Resident Education in Molecular and Genomic Pathology

Jeffrey E. Saffitz, MD, PhDMallinckrodt Professor of Pathology

Harvard Medical SchoolChair, Department of Pathology

Beth Israel Deaconess Medical Center(no disclosures)

Genomic Pathology will be aDisruptive 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 Period Genomes Turn-around time

FTEs Cost per genome

1998-2003 1. NIH reference2. Celera reference

~5 years ~2,000 ~$2-3 billion

2003-2009 ~10 additional ~6 months Dozens $300,000→38,000

2010-2011 103-104 4-6 weeks 3-4 $ 6,000 exome$ 9,500 genome

2012-2014 105 Days 2 $5,000→$1,000

2015-2020 Millions Hours? <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

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

Genome-Era Pathology

27 Stakeholders

- GovernmentNIH, 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

MedicalMicrobiology

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):1125-33, 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 CarePathology” 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

www.GenomicMedicineInitiative.org

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 Aims3) 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 2 Year 3Year 1

Online modules completed, deployed

Year 4 Year 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