Emerging Developments and Your Future in Pathology

1. Emerging Developments and Your Future in Pathology Jared N. Schwartz, MD, PhD, FCAP President, College of American Pathologists Presbyterian Health Charlotte, NC John Winbern Turner, MD, FCAP Johnston-Willis Hospital Richmond, VA

2. Emerging Developments and Your Future in Pathology • What is happening in healthcare? • How will that affect your career as a pathologist? • What are the emerging technologies? • What can you do to better prepare yourself? • What is the College doing to help you along the way?

3. Prediction is difficult, especially about the future Niels Bohr, 1885-1962

4. Traditional trial-and-error method of care is no longer acceptable Weight & age may affect drug selection & dosage or other intervention Doctor makes a “most likely” diagnosis, may order tests to confirm, and prescribes a treatment plan (usually drugs and/or surgery) Patient presents with symptoms Plan works or doesn’t work, +/- side effects? Treatment plan success Doctor revises treatment plan The occasional result: sub-optimal treatment, prolonged periods of trial and error, medical noncompliance, and increased cost—factors that can increase patient morbidity and mortality

5. In spite of all the money and effort devoted to biomedical research, the outcomes are not very satisfying • Over 60% of patients diagnosed with Type II diabetes have blood sugars that exceed the recommended target level • Only 17% of patients with heart disease ever reach the national guidelines treatment goals for cholesterol management • Among patients diagnosed with depression, only half report a 50% improvement in symptoms after using antidepressant medications • 32% of patients who received a placebo also experienced a 50% improvement in symptoms!

6. Patient response rates to a major drug in selected categories of therapy Source: Physicians’ Desk Reference

7. What does the consumer want? • High quality • Reasonable cost • Delivery as fast as possible • Minimal inconvenience • Access to care with the latest technology • Reduced risk • Confidence and trust

8. …and they are being ‘educated’ by the media

9. Help! • Fast and accurate results • Understandable and useful information • Direction on therapy • Low costs--may not be as important What does the patient’s treating physician want?

10. Market demand and emerging technologies are accelerating the shift to “Precision” medicine • Provision of care for diseases which can be precisely diagnosed and subsequently treated with predictably effective rules-based therapies • Precision technologies driving the disruption of existing healthcare business models • Precise diagnosis must precede predictably effective therapy • Requires technology progress on two fronts • Understanding the cause of disease • Ability to detect those casual factors Source: Christensen/Hwang

11. Precision medicine is not new; consider the history of infectious disease therapy • Earliest categorization schemes: immorality, weakness of faith • Unsanitary conditions in the city • Exposure to affected individuals; contact with certain insects and animals • Microscopes and various staining techniques • Identification of microbes that caused disease with overlapping symptoms offering clues to the aggressiveness and spread of disease and the prognosis • Tailored antibiotic therapy based on the species of organism • Molecular subtype and resistance profile of the involved strain

12. Lister adopts antiseptic technique in surgery Koch proves Germ Theory with discovery of B. anthracis Semmelweis proposes handwashing to prevent spread of disease 1670 1720 1770 1820 1870 1920 Reed proves mosquitoes are vector for yellow fever Pasteur explores Germ Theory of Disease Leeuwenhoek observes “little animals” under microscope Ehrlich introduces the acid-fast staining technique Jenner administers smallpox vaccine Fleming discovers Penicillin It took centuries of significant events to get us to this point The cost of diagnosing and treating infectious diseases has declined 5% per year since 1940 Source: Christensen/Hwang

13. Today, Cancer is experiencing a similar shift toward precision medicine Farber develops 1st chemotherapy for leukemia Novartis launches Gleevec, the 1st molecular targeted drug, to treat myeloid leukemia 2 types: leukemia & lymphoma 1920 1930 1940 1950 1960 1970 1980 1990 2000 2010 Disease of the blood 38 types of leukemia; 51 types of lymphoma 3 types of leukemia (acute, chronic, preleukemia) and 2 types of lymphoma (indolent, aggressive) Source: Mara Aspinall, Genzyme

14. Precision medicine implies personalization and all its benefits • Diagnosis predicting risk of disease • Determining whether a treatment is working • Monitoring healthy people to detect early signs of disease • Producing safer drugs by predicting potential for adverse effects earlier • Targeting groups of people most likely to benefit from a drug, while keeping its use from those who may be harmed by it • Producing better medical products • Ready access to information • Decreasing health care costs

15. Diagnostic tests and data integration are the critical links to the success of personalized medicine

16. Industry recognizes the opportunity and are willing to work with anyone Are diagnostics the new wonder drug on Wall Street?

17. What kinds of emerging technologies will impact my future practice?

18. Practice of medicine is moving from the treatment of illness to the aggressive promotion of wellness

19. IVDs will become increasingly vital components of the health care system • High value Dx provide critical information to help physicians make clinically relevant decisions • Molecular Dx and AP are fastest growing segments • AP market is growing at 15% CAGR and moving towards automation and digitalization • Continued growth of Pap is likely to slow down when MDx assays start gaining acceptance • Other high growth segments • ICH, ISH and special stains • Digital pathology • Tissue microarrays Source: Scientia

20. Signs & Symptoms In vivo Imaging Techniques In vitro Laboratory Tests Molecular diagnostics is at the core of the personalized medicine vision Diseases will be diagnosed long before the patient begins to manifest any evidence using traditional tools Molecular Diagnostics …and biomarkers will be a primary tool

21. Compression of the biomarker development timeline is accelerating progress 1977: FDA approves PSA for patients already diagnosed 2002-04: Period and retrospective analyses on survival 2007: “220 therapeutics emerging”; 100 in Phase II; 20 on market Preclinical exploratory Clinical assay & validation Retrospective longitudinal Prospective screening Cancer control 1996-7: 4 new chemical entity therapeutics approved for prostate cancer 1994: PSA approved as predictive indicator PSA Biomarker development: 30 years Source: Bartsch, et al, IBM (Imaging) Biomarker Summit III, Jan 2007

22. Technology Overview Potentially powerful predictors of progression-free survival Assays count rare events – epithelial tumor cells in the peripheral bloodstream and compare to established frequency profiles May predict treatment response more quickly than usual clinical practice with radiologic imaging (2-3 days vs 2-3 months), allowing rapid therapy modification FDA-approved for patients with metastatic breast cancer; tool for predicting progression-free and overall survival, monitoring disease progression Ongoing research evaluating efficacy for other tumor types Circulating Tumor CellsWhat is the impact of CTC assays on pathology? Technology Curve: CTC Assay 3 Consensus Adopters 4 Cautious Adopters 5 Late Adopters 2 Early Adopters 0 Pre-Clinical 1 Innovators Probability of Adoption into Clinical Use Other Metastatic Breast Cancer • Expected rate of adoption: Slow • Barriers: Only clinical evidence is in therapy monitoring for metastatic breast cancer • Accelerators: FDA approval of additional applications/tumor types

23. Impact may be dramatic…or not CTC Assays for Therapy Monitoring OP Test Volumes, US Market * Potential Impact by Indication Tests (Thousands) 35 30 25 20 15 10 5 0 2006 2008 2010 2012 2014 2016 • Current utilization almost exclusively limited to research • As clinical benefits are established, utilization will grow significantly * Source: Sg2 Analysis, 2007

24. Technology Overview VC uses CT technology as an alternative to optical screening colonoscopy VC digitally reconstructs the CT image into 2D and 3D pictures of colonic luminal surfaces (achievable, manipulatable, post procedure review) Early studies indicate VC offers sensitivity and specificity similar to OC; VC does not require sedation Patients with suspicious VC exams immediately referred for an optical colonscopy, often on same day, for possible biopsy and/or polyp excision Screening Virtual Colonoscopy What is the impact of Screening VC on pathology? Technology Curve: Screening VC 3 Consensus Adopters 4 Cautious Adopters 5 Late Adopters 2 Early Adopters 0 Pre-Clinical 1 Innovators Probability of Adoption into Clinical Use • Expected rate of adoption: Moderate • Barriers: Public preference; Payment—must be driven by provider • Accelerators: Publicity for screening, public preference

25. Q1 ‘04 Q2 ‘04 Q3 ‘04 Q4 ’04 Q1 ‘05 Destructive or positive impact? Growth in Virtual and Optical Colonoscopy, US Market * Total Colonoscopies (Virtual & Optical) University of Wisconsin * # of Procedures # of Procedures (Millions) 3000 2500 2000 1500 1000 500 0 9 8 7 6 5 4 3 2 1 0 Optical Colonoscopy (Screening) Virtual Optical -9% Optical Colonoscopy (Therapeutic) +59% >200% Virtual Colonoscopy (Screening) 2006 2008 2010 2012 2016 2014 • VC will increase colorectal cancer screening and therapeutic volumes • Pathology volumes for colon biopsy will mirror therapeutic colonoscopy volumes * Source: Sg2 Analysis, 2007

26. What is virtual microscopy? Mid-1700s: Cuff-style microscope; 1st to provide ease of use and accurate focusing mechanisms 1595: 1st Compound Microscope 1998: State of the art contains accessories for DIC, fluorescence, polarized light, phase contrast, and photomicrography 1680s: English Tripod Microscope 1899: Ernst Leitz Compound Binocular Microscope It has taken us 500 years to get to this point… It can’t just be about making pretty pictures!

27. Digitalization offers both advantages and challenges

28. 40-sec 20x scan 20-sec 20x scan 20-second 40x multi-angle scan Imaging Multispectral imaging Rapid secondary consultations Subspecialist work flow triage Applications Computer-aided detection Computer-aided diagnosis 100 Terabytes Petabytes 100 Petabytes Enterprise image management Storage Pathology PACS 2017 2007 2012 It’s just a matter of time * Source: Sg2 T3 Virtual Slide Imaging

29. Imaging Gene Expression Pharmacogenomics Biomarkers Traditional Pathology Pathologist Prognosis & Treatment The value of traditional pathology has not diminished. It simply will no longer be sufficient. Predisposition, Signs, Symptoms

30. Each pathologist and organization has a place on the Technology Adoption Curve Consensus Adopters Consensus Adopters — — Primary target for education Primary target for education and accreditation products and accreditation products Early Adopters Early Adopters — — target target Cautious Adopters Cautious Adopters — — Target Target for leadership and for leadership and for technology education for technology education resource committees resource committees Where is the specialty of pathology? Late Adopters Late Adopters — — Members at the Members at the Innovators Innovators — — target target sunset of their careers sunset of their careers for foundation grants for foundation grants 1 1 2 2 3 3 4 4 5 5

31. What does this mean for you?

32. We’re interested in your thoughts… • In 5 years, what will be your primary role as a clinician? How about 10 years? • What technology would you like for your program to teach but it doesn’t? Why? • What current technologies in pathology could be absorbed by other specialties and what technologies could pathology absorb? • How does the concept of personalized medicine affect pathology?

33. We’re interested in your thoughts… • How can the testing and certification programs in pathology training be re-oriented to the changing field of medicine? • What is the real difference between clinical and anatomic pathology anyway? • If your first job out of training required you to read a PET scan, could you / would you be willing to do it and how would you go about learning how? • How do other specialists view pathologists, and does that perception need improvement?

34. But I am just a resident… …words from the newly experienced

35. But I’m just a resident… Do you feel powerless as a trainee, or are you using your status as a crutch to avoid challenging the status quo?

36. How to prepare yourself for the future now… • In training • How you choose a job or fellowship • In early practice But I am just a resident…

37. During training • Take advantage of pioneers in your facility • Get exposure out of your training program • Insert yourself into the flow of patient care (e.g. projects, sign out)

38. Leaving training • Choose a job that will allow you to pursue your learning and practice goals • Ask about opportunities to be involved in new technologies and new activities • Find out what innovations have recently been implemented • Ask about decision-making processes • Get involved PATHOLOGISTS WANTED

39. In early practice • Re-learn skills of systems-based knowledge and challenge peers • “Keep your head up” for additional challenges/ opportunities

40. Will you experience frustration as you launch into your new career?

41. Yes…but CAP is implementing strategies to ensure you have the tools, education and advocacy necessary for a successful, relevant career in pathology

42. Vision of Pathologists Pathologists are physicians who take an active role in patient care, utilizing all available tools to integrate and interpret diagnostic information to provide an accurate diagnosis of disease. Pathologists work closely with other members of the medical team to assess the patient condition and prognosis in order to determine optimum therapy alternatives.

43. Pathology will assume a critical role in health care delivery Special Edition • Have a unique knowledge of disease processes • Are knowledge integrators • Can get access to all the diagnostic data necessary • Are responsible for the testing that is driving therapy Pathologists

44. Mission The CAP, the leading organization of board-certified pathologists, serves patients, pathologists, and the public by fostering and advocating excellence in the practice of pathology and laboratory medicine. Vision The CAP is the primary driver in the transformation of the specialty of pathology and pathologists. As the transformation agent, CAP will greatly strengthen and evolve its position into: The leading organization guiding pathologists The leader in promoting quality patient care The primary resource for information and education The most influential advocate for pathologists CAP is ready to pursue a transformational role for the specialty and pathologists

45. While maintaining a solid foundation, the CAP is pursuing change • Broad initiatives: The Four “Big Things” • Laboratory Quality & Improvement for the 21st Century (LQI-21) Ad Hoc Committee • Technology Assessment Committee • Personalized Medicine Committee • Diagnostic Database Initiative

46. Strategic Planning identified 4 initiatives that would contribute most significantly to the transformation of the specialty • Institute • Laboratory Quality & Patient Safety Center • Personalized Healthcare • EBIDA

47. Programs to support MOC, MOL and hospital privileging Certificate programs in emerging technologies, organ systems, etc. Practice management tools Research studies and publications Virtual and on-site practicums with an “Institute-approved” curriculum Education programs targeting system-based practice Re-training programs for qualified individuals interested in re-establishing active practice status Guidelines for “best practice” residency programs Program Director tools to assess resident medical knowledge and ability to apply this knowledge Comprehensive branding CAP Institute will deliver multifaceted leading-edge programs that provide you what they WANT today and what you will NEED in the future

48. CAP Laboratory Quality & Patient Safety Center Clearly define and develop programs that ensure quality in Dx medicine, its linkage with patient outcomes, and the role of the pathologist in improving quality and contributing to patient care Personalized Healthcare Develop and implement a comprehensive College-wide plan to maximize influence on the ongoing development of public policies designed to support current needs and the transformation of the specialty including a focus on personalized health care Education combined with the standards, best practice and policy to support pathology

49. And a solid foundation to ensure we can do everything we want to accomplish EBIDA from ongoing operations To ensure that the CAP has the resources to support the other three Big Things in addition to our normal operations, the College intends to maintain a positive cumulative EBIDA from ongoing operations for every three-year rolling period.

50. ‘Big Thing’ plan development and implementation has already begun • Establish member/staff planning team(s) • Identify strategies that help define the Big Things • Determine current operations that already fit; determine things that don’t fit • Develop high-level Institute plan for Board review in May • Launch Institute at CAP ’08 • Initiate Center plans • Ensure integration of ‘Big Things’