= Emerging. More than 5 years before clinical availability. (26.62%)
= Expected to be clinically available in 1 to 4 years. (38.91%)
= Clinically available now. (34.47%)
MSACL 2020 US : Frank

MSACL 2020 US Abstract

Topic: Practical Training

Podium Presentation in Room 6 on Wednesday at 11:00 (Chair: Elizabeth Frank / Jacqueline Hubbard)

Free Climb or Free Solo: Guidance and Accounts of Establishing Reference Intervals for LDT Mass Spectrometry Assays

Elizabeth Frank, Kelly Doyle

Presenter Bio(s): Elizabeth Frank, PhD, is a professor of pathology at the University of Utah and a medical director at ARUP Laboratories. She is a board-certified clinical chemist and a fellow of the AACC Academy. Dr. Frank's clinical scientific interests are focused on measurement of biogenic amines, porphyrins, and vitamins using HPLC and LC-MS/MS; evaluation of calculi composition using FTIR; and use of laboratory test results to evaluate health status.
Kelly Doyle, PhD, is a fellow of the AACC Academy and is a board-certified clinical chemist. As an assistant professor of pathology at the University of Utah and medical director at ARUP Laboratories, his interests involve the clinical application and implementation of mass spectrometry, emerging biomarkers, toxicology, endocrinology, and laboratory best practice. He has a special interest in training clinical chemistry fellows and pathology residents.

Authors: Elizabeth Frank, Kelly Doyle
University of Utah / ARUP Laboratories


Session description: Although assessment of reference intervals (RIs) is an integral component of laboratory medicine practice and so a requirement of LC-MS/MS assay development, establishing RIs using the traditional approach as described in the Clinical and Laboratory Standards Institute (CLSI) guidelines may not be feasible due to limited resources. Direct sampling is complicated by insufficient access to patients within varying interval partitions (e.g., pediatrics, pregnancy), and adoption or transferring of RIs is hindered by lack of assay standardization and unique population demographics. However, indirect sampling techniques using laboratory database results have significant practical advantages compared to direct sampling methods. The use of stored patient data can offer a faster and less costly means to developing RIs, particularly if multiple partitions based on characteristics such as age and sex are required or if selection criteria would cause much of a general healthy population to be excluded from participation in the study.

Numerous techniques designed to identify the distribution of healthy values in an uncharacterized dataset have been proposed. Recent reports have exposed flaws in the application of some techniques and reveal the need for careful evaluation of indirect methods to avoid potential limitations of these techniques and ensure development of accurate reference values.

In this practical training course, we will provide a brief review of the concept of RIs and the fundamentals for establishing, transferring, and verifying RIs. Our experience evaluating RIs for various LDT mass spectrometry assays with differing patient populations will be presented and examples of indirect methods using stored patient data to estimate RIs will be discussed.

Take Home Pearls

Attendees will gain knowledge of

1. Establishment and use of reference intervals in clinical laboratory practice.

2. Regulatory and guidance documents for establishing, transferring and verifying reference intervals.

3. Appropriate application of direct and indirect methods to determine population/sex/age-based reference intervals.

Financial Disclosure

SalaryyesUniversity of Utah
Board MemberyesAACC; ACLPS
IP Royaltyno

Planning to mention or discuss specific products or technology of the company(ies) listed above: