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

JMSACL Logo
Educational Grants supported in part by:
& Brian Kelly

Agenda (Preliminary) - View Program

Tuesday, April 5

Time

Sessions

Registration Desk Opens

Location: De Anza Foyer

Vendor Booth Set-Up

Location: Exhibit Hall - Serra

Workshop: A Clinical Proteomics Primer

Location: De Anza 1

Andy Hoofnagle, MD, PhD

University of Washington

Christopher Shuford, Ph.D.

Labcorp

Objective

To provide an interactive forum in which attendees will be introduced to critical aspects of clinical protein measurements.

Summary

The motivation for using mass spectrometry to quantify proteins in clinical research and in clinical care will be discussed as part of this interactive workshop. Technical topics uniquely affecting quantitative protein and peptides measurements by mass spectrometry will be a point of emphasis. Case studies from assay inception through validation will be presented and participants will work interactively to critique various aspects of clinical proteomic measurements.

Syllabus
- Protein vs Peptide Measurands
- Workflows
- Sample Preparation (Digestion & Enrichment)
- Internal standards
- Calibration
- Validation
- Quality control

Workshop: Why We Fail at Biomarkers

Location: De Anza 3

Tim Garrett, PhD

University of Florida College of Medicine

Objective

This workshop is designed to teach attendees reasons why most biomarkers do not translate to clinical diagnostics as a way to improve the process for future research

Summary

Biomarker discovery is one of the major areas of clinical research especially in metabolomics yet less than 1% of published biomarkers translate to clinical diagnostics. Biomarker discovery generally starts in phase 1 with a few samples to identify a biomolecule that differentiates the disease or disorder under investigation from control samples. Once a biomolecule is selected a targeted quantitative method would be developed in phase 2 to use on a larger number of samples to validate the results from phase 1. There are several common reasons for biomarker failure such as using samples that are not representative of the clinical population, not including diversity in the initial discovery phase, improper use of statistical approaches, not having a sufficient number of samples and improper quality control for analysis. With the growth of metabolomic methods recently, a discussion on approaches to help improve phase 1 of biomarker discovery is important to have confidence that the selected markers are indeed unique.

Syllabus

- Metabolomics in clinical research
- Quality control for better method assessment
- Experimental design
- Statistical analyses with validation
- Real-world samples

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

Location: Bonsai

Daniel Holmes, MD, FRCPC

St. Paul’s Hospital

Dustin Bunch, PhD, DABCC

Nationwide Children's Hospital

** Part In-Person (optional, also available pre-recorded) and Part Online **

This is the first segment (4 hr) of a three segment (16hr total), part in-person (optional) and part online, short course.

Segment 1 will be available both IN-PERSON on April 5 at the MSACL 2022 conference in Monterey, CA and ONLINE (pre-recorded) if you can't make it in person. Registration for Segment 1 is free (although to attend on-site you must be registered for MSACL 2022).

Segments 2 and 3 will take place ONLINE on April 29-30, 2022.

While the first SEGMENT is FREE, SEGEMENTS 2 and 3 that occur only ONLINE are fee-based. You can REGISTER HERE.

----------

Does Excel lag on you when you open a file bigger than 1000 rows? Has it ever changed your data to a date against your will? Are you ready to jump right past Tableau and into the world of Data Science using a real programming language?

Well, your wait is over because at MSACL we again will be offering a course for complete programming newbies that will help you get going analyzing real data related to LC-MS/MS assay development, validation, implementation and publication.

The only background expected is the ability to use a spreadsheet program. The skills that you will acquire will allow you to take advantage of the many tools already available in the R language and thereafter, when you see that your spreadsheet program does not have the capabilities to do what you need, you will no longer have to burst into tears.

The course will be run over three days (one in person to start and two online later) and time will be evenly split between didactic sessions and hands on problem solving with real data sets. Drs Holmes and Bunch will adopt a “no student left behind policy”. Students will be given ample time to solve mini problems taken from real life laboratory work and focused on common laboratory tasks. All attendees will need to bring a laptop with the R language installed R Studio interface installed. Students may use Windows, Mac OSX or Linux environments. Both R and R studio are free and open-source. No cash required.

Students should be prepared for learning what computer programming is really like. This may involve some personal frustration but it will be worth it.

Obtaining the Software

!!! DOWNLOAD PROGRAM PACKAGES PRIOR TO ARRIVAL ONSITE !!! THERE WILL NOT BE OPEN INTERNET WIFI IN THE CONFERENCE CENTER.

!!! POWER : Make sure your computer is charged to hold power for 4 hrs, as power outlets may not be available.

Instructions for installing the R language are here: http://cran.r-project.org/
Instructions for installing R Studio are here: http://www.rstudio.com/

Course Description

The course will cover:

  1. The major types of R variables: vectors (numerical, character, logical), matrices, data frames and lists.
  2. The important classes: numeric, character, list and changing between them
  3. Importing data from Excel
  4. Dealing with non-numeric instrument data
  5. Manipulating and cleansing your data
  6. Exporting data to Excel-like format.
  7. Basics of tidyverse: dplyr, filter, mutate, join
  8. Regressions: ordinary least squares,Passing Bablok, Deming, weighted regressions.
  9. Non-linear regressions
  10. Looping: Doing things repeatedly
  11. group_by and summarize
  12. Writing your own functions
  13. Making highly customized figures with base plot or ggplot
  14. Putting it all together projects:
  15. Preparing method comparison regression and Bland Altman plots
  16. Preparing mass spectrometry data for upload to LIS.
Short Course: LC-MSMS 101 : Hands-On Training Session (GROUP 1)

Location: Colton

Judy Stone, MT (ASCP), PhD, DABCC

UCSF

Jacqueline Hubbard, PhD, DABCC

QualiTox Laboratoires

Adina Badea, PhD, DABCC

Lifespan Health/Rhode Island Hospital & The Warren Alpert Medical School of Brown University

Robert Fitzgerald, PhD, DABCC

University of California San Diego

** Supplemental Hands-On Segment In-Person : Main Course is Online **

This is the supplemental bonus segment (2 hr) of a 16 hour online short course taking place on March 11-14, 2022. Attendance at this in-person segment is free, but REQUIRES pre-registration (separate from conference registration, coming soon) with priority given to online course registrants. There will be two instances of this segment (Group 1 and Group 2, both the same), with each to be capped at 20 participants.

You can register for the online course (fee-based) here.

----------

Is this workshop for you?

This two hour workshop is a supplement to the MSACL Online Short Course – “Getting Started with Quantitative LC-MS/MS in the Diagnostic Laboratory (LC-MS 101)”. The short course will be offered online, March 11-14, 2022 (register here). The hands-on workshop content is designed for attendees from the online short course, but the short course is not a prerequisite. Anyone starting out with quantitative LC-MS troubleshooting may find it useful.

Format and Content

The first 50 min session will include brief instructor demonstrations and then ample hands-on time for attendees to practice troubleshooting tasks, such as
- cutting (and recutting) PEEK tubing correctly
- connecting (and reconnecting) PEEK fittings to LC columns, other components
- changing LC pump check valves
- changing LC injection valve rotor seals
- reviewing chromatography problems caused by leaks, tubing/fitting mistakes and damage, excess LC dead volume, and aged LC components

The second 50 min session is a discussion of real world instrument troubleshooting cases from the instructors’ laboratories. Aside from the examples presented, the goal is to develop a standardized approach to troubleshooting complex LC-MS systems, including
- Know your LC flow path and LC components, how to avoid damaging the MS/MS
- How to look for leaks and sources of overpressure
- Using chromatogram overlays, pressure traces, maintenance chart review, system suitability testing and MS/MS infusion to locate the problem within the instrument

Workshop : How to Convince Admin THEY Want to Buy You a Mass Spectrometer

Location: De Anza 2

Joshua Hayden, PhD, DABCC, FACB

Norton Healthcare

Juan David Garcia, MBA MT

University Of Texas Medical Branch

Objectives

The objective of this workshop is to give attendees the knowledge necessary to put together a convincing business case for purchasing a mass spectrometer. This knowledge will be imparted by presenting and discussing successful and unsuccessful examples of such business cases. Throughout the course, essential business terminology will be presented and explained.

Summary

Many laboratorians can discuss the benefits of implementing mass spectrometry into the clinical laboratory. From improved confidence in results to minimization of interferences, there are substantial and well-discussed benefits to mass spectrometry. Unfortunately, mass spectrometers cost money and the individuals empowered to write checks rarely relate to such technical justifications. This workshop is designed to help clinical laboratorians understand what factors matter to financial decision makers. The presenters include a clinical laboratorian with experience successfully acquiring mass spectrometers and an experienced administrator with significant laboratory and financial expertise. The presenters will walk attendees through the process of preparing a business case. Attendees will be presented with numerous examples of business cases that need improved and the attendees will be given the chance to discuss what is wrong and what needs to be done to fix them. Attendees will also be given a chance to submit their own personal business cases ahead of time if desired. These can be discussed in private after the workshop or (with attendee permission) can be discussed in part as part of the workshop. The goal is to prepare attendees to put together and present a business case that supports the acquisition of a mass spectrometer in terms that matter to financial decision makers.

Syllabus/Topics

How to assemble the worst business case ever (and guarantee failure)
Attendees will begin the session with an introduction to the worst possible business case one can present. The numerous flaws will be pointed out and addressed in an effort to highlight the many ways business cases can go wrong.

From LCMS and qTOF to ROI and DEPR (speaking the language of finance)
After attendees have a chance to see what not to do, it will be time to discuss what administrators/finance officers are looking for in a business plan. The goal is that attendees walk away with an understanding of the important terms and metrics their business cases will be evaluated by. In addition, an overview of hospital accounting and do's and don't's of capital equipment purchasing will be given.

Estimating costs
The cost of a mass spectrometer is far more than the instrument itself. This section will help attendees begin to consider everything they need to account for when proposing how much mass spectrometry will cost- labor, supplies, service contract, etc.

Estimating reimbursement
This section will cover how to estimate revenue- whether it is insourcing from a reference lab or setting up a new service line. The importance of payer mix and inpatient vs outpatient will be addressed

What's wrong with my business case?
Ending where the course started, the final section will cover examples of business cases. These cases will be used to illustrate cases that are very strong and those with weaknesses that can be improved. If submitted by attendees ahead of time, these example cases will be anonymized versions of those submissions.

Short Course: LC-MSMS 101: Hands-On Training Session (GROUP 2)

Location: Colton

Judy Stone, MT (ASCP), PhD, DABCC

UCSF

Jacqueline Hubbard, PhD, DABCC

QualiTox Laboratoires

Adina Badea, PhD, DABCC

Lifespan Health/Rhode Island Hospital & The Warren Alpert Medical School of Brown University

Robert Fitzgerald, PhD, DABCC

University of California San Diego

** Supplemental Hands-On Segment In-Person : Main Course is Online **

This is the supplemental bonus segment (2 hr) of a 16 hour online short course taking place on March 11-14, 2022. Attendance at this in-person segment is free, but REQUIRES pre-registration (separate from conference registration, coming soon) with priority given to online course registrants. There will be two instances of this segment (Group 1 and Group 2, both the same), with each to be capped at 20 participants.

You can register for the online course (fee-based) here.

----------

Is this workshop for you?

This two hour workshop is a supplement to the MSACL Online Short Course – “Getting Started with Quantitative LC-MS/MS in the Diagnostic Laboratory (LC-MS 101)”. The short course will be offered online, March 11-14, 2022 (register here). The hands-on workshop content is designed for attendees from the online short course, but the short course is not a prerequisite. Anyone starting out with quantitative LC-MS troubleshooting may find it useful.

Format and Content

The first 50 min session will include brief instructor demonstrations and then ample hands-on time for attendees to practice troubleshooting tasks, such as
- cutting (and recutting) PEEK tubing correctly
- connecting (and reconnecting) PEEK fittings to LC columns, other components
- changing LC pump check valves
- changing LC injection valve rotor seals
- reviewing chromatography problems caused by leaks, tubing/fitting mistakes and damage, excess LC dead volume, and aged LC components

The second 50 min session is a discussion of real world instrument troubleshooting cases from the instructors’ laboratories. Aside from the examples presented, the goal is to develop a standardized approach to troubleshooting complex LC-MS systems, including
- Know your LC flow path and LC components, how to avoid damaging the MS/MS
- How to look for leaks and sources of overpressure
- Using chromatogram overlays, pressure traces, maintenance chart review, system suitability testing and MS/MS infusion to locate the problem within the instrument

Workshop: Design of Experiments for Development and Optimization of LC-MS Clinical Diagnostic Assay

Location: Steinbeck 1

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 bioanalytical assays. The workshop is focused on practical implementation of DoE and will demonstrate how method development of UPLC-MS/MS clinical diagnostic methods can become much more efficient by utilizing DoE.

Summary

The chemometric approach, design of experiments (DoE) is an efficient tool for development and optimization of UPLC-MS/MS for quantification of biomarkers in complex biological matrices. The UPLC-MS/MS platform is composed of several processes which involves many experimental factors that need to be simultaneously optimized to obtain maximum sensitivity with adequate resolution at minimum retention time. DoE offers a practical approach for performing experiments in accordance to predefined plan, modelling by empirical functions, and graphical visualization. Basic concept of DoE will be presented with emphasis on practical implementation of DoE which include the three main stages, screening, optimization, and robustness testing. Example from optimization of a UPLC-MS/MS method for clinical diagnostic purposes and therapeutic drug monitoring will be used to show the cost-effective benefit of DoE, where it 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. A fractional factorial design was used for experimental screening to reveal the most influential experimental factors. When multi-levels qualitative factors were included in the screening experiments D-optimal design was applied. Significant factors were studied via central composite design and related to sensitivity, resolution and retention time utilizing partial least square (PLS)-regression. A specific and reliable UPLC-MS/MS assay for simultaneous quantification of urinary 2,8-dihydroxyadenine (DHA) and adenine was optimized efficiently with DoE. The assay has been implemented for clinical diagnosis and therapeutic drug monitoring of patients with adenine phosphoribosyltransferase (APRT) deficiency, which is an inborn error of purine metabolism.

Syllabus
-- Design of Experiments (DoE) - Get it right from the beginning
-- Basic concept and assessment of DoE
-- Optimization of LC-MS based clinical assay by DoE

Short Course & Workshop Lunch Mixer

Location: Steinbeck Foyer

Workshop: Ion Mobility in the Clinical Lab?

Location: Steinbeck 1

Christopher Chouinard, PhD

Florida Institute of Technology

Robin Kemperman, PhD

Children's Hospital of Philadelphia

Objective

Workshop attendees will learn about the basic operating principles of various ion mobility techniques, the potential benefits and challenges to its routine implementation in the clinical lab, and several potential 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 and folding dynamics. Despite its many 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 IMS techniques/vendor platforms. This workshop will introduce the common IMS techniques (e.g., drift tube, traveling wave, FAIMS/DMS, etc.) and their operating principles, expanding upon the benefits of incorporating IMS into conventional LC-MS/MS workflows and discussing the challenges that have limited such incorporation. 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 current (and potentially future) applications of IMS to the clinical lab

Syllabus
1. Basic Operating Conditions of IMS: Electric field application, experimental conditions (temperature, pressure, gas composition)
2. Different IMS techniques: Drift tube/traveling wave, field asymmetric/differential mobility, emerging techniques (i.e., TIMS, SLIM, cIMS, etc.)
3. Applications: Current examples from metabolomics, lipidomics, and proteomics

Welcome Orientation

Location: De Anza

Chris Herold, PhD, MBA

MSACL

Stephen Master, MD, PhD

Children's Hospital of Philadelphia

Tim Garrett, PhD

University of Florida College of Medicine

Kara Lynch, PhD

University of California San Francisco

Alan Rockwood, PhD, DABCC

University of Utah, School of Medicine

Cory Bystrom, PhD

Ultragenyx

Opening Orientation with (1) a brief welcome from Chris Herold, (2) a brief presentation from Stephen Master (President of AACC), (2) an introduction to our new JMSACL co-Editors-in-Chief, Kara Lynch and Tim Garrett (and acknowledgement of founding co-Editors-in-Chief, Alan Rockwood and Michael Vogeser, who brought the journal to this point), and (3) an official welcome from the Chair of the MSACL 2022 Steering Committee, Cory Bystrom.

State of the Science

Location: De Anza

Cory Bystrom, PhD

Ultragenyx

Michael Angelo, MD, PhD

Stanford University School of Medicine

Kara Lynch, PhD

University of California San Francisco

Stefani Thomas, PhD, DABCC, NRCC

University of Minnesota

Break

Location: De Anza Foyer

Beyond the Human Genome: A Million Person Precision Population Health Project

Location: De Anza

Leroy Hood, MD, PhD

Institute for Systems Biology

The vision of this project is that we will develop the infrastructure to employ a data-driven approach to optimizing the health trajectory of individuals for body and brain. We have two large populations (5,000 and 10,000) that have validated this approach for body and brain health, respectively. These studies have led to us pioneering the science of wellness and prevention. This project will require the acquisition of key partners for execution, which will be delineated. We are approaching the Federal Government for funding, as we did for the first Human Genome Project. This project will lead to striking new knowledge about medicine, it will catalyze the initiation of start-up companies and it will catalyze a paradigm shift in healthcare from a disease orientation to a wellness and prevention orientation. This will catalyze the largest paradigm shift in medicine, ever.

Break

Location: De Anza Foyer

The Clinical Laboratory Perspective on Wellness Testing: Let’s Take a Look Under the Hood

Location: De Anza

Geoff Baird, MD, PhD

University of Washington

As medical science continues to make gains in the elucidation of disease pathophysiology and the discovery of cures , some have questioned the value of dedicating dwindling financial resources to maintaining wellness rather than to fighting disease per se. While both approaches are meritorious and complementary, neither approach is alone sufficient to ensure the health of a population. One major problem with the focus on wellness is the Bayesian dilemma that the positive predictive value of clinical laboratory testing in apparently healthy people is often low, as the specificities of few clinical tests are high enough to ensure that most positive results are true. The impact of this dilemma on laboratory-based wellness approaches will be discussed.

Break

Location: De Anza Foyer

The Michael S. Bereman Award for Innovative Clinical Proteomics : Seeing the Forest for the Trees: Taking a Step Back to Move Proteomics Forward in the Clinical Lab

Location: De Anza

Mari DeMarco, PhD, DABCC, FACB, FCACB

University of British Columbia

Want to run a new test in your clinical lab that takes multiple days to prep, has a complicated (and costly) calibration scheme, and a detection approach so selective it could miss the analyte of interest? If that doesn’t sound appealing, you would be in the majority! While the analytical advantages of mass spectrometry resulted in it decisively displacing ligand binding methods as the gold standard approach for protein quantitation, making progress on the routine testing front has taken additional effort. Here we look at how re-evaluating the status quo in clinical proteomics has helped us take leaps forward and implement protein mass spectrometry to improve patient care. About the Award

Opening Exhibits Reception

Location: Exhibit Hall - Serra

Mentor Booth Tours

Location: Exhibit Hall - Serra

Meet at Poster #50

Troubleshooting Poster Session

Location: Exhibit Hall - Serra

Hospitality Lounge

Location: Jacks

Inside of Jacks Club Room (Portola Hotel)