Thursday April 6, 2017 A01 Molecular and Genetic Testing: How to Position your Laboratory for New Technology Megan Schmidt Vice President of Product Management, CompuGroup Medical DESCRIPTION: Molecular testing is transitioning from research to clinical laboratories. With this change, clinical laboratories are faced with new requirements and challenges to standardize, document and follow test procedures. Laboratories must also demonstrate end to end sample traceability and comply with CLIA and other accreditation organizations. This presentation will provide a basic background for clinical molecular testing, key examples of some of the challenges facing laboratories and the support provided by laboratory information systems with the management of data. OBJECTIVES: At the end of the session, participants will be able to: Define molecular testing and its transition into the clinical laboratory. Describe key examples of some of the challenges encountered in the clinical laboratory. Recognize the functionality that Laboratory Information Systems provide to support molecular testing COLA Resources, Inc. and COLA do not endorse, directly or indirectly, the presentations given at this conference or the products or services provided by the exhibiting vendors. Presentations are intended to be free of bias. The use of any particular product is for demonstration purposes only, and does not imply an endorsement of the product by the presenter or the sponsors of the symposium. 2017 CRI
Molecular and Genetic Testing: How to Position Your Laboratory for New Technology Megan Schmidt VP Product Management CGM This Presentation Description Molecular testing is transitioning from research to clinical laboratories. With this change, clinical laboratories are faced with new requirements and challenges to standardize, document and follow test procedures. Laboratories must also demonstrate end to end sample traceability and comply with CLIA and other accreditation organizations. This presentation will provide a basic background for clinical molecular testing, key examples of some of the challenges facing laboratories and the support provided by laboratory information systems with the management of data. Objectives At the end of the session participants will be able to: Define molecular testing and its transition into the clinical laboratory Describe key challenges encountered in the clinical laboratory Recognize the functionality that LIS provides to support molecular testing
Agenda Market Definitions and Core Technology Common Applications Workflow Challenges LIS functionality MARKET CHANGES Testing Labs Opening Oversight
Our Reality U.S. healthcare organizations are coping with increasing pressure to contain costs The laboratory must optimize testing, leverage information technology and improve productivity Automation helps to achieve these goals, as does making the best use of your available laboratory resources The Molecular Era 1980s Assays for bacterial ribosomal RNA Adaptation of research amplification assays for use in clinical laboratories Automated testing platforms and detection of amplified targets in real time Today Multiplex assays, partial/whole genome sequencing assays and microarray
Molecular Market Molecular testing is expanding Molecular testing for Infectious Disease has been highly adopted in hospital clinical labs for years 2015 marketplace revenue estimates range from $9.1 billion $9.7B 1 In 2016, estimated 600 independent (non hospital) clinical laboratories offered some molecular testing 1 In 2016, estimated 550 800 clinical laboratories, hospital or independent, offer some next generation sequencing (NGS) 1 Molecular Diagnostics testing market has estimated CAGR of 9 10% through 2020 1 NGS market is expected to grow at a CAGR of 20.8% 2 1. G2 US Clinical Laboratory and Pathology 2013 2015 2. RNCOS Oversight Interests FDA CLIA 88 Joint Commission (JCAHO/JCI) College of American Pathologists ISO15189 State Health Departments Payers
DEFINITIONS DNA PCR Sequencing The Double Helix DNA is the hereditary material that is in humans and most other organisms. Most of our DNA is located in the nucleus of our cells, packaged in chromosomes. DNA consists of 4 nucleotides (A, T, C, G) repeated millions of times. Specific sequences of those nucleotides are our genes.
Terminology Genomics, Genetics, huh? Genomics deals with entirety of an individual s genetic info Genetics can include the genome, but can also be more narrowly focused on a specific gene or mutation Molecular is the term most often used to describe this work in a laboratory, as in Molecular Genetics or Molecular Pathology; testing leverages molecular attributes of DNA or RNA, such as electric charge, bonding affinity, size, etc. Cytogenetics and FISH are sometimes incorporated into Molecular laboratories and sometimes operate independently, but still rely on genetic principles for testing Molecular Diagnostics (MDx) An assay which works by detecting and classifying genetic material (DNA or RNA) as opposed to: Immunological testing Chemistry testing Biochemical phenotype testing MDx market includes testing for genetic sequences using a variety of methodologies Nucleic acid assays polymerase chain reactions (PCR), sequencing, in site hybridization (FISH), microarrays, cytogenetics Genomic immunohistochemistry (IHC) oncology immunohistochemistry tests like estrogen receptor amplifications
PCR Exponential Duplication We started with one copy and ended with 8!!! Sequencing by Capillary Electrophoresis C C C C C C C A A A A A A G G G G G C C C
Next Generation Sequencing Massive Parallel sequencing (high throughput) Next generation sequencing of partial or whole genomes is achieved by parallelizing the sequencing process, yielding thousands or even millions of overlapping sequences An extremely sensitive ph meter to identify which nucleic acids are passing through the instrument COMMON APPLICATIONS Pathogen Detection Tumor Typing Inherited Disorders
Applications for Molecular Diagnostics Pathogen detection Targeted genotyping Inherited metabolic disorders Pharmacogenomics / Drug responsiveness Cytogenetics Oncology Tumor classification Treatment monitoring Identity tracking Forensics Human leukocyte antigen Transplant matching Detection of Targets by Multiplex PCR Multiplex PCR involves amplification of many targets simultaneously in one reaction The Luminex xtag assay detects the amplified targets by hybridization with probes bound to dyed microspheres The microspheres are interrogated in a flow cytometer with dual lasers to identify the color dyes in each particle and the reporter dye attached to amplified targets http://www.pri.wur.nl
Pathogen Detection by Microarray Testing Thousands of DNA oligomer capture probes of known specificity are immobilized on the solid surface of a silicon chip Fluorescent dye labeled amplified targets hybridize to the capture probes, are washed, and then scanned with UV light to detect the resultant fluorescence Infectious disease microarray testing is a molecular analog of culture in that hundreds or even thousands of pathogens can be sought simultaneously in a specimen http://www.tessarae.com Sequencing to Recognize Genes and Mutations Targeted sequencing of single genes is used for phylogenetic studies and for detection of mutations Pathogenic microorganisms can be identified, virulence factors recognized and antibiotic resistance detected http://upload.wikimedia.org
Cytogenetics If our Genome was a set of encyclopedias Each chromosome would be a different volume or book Cytogenetics testing assesses if you have all the necessary books and if you in fact got one copy of each book from each parent Molecular versus Other Diagnostics Traditional assays are being replaced with molecular techniques PCR dominates market technology Sequencing expected to have most growth Advantages: High sensitivity High specificity Rapid assay design Easy automation Disadvantages: Risk of contamination Genotypic data /= phenotype Costs
WORKFLOWS PCR NGS Complex Workflows Most Molecular based assays are heavily regulated and rely heavily on paper driven systems Small volumes, small containers, and batching require calculations, tracking, and tray maps Data often requires multiple interpretive steps The industry is often research driven, which means instruments and assays are not initially suited for LIS incorporation
The Molecular Workflow Workflow Example PCR 1. Build Tray Maps and Worklists 2. Perform Extractions 3. Prepare MasterMix in Clean Room 4. Add Patient Sample to MasterMix 5. Run PCR Amplification 6. Process Results Instrument Interface LIS
Automation in Molecular Diagnostics While automated testing is common in clinical chemistry and hematology, molecular testing remains primarily manual A small number of automated sample to result testing platforms exist, but they are restricted primarily to diagnosis of a limited number of infectious diseases What are lacking and are currently under development are integrated automated approaches to molecular diagnostic testing as we know it today Genetics Workflow Provider Order Entry Clinical Management/ Decision Support Wet Bench Work Bioinformatics Annotation Filtration and Variant Assessment Reporting Laboratory
CHALLENGES Complex Workflows Regulatory Compliance The Transition of Molecular Testing From Research We determine what works best. Each tech can change steps or reagents as needed. What is a QC reagent and why would we need it? We keep all records on paper. To Clinical Testing Need to standardize, document and follow test procedures. Should comply with regulatory performance standards. Be prepared to demonstrate end to end sample traceability to an auditor.
Challenges Facing Genetics Labs Complex workflows Current molecular testing is manual, laborious and essentially nonstandardized, interspersed with sophisticated instrumentation, leading to errors that impact patient safety Shortages of highly skilled molecular diagnostics technologists exist in many parts of the world there is a graying of the laboratory workforce Big Data Large data sets that require bioinformatics Interpretation Results need interpretation, required acquisition and application of knowledge Multiple layers of result and report review CLIA / CAP compliance Lab developed tests are not provided by a manufacturer = more ownership of risk to lab Challenges Facing Molecular Labs Lack of integration QC/QA performed outside of LIS Heavy dependence on paper records and Excel Instruments lack ASTM specifications > not interfaced > manual transcription of data Inventory Management Multiple reagents and controls, some created in house Multi well Plate Formats Many patients and controls in small containers
Areas for Concern or Failure People do NOT do well working in multiple systems to do tasks they view as non essential Preparing for inspection by backtracking through reports, sending piles of documents for signatures, etc. Other issues Slow workflow Opportunity for error Limits capacity from expanding to meet the projected demand for molecular testing Goals Reduce paper dependent systems Incorporate daily tasks into standard workflow Provide systems that track key performance indicators in real time and according to requirements Lean strategies for laboratory testing call for greater reliance on automation to streamline this testing workflow
Strategies Being Employed Not fully leveraging the power of the LIS Paper based Systems Well thought out, but not scalable Homegrown Systems High risk for supportability Research based LIMS Lack patient centric view Limited use of the LIS Orders and results only Concerns With Non LIS Solutions Is operating outside the LIS the right solution? Stand alone orders, inventory or specimen management lacks integration and analytics Molecular specific workflow not well supported Lack of Instrument interfaces Manual result entry is prone to clerical errors Use of excel and charts for traymap layout and calculations is laborious Non integrated reporting is inefficient Disparate documentation created from pre to post analytics 36
LIS SUPPORT Traceability Automation Integration Solution Bring the molecular lab workflow into the clinical setting and into your LIS Fully integrate your molecular workflow with the LIS Take advantage of existing LIS features and maintenance Integrate with HIS and other systems
Core LIS Capability Barcoding Order interfaces to integrate lab work to reduce paper and manual transcription Robust rules to drive actions combine or delete tests or orders; order additional tests; check for appropriateness of test; route orders based on patient insurance Results review screen to make previous patient results available in tabular or graphical format QC features to protect result quality: delta and normal range checking; highlight abnormal results; QC failures can block resulting from filing Interface instrumentation to accept instrument outputs in various formats including Excel, ASCII, CSV Biomarker and genetic results handled as discrete results Use of panels and reflex testing each step with its own result, QC and decisions Management Review of results and reports Molecular Laboratories Manage Complexity Reagent Management Workflow Management Plate Maps Tracking Workflow Management Inventory Tracking Plate maps Reagent Management Workflow Management
Example: Inventory Labs need to: Track reagents Controls & non control inventory items Lots and shipments Receive/Expiration dates Check availability Uses on hand Low balance alerts Quality Control Definitions CONCLUSION Molecular is a reality Are you ready? Leverage your LIS
Forecast Careful thought must be given to the future when considering the expenditure of large amounts of money on technology The laboratory of tomorrow will become increasingly dependent upon molecular approaches for diagnosing and managing patients with infectious and genetic diseases Traditional testing will not disappear, but will become minor activities of the laboratory in the future Projections for the Future Automation of molecular testing will enable increasing numbers of laboratories Molecular testing will become more standardized and amenable to Lean based improvement LIS vendors will add the processing power, storage capacity and system flexibility to handle increasingly complex molecular testing
Considerations in Implementing Molecular Ask Yourself Is molecular really needed for this purpose? Does the intended platform meet the need? What other assays of use could share this platform? What other platforms could also meet this need, and what are the pros and cons of each? Is there a likely soon emerging disruptive technology in this space? Is it desirable to go with today s technology, or can it wait a year? How can I leverage LIS to support my goals? Conclusion Molecular Diagnostics tools are powerful and increasingly essential Molecular clinical diagnostics contribute to better health management Many platforms and approaches can be used due diligence to get best value and impact Leverage your LIS
Questions? Thank you for your time