorescence components, a Visiopharm image analysis workstation featuring HER2-Connect, and their new VS800 scanner.  The VS800 was impossible to miss with it’s large footprint and blue panel.  It has capacity for 300 slides, a custom designed objective, simultaneous parallel slide loading and unloading, real-time auto focus which eliminates the need to create a focal map, and brand new software to run the scanner and manage the data.

Leica Microsystems

Leica’s new tagline is “Total Digital Pathology” designed to create a similar message to their “Total Histology” solutions.  Although Leica was not showcasing any new digital pathology technology, they were demonstrating their total solution with the SCN400, Ariol for clinical breast panel analysis, and SlidePath software to support the data management of either the SCN400 or Ariol scanned slides. Both Genetix (acquired by Danaher in March 2010) and SlidePath (acquired by Genetix in May 2009) are now represented as an integrated part of Leica Microsystems, and their “Total Digital Pathology” solutions.

Philips

Philips demonstrated their high throughput (300 slides) scanner, Pathology PACS workflow software, and a new integrated DAKO HER2 algorithm.  Their system is designed for the “bench” with a simple, intuitive touch screen, large bright lights indicating the scanning process (to be monitored from across the lab), and the batch can be interrupted to pull out finished slides and to load new ones.  Within the PACS software is the Dako algorithm for the Herceptest (HER2).  This was one of my favorite features at Philips.  Based on the slide barcode the software knows what the stain is and “automatically” applies the algorithm to the slide and generates the score.  The user (aka pathologist) only has to delineate an area of interest(s).  The algorithm is calibrated to the stain and is very, very easy to use!  Further image analysis initiatives by Philips include integration with Definiens for specific algorithms; however, Philips will have an open architecture for image analysis. The entire Philips solution is available today but for research use only.  Clinical trials are set to begin at three customer sites in Q2.

Special thanks to Ole at Aperio and his blog for a few of my pictures, and stay tuned for tomorrow’s post- USCAP Part 2: Innovation Trends in Digital Pathology.

The United States & Canadian Association of Pathology (USCAP) annual meeting, the first big pathology meeting of the year, is set to kick off in San Antonio TX and celebrate its’ 100th year this weekend.   The topic of the meeting is “Education & Innovation For The Next 100 Years” and will feature lots of information on digital pathology.

Over the past three years USCAP has really become a hot spot for digital pathology companies to make a statement; the exhibit booths just get bigger and bigger! In my summary of USCAP last year I blogged about how there were sixteen companies who represented digital pathology products (see post: All Aboard! The Digital Pathology Bandwagon); this year will be even more impressive- just wait and see!

USCAP ’11 Digital Pathology Highlights

• CAP Companion Meeting, Saturday 2/26 at 7 PM:  Whole Slide Imaging: The Here & Now
• DICOM WG-26 Meeting, Sunday 2/27 from 8 AM – 12 PM at the Marriott Riverwalk
• Lots of great posters! My personal favorite topics will be Quality Assurance, Informatics, Education, and Techniques. These topics will all have examples of how institutions are using digital pathology.
• There are also two short courses on Thursday 3/3 that will discuss or use digital pathology.
  • Short Course #39 – Virtual Cytopathology Challenges for Practicing Pathologists
  • Short Course #32 – Microscopy for the New Millennium
• The Exhibit Hall on Monday, Tuesday, and Wednesday from 9:30 AM – 4:30 PM will be full of digital pathology excitement! New companies, lots of hardware and software advancements, workflow improvements, new integrations with third party companies, etc.

I will of course be there and welcome the opportunity to meet and greet with any of my blog readers or anyone interested in learning more about Digital Pathology Consultants. Send me an email if you would like to set up a time to meet and/or follow me on twitter during the meeting at DPConsultant and look for tweets with #USCAP11.

You spend so much of your life working- find a job you love and can be passionate about!  Just over a year ago I started my consulting business; a risky change from the comforts of my successful sales career.  My passion for digital pathology energizes the work I do every day, and my personal conviction for success is what has driven my company to grow and thrive in 2010.  The risky change was worth it, and the best decision I ever made.  How about you, are you ready for a change?   What career change will you take now or in 2011?

The unemployment rate is a hot topic on the news every day in our country and around the world.  But in digital pathology, the demand is greater than the number of applicants with experience in digital pathology.  I receive calls from recruiters all the time asking if I’m looking for a job, or know someone with digital pathology experience looking for a job.   There are all types of companies looking for great people including big corporations, small companies, pharmaceutical companies, and laboratories.   The type of positions vary greatly too and include software programmers, product developers, engineers, sales reps, marketing, project managers, administrative roles, technicians, etc.

Within the past few months, several companies have launched hiring efforts including Leica Microsystems, GE/Omnyx, and Philips to expand their teams. Other established companies like Aperio, Ventana, and Olympus have positions available too.  Some efforts are large, for example GE Healthcare currently lists 16 digital pathology positions for their collaboration with Omnyx.    This is optimistic for our economy but also exciting for the future of digital pathology.  Organizations are investing in people to build, refuel, and drive their business efforts forward.

Find a job you love and can be proud to do every day. Life is too short to work any other way!

If you are looking for a job, check out the Career Board at www.thedigitalpathologywiki.com.  I routinely update the companies who are hiring.  Also, the Digital Pathology group on LinkedIn is an excellent resource; I always encourage recruiters to post their positions there.  If you are hiring, please feel free to post a comment if you have a job available.

Olympus CEO Mark Gumz announced some exciting news today in a blog article/interview written by Steve Tobak.  Olympus is applying for FDA approval in digital pathology, and he also used digital pathology as an example to highlight “Enterprise Innovation” at Olympus.  Every FDA approval gained in digital pathology is a huge step forward for our industry and it’s great to see that Olympus is applying to the FDA for approval. The blog post, titled “Enterprise Innovation: A Key to Untapped Business Growth“ summarized a recent interview with the CEO.

Enterprise innovation is defined as “Transformative business processes, practices, organizational planning and models that enable a business of any size to operate more effectively, profitably, and/or competitively,” according to this article and a Harris Interactive survey of Fortune 1000 executives. Mark Gumz states in the article,

…The status quo is the greatest inhibitor to growth. Enterprise innovation is something that’s within our control as an industry and as a nation.

The FDA quote from Mark Gumz is as follows:

We’re currently applying for FDA approval for clinical digital pathology, the ability to send a clinical slide over the Internet. During a surgical procedure, a surgeon could take a biopsy and send it to a pathologist anywhere in the world to get a second opinion – do I take out more or not? That will ultimately be a huge cost saver. Ultimately, enterprise innovation has to come down to return on investment.

So what do you get if you put Mr. Gumz’s vision of “Enterprise Innovation” together with an application for FDA approval of clinical digital pathology?  My guess…not a whole lot in the near future!  There are too many unanswered questions and likely a lot of work to be done. Some of these unanswered questions are:

• What instrument, software, algorithm, technique, etc are being used in the application to the FDA? This is very confusing since Olympus America offers their own VS110 microscope-based slide scanner and software, distributes the NanoZoomer and it’s software from Hamamatsu, distributes image analysis software from Visiopharm on both hardware platforms, and still has server and viewer software from Bacus Laboratories, Inc (a company  they acquired in 2006).
• With whom are the clinical trials being conducted and what type of data is being gathered for application to the FDA? Several  competitors of Olympus have publicly announced and or have discussed details of their clinical trials.  For example, Aperio’s Project Pink is a primary diagnosis concordance study focused on breast tissue with four sites in the United States, and one of those sites is MD Anderson.  Omnyx announced in a recent press release the start of their clinical trials with three sites in the Unites States and one in Canada.  However, I have never seen or heard anything about clinical trials with Olympus.
• What is going to or has changed within the Olympus digital pathology product line to be more clinically oriented? They primarily sell hardware with a data management/viewer software solution that typically functions in a stand-alone research environment.  Clinically oriented hardware and software products from their competitors are very different and are designed with consideration for the histology lab and the diagnostic routine of a pathologist.
• What is being done to support laboratory workflow and interoperability within the pathology department and hospital? At Pathology Visions a Pathologist and I spoke with marketing staff at Olympus about this.  As of a few weeks ago Olympus did not have integration with any LIS vendors.  Also, they explained to the pathologist I was with that they do not support the DICOM format (WG-26 Supplement 145) recently approved for digital pathology.
• What about that ROI mentioned in the FDA quote above? I have not seen or heard of any marketed or published data showing Olympus’s efforts to create an ROI business model in digital pathology.  Maybe that’s in the works??

I realize that all companies working toward FDA approval are faced with many questions and tough regulatory hurdles, especially since the FDA has not provided any clear guidance to manufacturers on this topic.  However, based on the current public information out there about Olympus, their digital pathology product portfolio, and the information displayed on their website (which is 100% research and/or education focused) I have to imagine their FDA application is probably a rough draft and a long way off from being complete.

Patients do not understand the importance of a pathologist in the diagnosis of their disease.  They also have no idea about digital pathology.   But that could all change with a simple, powerful marketing campaign by GE’s Healthymagination. Can you imagine it?  I can, and I have been for years.  A Healthymagination commercial would bring attention, good attention to the practice of pathology.

Although no commercial has aired, it has been a busy week for GE in the world of pathology.  On October 22nd GE announced the purchase of Clarient in a $587 million deal to accelerate GE Healthcare’s ability to predict and diagnose diseases;  and yesterday GE healthcare’s joint venture with UPMC, Omnyx, announced the start of clinical trials for their digital pathology solutions.   Although Omnyx was not involved in the purchase of Clarient, it makes sense that they will come together to further GE Healthcare’s $6 billion healthymagination initiative to improve cost, quality, and access in healthcare; or in our world- pathology.

In addition, GE and Omnyx executives spent the past few days promoting their innovation and advancements at two conferences in San Diego, CA- Pathology Visions and TEDMED.  At TEDMED Mike Barber, GE’s VP of Healthymagination, gave an 18 minute power presentation which included digital pathology.  Mr. Barber was quoted,

I don’t say this lightly – while digitization may seem like a relatively simple change in today’s tricked-out techno world, it’s a revolutionary step in pathology that may lead to the transformation of the practice, and the evolution of our understanding of cell biology.”

Digital pathology is no longer a new topic in pathology.  However, it needs to become a new topic in healthcare and with patients.  So while we wait for a Healthymagination commercial let’s start to spread the word of our amazing future to anyone who will listen.

There have been some exciting developments in work to expand the number of markers that can be measured in tissue. The constraints are cost and regulatory acceptance. Multiplexing of proteins in soluble samples (e.g. serum, plasma, urine) have advanced to true high-throughput, with arrays of ELISA-related technologies. However, tissue multiplexing remains difficult.

Immunofluorescence can easily do 3-4 antibodies on a tissue, and quantum dot approaches promise more, but quantum dots are unlikely to be run in the clinic for a number of reasons. Immunofluorescence in general suffers from two disadvantages — regulatory and tissue context. There are a total of 16 IHC based FDA clearances for protein expression with digital imaging using brightfield, and none using fluorescence (FISH doesn’t count). In companion diagnostics development, pharma cannot afford the risk to be first, waiting on clearance and acceptance for a novel technology. There are enough difficulties and risk along the long road of therapeutic development, adding in an unproven regulatory path on a companion diagnostics won’t help. The other difficult with immunofluorescence is the lack of the tissue context. Despite claims to the contrary (watch for these in presentations!), there are no antibodies that will perfectly bind to tumor with no other unwanted binding effect. If you happen to have one, immediately start your own biotech company, you have the holy grail of tumor targets in your hand. Thus any approach that looks to mask tumor with an antibody will require QA by a technician and then a pathologist. We do this regularly at Flagship in our digital pathology services. In brightfield with whole slide images this pathology review of image analysis is fast and cost-effective.

There are at least three emerging technologies to keep an eye on in tissue multiplexing.

20/20 Gene Systems in Maryland have a novel approach called L-IHC (layered IHC), where they sequentially pull off an antibody onto a absorbed layer, with a DNA probe that can hybridize to a fluorochrome.

GE has an approach that was presented at Pathology Informatics where they sequentially bind a fluorochrome-labeled antigen, image, remove, and bind the next one, image, remove, all on the same slide.

And finally, at Flagship we have just launched a new technology called FACTS (Feature Analysis on Consecutive Tissue Sections), where we utilize thin histology sections with image registration techniques from radiology to multiplex from 4 to 8 markers. I suspect we will hear more about multiplexing with digital pathology at Path Visions next week. The new techniques are exciting, with the end goal being an expansion of usage of tissue-based IVDMIAs.

I was walking through the grocery store yesterday and saw the cover of Denver’s 5280 magazine, Top Docs for 2010.  I thought to myself… I wonder if there are any pathologists listed?  If there are, I’ll buy it and can find out what makes these pathologists “Top Docs.”  Sure enough, there were three pathologists! Happy to see this, I checked out with my chicken,vegetables, egg noodles (I was making homemade chicken noodle soup for dinner) and the 5280 magazine.

After my yummy dinner, I settled down to read the article.  Quickly I realized this article was not going to be what I had hoped for; it was just a list.   A list that is created by physicians who vote on each other, not who are voted on by their patients.  Sadly, I now knew why pathologists were listed.    It would be rare for patients to have interaction with their pathologist; however physicians would (I hope!) have had some interaction.  Yet this still brings me to the bigger question, what really makes a Top Doc or in our case a Top Pathologist?

In Denver, the top three pathologists are:

• Steve D. Groshong (2x winner!)- National Jewish
• Derek J. Konopka- St. Anthony Central, St. Anthony North
• John Truell (8x winner!)- Sky Ridge, Swedish

Although I am not sure why these docs won, I am curious to understand what you think makes a great pathologist?

As for the Top Doc lists, these should be created by surveying physicians and area residents; furthermore, they should have a description of what makes these “Top Docs” special and/or unique.   There wasn’t even a profile for the doctor on the cover, a diagnostic radiologist.  What made him soo special to be on the cover?  Could it be his good looks? Understanding”why” a doctor was chosen is the reason people buy this or other similar Top Doc city magazines.

If you are physician, and have taken one of these surveys for your city I would appreciate your comments and impression of the process and outcome.  Do you feel this fairly markets “Top Docs” to area residents or is just a bunch of show to sell magazines? As for me, I lost my blind faith in healthcare and doctors a long time ago; I need facts!  So unless the survey process changes and/or provides more “why” information, I will not buy this issue again.