Laboratory Test Names Matter: A Survey on What Works and What Doesn't Work for Orders and Results.

CONTEXT.­: Health care providers were surveyed to determine their ability to correctly decipher laboratory test names and their preferences for laboratory test names and result displays. OBJECTIVE.­: To confirm principles for laboratory test nomenclature and display and to compare and contrast the abilities and preferences of different provider groups for laboratory test names. DESIGN.­: Health care providers across different specialties and perspectives completed a survey of 38 questions, which included participant demographics, real-life examples of poorly named laboratory orders that they were asked to decipher, an assessment of vitamin D test name knowledge, their preferences for ideal names for tests, and their preferred display for test results. Participants were grouped and compared by profession, level of training, and the presence or absence of specialization in informatics and/or laboratory medicine. RESULTS.­: Participants struggled with poorly named tests, especially with less commonly ordered tests. Participants' knowledge of vitamin D analyte names was poor and consistent with prior published studies. The most commonly selected ideal names correlated positively with the percentage of the authors' previously developed naming rules (R = 0.54, P < .001). There was strong consensus across groups for the best result display. CONCLUSIONS.­: Poorly named laboratory tests are a significant source of provider confusion, and tests that are named according to the authors' naming rules as outlined in this article have the potential to improve test ordering and correct interpretation of results. Consensus among provider groups indicates that a single yet clear naming strategy for laboratory tests is achievable.

Proceedings of the Association for Pathology Informatics Bootcamp 2022.

The Pathology Informatics Bootcamp, held annually at the Pathology Informatics Summit, provides pathology trainees with essential knowledge in the rapidly evolving field of Pathology Informatics. With a focus on data analytics, data science, and data management in 2022, the bootcamp addressed the growing importance of data analysis in pathology and laboratory medicine practice. The expansion of data-related subjects in Pathology Informatics Essentials for Residents (PIER) and the Clinical Informatics fellowship examinations highlights the increasing significance of these skills in pathology practice in particular and medicine in general. The curriculum included lectures on databases, programming, analytics, machine learning basics, and specialized topics like anatomic pathology data analysis and dashboarding.

Influence of user-centered clinical decision support on pediatric blood product ordering errors.

BACKGROUND: Children are at increased risk from transfusion-related medical errors. Clinical decision support (CDS) can enhance pediatric providers' decision-making regarding transfusion practices including indications, volume, rate, and special processing instructions. Our objective was to use CDS in a pediatric health system to reduce:blood product-related safety events from ordering errors;special processing ordering errors for patients with T-cell dysfunction, sickle cell disease (SCD), or thalassemia;transfusions administered faster than 5 mL/kg/h. MATERIALS AND METHODS: In this single-center before and after quality improvement study, we evaluated how user-centered design of pediatric blood product orders influenced pediatric transfusion practices and outcomes. Safety events were identified through active and passive surveillance. Other clinically relevant outcomes were identified through electronic health record queries. RESULTS: Blood product-related safety events from ordering errors did not change significantly from the baseline period (6 events, 0.4 per month, from 1/1/2018-3/27/2019) to the intervention period (1 event, 0.1 per month, from 3/28/2019-12/31/2019; rate ratio: 0.27 [0.01-2.25]). Packed red blood cell (PRBC) and platelet orders for patients with T-cell dysfunction that did not specify irradiation decreased significantly from 488/12,359 (3.9%) to 204/6,711 (3.0%, risk ratio: 0.77 [0.66-0.90]). PRBC orders for patients with SCD or thalassemia that did not specify phenotypically similar units fell from 386/2,876 (13.4%) to 57/1,755 (3.2%, risk ratio: 0.24 [0.18-0.32]). Transfusions administered faster than 5 mL/kg/h decreased from 4,112/14,641 (28.1%) to 2,125/9,263 (22.9%, risk ratio: 0.82 [0.78-0.85]). DISCUSSION: User-centered design of CDS for pediatric blood product orders significantly reduced special processing ordering errors and inappropriate transfusion rates. Larger studies are needed to evaluate the impact on safety events.

Comprehensive Genomic Profiling of High-Risk Pediatric Cancer Patients Has a Measurable Impact on Clinical Care.

PURPOSE: Profiling of pediatric cancers through deep sequencing of large gene panels and whole exomes is rapidly being adopted in many clinical settings. However, the most impactful approach to genomic profiling of pediatric cancers remains to be defined. METHODS: We conducted a prospective precision medicine trial, using whole-exome sequencing of tumor and germline tissue and whole-transcriptome sequencing (RNA Seq) of tumor tissue to characterize the mutational landscape of 127 tumors from 126 unique patients across the spectrum of pediatric brain tumors, hematologic malignancies, and extracranial solid tumors. RESULTS: We identified somatic tumor alterations in 121/127 (95.3%) tumor samples and identified cancer predisposition syndromes on the basis of known pathogenic or likely pathogenic germline mutations in cancer predisposition genes in 9/126 patients (7.1%). Additionally, we developed a novel scoring system for measuring the impact of tumor and germline sequencing, encompassing therapeutically relevant genomic alterations, cancer-related germline findings, recommendations for treatment, and refinement of risk stratification or prognosis. At least one impactful finding from the genomic results was identified in 108/127 (85%) samples sequenced. A recommendation to consider a targeted agent was provided for 82/126 (65.1%) patients. Twenty patients ultimately received therapy with a molecularly targeted agent, representing 24% of those who received a targeted agent recommendation and 16% of the total cohort. CONCLUSION: Paired tumor/normal whole-exome sequencing and tumor RNA Seq of de novo or relapsed/refractory tumors was feasible and clinically impactful in high-risk pediatric cancer patients.

Electronic Health Records and Genomics: Perspectives from the Association for Molecular Pathology Electronic Health Record (EHR) Interoperability for Clinical Genomics Data Working Group.

The use of genomics in medicine is expanding rapidly, but information systems are lagging in their ability to support genomic workflows both from the laboratory and patient-facing provider perspective. The complexity of genomic data, the lack of needed data standards, and lack of genomic fluency and functionality as well as several other factors have contributed to the gaps between genomic data generation, interoperability, and utilization. These gaps are posing significant challenges to laboratory and pathology professionals, clinicians, and patients in the ability to generate, communicate, consume, and use genomic test results. The Association for Molecular Pathology Electronic Health Record Working Group was convened to assess the challenges and opportunities and to recommend solutions on ways to resolve current problems associated with the display and use of genomic data in electronic health records.

A Survey of LOINC Code Selection Practices Among Participants of the College of American Pathologists Coagulation (CGL) and Cardiac Markers (CRT) Proficiency Testing Programs.

CONTEXT.­: Biomedical terminologies such as Logical Observation Identifiers, Names, and Codes (LOINC) were developed to enable interoperability of health care data between disparate health information systems to improve patient outcomes, public health, and research activities. OBJECTIVE.­: To ascertain the utilization rate and accuracy of LOINC terminology mapping to 10 commonly ordered tests by participants of the College of American Pathologists (CAP) Proficiency Testing program. DESIGN.­: Questionnaires were sent to 1916 US and Canadian laboratories participating in the 2018 CAP coagulation (CGL) and/or cardiac markers (CRT) surveys requesting information on practice setting, instrument(s) and test method(s), and LOINC code selection and usage in the laboratory and electronic health records. RESULTS.­: Ninety of 1916 CGL and/or CRT participants (4.7%) responded to the questionnaire. Of the 275 LOINC codes reported, 54 (19.6%) were incorrect: 2 codes (5934-2 and 12345-1) (0.7%) did not exist in the LOINC database and the highest error rates were observed in the property (27 of 275, 9.8%), system (27 of 275, 9.8%), and component (22 of 275, 8.0%) LOINC axes. Errors in LOINC code selection included selection of the incorrect component (eg, activated clotting time instead of activated partial thromboplastin time); selection of panels that can never be used to obtain an individual analyte (eg, prothrombin time panel instead of international normalized ratio); and selection of an incorrect specimen type. CONCLUSIONS.­: These findings of real-world LOINC code implementation across a spectrum of laboratory settings should raise concern about the reliability and utility of using LOINC for clinical research or to aggregate data.

Formative Usability Testing Reduces Severe Blood Product Ordering Errors.

BACKGROUND: Medical errors in blood product orders and administration are common, especially for pediatric patients. A failure modes and effects analysis in our health care system indicated high risk from the electronic blood ordering process. OBJECTIVES: There are two objectives of this study as follows:(1) To describe differences in the design of the original blood product orders and order sets in the system (original design), new orders and order sets designed by expert committee (DEC), and a third-version developed through user-centered design (UCD).(2) To compare the number and type of ordering errors, task completion rates, time on task, and user preferences between the original design and that developed via UCD. METHODS: A multidisciplinary expert committee proposed adjustments to existing blood product order sets resulting in the DEC order set. When that order set was tested with front-line users, persistent failure modes were detected, so orders and order sets were redesigned again via formative usability testing. Front-line users in their native clinical workspaces were observed ordering blood in realistic simulated scenarios using a think-aloud protocol. Iterative adjustments were made between participants. In summative testing, participants were randomized to use the original design or UCD for five simulated scenarios. We evaluated differences in ordering errors, time on task, and users' design preference with two-sample t-tests. RESULTS: Formative usability testing with 27 providers from seven specialties led to 18 changes made to the DEC to produce the UCD. In summative testing, error-free task completion for the original design was 36%, which increased to 66% in UCD (30%, 95% confidence interval [CI]: 3.9-57%; p = 0.03). Time on task did not vary significantly. CONCLUSION: UCD led to substantially different blood product orders and order sets than DEC. Users made fewer errors when ordering blood products for pediatric patients in simulated scenarios when using the UCD orders and order sets compared with the original design.

Expanding the Scope of The Journal of Molecular Diagnostics to the Informatics Subdivision of the Association for Molecular Pathology.

This editorial describes the expanded scope of The Journal of Molecular Diagnostics, to include informatics-based articles.

Host Genome Variation is Associated with Neurocognitive Outcome in Survivors of Pediatric Medulloblastoma.

Host genome analysis is a promising source of predictive information for long-term morbidity in cancer survivors. However, studies on genetic predictors of long-term outcome, particularly neurocognitive function following chemoradiation in pediatric oncology, are limited. Here, we evaluated variation in host genome of long-term survivors of medulloblastoma and its association with neurocognitive outcome. Whole-genome sequencing was conducted on peripheral blood of long-term survivors of pediatric medulloblastoma who also completed neuropsychological testing. Cognitively impaired and less impaired survivors did not differ in exposure to chemoradiation therapy or age at treatment. Unsupervised consensus clustering yielded two distinct variant clusters that were significantly associated with neurocognitive outcome. Interestingly, 34 of the 36 significant variants were found in noncoding DNA regions with unknown regulatory function. A separate unsupervised cluster analysis of variants within DNA repair genes identified discrete variant groups that were not associated with neurocognitive outcome, suggesting that variations in genes corresponding to a single functional group may be insufficient to predict long-term outcome alone. These findings are supportive of the presence of a genetic diathesis for treatment-related neurocognitive morbidity in medulloblastoma that may be driven by variation in noncoding regulatory elements.

A Model Information Management Plan for Molecular Pathology Sequence Data Using Standards: From Sequencer to Electronic Health Record.

Incorporating genetic variant data into the electronic health record (EHR) in discrete computable fashion has vexed the informatics community for years. Genetic sequence test results are typically communicated by the molecular laboratory and stored in the EHR as textual documents. Although text documents are useful for human readability and initial use, they are not conducive for data retrieval and reuse. As a result, clinicians often struggle to find historical gene sequence results on a series of oncology patients within the EHR that might influence the care of the current patient. Second, identification of patients with specific mutation results in the EHR who are now eligible for new and/or changing therapy is not easily accomplished. Third, the molecular laboratory is challenged to monitor its sequencing processes for nonrandom process variation and other quality metrics. A novel approach to address each of these issues is presented and demonstrated. The authors use standard Health Level 7 laboratory result message formats in conjunction with international standards, Systematized Nomenclature of Medicine Clinical Terms and Human Genome Variant Society nomenclature, to represent, communicate, and store discrete gene sequence data within the EHR in a scalable fashion. This information management plan enables the support of the clinician at the point of care, enhances population management, and facilitates audits for maintaining laboratory quality.

Considerations for Genomic Data Privacy and Security when Working in the Cloud.

Next-generation sequencing produces large amounts of data. The complexity and data management issues associated with next-generation sequencing have led many laboratories to turn to cloud services, especially when internal information technology infrastructure is inadequate to support data requirements. In addition, public cloud repositories of variants are being increasingly utilized, and their data sets are being populated through crowdsourcing submissions of human genetic variation identified within laboratories. The purpose of this review is to describe the challenges of managing genomic data in the cloud and to discuss potential strategies to surmount these challenges in a compliant manner. The definitions and advantages of cloud systems are outlined. Special regulatory considerations for laboratories are included, and strategies for compliance in the US regulatory environment for genetic information in clinical patient care as well as in research and public databases are also discussed.

The Impact of Disruption of the Care Delivery System by Commercial Laboratory Testing in a Children's Health Care System.

CONTEXT.­: Disruption of outpatient laboratory services by routing the samples to commercial reference laboratories may seem like a cost-saving measure by the payers, but results in hidden costs in quality and resources to support this paradigm. OBJECTIVE.­: To identify differences when outpatient tests are performed at the Children's Healthcare of Atlanta (Children's) Hospital lab compared to a commercial reference lab, and the financial costs to support the reference laboratory testing. DESIGN.­: Outpatient testing was sent to 3 different laboratories specified by the payer. Orders were placed in the Children's electronic health record, blood samples were drawn by the Children's phlebotomists, samples were sent to the testing laboratory, and results appeared in the electronic health record. Data comparing the time to result, cancelled samples, and cost to sustain the system of ordering and reporting were drawn from multiple sources, both electronic and manual. RESULTS.­: The median time from phlebotomy to result was 0.7 hours for testing at the Children's lab and 20.72 hours for the commercial lab. The median time from result posting to caregiver acknowledgment was 5.4 hours for the Children's lab and 18 hours for the commercial lab. The commercial lab cancelled 2.7% of the tests; the Children's lab cancelled 0.8%. The financial cost to support online ordering and reporting for testing performed at commercial labs was approximately $640,000 per year. CONCLUSIONS.­: Tangible monetary costs, plus intangible costs related to delayed results, occur when the laboratory testing system is disrupted.

Laboratory Information Systems and Instrument Software Lack Basic Functionality for Molecular Laboratories.

Laboratory information systems (LISs) have some basic functionality necessary for molecular workflow that is glaringly absent. This study determined functionality gaps of LISs in molecular laboratories and the associated impact to workflow, efficiency, and security by collecting anonymous survey data from clinical laboratory professionals. A 34-question survey (30 required + 4 optional) was compiled using an online survey tool. Participants were recruited through several professional molecular society listservs and given 4 weeks to complete the survey. Data collected included participant demographics, scope of testing, software capabilities for the LIS and molecular instruments, and comments. Eighty respondents completed the entire survey. Many desired versus actual functionality gaps were identified. Prominent among these were bar coding, LIS interfacing, storage of preanalytical data, Health Insurance Portability and Accountability Act compliance/information security, and reporting. Much basic functionality is lacking in molecular LISs and molecular instrument software. Some of these results indicate that instruments and LISs are not compliant with the Health Insurance Portability and Accountability Act. Collaboration between molecular professionals and manufacturers of instruments and software is necessary to correct these deficits and is critically important to ensure the continued high quality and safety of molecular practice as the volume of testing skyrockets.

Standards and Guidelines for Validating Next-Generation Sequencing Bioinformatics Pipelines: A Joint Recommendation of the Association for Molecular Pathology and the College of American Pathologists.

Bioinformatics pipelines are an integral component of next-generation sequencing (NGS). Processing raw sequence data to detect genomic alterations has significant impact on disease management and patient care. Because of the lack of published guidance, there is currently a high degree of variability in how members of the global molecular genetics and pathology community establish and validate bioinformatics pipelines. Improperly developed, validated, and/or monitored pipelines may generate inaccurate results that may have negative consequences for patient care. To address this unmet need, the Association of Molecular Pathology, with organizational representation from the College of American Pathologists and the American Medical Informatics Association, has developed a set of 17 best practice consensus recommendations for the validation of clinical NGS bioinformatics pipelines. Recommendations include practical guidance for laboratories regarding NGS bioinformatics pipeline design, development, and operation, with additional emphasis on the role of a properly trained and qualified molecular professional to achieve optimal NGS testing quality.

Twenty Years of Digital Pathology: An Overview of the Road Travelled, What is on the Horizon, and the Emergence of Vendor-Neutral Archives.

Almost 20 years have passed since the commercial introduction of whole-slide imaging (WSI) scanners. During this time, the creation of various WSI devices with the ability to digitize an entire glass slide has transformed the field of pathology. Parallel advances in computational technology and storage have permitted rapid processing of large-scale WSI datasets. This article provides an overview of important past and present efforts related to WSI. An account of how the virtual microscope evolved from the need to visualize and manage satellite data for earth science applications is provided. The article also discusses important milestones beginning from the first WSI scanner designed by Bacus to the Food and Drug Administration approval of the first digital pathology system for primary diagnosis in surgical pathology. As pathology laboratories commit to going fully digitalize, the need has emerged to include WSIs into an enterprise-level vendor-neutral archive (VNA). The different types of VNAs available are reviewed as well as how best to implement them and how pathology can benefit from participating in this effort. Differences between traditional image algorithms that extract pixel-, object-, and semantic-level features versus deep learning methods are highlighted. The need for large-scale data management, analysis, and visualization in computational pathology is also addressed.

Next-Generation Sequencing Informatics: Challenges and Strategies for Implementation in a Clinical Environment.

CONTEXT: -Next-generation sequencing (NGS) is revolutionizing the discipline of laboratory medicine, with a deep and direct impact on patient care. Although it empowers clinical laboratories with unprecedented genomic sequencing capability, NGS has brought along obvious and obtrusive informatics challenges. Bioinformatics and clinical informatics are separate disciplines with typically a small degree of overlap, but they have been brought together by the enthusiastic adoption of NGS in clinical laboratories. The result has been a collaborative environment for the development of novel informatics solutions. Sustaining NGS-based testing in a regulated clinical environment requires institutional support to build and maintain a practical, robust, scalable, secure, and cost-effective informatics infrastructure. OBJECTIVE: -To discuss the novel NGS informatics challenges facing pathology laboratories today and offer solutions and future developments to address these obstacles. DATA SOURCES: -The published literature pertaining to NGS informatics was reviewed. The coauthors, experts in the fields of molecular pathology, precision medicine, and pathology informatics, also contributed their experiences. CONCLUSIONS: -The boundary between bioinformatics and clinical informatics has significantly blurred with the introduction of NGS into clinical molecular laboratories. Next-generation sequencing technology and the data derived from these tests, if managed well in the clinical laboratory, will redefine the practice of medicine. In order to sustain this progress, adoption of smart computing technology will be essential. Computational pathologists will be expected to play a major role in rendering diagnostic and theranostic services by leveraging "Big Data" and modern computing tools.

Computational Pathology: A Path Ahead.

CONTEXT: We define the scope and needs within the new discipline of computational pathology, a discipline critical to the future of both the practice of pathology and, more broadly, medical practice in general. OBJECTIVE: To define the scope and needs of computational pathology. DATA SOURCES: A meeting was convened in Boston, Massachusetts, in July 2014 prior to the annual Association of Pathology Chairs meeting, and it was attended by a variety of pathologists, including individuals highly invested in pathology informatics as well as chairs of pathology departments. CONCLUSIONS: The meeting made recommendations to promote computational pathology, including clearly defining the field and articulating its value propositions; asserting that the value propositions for health care systems must include means to incorporate robust computational approaches to implement data-driven methods that aid in guiding individual and population health care; leveraging computational pathology as a center for data interpretation in modern health care systems; stating that realizing the value proposition will require working with institutional administrations, other departments, and pathology colleagues; declaring that a robust pipeline should be fostered that trains and develops future computational pathologists, for those with both pathology and nonpathology backgrounds; and deciding that computational pathology should serve as a hub for data-related research in health care systems. The dissemination of these recommendations to pathology and bioinformatics departments should help facilitate the development of computational pathology.