Resident Education in Molecular and Genomic Pathology Jeffrey E. Saffitz, MD, PhD Mallinckrodt Professor of Pathology Harvard Medical School Chair, Department of Pathology Beth Israel Deaconess Medical Center (no disclosures)

Genomic Pathology will be a Disruptive Innovation Genomic Pathology - a concept founded on the premise that sequencing the human genome will become so routine and inexpensive that it will inevitably find its way into fundamental aspects of health care – not only in disease diagnosis and management, but also disease prevention, risk mitigation and health maintenance. The disruptive innovation that will make this possible is next generation sequencing (NGS) and other high-throughput technologies to define in exquisite detail an individual human being’s genome, transcriptome, proteome, metabolome, lipidome and microbiome.

Medical Genomics: Drivers and Potential for Disruptive Change Time PeriodGenomesTurn-around time FTEsCost per genome NIH reference 2.Celera reference ~5 years~2,000~$2-3 billion ~10 additional~6 monthsDozens$300,000→38, weeks3-4$ 6,000 exome $ 9,500 genome Days2$5,000→$1, MillionsHours?<1<$1,000

Slide courtesy of Eric Green, NHGRI

Source: National Human Genome Research Institute.

NEJM, 376:2538; Dec 2012

Banbury Center, Cold Spring Harbor Laboratory Oct 13-15, 2010 Meeting on Genome-Era Pathology

27 Stakeholders - Government NIH, Air Force Surgeon General’s Office - Academy - Industry/Advocacy Groups Illumina, Affymetrix, Personalized Medicine Coalition, Aetna, Medco - National pathology organizations College of American Pathologists (CAP) Association for Molecular Pathology (AMP) American Society of Clinical Pathologists (ASCP) US/Canadian Academy of Pathology (USCAP)

How do we re-engineer Next Generation Sequencing Technologies and Whole Genome Analysis to move from the research setting to the clinical setting?

Genomic Pathology – The “Value Proposition” We will have less money for patient care but will be held to higher standards of care. High-throughput technologies in pathology must replace much of what we do in tissue diagnostics and laboratory medicine. Advantage: we will determine who will benefit from very expensive but potentially very effective targeted therapies. The real “value proposition” in genomic pathology will come from preventing disease. Advantage: we will adopt a new, proactive role in health maintenance and risk mitigation.

Banbury Recommendation: Define the scope of NGS clinical testing Compile and analyze the full range of current testing offered by pathologists in tissue diagnostics and laboratory medicine, and determine which tests might be replaced by NGS or other high-throughput technologies.

Whole Genome Analysis as a Universal Diagnostic Medical Microbiology Molecular mechanisms of disease Pharmacogenomics Medical genetics, preventive medicine Natural history of disease, response to therapy Surgical pathology Kahvejian A., Quackenbush J., Thompson J.F. What would you do if you could sequence everything? Nat Biotechnol. 26(10): , 2008

More Evidence-Based Medicine (more targeted therapies, more lab testing) Source: ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

Banbury Recommendation: We Must Embrace the Concept of “Primary Care Pathology” in Genome-Era Medicine The number of healthy individuals undergoing genome analysis will increase dramatically in the next several years. A substantial opportunity exists in analysing this information and advising primary care physicians in risk management and health preservation strategies. Pathologists have an opportunity to participate in this activity and partner with other health care professionals, such as genetic counsellors, to develop direct patient interactions as part of the new practice of primary care pathology.

How do we fulfill the promise of personalized medicine and ensure that the discipline of pathology is at the forefront?

Number 1 Banbury Recommendation: Pathologist training for the future Banbury led to the establishment of a nationwide pilot program and a national working group (TRIG – Training Residents in Genomics) to ensure that every ACGME-approved residency in pathology in North America includes a mandatory curriculum in genomics and personalized medicine.

Professional Education and Training TRIG: Training Residents in Genomics

Training Residents in Genomics (TRIG) Working Group

NCI R25: Specific Aims 1)To develop a pathology resident genomic medicine curriculum, with a major focus on cancer care, as well as tools for national implementation. – The TRIG Working Group will collaborate with the ASCP Continuing Professional Development (CPD) team. – Both instructional guides and online education modules will be developed. 2)To evaluate the curriculum using a pre/post-test design at four pathology residency programs using validated assessment tools. – Assessment tools will be created to evaluate knowledge, communication skills and attitudes related to genomics. – The residency directors at the four sites are Dr. Richard Haspel, Dr. Karen Kaul, Dr. Debra Leonard and Dr. Henry Rinder. All are TRIG Working Group members and are key personnel on the grant.

NCI R25: Specific Aims 3)To promote curriculum implementation using the resources of major national pathology organizations so that >90% of pathology residency programs nationwide have high- quality training in cancer genomics by the end of year 5. – Build on the current success of the TRIG Working Group in promoting genomics education through major pathology organizations. 4)To assess the degree of nationwide implementation and efficacy of curricula in genomic medicine using the pathology resident in-service exam (RISE). – This aspect of the grant will build on the current success of the TRIG Working Group in developing exam and survey questions for the RISE. Awarded $1.3 million over next 5 years

Lectures and instructional guide completed, made available Year 2Year 3 Year 1 Online modules completed, deployed Year 4Year 5 Online modules tested at five residency programs Assessment tool completed Questions on RISE Cancer genomics training in >90% of US pathology residency programs, assessed by RISE Dissemination at conferences, Year 3: Begin “Train-the-Trainer” sessions Funding: A new TRIG timeline