An Integrated Genomic Pathology Curriculum: Development, Design, and Pilot Implementation

1. An Integrated Genomic Pathology Curriculum: Development, Design, and Pilot Implementation John Pfeifer, MD, PhD Tina Lockwood, PhD, DABCC

2. Historical training in molecular pathologyAP Residency • Molecular diagnostics: • 3 weeks • Cytogenetics, microarray, NGS: • 3 weeks

3. Historical training in molecular pathology CP Residency • Molecular diagnostics: • 2 weeks • Cytogenetics: • 2 weeks • HLA: • 1 week • Informatics (added 2009): • 2 weeks

4. Goals of education • Align content with contemporary practice • Train residents to critically evaluate data • Combine didactic and experiential learning • Integrate the curriculum Analytical Informatics Interpretation

5. Genomics curriculum implemented 2011-2012 AP CP • NGS

6. Current CP structure 4 weeks 2 weeks 2 weeks 1 week 1 week 1 week 1 week

7. Variable learning styles (Yale residents’ ranking of teaching modalities) RinderHM and Smith BR, Clinics in Lab Med. 2007;27:257-266

8. Modules incorporate “doing” • Fundamental premise that learning wet and dry components is crucial • Present concepts through didactics or interactive discussion • Reinforce with experiential learning • Laboratories: perform assays • Informatics: computational exercises

9. Hands-on experience is essential • Review test procedures • Observation • Hands-on experience • Extract nucleic acids • PCR • Restriction enzyme digest • Gel electrophoresis • Interpret results

10. Rotation is tailored to each trainee: MDL rotation • Perform a clinical project • Validate new reagents • Quality improvement • Design and validation of a new assay • Sign out participation • Preview results • Generate a preliminary report Fragile X testing

11. Assessment varies for each rotation • Service-based rotations assess whether trainees can interpret patient results • Non-service rotations assign readings with trainee-led discussion

12. Revise rotations based on evaluations

13. Week 1: Informatics & NGS • Shadow lab • technologists • Consensus • sign out • Formal instruction • Computational training • Pre-analytic • Public databases • Technologies • Integrative Genomics Viewer/IGV • Informatics pipeline • Clinical GenomicistWorkstation • Clinical sequence analysis tools • Regulatory

14. Week 2: Interpreting clinical NGS

15. Practicum experience • Assigned a de-identified patient sequencing case • Assess whether SNVs are polymorphisms • Incorporate public databases • Determine if variants have any clinical significance • Must critically evaluate literature • Goal: create a clinical report with references

16. Week 3: Interpreting clinical NGS

17. patient care • Preview sequencing results • Retrieve relevant patient history • Draft a preliminary report • Present at consensus conference

18. American Journal of Clinical Pathology 2010; 133: 832-834, Supplemental

19. Recognized Weakness: Didactics • Takes a lot of time to develop lectures, so faculty are not excited to do it • Repeating the same lecture three times a year is not interesting, so faculty are not excited to do it • Faculty expertise is lacking in some areas • Content requires constant updating • The solution is obvious: utilize resources developed by other stakeholders

20. Lecture series proposed:Training Residents In Genomics/TRIG Lecture I: Genomic Pathology: An Introduction Lecture II: Genomic Methods Lecture III: Interpreting Genomic Information for Clinical Care Lecture IV: Genomic Medicine: Communicating with the Patient

21. Other key challenges • Develop objective metrics to measure success of training • Design clinically relevant statistics and informatics exercises • Develop and implement effective web-based resources

22. Acknowledgements • Tina Lockwood! • Molecular Diagnostics-Jacqueline Payton • Statistics-Josh Swamidass • Informatics -Rakesh Nagarajan • Cytogenetics-Shashi Kulkarni, Cathy Cottrell, Hussam Al-Kateb • Informatics II/ NGS-Mark Watson, Rakesh Nagarajan, Eric Duncavage • Tissue Banking-Sandra McDonald • HLA-Jerry Morris