the new world of laboratory medicine: it s not just your father s microscope anymore

1. The New World of Laboratory Medicine: It�s Not Just Your Father�s Microscope Anymore Richard C Friedberg, MD, PhD Chairman, Department of Pathology Baystate Health Springfield, MA

3. Outline The Box ? Evolution of Today�s Diagnostic Environment Drivers of Change Likely Evolution Positioning Yourself

4. What is �The Box� ? Outside Do they care about AP/CP distinction? What do they want from us � �Demands� And know they want? And don�t know they want? Non-Path Nuclear, imaging, in vivo imaging Outside Do they care about AP/CP distinction? What do they want from us � �Demands� And know they want? And don�t know they want? Non-Path Nuclear, imaging, in vivo imaging

5. Evolution of Today�s Diagnostic Environment Long Term Trends

6. Trend #1: Discrete to Multiplex Clinical pathology has long been quantitative, integrating information from different parts of the laboratory. The key driver of efficiency in clinical pathology has been automation and integration. 1980�s Discrete, independent Instruments - 1 technique/box 90�s Platforms combining multiple techniques into a single box Images � few, some digital (eg, UA) There are other long-term trends to look at Clinical pathology has long been quantitative, integrating information from different parts of the laboratory. The key driver of efficiency in clinical pathology has been automation and integration. 1980�s Discrete, independent Instruments - 1 technique/box 90�s Platforms combining multiple techniques into a single box Images � few, some digital (eg, UA) There are other long-term trends to look at

7. Trend #2: Structural to Functional What about the evolution in anatomic pathology? Anatomic pathology started off looking at structure. H&E is pretty structural. Electron microscopy (EM) adds a bit more information, but it is still microstructure. With immunohistochemistry (IHC), we start to get functional information, especially with antibodies targeting functional proteins. Later, the advent of various forms of in situ hybridization (FISH, CISH, SISH, xISH) allowed targeting of known nucleic acids sequences added even more information about function. The evolutionary pattern is clearly from structural to functional. What about the evolution in anatomic pathology? Anatomic pathology started off looking at structure. H&E is pretty structural. Electron microscopy (EM) adds a bit more information, but it is still microstructure. With immunohistochemistry (IHC), we start to get functional information, especially with antibodies targeting functional proteins. Later, the advent of various forms of in situ hybridization (FISH, CISH, SISH, xISH) allowed targeting of known nucleic acids sequences added even more information about function. The evolutionary pattern is clearly from structural to functional.

8. Trend #3: Qualitative to Quantitative Concurrently, there has been an evolution from qualitative to quantitative. Earlier, we mentioned ELISA, and here IHC. The fascinating thing about IHC and ELISA is that they are fundamentally the same technology. In both situations, a specific antibody is used to identify a specific marker, unbound antibody is washed, and an agent is used to visualize the bound antibody. Finally, the signal is measured to assess how many antibodies found their target on the specimen in question. Essentially, the same technology in clinical pathology was quantitative, but in anatomic pathology was qualitative. The signal for IHC uses a stain, and is then assessed for intensity (whether it�s dark, or really dark, or not too dark), usually estimated on a 0+ to 4+ scale. And what�s happened recently? We realized that we aren't that good at estimating intensity but must use digital imaging tools to quantitate the staining. In essence, �stains� are becoming �assays�. Concurrently, there has been an evolution from qualitative to quantitative. Earlier, we mentioned ELISA, and here IHC. The fascinating thing about IHC and ELISA is that they are fundamentally the same technology. In both situations, a specific antibody is used to identify a specific marker, unbound antibody is washed, and an agent is used to visualize the bound antibody. Finally, the signal is measured to assess how many antibodies found their target on the specimen in question. Essentially, the same technology in clinical pathology was quantitative, but in anatomic pathology was qualitative. The signal for IHC uses a stain, and is then assessed for intensity (whether it�s dark, or really dark, or not too dark), usually estimated on a 0+ to 4+ scale. And what�s happened recently? We realized that we aren't that good at estimating intensity but must use digital imaging tools to quantitate the staining. In essence, �stains� are becoming �assays�.

9. Trend #4: Analog to Digital More recently, anatomic pathology has begun the early stages of evolving from analog to digital. The transition from qualitative IHC staining of images to quantitative assessment of IHC staining is evidence of this transition. Biomarker development pushing AP towards a quantitative discipline Digital Imaging Revolution ? Is the Digital Imaging revolution (tremendous impact upon Radiology) spilling over to AP? More recently, anatomic pathology has begun the early stages of evolving from analog to digital. The transition from qualitative IHC staining of images to quantitative assessment of IHC staining is evidence of this transition. Biomarker development pushing AP towards a quantitative discipline Digital Imaging Revolution ? Is the Digital Imaging revolution (tremendous impact upon Radiology) spilling over to AP?

10. Anatomic Pathology Evolution It�s important to think about what�s internally driven and what�s externally driven. When it was just us looking at the tissue in the slides, we were happy to look at just the structure. Function became important, then quantitation became important, and now digital is becoming important � increasingly pushed by outside demands. Of course, everything has been happening at the same time. It�s important to think about what�s internally driven and what�s externally driven. When it was just us looking at the tissue in the slides, we were happy to look at just the structure. Function became important, then quantitation became important, and now digital is becoming important � increasingly pushed by outside demands. Of course, everything has been happening at the same time.

11. Imaging Evolution How does this evolution and these trends compare to what happened to imaging? Radiology used to have just X-rays, then later fluoroscopy, then CT, then MR, then PET scanners. They made the same structural to functional shift that anatomic pathology underwent. They now have a powerful marriage of anatomical and functional imaging. They went from qualitative to quantitative � X-ray films to X-ray images on a computer monitor. They went from analog to digital. They went from internally driven to externally driven. Technology development is pushing Radiology to quantitation. In many ways, the evolution of imaging has been very similar to much of pathology. How does this evolution and these trends compare to what happened to imaging? Radiology used to have just X-rays, then later fluoroscopy, then CT, then MR, then PET scanners. They made the same structural to functional shift that anatomic pathology underwent. They now have a powerful marriage of anatomical and functional imaging. They went from qualitative to quantitative � X-ray films to X-ray images on a computer monitor. They went from analog to digital. They went from internally driven to externally driven. Technology development is pushing Radiology to quantitation. In many ways, the evolution of imaging has been very similar to much of pathology.

12. Trend #5: AP Evolution Mimics CP Greater concern with analytical precision, reproducibility, accuracy, specificity, reliability �� the demand for quantification has become paramount; it is no longer enough that the �stain� is there; rather it is a question of �How much is there?� � [Taylor & Levenson , Histopath 49:411-24, 2006] Results directly tied to treatment Not just prognosis Diminishing reliance upon a �guild mentality� with �anointed experts� �Evidence-based� or �Eminence-based�??? �CP-minded� pathologists comfortable with screening tests for finding subclinical disease �AP-minded� pathologists more comfortable with recognizing established disease Timeline? Already happened Examples IHC and ELISA Her2/neu and Herceptin The net result is that we are relying less upon a �guild mentality� with �anointed experts�. One way to think about this is that we are shifting to �evidence-based� practice in pathology whereas we have been �eminence-based�. We used to define our define authorities based on perceived prestige, authorship, or academic heritage. That�s really the archaic guild concept of authority.�CP-minded� pathologists comfortable with screening tests for finding subclinical disease �AP-minded� pathologists more comfortable with recognizing established disease Timeline? Already happened Examples IHC and ELISA Her2/neu and Herceptin The net result is that we are relying less upon a �guild mentality� with �anointed experts�. One way to think about this is that we are shifting to �evidence-based� practice in pathology whereas we have been �eminence-based�. We used to define our define authorities based on perceived prestige, authorship, or academic heritage. That�s really the archaic guild concept of authority.

13. Trend #6: AP Evolution Mimics Radiology Analog images establish the field Market and technology forces drive digital imaging Scanning of analog images yields to digital acquisition Digitalization allows new applications Significant workload and throughput implications Digitalization of Pathology (next 15 years) compared to Radiology (last 15 yrs) Path images have greater complexity (color, depth, texture) 3D with multiple focal planes vs 2D with single focal plane 20GB per focal plane per slide x multiple planes per slide x 1-30 slides per case Image acquisition time 4-5 min per focal plane per slide vs seconds Image quality often depends upon preanalytical variables, day to day controls Timeline - What may affect the speed of acceptance of digital path Digital image acquisition (still optical) Need to fix/process/embed/cut tissue and create slides prior to image acquisition Technology to increase speed of multiparameter data acquisition, such as 3D images, multislice scanning, spectral imaging, windowing, coincidence imaging as well as multiparameter data display (dynamic images, coincidence, windowing, PACS) Functional telediagnostics vs teleconsultation Digitalization of Pathology (next 15 years) compared to Radiology (last 15 yrs) Path images have greater complexity (color, depth, texture) 3D with multiple focal planes vs 2D with single focal plane 20GB per focal plane per slide x multiple planes per slide x 1-30 slides per case Image acquisition time 4-5 min per focal plane per slide vs seconds Image quality often depends upon preanalytical variables, day to day controls Timeline - What may affect the speed of acceptance of digital path Digital image acquisition (still optical) Need to fix/process/embed/cut tissue and create slides prior to image acquisition Technology to increase speed of multiparameter data acquisition, such as 3D images, multislice scanning, spectral imaging, windowing, coincidence imaging as well as multiparameter data display (dynamic images, coincidence, windowing, PACS) Functional telediagnostics vs teleconsultation

14. Overall Evolution of Diagnostics Diagnostics clearly evolving with data integration Increasing dependence upon integrated structural, functional, molecular, genetic, proteomic, and genomic information, regardless of the �historical� source Traditionally qualitative �pattern recognition� fields and technology Increasing focus up on precision, accuracy, reliability, and measurability � becoming more quantitative Once information is digital, integration shifts into high gear Once information has shifted into digital, integration shifts into high gear very quickly. And it doesn�t matter where it comes from. When radiology became digital, suddenly they could put all the things together and improve their workflow, and the field took off. Once information has shifted into digital, integration shifts into high gear very quickly. And it doesn�t matter where it comes from. When radiology became digital, suddenly they could put all the things together and improve their workflow, and the field took off.

16. With increasing additions to the diagnostic armamentarium, traditional pathology is proportionately less and less of the diagnostic processWith increasing additions to the diagnostic armamentarium, traditional pathology is proportionately less and less of the diagnostic process

17. Drivers of Change

18. Drivers in Diagnostic Medicine Resources Healthcare $$$$ R&D $$ Adequately trained personnel ???? Demand Demographics Expectations Technology Evolving roles of impact players Pharmaceutical and diagnostic corporations Insurers and payers Resources can be both financial and personnel. Financial resources include the funds we are willing to pay for delivery of care as well as for the research and development of novel healthcare opportunities. As to personnel resources, the significant costs of training the workforce of the future may limit our capability to maintain a sufficient number of adequately trained personnel. But funding can only come from a few sources. Over the past 20 years or so, the insurers and companies that pay the bills have taken a leadership role in defining and implementing cost-effective care delivery. Given the widespread concern and publicity about the cost of health care today, many expect that the future dollar flow will be more restrained. Demand comes from a variety of angles. The consumer demand for better and more effective care delivery is evident in the increased expectations of quality of care, comfort, convenience, and efficiency. People are living longer as the improvements in care delivery result in increased post-diagnosis survival. Many diseases that used to be fatal in the short term have become manageable in the long term. More and more acute diseases are now chronic diseases. This extension of life is part of the reason that the number of diagnostic tests per patient increases with age. Technology is clearly a driver. Advances in imaging technology have revolutionized radiology. Molecular technology promises earlier and more precise diagnosis, and perhaps a significant convenience to the consumer if serum or other easily obtainable bodily fluids can replace the tissue biopsy or surgical specimen. Molecular diagnostics has the same promise for pathology and imaging technology did for radiology. The advances in pharmaceutical fields are also critical. And the ability of the insurers and payers to afford this advanced technology is part of the funding resources already mentioned. Consequently, with the aging of the population and the increase in chronic management health care, the workload of diagnostic medicine will steadily increase. The other side of demographics is evident in the pending difficulties we will have with pathologists and medical technologists. With an average age well into the 50�s, there is likely to be a staffing squeeze in both MDs and MTs. The net result of the demographics is that there will be fewer practicing pathologists and technologists, but more pathology to do. Resources can be both financial and personnel. Financial resources include the funds we are willing to pay for delivery of care as well as for the research and development of novel healthcare opportunities. As to personnel resources, the significant costs of training the workforce of the future may limit our capability to maintain a sufficient number of adequately trained personnel. But funding can only come from a few sources. Over the past 20 years or so, the insurers and companies that pay the bills have taken a leadership role in defining and implementing cost-effective care delivery. Given the widespread concern and publicity about the cost of health care today, many expect that the future dollar flow will be more restrained. Demand comes from a variety of angles. The consumer demand for better and more effective care delivery is evident in the increased expectations of quality of care, comfort, convenience, and efficiency. People are living longer as the improvements in care delivery result in increased post-diagnosis survival. Many diseases that used to be fatal in the short term have become manageable in the long term. More and more acute diseases are now chronic diseases. This extension of life is part of the reason that the number of diagnostic tests per patient increases with age. Technology is clearly a driver. Advances in imaging technology have revolutionized radiology. Molecular technology promises earlier and more precise diagnosis, and perhaps a significant convenience to the consumer if serum or other easily obtainable bodily fluids can replace the tissue biopsy or surgical specimen. Molecular diagnostics has the same promise for pathology and imaging technology did for radiology. The advances in pharmaceutical fields are also critical. And the ability of the insurers and payers to afford this advanced technology is part of the funding resources already mentioned. Consequently, with the aging of the population and the increase in chronic management health care, the workload of diagnostic medicine will steadily increase. The other side of demographics is evident in the pending difficulties we will have with pathologists and medical technologists. With an average age well into the 50�s, there is likely to be a staffing squeeze in both MDs and MTs. The net result of the demographics is that there will be fewer practicing pathologists and technologists, but more pathology to do.

19. What Do Patients Want? All possible helpful information Available as soon as technically possible To make the best informed decision possible In order to reduce as much as possible the risk of� Besides comfort & convenienceBesides comfort & convenience

20. Shotgun/Reactive Patient Management The impact of these drivers is evident in many areas of healthcare. Even patient management is changing. The older model was, �Well, I�m not feeling quite right, I don�t at all feel so good, so I�ll go visit a doctor.� And the doctor would employ a broad system-based diagnostic approach, order a few lab tests or imaging studies, and see what general treatment the results implied. Costs for the drugs may be a concern, but the approach was to try one, then another. If a new drug were available, that often jumped to the top of the list. With this model, the patient could expect to recover, revisit, forget the problem, or ignore the problem. This was a shotgun, reactive approach. The impact of these drivers is evident in many areas of healthcare. Even patient management is changing. The older model was, �Well, I�m not feeling quite right, I don�t at all feel so good, so I�ll go visit a doctor.� And the doctor would employ a broad system-based diagnostic approach, order a few lab tests or imaging studies, and see what general treatment the results implied. Costs for the drugs may be a concern, but the approach was to try one, then another. If a new drug were available, that often jumped to the top of the list. With this model, the patient could expect to recover, revisit, forget the problem, or ignore the problem. This was a shotgun, reactive approach.

21. Targeted/Proactive Patient Management More recent demand had pushed for a more targeted, proactive approach using focused screening, monitoring and prevention, and targeted diagnostics. Curiously, it doesn�t matter where the diagnostic sits - anatomic pathology, molecular diagnostics, clinical pathology, radiology - they�re all just diagnostic tools. The result is a more efficient, personalized treatment. This is the money is going: more focused treatments, earlier treatments, right treatments. You can forget the older style trial-by-error type treatments. More recent demand had pushed for a more targeted, proactive approach using focused screening, monitoring and prevention, and targeted diagnostics. Curiously, it doesn�t matter where the diagnostic sits - anatomic pathology, molecular diagnostics, clinical pathology, radiology - they�re all just diagnostic tools. The result is a more efficient, personalized treatment. This is the money is going: more focused treatments, earlier treatments, right treatments. You can forget the older style trial-by-error type treatments.

25. Integrated Diagnostics Earlier diagnosis and earlier cure by advancing the optimal point of medical intervention earlier in the natural course of a disease

26. Likely Evolution Where Are We Going?

27. What is Changing Today ?? Identification and measurement of markers of interest has progressed exponentially over the past decades Clinical expectations, technology, and novel biomarkers are pushing all of diagnostics into a quantitative and digital era What is different now is the capability to Combine data at hand with massive historical databases to create information Simultaneously assess multiple markers as data elements Integrate information across technological domains into useful knowledge

28. Diagnosis Tomorrow Dependent up the ability to integrate disparate bits of information Utilize mathematical algorithms optimized to meta-interpret data Diagnostic report is more than just a label Moving beyond labeling things with a diagnosis The identification and measurement of markers of interest has progressed significantly over the past century. Clinical expectations, technology, and novel biomarkers are pushing traditional anatomic pathology into a quantitative and digital era. The future of diagnosis is not just going to be the anatomic component, nor just the clinical, nor just the molecular. It�s going to be the answer to �What�s the diagnosis?� using get all the available information from all the tools that you can. And you�re going to end up relying heavily on operationalizing mathematical algorithms. Mathematical algorithms are going to be used to help you make the diagnosis, and to meta-interpret data. You will take a little bit of this data and a little bit of that and create a larger diagnostic picture out of it. Pathology is evolving beyond labeling things with a diagnosis The identification and measurement of markers of interest has progressed significantly over the past century. Clinical expectations, technology, and novel biomarkers are pushing traditional anatomic pathology into a quantitative and digital era. The future of diagnosis is not just going to be the anatomic component, nor just the clinical, nor just the molecular. It�s going to be the answer to �What�s the diagnosis?� using get all the available information from all the tools that you can. And you�re going to end up relying heavily on operationalizing mathematical algorithms. Mathematical algorithms are going to be used to help you make the diagnosis, and to meta-interpret data. You will take a little bit of this data and a little bit of that and create a larger diagnostic picture out of it. Pathology is evolving beyond labeling things with a diagnosis

29. Useful Patterns in Data What happens when we take multiple bits of information and aggregate? Data Information Knowledge It becomes useful! Doesn�t matter where the bits come from Anatomic Pathology Clinical Pathology Radiology Molecular Key tools � microarrays & bioinformatics Makes use of vase wealth of data to describe gene & protein functions and interactions Must be applied to the correct population of normal and abnormal cells (people too); microdissection, MD determination of target; membrane vs cytoplasm, vs nuclear vs stroma SNP, GWAS, mutation and polymorphism analysis Has led to deeper understanding Molecular histopathology � molecular data in the context of morphology Molecular and genomic detection tools - ISHs, IHCs, PCRs FISH vs CISH vs SISH Problems with ISHs � inattention to endogenous controls Specialized microscope availability, permanence, visible light architecture Wish list for future in situ methods (next gen ISH) IT Data Mining When we interpret information, what we are doing is looking for patterns that we know are associated with particular outcomes. Consider what has happened in the world of hematologic oncology where the diagnostic process has been essentially rewritten in the past 10-15 years. It�s highly dependent upon all molecular data now. If you were trained in hematopathology in the late 1980�s and didn�t stay up-to-date, you would need a long refresher course to practice now. Key tools � microarrays & bioinformatics Makes use of vase wealth of data to describe gene & protein functions and interactions Must be applied to the correct population of normal and abnormal cells (people too); microdissection, MD determination of target; membrane vs cytoplasm, vs nuclear vs stroma SNP, GWAS, mutation and polymorphism analysis Has led to deeper understanding Molecular histopathology � molecular data in the context of morphology Molecular and genomic detection tools - ISHs, IHCs, PCRs FISH vs CISH vs SISH Problems with ISHs � inattention to endogenous controls Specialized microscope availability, permanence, visible light architecture Wish list for future in situ methods (next gen ISH) IT Data Mining When we interpret information, what we are doing is looking for patterns that we know are associated with particular outcomes. Consider what has happened in the world of hematologic oncology where the diagnostic process has been essentially rewritten in the past 10-15 years. It�s highly dependent upon all molecular data now. If you were trained in hematopathology in the late 1980�s and didn�t stay up-to-date, you would need a long refresher course to practice now.

30. So, Where Are We Headed? Diagnostic information Subject to validation, accuracy, reproducibility, precision, QI/QA/QC Aggregated and analyzed using disparate tools Image-based computer-assisted analytic tools to �assay� specimens Intelligently designed PACS will revolutionize pathology workflow Net result Improved efficiency Novel opportunities Increased reliance upon pathology

31. Imagining the Future of Diagnostics If you want to think what the future is going to be like with digital pathology, just think of everything that you could you do better, faster, deeper if you had� The future of diagnosis is not just going to be the anatomic component, nor just the clinical, nor just the molecular. It�s going to be the answer to �What�s the diagnosis?� using get all the available information from all the tools that you can. And you�re going to end up relying heavily on operationalizing mathematical algorithms. Mathematical algorithms are going to be used to help you make the diagnosis, and to meta-interpret data. You will take a little bit of this data and a little bit of that and create a larger diagnostic picture out of it. If you want to think what the future is going to be like with digital pathology, just think of everything that you could you do better, faster, deeper if you had� The future of diagnosis is not just going to be the anatomic component, nor just the clinical, nor just the molecular. It�s going to be the answer to �What�s the diagnosis?� using get all the available information from all the tools that you can. And you�re going to end up relying heavily on operationalizing mathematical algorithms. Mathematical algorithms are going to be used to help you make the diagnosis, and to meta-interpret data. You will take a little bit of this data and a little bit of that and create a larger diagnostic picture out of it.

32. Hold On! � Wait A Minute! Where are algorithms taking us? �Digital Imaging?� Diagnosis by computer? Can this be accomplished better/faster/cheaper� Without a microscope? Without a laboratory? Without a specimen? Without a technologist? Without a pathologist? Without me?

33. Diagnostic Workstation

34. Positioning Yourself Implications and Opportunities

35. Diagnostic Intelligence �the accumulation, management, and use of patient information, clinical observations, diagnostic test results, and reference material to make diagnostic decisions, prognostic judgments, and therapeutic recommendations

36. Implications � What Does This Mean? What should I/we do? How should you be positioned to meet the demand?

37. Patterns of History are Clear Qualitative evolves to quantitative Analog evolves to digital Distinct evolves to integrated Data becomes aggregated into information Information with context becomes knowledge

38. Who Will Make Diagnoses? Those with knowledge and tools will make the diagnoses There will be a transition, we just don�t know how long it will take You have made a career of recognizing patterns How do you want to be involved?

39. Differentiators � Tools & Skills Take advantage of long term trends Red vs blue oceans Volume vs innovation Tyranny of the tool Diagnosticians vs Microscopists Data vs knowledge WGA, GWAS Digital imaging A recent survey of CAP membership demonstrate that there is already a tremendous level of engagement on this issue. Nearly 70% of pathologists believe that it is important that the specialty of pathology be substantively transformed in order to remain relevant and competitive in the years ahead. The survey also showed that CAP members clearly understand the importance of molecular genetic testing with 82% agreeing that it is very important to develop expertise in molecular and genetic testing to remain relevant and competitive. Already, nearly 50% are doing single gene testing, and 10% are consulting directly with patients using their genetic information. With Whole Genome Sequencing soon cost the same or less than existing gene panels today, the expectation is that in only three years, whole genome analysis will be standard of care for certain cancers. As far as adopting digital imaging, the data shows that 18% already use whole slide imaging, and an additional 25% are somewhat or very likely to adopt it in the next 3 to 5 years.A recent survey of CAP membership demonstrate that there is already a tremendous level of engagement on this issue. Nearly 70% of pathologists believe that it is important that the specialty of pathology be substantively transformed in order to remain relevant and competitive in the years ahead. The survey also showed that CAP members clearly understand the importance of molecular genetic testing with 82% agreeing that it is very important to develop expertise in molecular and genetic testing to remain relevant and competitive. Already, nearly 50% are doing single gene testing, and 10% are consulting directly with patients using their genetic information. With Whole Genome Sequencing soon cost the same or less than existing gene panels today, the expectation is that in only three years, whole genome analysis will be standard of care for certain cancers. As far as adopting digital imaging, the data shows that 18% already use whole slide imaging, and an additional 25% are somewhat or very likely to adopt it in the next 3 to 5 years.

40. Opportunities - Practice New practice models Virtual large groups ACOs Accountable Care Organizations AQCs Alternative Quality Contracts Medical Homes Focus on efficiency measurement and management Surveys show that the number of pathologists practicing in small groups (10 or less) has dropped by about 30% in the last 5 years, while the number practicing in larger groups (20-30) has quadrupled in the same period. It is clear that Pathology practices are pursuing economies of scale. We can pursue new practice models. For example, smaller practices can band together collaboratively into more competitive "virtual large practices" using a network practice model, bringing economies of scale without changing the ownership structure. Case for Change survey data shows that 76% of CAP members are completely unfamiliar with ACOs and that 83% have not yet begun to engage in any dialogue around ACOs The survey showed that 21% of members are currently performing cost efficiency measurement and management and 26% are already performing patient outcomes measurement.Surveys show that the number of pathologists practicing in small groups (10 or less) has dropped by about 30% in the last 5 years, while the number practicing in larger groups (20-30) has quadrupled in the same period. It is clear that Pathology practices are pursuing economies of scale. We can pursue new practice models. For example, smaller practices can band together collaboratively into more competitive "virtual large practices" using a network practice model, bringing economies of scale without changing the ownership structure. Case for Change survey data shows that 76% of CAP members are completely unfamiliar with ACOs and that 83% have not yet begun to engage in any dialogue around ACOs The survey showed that 21% of members are currently performing cost efficiency measurement and management and 26% are already performing patient outcomes measurement.

41. Opportunities � �On-shoring?� On-shoring ? Do I mean �Off-shoring� ? Does off-shoring work in Radiology? Often, it can Why? Will off-shoring work in Pathology? Unlikely Why? Off-shoring is when a company says �Hey, I can make this tape measure cheaper in Bermuda than in Connecticut, so I�m going to send all my things to them and have it made up there� Then, what is on-shoring? Most of the world�s pathologists are in the US; certainly the vast majority of the world�s subspecialty pathologists are in the US. If you have a digital imaging system, what is to stop you from setting up a clinic in a well-to-do foreign country, where somebody else can take biopsies, process them, and send you the image to read? Off-shoring for Radiology - Radiology was able to offshore, using radiologists in Australia, Singapore, India, and China, where they have the great advantage of being on the other side of the world. So if at two o�clock in the morning some kid comes in with a sore neck who was in a car wreck, and the ER wants to find out if there was a C-spine fracture. They need a certain specialist to read that image. If that image is collected digitally, it will show up on the other side of the world at the same time it shows up next door. In India, they are awake! They are often well-trained, typically US trained radiologists. So that�s why radiology is subject to offshore. Because once you acquire a digital image, it can go anywhere: it�s small enough. On-shoring for Pathology - We will probably do on-shoring in pathology. We�ve got the brains here, we got the specialists and subspecialists. Once we have the imaging devices to pass on our images, it�s a lot easier to accept images from the outside. Once we get that here, and you don�t need a stat read like that neck film at two o�clock in the morning, we can have it sent to us for a read. There are plenty of parts of the world where somebody has enough money who would rather pay $50 for a US read than $5 for a local read, to get the right answer. So on-shoring is going to be interesting; I think you�ll hear more about that term. That�s sort of a blue ocean there. Off-shoring is when a company says �Hey, I can make this tape measure cheaper in Bermuda than in Connecticut, so I�m going to send all my things to them and have it made up there� Then, what is on-shoring? Most of the world�s pathologists are in the US; certainly the vast majority of the world�s subspecialty pathologists are in the US. If you have a digital imaging system, what is to stop you from setting up a clinic in a well-to-do foreign country, where somebody else can take biopsies, process them, and send you the image to read? Off-shoring for Radiology - Radiology was able to offshore, using radiologists in Australia, Singapore, India, and China, where they have the great advantage of being on the other side of the world. So if at two o�clock in the morning some kid comes in with a sore neck who was in a car wreck, and the ER wants to find out if there was a C-spine fracture. They need a certain specialist to read that image. If that image is collected digitally, it will show up on the other side of the world at the same time it shows up next door. In India, they are awake! They are often well-trained, typically US trained radiologists. So that�s why radiology is subject to offshore. Because once you acquire a digital image, it can go anywhere: it�s small enough. On-shoring for Pathology - We will probably do on-shoring in pathology. We�ve got the brains here, we got the specialists and subspecialists. Once we have the imaging devices to pass on our images, it�s a lot easier to accept images from the outside. Once we get that here, and you don�t need a stat read like that neck film at two o�clock in the morning, we can have it sent to us for a read. There are plenty of parts of the world where somebody has enough money who would rather pay $50 for a US read than $5 for a local read, to get the right answer. So on-shoring is going to be interesting; I think you�ll hear more about that term. That�s sort of a blue ocean there.

42. What Choice(s) Do You Have? You have choices. Staying put is not one of the good ones.