Next Generation Sequencing (NGS) Workgroup · 11-04-2019 · Next Generation Sequencing (NGS)...
Transcript of Next Generation Sequencing (NGS) Workgroup · 11-04-2019 · Next Generation Sequencing (NGS)...
Next Generation Sequencing (NGS) Workgroup
Report to CLIAC April 11, 2019
Dr. Jordan Laser, Workgroup Chair
Workgroup Members
Chair: Jordan Laser, MD
Members:Joe Campos, PhD, DAPMM, FAMMAlexis Carter, MDMarc Couturier, PhD, D(ABMM)David Dimmock, MDTina Hambuch, PhD, FACMGSteven Hinrichs, MDGianella Garcia Hughes, PhDZahra Mehdizadeh Kashi, PhD, HCLDEric Klee, PhDJennifer LeftwichStan Letovsky, PhD
Jason Merker, MD, PhDSteve Miller, MD, PhDKevin Modarress, PhDSomak Roy, PhDErasmus Schneider, PhDMarty Soehnlen, PhD, MPH, PHLD(ABB)Colleeen Stevens, PhDFredrik Vannberg, DphilKarl Voeklerding, MD, FCAPElizabeth Worthey, PhD
HHS Workgroup Members and Subject Matter Experts Designated Federal Officer:
Heather Stang, MS, MT(AMT) Ex Officio Members:
Collette Fitzgerald, PhDZivana Tezak, PhDFelicidad Valcarcel, MS, MT(AMT)
Agency Staff Subject Matter Experts:Marie Earley, PhDRachel Jacobs, MSHS(CRA). HCM, SCT(ASCP)Shyam Kalavar, MPH, CT(ASCP)Lisa Kalman, PhDPenny Keller, BS, MB(ASCP)Ira Lubin, PhD, FACMGAmy Zale, MT(ASCP), PMP, GWCFPM
NGS Charge
Provide input to CLIAC for consideration in developing recommendations to CDC, CMS, and FDA for assuring quality of next generation sequencing based testing in clinical laboratory settings.
Workgroup Tasks: Identify challenges in applying the existing regulatory framework Identify challenges and gaps in guidance Consider and suggest strategies to address the identified gaps and
challenges Consider and suggest strategies for assuring workforce competency
Discussion Question #1What consultation or other assistance does the laboratory provide to help clinicians order the appropriate tests for their patients?
# 1 Discussion Points
Personnel Director-Provider Genetic Counselors Client Services
Support is critical Education/ operations (PA/BI)
Small vs Large lab resources
Clinical Utility/Diagnostic Yield Needs:
Standard definitions, education
Discussion Question #2What consultation or other assistance does the laboratory provide to help clinicians understand and use NGS-based test results?
# 2 Discussion Points Personnel MD/DO/PhD (+boards) Genetic Counselors
Scope?
Method Phone calls (pro vs reactive) Online resources Tumor board style meetings
Report “First page phenomenon” Loss of fidelity workflow
# 3 Discussion Points Guidelines Availablemore
Entire analytical process
Validation/Revalidation
Performance Characteristics Determined and clear
Challenging to determine
Application specific
Validation Issues Definition of test detects/limitations
Oversight by experienced professionals
Needs Inspection expertise
Minimum standards (exomes/genomes)
Specimen (GeTRM)
Discussion Question #4
What are the challenges for clinical laboratories in performing NGS quality control and quality assurance?
#4 Discussion Points QA/QC resource intensive Traditional QM differs from NGS
+ Control/ NTC One size not fit all Current QM framework? Guidelines exist
AMP/CAP Needs
NGS appropriate QM definitionsAgile frameworktechnology
Discussion Question #5What reference materials (physical and/or electronic) are important to include for developing validation and quality control procedures?
# 5 Discussion Points
Currently available:Genome in a Bottle ConsortiumATCC Microbiome StandardsMedical Device Innovation
ConsortiumCDC GeT-RM
Needs: In silico clearinghouseDepth of current RM
Discussion Question #6What proficiency testing programs or alternate assessment schemes are available for NGS?
# 6 Discussion PointsElementsWet/DryAvailable:
CAP, CDC PulseNet PT, Regional consortia, Precision FDA, Ass. Biomol. Resource FacilitiesGenerally too easy?
Alternative AssessmentDistributive model PT referralNeeds:
More/challenging/distributive
Discussion Question #7What are the challenges to developing, establishing quality control, and implementing a bioinformatics pipeline within a clinical laboratory setting?
#7 Discussion PointsQC in Pipelines
Regs/Standards+/- vs NGS
PersonnelBioinformaticians/Inspectors
PipelineUse case specificExternal databasesVersioning
Needs:Training setsExpertise to assist
Discussion Question #8What are the challenges associated with using and assuring the quality of external data (e.g., data annotation) to inform the bioinformatics analysis?
#8 Discussion PointsDatabases:GuidelinesData behind the data?Balance privacy vs metadata
CurationVariants interpreted each time
Needs:MetadataQC for inputMandate to share?
Discussion Question #9What are the laboratory practices and challenges to NGS software and data management with respect to: Data sharing (e.g., for QC, populating external
databases, availability to patients)
#9 Discussion Points Patient:
Federal lawFiles?
3rd party interpretationsUnvalidated data
Professionals: Criticalknowledge
Curation/metadata Interoperability
LOINC Consent:
Various (Opt in/out) Environment Privacy/curation
Discussion Question #9 Continued
What are the laboratory practices and challenges to NGS software and data management with respect to: Data and software storage/retention/upgrades
#9 Discussion Points continuedStorage:
No consensusCAP- 2 years, reanalysis
? Files, lossiness, latencyintentSoftware:
Mods regression / unitVersioning
Re-verify/validate:Encryption, upgrades
Needs:Why? Unity, Guidelines
Discussion Question #10What are the real world and recommended practices and challenges in reporting clinically significant secondary findings that are not related to the test that was ordered?
#10 Discussion Points Secondary vs Incidental
Secondary- Purpose A, other actionable findingsWES inherited cancer syndrome
Incidental Purpose A, findings significant for disease outside of intentKras Noonan
ACMG Guidelinesreevaluate Refine Consenting Reporting Impact Resources
Discussion Question #11What training and competencies are performed or considered essential to demonstrate that qualified personnel are testing specimens and analyzing data?
#11 Discussion PointsWet well covered CLIADry GAPS in CLIA
BioinformaticiansDeveloper vs Scientist vs Analyst
Lab vs Manufacturer Recommendations:
SurveyJDs, qualifications, education
WorkgroupDefine BI categories crosswalk