An Integrated Process for Co-Developing and Implementing Written and Computable Clinical Practice Guidelines.

The goal of this article is to describe an integrated parallel process for the co-development of written and computable clinical practice guidelines (CPGs) to accelerate adoption and increase the impact of guideline recommendations in clinical practice. From February 2018 through December 2021, interdisciplinary work groups were formed after an initial Kaizen event and using expert consensus and available literature, produced a 12-phase integrated process (IP). The IP includes activities, resources, and iterative feedback loops for developing, implementing, disseminating, communicating, and evaluating CPGs. The IP incorporates guideline standards and informatics practices and clarifies how informaticians, implementers, health communicators, evaluators, and clinicians can help guideline developers throughout the development and implementation cycle to effectively co-develop written and computable guidelines. More efficient processes are essential to create actionable CPGs, disseminate and communicate recommendations to clinical end users, and evaluate CPG performance. Pilot testing is underway to determine how this IP expedites the implementation of CPGs into clinical practice and improves guideline uptake and health outcomes.

An Evaluation Framework for a Novel Process to Codevelop Written and Computable Guidelines.

Clinical practice guidelines (CPGs) support individual and population health by translating new, evidence-based knowledge into recommendations for health practice. CPGs can be provided as computable, machine-readable guidelines that support the translation of recommendations into shareable, interoperable clinical decision support and other digital tools (eg, quality measures, case reports, care plans). Interdisciplinary collaboration among guideline developers and health information technology experts can facilitate the translation of written guidelines into computable ones. The benefits of interdisciplinary work include a focus on the needs of end-users who apply guidelines in practice through clinic decision support systems as part of the Centers for Disease Control and Prevention's (CDC's) Adapting Clinical Guidelines for the Digital Age (ACG) initiative, a group of interdisciplinary experts proposed a process to facilitate the codevelopment of written and computable CPGs, referred to as the "integrated process (IP)."1 This paper presents a framework for evaluating the IP based on a combination of vetted evaluation models and expert opinions. This framework combines 3 types of evaluations: process, product, and outcomes. These evaluations assess the value of interdisciplinary expert collaboration in carrying out the IP, the quality, usefulness, timeliness, and acceptance of the guideline, and the guideline's health impact, respectively. A case study is presented that illustrates application of the framework.

The Clinical Laboratory Is an Integral Component to Health Care Delivery : An Expanded Representation of the Total Testing Process.

OBJECTIVES: Developing an expanded representation of the total testing process that includes contemporary elements of laboratory practice can be useful to understanding and optimizing testing workflows across clinical laboratory and patient care settings. METHODS: Published literature and meeting reports were used by the coauthors to inform the development of the expanded representation of the total testing process and relevant examples describing its uses. RESULTS: A visual representation of the total testing process was developed and contextualized to patient care scenarios using a number of examples covering the detection of blood culture contamination, use of next-generation sequencing, and pharmacogenetic testing. CONCLUSIONS: The expanded representation of the total testing process can serve as a model and framework to document and improve the use of clinical testing within the broader context of health care delivery. This representation recognizes increased engagement among clinical laboratory professionals with patients and other health care providers as essential to making informed decisions. The increasing use of data is highlighted as important to ensuring quality, appropriate test utilization, and sustaining an efficient workflow across clinical laboratory and patient care settings. Maintaining a properly resourced and competent workforce is also featured as an essential component to the testing process.

Use of large scale EHR data to evaluate A1c utilization among sickle cell disease patients.

BACKGROUND: The glycated hemoglobin (A1c) test is not recommended for sickle cell disease (SCD) patients. We examine ordering patterns of diabetes-related tests for SCD patients to explore misutilization of tests among this underserved population. METHODS: We used de-identified electronic health record (EHR) data in the Cerner Health Facts™ (HF) data warehouse to evaluate the frequency of A1c and fructosamine tests during 2010 to 2016, for 37,151 SCD patients from 393 healthcare facilities across the United States. After excluding facilities with no A1c data, we defined three groups of facilities based on the prevalence of SCD patients with A1c test(s): adherent facilities (no SCD patients with A1c test(s)), minor non-adherent facilities, major non-adherent facilities. RESULTS: We determined that 11% of SCD patients (3927 patients) treated at 393 facilities in the US received orders for at least one A1c test. Of the 3927 SCD patients with an A1c test, only 89 patients (2.3%) received an order for a fructosamine test. At the minor non-adherent facilities, 5% of the SCD patients received an A1c test while 58% of the SCD patients at the least adherent facilities had at least one A1c test. Overall, the percent of A1c tests ordered for SCD patients between 2010 and 2016 remained similar. CONCLUSIONS: Inappropriate A1c test orders among a sickle cell population is a significant quality gap. Interventions to advance adoption of professional recommendations that advocate for alternate tests, such as fructosamine, can guide clinicians in test selection to reduce this quality gap are discussed. The informatics strategy used in this work can inform other largescale analyses of lab test utilization using de-identified EHR data.

Creation of an Expert Curated Variant List for Clinical Genomic Test Development and Validation: A ClinGen and GeT-RM Collaborative Project.

Modern genomic sequencing tests often interrogate large numbers of genes. Identification of appropriate reference materials for development, validation studies, and quality assurance of these tests poses a significant challenge for laboratories. It is difficult to develop and maintain expert knowledge to identify all variants that must be validated to ensure analytic and clinical validity. Additionally, it is usually not possible to procure appropriate and characterized genomic DNA reference materials containing the number and scope of variants required. To address these challenges, the Centers for Disease Control and Prevention's Genetic Testing Reference Material Program (GeT-RM) has partnered with the Clinical Genome Resource (ClinGen) to develop a publicly available list of expert curated, clinically important variants. ClinGen Variant Curation Expert Panels nominated 546 variants found in 84 disease-associated genes, including common pathogenic and difficult-to-detect variants. Variant types nominated included 346 single nucleotide variants, 104 deletions, 37 copy number variants, 25 duplications, 18 deletion-insertions, 5 inversions, 4 insertions, 2 complex rearrangements, 3 difficult-to-sequence regions, and 2 fusions. This expert-curated variant list is a resource that provides a foundation for designing comprehensive validation studies and for creating in silico reference materials for clinical genomic test development and validation.

Bringing the clinical laboratory into the strategy to advance diagnostic excellence.

OBJECTIVES: Clinical laboratory testing provides essential data for making medical diagnoses. Generating accurate and timely test results clearly communicated to the treating clinician, and ultimately the patient, is a critical component that supports diagnostic excellence. On the other hand, failure to achieve this can lead to diagnostic errors that manifest in missed, delayed and wrong diagnoses. CONTENT: Innovations that support diagnostic excellence address: 1) test utilization, 2) leveraging clinical and laboratory data, 3) promoting the use of credible information resources, 4) enhancing communication among laboratory professionals, health care providers and the patient, and 5) advancing the use of diagnostic management teams. Integrating evidence-based laboratory and patient-care quality management approaches may provide a strategy to support diagnostic excellence. Professional societies, government agencies, and healthcare systems are actively engaged in efforts to advance diagnostic excellence. Leveraging clinical laboratory capabilities within a healthcare system can measurably improve the diagnostic process and reduce diagnostic errors. SUMMARY: An expanded quality management approach that builds on existing processes and measures can promote diagnostic excellence and provide a pathway to transition innovative concepts to practice. OUTLOOK: There are increasing opportunities for clinical laboratory professionals and organizations to be part of a strategy to improve diagnoses.

Challenges and opportunities for integrating genetic testing into a diagnostic workflow: heritable long QT syndrome as a model.

BACKGROUND: An increasing number of diagnostic evaluations incorporate genetic testing to facilitate accurate and timely diagnoses. The increasing number and complexity of genetic tests continue to pose challenges in deciding when to test, selecting the correct test(s), and using results to inform medical diagnoses, especially for medical professionals lacking genetic expertise. Careful consideration of a diagnostic workflow can be helpful in understanding the appropriate uses of genetic testing within a broader diagnostic workup. CONTENT: The diagnosis of long QT syndrome (LQTS), a life-threatening cardiac arrhythmia, provides an example for this approach. Electrocardiography is the preferred means for diagnosing LQTS but can be uninformative for some patients due to the variable presentation of the condition. Family history and genetic testing can augment physiological testing to inform a diagnosis and subsequent therapy. Clinical and laboratory professionals informed by peer- reviewed literature and professional recommendations constructed a generalized LQTS diagnostic workflow. This workflow served to explore decisions regarding the use of genetic testing for diagnosing LQTS. SUMMARY AND OUTLOOK: Understanding the complexities and approaches to integrating genetic testing into a broader diagnostic evaluation is anticipated to support appropriate test utilization, optimize diagnostic evaluation, and facilitate a multidisciplinary approach essential for achieving accurate and timely diagnoses.

Technology-Enabled Outreach to Patients Taking High-Risk Medications Reduces a Quality Gap in Completion of Clinical Laboratory Testing.

Clinical laboratory quality improvement (QI) efforts can include population test utilization. The authors used a health care organization's Medical Data Warehouse (MDW) to characterize a gap in guideline-concordant laboratory testing recommended for safe use of antirheumatic agents, then tested the effectiveness of laboratory-led, technology-enabled outreach to patients at reducing this gap. Data linkages available through the Kaiser Permanente Colorado MDW and electronic health record were used to identify ambulatory adults taking antirheumatic agents who were due/overdue for alanine aminotransferase (ALT), aspartate aminotransferase (AST), complete blood count (CBC), or serum creatinine (SCr) testing. Outreach was implemented using an interactive voice response system to send patients text or phone call reminders. Interrupted time series analysis was used to estimate reminder effectiveness. Rates of guideline-concordant testing and testing timeliness in baseline vs. intervention periods were determined using generalized linear models for repeated measures. Results revealed a decrease in percentage of 3763 patients taking antirheumatic agents due/overdue for testing at any given time: baseline 24.3% vs. intervention 17.5% (P < 0.001). Among 3205 patients taking conventional antirheumatic agents, concordance for all ALT testing was baseline 52.8% vs. intervention 65.4% (P < 0.001) among patients chronically using these agents and baseline 20.6% vs. intervention 26.1% (P < 0.001) among patients newly starting these agents. The 95th percentiles for days to ALT testing were baseline 149 vs. intervention 117 among chronic users and baseline 134 vs. intervention 92 among new starts. AST, CBC, and SCr findings were similar. Technology-enabled outreach reminding patients to obtain laboratory testing improves health care system outcomes.

Identifying Preanalytic and Postanalytic Laboratory Quality Gaps Using a Data Warehouse and Structured Multidisciplinary Process.

CONTEXT.­: The laboratory total testing process includes preanalytic, analytic, and postanalytic phases, but most laboratory quality improvement efforts address the analytic phase. Expanding quality improvement to preanalytic and postanalytic phases via use of medical data warehouses, repositories that include clinical, utilization, and administrative data, can improve patient care by ensuring appropriate test utilization. Cross-department, multidisciplinary collaboration to address gaps and improve patient and system outcomes is beneficial. OBJECTIVE.­: To demonstrate medical data warehouse utility for characterizing laboratory-associated quality gaps amenable to preanalytic or postanalytic interventions. DESIGN.­: A multidisciplinary team identified quality gaps. Medical data warehouse data were queried to characterize gaps. Organizational leaders were interviewed about quality improvement priorities. A decision aid with elements including national guidelines, local and national importance, and measurable outcomes was completed for each gap. RESULTS.­: Gaps identified included (1) test ordering; (2) diagnosis, detection, and documentation, and (3) high-risk medication monitoring. After examination of medical data warehouse data including enrollment, diagnoses, laboratory, pharmacy, and procedures for baseline performance, high-risk medication monitoring was selected, specifically alanine aminotransferase, aspartate aminotransferase, complete blood count, and creatinine testing among patients receiving disease-modifying antirheumatic drugs. The test utilization gap was in monitoring timeliness (eg, >60% of patients had a monitoring gap exceeding the guideline recommended frequency). Other contributors to selecting this gap were organizational enthusiasm, regulatory labeling, and feasibility of a significant laboratory role in addressing the gap. CONCLUSIONS.­: A multidisciplinary process facilitated identification and selection of a laboratory medicine quality gap. Medical data warehouse data were instrumental in characterizing gaps.

Principles and Recommendations for Standardizing the Use of the Next-Generation Sequencing Variant File in Clinical Settings.

A national workgroup convened by the Centers for Disease Control and Prevention identified principles and made recommendations for standardizing the description of sequence data contained within the variant file generated during the course of clinical next-generation sequence analysis for diagnosing human heritable conditions. The specifications for variant files were initially developed to be flexible with regard to content representation to support a variety of research applications. This flexibility permits variation with regard to how sequence findings are described and this depends, in part, on the conventions used. For clinical laboratory testing, this poses a problem because these differences can compromise the capability to compare sequence findings among laboratories to confirm results and to query databases to identify clinically relevant variants. To provide for a more consistent representation of sequence findings described within variant files, the workgroup made several recommendations that considered alignment to a common reference sequence, variant caller settings, use of genomic coordinates, and gene and variant naming conventions. These recommendations were considered with regard to the existing variant file specifications presently used in the clinical setting. Adoption of these recommendations is anticipated to reduce the potential for ambiguity in describing sequence findings and facilitate the sharing of genomic data among clinical laboratories and other entities.

Guidelines for Validation of Next-Generation Sequencing-Based Oncology Panels: A Joint Consensus Recommendation of the Association for Molecular Pathology and College of American Pathologists.

Next-generation sequencing (NGS) methods for cancer testing have been rapidly adopted by clinical laboratories. To establish analytical validation best practice guidelines for NGS gene panel testing of somatic variants, a working group was convened by the Association of Molecular Pathology with liaison representation from the College of American Pathologists. These joint consensus recommendations address NGS test development, optimization, and validation, including recommendations on panel content selection and rationale for optimization and familiarization phase conducted before test validation; utilization of reference cell lines and reference materials for evaluation of assay performance; determining of positive percentage agreement and positive predictive value for each variant type; and requirements for minimal depth of coverage and minimum number of samples that should be used to establish test performance characteristics. The recommendations emphasize the role of laboratory director in using an error-based approach that identifies potential sources of errors that may occur throughout the analytical process and addressing these potential errors through test design, method validation, or quality controls so that no harm comes to the patient. The recommendations contained herein are intended to assist clinical laboratories with the validation and ongoing monitoring of NGS testing for detection of somatic variants and to ensure high quality of sequencing results.

Electronic health record interventions at the point of care improve documentation of care processes and decrease orders for genetic tests commonly ordered by nongeneticists.

OBJECTIVE: To determine whether electronic health record (EHR) tools improve documentation of pre- and postanalytic care processes for genetic tests ordered by nongeneticists. METHODS: We conducted a nonrandomized, controlled, pre-/postintervention study of EHR point-of-care tools (informational messages and template report) for three genetic tests. Chart review assessed documentation of genetic testing processes of care, with points assigned for each documented item. Multiple linear and logistic regressions assessed factors associated with documentation. RESULTS: Preimplementation, there were no significant site differences (P > 0.05). Postimplementation, mean documentation scores increased (5.9 (2.1) vs. 5.0 (2.2); P = 0.0001) and records with clinically meaningful documentation increased (score >5: 59 vs. 47%; P = 0.02) at the intervention versus the control site. Pre- and postimplementation, a score >5 was positively associated with abnormal test results (OR = 4.0; 95% CI: 1.8-9.2) and trainee provider (OR = 2.3; 95% CI: 1.2-4.6). Postimplementation, a score >5 was also positively associated with intervention site (OR = 2.3; 95% CI: 1.1-5.1) and specialty clinic (OR = 2.0; 95% CI: 1.1-3.6). There were also significantly fewer tests ordered after implementation (264/100,000 vs. 204/100,000; P = 0.03), with no significant change at the control site (280/100,000 vs. 257/100,000; P = 0.50). CONCLUSIONS: EHR point-of-care tools improved documentation of genetic testing processes and decreased utilization of genetic tests commonly ordered by nongeneticists.Genet Med 19 1, 112-120.

Assuring the Quality of Next-Generation Sequencing in Clinical Microbiology and Public Health Laboratories.

Clinical microbiology and public health laboratories are beginning to utilize next-generation sequencing (NGS) for a range of applications. This technology has the potential to transform the field by providing approaches that will complement, or even replace, many conventional laboratory tests. While the benefits of NGS are significant, the complexities of these assays require an evolving set of standards to ensure testing quality. Regulatory and accreditation requirements, professional guidelines, and best practices that help ensure the quality of NGS-based tests are emerging. This review highlights currently available standards and guidelines for the implementation of NGS in the clinical and public health laboratory setting, and it includes considerations for NGS test validation, quality control procedures, proficiency testing, and reference materials.

Reporting incidental findings in genomic scale clinical sequencing--a clinical laboratory perspective: a report of the Association for Molecular Pathology.

Advances in sequencing technologies have facilitated concurrent testing for many disorders, and the results generated may provide information about a patient's health that is unrelated to the clinical indication, commonly referred to as incidental findings. This is a paradigm shift from traditional genetic testing in which testing and reporting are tailored to a patient's specific clinical condition. Clinical laboratories and physicians are wrestling with this increased complexity in genomic testing and reporting of the incidental findings to patients. An enormous amount of discussion has taken place since the release of a set of recommendations from the American College of Medical Genetics and Genomics. This discussion has largely focused on the content of the incidental findings, but the laboratory perspective and patient autonomy have been overlooked. This report by the Association of Molecular Pathology workgroup discusses the pros and cons of next-generation sequencing technology, potential benefits, and harms for reporting of incidental findings, including the effect on both the laboratory and the patient, and compares those with other areas of medicine. The importance of genetic counseling to preserve patient autonomy is also reviewed. The discussion and recommendations presented by the workgroup underline the need for continued research and discussion among all stakeholders to improve our understanding of the effect of different policies on patients, providers, and laboratories.

Current landscape and new paradigms of proficiency testing and external quality assessment for molecular genetics.

CONTEXT: Participation in proficiency testing (PT) or external quality assessment (EQA) programs allows the assessment and comparison of test performance among different clinical laboratories and technologies. In addition to the approximately 2300 tests for individual genetic disorders, recent advances in technology have enabled the development of clinical tests that quickly and economically analyze the entire human genome. New PT/EQA approaches are needed to ensure the continued quality of these complex tests. OBJECTIVES: To review the availability and scope of PT/EQA for molecular genetic testing for inherited conditions in Europe, Australasia, and the United States; to evaluate the successes and demonstrated value of available PT/EQA programs; and to examine the challenges to the provision of comprehensive PT/EQA posed by new laboratory practices and methodologies. DATA SOURCES: The available literature on this topic was reviewed and supplemented with personal experiences of several PT/EQA providers. CONCLUSIONS: Proficiency testing/EQA schemes are available for common genetic disorders tested in many clinical laboratories but are not available for most genetic tests offered by only one or a few laboratories. Provision of broad, method-based PT schemes, such as DNA sequencing, would allow assessment of many tests for which formal PT is not currently available. Participation in PT/EQA improves the quality of testing by identifying inaccuracies that laboratories can trace to errors in their testing processes. Areas of research and development to ensure that PT/EQA programs can meet the needs of new and evolving genetic tests and technologies are identified and discussed.

Effective communication of molecular genetic test results to primary care providers.

PURPOSE: We evaluated a template for molecular genetic test reports that was developed as a strategy to reduce communication errors between the laboratory and ordering clinician. METHODS: We surveyed 1,600 primary care physicians to assess satisfaction, ease of use, and effectiveness of genetic test reports developed using our template and reports developed by clinical laboratories. Mean score differences of responses between the reports were compared using t-tests. Two-way analysis of variance evaluated the effect of template versus standard reports and the influence of physician characteristics. RESULTS: There were 396 (24%) respondents. Template reports had higher scores than the standard reports for each survey item. The gender and specialty of the physician did not influence scores; however, younger physicians gave higher scores regardless of report type. There was significant interaction between report type and whether physicians ordered or reviewed any genetic tests (none versus at least one) in the past year, P = 0.005. CONCLUSION: For each survey item assessing satisfaction, ease of use, and effectiveness, physicians gave higher ratings to genetic test reports developed with the template than standard reports used by clinical laboratories. Physicians least familiar with genetic test reports, and possibly having the greatest need for better communication, were best served by the template reports.