Improving patient outcomes by overcoming the challenges
of implementing high value tests in the clinical lab

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Educational Grantee Partners:

Brian Kelly, Dustin Bunch, Tim Collier, Joshua Hayden, Joyce Liao, Amanda Paulovich, Heather Stieglitz, Jenny Van Eyk


Agenda (Preliminary) - View Program

Tuesday, April 4

Time

Sessions

Morning Sunrise Activity

Location: Ferrantes

Short Course : Data Science 101 : Breaking up with Excel: An Introduction to the R Statistical Programming Language

Location: Steinbeck 1

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Short Course : GlycoProteomics 101 : Clinical glyco(proteo)mics by mass spectrometry

Location: Steinbeck 2

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Short Course : Sample Prep 201 : Sample Preparation and Alternative Matrices for LC-MS Assays

Location: Steinbeck 3

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Short Course : LC-MSMS 101 : Getting Started with Quantitative LC-MSMS in the Diagnostic Laboratory

Location: Colton

IN-PERSON & ON-LINE

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Short Course : Data Science 201 : Flexing with R : Databases to Dashboards

Location: Stevenson 2

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Short Course : Metabolomics 201 : Measuring Metabolism from Dried Blood Spots to Microsampling and more

Location: De Anza 1

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Short Course : Clinical Proteomics 101 : Clinical Proteomics

Location: De Anza 2

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Short Course : LC-MSMS 201 : LC-MSMS Technology and Techniques in the Clinical Lab

Location: De Anza 3

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Lunch Break

Location: Off-site

Workshop : Ion Mobility: How to Get it into YOUR Lab

Location: Steinbeck 1

Christopher Chouinard, PhD

Clemson University

Robin Kemperman, PhD

Children’s Hospital of Philadelphia

Objective

Attendees will learn the basic principles of ion mobility, benefits and challenges to routine implementation in the clinical lab, method development, and current applications.

Summary

Ion mobility-mass spectrometry (IM-MS) has become a cornerstone of biomedical analysis, with applications ranging from isomeric small molecule differentiation to the study of protein structure. Despite its advantages, IM-MS has yet to see routine implementation in the clinical lab due to challenges in quantitation, limited universal standards, data processing software, and reproducibility across different IM techniques/vendor platforms. This workshop will introduce common IM techniques and their operating principles, expanding upon the benefits of incorporating IM into conventional LC-MS/MS workflows and discussing its challenges. A discussion of method design and development will focus on how users might go about integrating IM into their existing (or new) assays. Finally, an overview of current applications (including metabolomics, lipidomics, and proteomics examples) will be provided.

Objective 1: Understand the basic operating principles of IMS and the differences between the different techniques (e.g., drift tube, traveling wave, FAIMS/DMS, etc.)
Objective 2: Recognize the benefits and limitations to incorporating IMS into conventional LC-MS/MS workflows in the clinic
Objective 3: Become familiar with method design and development and current/future applications

Syllabus

  • Basic Operating Conditions of IMS: Electric field application, experimental conditions (temperature, pressure, gas composition)
  • Different IMS techniques: Drift tube/traveling wave, field asymmetric/differential mobility, emerging techniques (i.e., TIMS, SLIM, cIMS, etc.)
  • Applications: Current examples from metabolomics, lipidomics, and proteomics
Workshop : Design of Experiments for Optimization of LC-MS Clinical Assays

Location: Steinbeck 2

Margret Thorsteinsdottir, PhD

Faculty of Pharmaceutical Sciences, University of Iceland

Finnur Eiriksson, PhD

ArticMass

Objectives

The objective of the workshop is to provide an introduction into design of experiments (DoE) for clinical application with special focus on optimization of MS-based clinical assays. The workshop is focused on practical implementation of DoE and will demonstrate how method development of sample preparation and UPLC-MS/MS method for quantification of clinical biomarkers can become much more efficient by utilizing DoE.

Summary

Design of experiments (DoE) is an efficient tool for development and optimization of UPLC-MS/MS platform for quantification of biomarkers in complex biological matrices. The UPLC-MS/MS platform is composed of several processes which involve many experimental factors that need to be simultaneously optimized to obtain a true maximum sensitivity with adequate resolution at minimum retention time. DoE offers a practical approach for performing experiments in accordance with a predefined plan, modelling by empirical functions, and graphical visualization. Basic concept of DoE will be presented with emphasis on practical implementation of DoE which includes the three main stages, screening, optimization, and robustness testing. To demonstrate the cost-effective benefit of DoE, which allows the effect of variables to be assessed with only a fraction of the experiments that would be required by changing one-separate-factor-at-time (COST) approach, two case studies will be presented. The first case is optimization of sample preparation in bottom-up targeted protein LC-MS workflow using DoE. The second case is an optimization of a UPLC-MS/MS assay for clinical diagnostic and therapeutic drug monitoring of patients with adenine phosphoribosyltransferase (APRT) deficiency, which is an inborn error of purine metabolism. A polynomial model which corresponds to the objective of the case study is specified and an experimental design that supports the selected model is generated. Significant factors were studied via central composite design and related to responses utilizing partial least square (PLS)-regression. Both cases showed that DoE is an excellent tool for optimization of sample preparation for biological samples and UPLC-MS/MS quantification method for clinical biomarkers. A significant reduction of sample preparation time was achieved with increased yields for selected peptides and a reliable UPLC-MS/MS assay for simultaneous quantification of urinary 2,8-dihydroxyadenine (DHA) and adenine was optimized efficiently with DoE.

Syllabus

  • Design of Experiments (DoE) – Get it right from the beginning
  • Basic concept and assessment of DoE
  • Optimization of sample preparation and UPLC-MS/MS clinical assay by DoE
Workshop : The Value, Impact, and Regulatory Landscape of Laboratory Developed Tests

Location: Steinbeck 3

Melissa Budelier, PhD

TriCore Reference Laboratories

Jacqueline Hubbard, PhD, DABCC

Three Rivers Diagnostics

Objectives

  • Recognize the role of laboratory developed tests (LDTs) in patient care
  • Describe the current regulatory landscape of LDTs
  • Define the VALID act and discuss its potential implications to the practice of laboratory medicine and patient care

Summary

Laboratory Developed Tests (LDTs) play a critical role in patient care. They are developed by expert laboratorians to bridge gaps between patient needs and available FDA-approved assays. LDTs are used to help diagnose and manage treatment for a variety of health conditions. These tests undergo extensive validation prior to implementation and, within the United States, are federally regulated by CLIA. The proposed Verifying Accurate Leading-edge IVCT Development Act of 2022 (“VALID Act”) includes additional regulation of LDTs by the FDA. If passed, the VALID Act would limit LDT access and the ability to provide timely laboratory testing to providers and patients, resulting in significant care gaps.

This interactive workshop will provide an overview on what LDTs are, how they are validated and the current regulatory framework, highlighting papers published in the recent JMSACL special issue – Laboratory Developed Tests: Regulation, Assay Development, and Impact on Patient Care. We’ll also provide an overview on the status and potential implications of the VALID act. In the second half of the workshop, the audience will have a chance to share their opinions, questions, and concerns in a flipped classroom Q & A.

Short Course : LC-MSMS 101 : Getting Started with Quantitative LC-MSMS in the Diagnostic Laboratory

Location: Colton

IN-PERSON & ON-LINE

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NOTE: THIS OCCURS AT THE SAME TIME as the WORKSHOPS.

Workshop : Pre-Analytical Considerations as Prerequisite for Successful Clinical Application of Lipidomics

Location: Stevenson 1

Robert Gurke, PhD

Fraunhofer Institute for Translational Medicine and Pharmacology Itmp

Anne K. Bendt, PhD

Singapore Lipidomics Incubator (SLING), National University of Singapore

Bo Burla, PhD

Sling @ National University of Singapore

Objectives

It is the objective of the workshop to provide an introduction into pre-analytical considerations for clinical application of MS-based analytics, with a special focus on lipids. However, these considerations are in many cases independent of specific analytes of interest and can hence be applied for polar metabolites as well as proteins. The workshop is focused on main hurdles to be considered when performing clinical research using LC-MS based determination of lipids namely: (I) pre-analytical sample handling, (II) frequent generation of patient samples as well as (III) overall cohort and study design.

Summary

Lipids are involved in a broad spectrum of functionalities in the organism and implicated in a variety of physiological and pathological processes. Changes in lipid levels are promising biomarkers for early diagnosis, prognosis of disease progression, or guidance for selecting promising therapeutic approaches. However, biomarker discovery in the field of lipidomics is a very challenging process since lipids require specific procedures regarding sampling (including selection of sample type and collection procedures, storage conditions and number of freeze-thaw cycles), sample preparation and analysis for reliable determination. As especially pre-analytical sample handling is a critical step for the reliable analysis of the lipidome, a close cooperation with the clinicians is necessary. This ensures following a highly standardized protocol for venous blood sampling to avoid several pre-analytical pitfalls potentially changing the lipid profile ex vivo. As collecting venous blood samples is very laborious for patients as well as clinicians, other ways for a more frequent sample collection are necessary. Therefore, capillary blood sampling using microsampling devices is an auspicious way to complement the strategy of analyzing venous blood-based samples taken in the clinics. Besides considering the right sampling strategy, the structured recording of sampling details and subject metadata, the overall planning of the study and also the cohorts to be included is of high relevance. All mentioned points have to be considered before starting a clinical research project applying lipidomics to generate high quality data making biomarker discovery possible.

Workshop : Surgical Mass Spectrometry - Delivering the Technology to the Operating Room

Location: Stevenson 2

Zoltan Takats, PhD

Imperial College

Objectives

The objective of the workshop is to identify and overcome potential roadblocks preventing mass spectrometry-guided surgery to become routinely used in the clinical interventional world. The workshop will focus on the side-by-side comparison of existing technology and clinical needs, as also on the embedding of the technology into existing healthcare settings and regulatory aspects. The workshop is envisioned to outline the strategy for the clinical translation of these technologies.

Summary

The need for in-situ, real-time tissue identification has been dramatically increasing with the development and deployment of robotic and other high-precision surgical approaches. While surgical mass spectrometry techniques have been continuously developed, published and demonstrated in human surgical environment, none of these approaches have reached regulatory approval and routine application in surgery. We are planning to use the meeting to understand where the roadblocks are and how we can get around them to deliver the technology for patients and healthcare professionals equally needing it. The workshop is envisioned to map out the current technology landscape and identify the strengths and weaknesses of each solution together with their respective low-hanging fruit applications as the first main topic. This mapping exercise will be followed by discussing the embedding of the approach both into existing oncology and clinical diagnostic systems. The approach is expected to change how interventional cancer care (and potentially a few other treatments) is delivered, hence it is of utmost importance to understand this aspect from the point of view of pathologists, oncologists and medical imaging professionals. Furthermore, the technology will also be the forerunner of a universal, mass spectrometry-based diagnostic system, bringing LC-MS and MS imaging experts to the table. Beyond the embedding of the technology, we are also keen to discuss the regulatory and health economic aspects of the approach in the third part of the workshop.

Syllabus/Topics

  • Surgical mass spectrometry methods – strengths, weaknesses, applications and future perspectives
  • Embedding of technology into healthcare systems. Interactions with oncology, pathology, imaging and clinical chemistry. Synergism with other MS-based diagnostic technologies.
  • Regulatory and health economics aspects
Coffee Break & Happy Half Hour

Location: Steinbeck Foyer

Welcome & Scientific Orientation

Location: Steinbeck

The Michael S. Bereman Award for Innovative Clinical Proteomics : Translating Multiplexed Proteomic Assays to the Clinic and Beyond: Lessons from a Road Less Traveled

Location: Steinbeck

Timothy Collier, PhD

Quest Diagnostics

MICHAEL S. BEREMAN AWARD LECTURE

The process of translating mass spectrometry (MS)-based proteomic assays from basic research to the clinical laboratory remains a significant challenge for many laboratorians. The road to using innovative assays to aid in patient treatment is often fraught with obstacles, be they technical, financial, or regulatory. Over the past several years, our laboratory has had success in the research and development, validation, and commercialization of a multi-marker assay of high-density lipoprotein (HDL)–associated proteins. The validated clinical assay provides insight into a patient’s cholesterol efflux capacity (the ability of HDL cholesterol to transport cholesterol away from the artery wall). The assay helps assess the patient’s risk for developing coronary artery disease and, ultimately, cardiovascular death. The assay is also a component in several clinical studies to further assess its utility. Furthermore, the research framework upon which this assay was designed continues to yield new insights into other pathologies, including non-alcoholic fatty liver disease (NAFLD), metabolic syndrome, and diabetes. In this presentation I will summarize our efforts, our successes, and lessons learned on the road from basic research to clinical deployment.

Distinguished Contribution Award Plenary

Location: Steinbeck

Jennifer Van Eyk, PhD

Cedars-Sinai Heart Institute

Opening Exhibits Reception

Location: Exhibit Hall - Serra

MSACL Lounge

Location: Club Room