Journal:A model for design and implementation of a laboratory information management system specific to molecular pathology laboratory operations

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Full article title A model for design and implementation of a laboratory information management system specific to molecular pathology laboratory operations
Journal The Journal of Molecular Diagnostics
Author(s) Tomlinson, Eban; Goodman, Jennifer; Loftus, Margaret; Bitto, Stephen; Carpenter, Erica; Oddo, Richard; Judis, LuAnn; Ali, Shabab; Robinson, Wyatt E.; Carver, Miranda; Ganea, Mariana; McDonnell, Kristen; O'Neill, Diane; Starbuck, Jennifer; Johnson, Eric; Meister, Erik; Pohl, Jonathan; Spildener, Jessica; Shurtleff, Sheila; Sovie, Sheryl; Melendez, Cathleen; Krebs, Pamela; Riley, Jacquelyn D.; Wensel, Christine; Astbury, Caroline; Azzato, Elizabeth M.; Bosler, David S.; Brock, Jay E.; Cook, James R.; Cheng, Yu-Weu; Tu, Zheng J.; Cruise, M.; Henricks, Walter H.; Farkas, Daniel H.
Author affiliation(s) Semaphore Solutions, Cleveland Clinic
Primary contact Email: farkasd2 at ccf dot org
Year published 2022
Volume and issue S1525-1578(22)
Page(s) 00012-5
DOI 10.1016/j.jmoldx.2022.01.002
ISSN 1525-1578
Distribution license Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Website https://www.jmdjournal.org/article/S1525-1578(22)00012-5/fulltext
Download https://www.jmdjournal.org/action/showPdf?pii=S1525-1578%2822%2900012-5 (PDF)

Abstract

The Molecular Pathology Section of Cleveland Clinic (Cleveland, OH) has undergone enhancement of its testing portfolio and processes. An electronic- and paper-based data management system was replaced with a commercially available laboratory information management system (LIMS) solution, a separate bioinformatics platform, customized test-interpretation applications, a dedicated accessioning service, and a results-releasing solution. The LIMS solution manages complex workflows, large-scale data packets, and process automation. However, a customized approach was required for the LIMS since a survey of commercially available off-the-shelf (COTS) software solutions revealed none met the diverse and complex needs of Cleveland Clinic's molecular pathology service. The project utilized the expertise of clinical laboratorians, pathologists, genetics counselors, bioinformaticians, and systems analysts in partnering with software-engineering consultants to design and implement a solution. Concurrently, Agile software development best practices were formulated, which may be emulated for scalable and cost-effective laboratory-authored software.

Keywords: molecular pathology, laboratory information management system, LIMS, bioinformatics, software development, Agile-Scrum

Introduction

Data management needs in clinical molecular pathology laboratories differ in substantive ways from those in other clinical laboratories and anatomical pathology labs. [1,2,3,4] Conventional laboratory information systems (LISs) historically have not inherently supported the needs of molecular pathology laboratories to the extent that they have in other laboratory disciplines and operations. [2] Molecular pathology laboratories have often relied on a combination of manual methods, spreadsheets, and nonintegrated and/or modular software to meet data management and operational needs.

Such was the situation in the Molecular Pathology Section, Pathology & Laboratory Medicine Institute, Cleveland Clinic (Cleveland, OH) in early 2017. A revitalization and growth plan for the section—which included expansion of personnel, equipment, testing platforms, and test development—was undertaken. An improvement deemed fundamental to this re-invention process was a new laboratory information management system (LIMS) to reduce and eventually replace the outdated, largely paper- and electronic spreadsheet–based information and workflow management system.

While the overhaul of the laboratory service was substantial, the focus of this report is limited to a description of a replicable process for the modernization of information and workflow management specific to a clinical molecular pathology laboratory. The process employed a customer–vendor relationship. Out of necessity, the relationship was a partnership due to the complementary and nontechnical skill sets of each party. The overall goal was to digitize workflow based on paper and Excel (Microsoft, Redmond, WA) across a complex, multidisciplinary molecular pathology and cytogenomics clinical laboratory service. This digitization was accomplished through a custom-architected software solution.

This article describes a model for the design and implementation of a LIMS that meets the diverse information management needs of a full-service clinical molecular pathology laboratory, emphasizes the integral importance of a well-structured development process, and describes a novel application of modern software-based project management methods and third-party partnerships for building and deploying a LIMS suitable for a modern molecular pathology laboratory.

Materials and methods

Scope definition

The goal of the project was to deploy a LIMS to modernize data and workflow management of the clinical molecular pathology laboratory, including cytogenomics workflows. The project encompassed a complete overhaul of paper and electronic spreadsheet–based data handling methods into a comprehensive, integrated electronic platform. Objectives were identified to define the scope and focus priorities of the project:

  1. Design and implement an electronic information system to support the specialized requirements and workflow of a full-service clinical molecular pathology laboratory, and to fulfill needs unmet by conventional LISs.
  2. Support the range of clinical testing performed, including adult, pediatric, and somatic mutation detection in tumor tissues, blood, and bone marrow; chromosome analysis; germline genetic testing for diagnosis and/or carrier screening; and pharmacogenomics.
  3. Support the range of complex data management of analytical methods (and applications) in use, including polymerase chain reaction (PCR); reverse transcription polymerase chain reaction (RT-PCR); next-generation sequencing (NGS); B- and T-cell gene rearrangement (PCR + capillary electrophoresis); chromosomal microarray analysis; fluorescence in situ hybridization (FISH); cytogenetic testing; and (genotyping by) mass spectrometry.
  4. Integrate into the information technology (IT) environment of the institution for accessioning and resulting, particularly the electronic health record (EHR) system and the conventional clinical laboratory and anatomical pathology information systems. (More specifically, Cleveland Clinic was using Sunquest Laboratory version 7.2 [Sunquest Information Systems, Tucson, AZ] and CoPath version 2014 [Cerner, N. Kansas City, MO] at the time, but these are now in the process of being replaced by Epic Beaker version November 2020 [Epic Systems, Verona, WI].)

Needs assessment and partner selection

Given the complexity and multifaceted nature of the project, two key needs were recognized: professional project management guided by domain expertise in molecular testing laboratories, and experienced and expert software development professionals who could bring to bear state-of-the-art software development tools and techniques. Between two and four software developers were dedicated to the project at various stages. One business-based quality assurance analyst was included, who served as the conduit for the translation of laboratory-specific requirements into software requirements. A Ph.D.-level molecular biologist with project management expertise was hired to apply process rigor and organization to direct LIMS development and implementation (among other projects). [5] Laboratory-based personnel participated in their various subject matter domains as their primary responsibilities to patient care allowed. Partnership with a team of software engineers was established. This team worked with molecular pathologists and laboratory personnel (subject matter experts) to design and build the full software solution. Peer-to-peer relationships were formed between the clinical laboratory project manager and software project managers as control points for the project.

Prior to the beginning of this extensive development project, due diligence was undertaken to evaluate whether, or to what extent, commercially available information systems could meet the needs at hand. This assessment indicated that some systems on the market could provide some of the functional requirements, and that development entirely from scratch was not required. NGS–centric LIMS software was selected for licensure (BaseSpace Clarity LIMS by Illumina, San Diego, CA). As licensed, this software was focused narrowly on supporting particular elements of NGS workflows. Its distinguishing characteristics were customizability and extensibility that could ultimately support the objectives of the laboratory, including a wide portfolio of molecular diagnostics tests performed and the need for systems integration. Compatibility with the third-party commercial bioinformatics software that the laboratory had previously chosen (Clinical Genomics Workspace version 6.15.1 by PierianDx, Creve Couer, MO) was another key deciding criterion.

Technology platforms and software tools

The software engineering team used Jira and Confluence web-based software (Atlassian, San Francisco, CA) to organize development tasks and to project documentation, respectively. Version control was implemented in the web-based GitHub software host (San Francisco, CA). A continuous-integration pipeline (Table 1) was built using TeamCity software version 2019.1 (JetBrains, Prague, Czech Republic). The PyCharm version 2019.1 (JetBrains), Docker Desktop Community version 2.1.0.5 (Docker, Palo Alto, CA), VirtualBox version 6.1 (Oracle, Austin, TX), and Postman version 8.1 (Postman, San Francisco, CA) software solutions were used to facilitate local testing and development.

Table 1. Definitions of terms for the Agile-Scrum software development method applied.
Term Definition
Stakeholders The group of individuals who work with, and would be impacted by, the software system being developed (i.e., laboratory and medical directors, laboratory managers, laboratory supervisors, medical/laboratory technologists, pathologists, geneticists, bioinformaticians, staff scientists, clinical systems analysts, and a revolving cast from the larger Cleveland Clinic information-technology group).
Agile project management A system of practice to manage project delivery using an iterative approach. Optimization is achieved via continuous releases that include changes based on stakeholder review at each iteration. The process is useful for addressing highly complex problems in a mechanistic, incremental way.
Scrum Agile framework that encourages cross-functional team progress through short, measured iterations. Each problem is addressed in focused iterations called sprints, in which engineering management and build practices are used for addressing the complexity at hand. Outcomes are predicted and control of risk is assessed incrementally and via empirical observation.
LIMS workflow Clinical laboratory test workflows have three components: i) pre-analytical, ii) analytical, and iii) post-analytical. A LIMS, or other supporting software, digitally models test workflows, storing and classifying large volumes of laboratory workflow data, while also automating laborious, repetitive workflow tasks that risk compounding human error. The term "LIMS workflow" alludes to customized, digital workflow models that span the pre-analytical, analytical, and post-analytical stages.
External program plug-in (EPP) A Clarity LIMS–specific term that refers to a standalone script file accessible within the LIMS to perform calculations, transformations, or integrations too complex or cumbersome to configure within the LIMS itself.
Application programming interface (API) Software intermediary that serves to connect multiple applications, allowing them to exchange information. An API dictates what information can be sent and received by a given application and may add security restrictions. It also abstracts underlying code when interacting with other software. An analogy is a person (application A) ordering at a restaurant (application B); the menu represents the API.
Continuous integration (CI) pipeline The practice of automating the grouping of changes (typically software code, but also software build pipelines and automated tests) from multiple contributors into a single software project; this is software industry best practice, allowing developers to incorporate code changes into a central repository where builds and tests can be run more frequently and easily.
Development environment System in which new features are actively developed.
Test environment System in which newly developed features are tested. User-acceptance testing occurs in this environment; if the test fails, the software goes back to development, and if it passes, it is promoted to staging.
Staging environment System used for validating changes prior to promotion to production. The system should mirror production in all ways except those new changes to be tested.
Production environment The active system processing patient samples. This environment processes protected health information (PHI) and needs to be treated in accordance with HIPAA regulations.

Python (Python Software Foundation, Wilmington, DE), a popular, general-purpose, high-level programming language with well-documented, well-supported engineering standards, was used to develop external program plug-ins, automated test scripts, report templates, and other services. A report-generation and sign-out application named AVRO (analytically validated reporting object; see subsequent sections) was built on a Python server with an Angular JavaScript front-end. For LIMS workflows, the open-source Python S4-Clarity library[1] was used to support batch-analyte data (spreadsheet-formatted) parsing, laboratory instrument integrations, complex library pooling, de-multiplexing, and other computations on analytes. The Jinja web-based template engine library[2] was used for default report-content templating to support clinical interpretation and clinical report generation in AVRO.

Project management

The general project management process used was Agile-Scrum in Jira, chosen by the owner of the critical path for project completion (i.e., the software development team). In the project, Agile-Scrum was supplemented with additional roles and processes tailored to work in the hybrid clinical laboratory service/software development consultant environment. It became obvious that definitions and vocabulary differed between these two groups of subject matter experts (i.e., clinical laboratory and software engineering professionals). Selected terms are defined in Table 1. Key roles and activities of the Agile-Scrum development process, as applied in this project, are described in the next subsection.

Key roles

Four key roles corresponding to major development and validation phases were identified as gatekeepers of the development process. These gatekeepers controlled the promotion of a deliverable through the process and, thus, control of a rapidly evolving process was retained. The subject matter experts in these roles worked in tight collaboration to ensure that the highest possible quality was achieved. Note that at relevant steps, bioinformatics professionals, Ph.D.-level laboratory director-designees, and/or M.D.-level pathologists reviewed and approved changes as appropriate.

Key Role 1: Business Analyst (Extant within Software Development Team)

The business analyst assumed responsibility and accountability for the elicitation and decomposition of requirements into granular requirements that were logically defined and complete. This work output was added to the stakeholder consensus process.

Key Role 2: Software Development Team

The software development team was the consumer of approved granular requirements and the developer of software designed to meet those requirements. This team was involved in developing automated tests to validate that the software written did in fact meet the granular requirements as specified. This work output was collected into a release candidate and, upon passing the automated tests, was released into Phase 3, user acceptance testing. This team was self-organizing and chose the Scrum framework to align themselves into two-week iterations (.e., sprints).

Key Role 3: Clinical Systems Analyst (Extant within Laboratory Team)

The clinical systems analyst served as the first round of testing for the laboratory service, owing to the proximity of the role to the laboratory and to the expertise in the laboratory's process and informatics architecture. The work assigned to this role was to coordinate and, in some cases, to perform the tasks in development/validation (Phase 3), user acceptance testing. The output of this work was a pass/fail decision that either sent the release candidate back to development or promoted the release candidate to staging.

Key Role 4: Laboratory Manager

The laboratory manager signed documentation approving the release candidate for promotion to the production environment after review of successful pre-production runs that were performed using test samples in the laboratory and after verification that all test plans and checklists were completed.

Key activities

References

  1. Semaphore Solutions (6 April 2021). "SemaphoreSolutions / s4-clarity-lib". GitHub. https://github.com/SemaphoreSolutions/s4-clarity-lib. Retrieved 04 August 2021. 
  2. Ronacher, A. (18 May 2021). "pallets / jinja". GitHub. https://github.com/pallets/jinja. Retrieved 04 August 2021. 

Notes

This presentation is faithful to the original, with only a few minor changes to presentation, grammar, and punctuation. In some cases important information was missing from the references, and that information was added. Everything else remains true to the original article, per the "NoDerivatives" portion of the distribution license.