Management Systems to Structure Continuous Quality Improvement.

OBJECTIVES: This review describes the processes and effectiveness of the primary management systems that structure and sustain consistent behaviors and result in a transformed culture of continuous quality improvement (CQI) from top to bottom throughout the Henry Ford medical laboratory enterprise. METHODS: Through a 17-year focus to achieve a functional CQI enterprise, quality management systems were developed and continuously improved by teams of laboratory leaders, managers, and quality specialists to coordinate and standardize human efforts, and provide actionable knowledge and data to engage improvement efforts at all levels of work. Lean and ISO 15189 discipline and requirements were addressed in annual management review of functionality and effectiveness to close gaps and further refine the management systems. RESULTS: Improvements in the use and effectiveness of 4 management systems are illustrated. CONCLUSIONS: The 4 primary management systems that provide structure and support transformation to a culture of CQI are the team leader, Plan-Do-Check-Act problem-solving, deviation management, and daily management systems. These management systems are designed to deepen the effectiveness of the continuous improvement culture by helping managers understand variation in the work they oversee and providing guidance for more effective employee engagement in the daily processes of quality improvement.

Deviation Management: Key Management Subsystem Driver of Knowledge-Based Continuous Improvement in the Henry Ford Production System.

OBJECTIVES: To develop a business subsystem fulfilling International Organization for Standardization 15189 nonconformance management regulatory standard, facilitating employee engagement in problem identification and resolution to effect quality improvement and risk mitigation. METHODS: From 2012 to 2016, the integrated laboratories of the Henry Ford Health System used a quality technical team to develop and improve a management subsystem designed to identify, track, trend, and summarize nonconformances based on frequency, risk, and root cause for elimination at the level of the work. RESULTS: Programmatic improvements and training resulted in markedly increased documentation culminating in 71,641 deviations in 2016 classified by a taxonomy of 281 defect types into preanalytic (74.8%), analytic (23.6%), and postanalytic (1.6%) testing phases. The top 10 deviations accounted for 55,843 (78%) of the total. CONCLUSIONS: Deviation management is a key subsystem of managers' standard work whereby knowledge of nonconformities assists in directing corrective actions and continuous improvements that promote consistent execution and higher levels of performance.

A Proposed Set of Metrics to Reduce Patient Safety Risk From Within the Anatomic Pathology Laboratory.

BACKGROUND: Anatomic pathology laboratory workflow consists of 3 major specimen handling processes. Among the workflow are preanalytic, analytic, and postanalytic phases that contain multistep subprocesses with great impact on patient care. A worldwide representation of experts came together to create a system of metrics, as a basis for laboratories worldwide, to help them evaluate and improve specimen handling to reduce patient safety risk. METHOD: Members of the Initiative for Anatomic Pathology Laboratory Patient Safety (IAPLPS) pooled their extensive expertise to generate a list of metrics highlighting processes with high and low risk for adverse patient outcomes. RESULTS: : Our group developed a universal, comprehensive list of 47 metrics for patient specimen handling in the anatomic pathology laboratory. Steps within the specimen workflow sequence are categorized as high or low risk. In general, steps associated with the potential for specimen misidentification correspond to the high-risk grouping and merit greater focus within quality management systems. Primarily workflow measures related to operational efficiency can be considered low risk. CONCLUSION: Our group intends to advance the widespread use of these metrics in anatomic pathology laboratories to reduce patient safety risk and improve patient care with development of best practices and interlaboratory error reporting programs.

Daily Management System of the Henry Ford Production System: QTIPS to Focus Continuous Improvements at the Level of the Work.

OBJECTIVES: To support our Lean culture of continuous improvement, we implemented a daily management system designed so critical metrics of operational success were the focus of local teams to drive improvements. METHODS: We innovated a standardized visual daily management board composed of metric categories of Quality, Time, Inventory, Productivity, and Safety (QTIPS); frequency trending; root cause analysis; corrective/preventive actions; and resulting process improvements. RESULTS: In 1 year (June 2013 to July 2014), eight laboratory sections at Henry Ford Hospital employed 64 unique daily metrics. Most assessed long-term (>6 months), monitored process stability, while short-term metrics (1-6 months) were retired after successful targeted problem resolution. Daily monitoring resulted in 42 process improvements. CONCLUSIONS: Daily management is the key business accountability subsystem that enabled our culture of continuous improvement to function more efficiently at the managerial level in a visible manner by reviewing and acting based on data and root cause analysis.

Autoantibodies in breast cancer sera are not epiphenomena and may participate in carcinogenesis.

BACKGROUND: The objective of this work was to demonstrate that autoantibodies in breast cancer sera are not epiphenomena, and exhibit unique immunologic features resembling the rheumatic autoimmune diseases. METHODS: We performed a comprehensive study of autoantibodies on a collection of sera from women with breast cancer or benign breast disease, undergoing annual screening mammography. All women in this study had suspicious mammography assessment and underwent a breast biopsy. We used indirect immunofluorescence, the crithidia assay for anti-dsDNA antibodies, and multiple ELISAs for extractable nuclear antigens. RESULTS: Autoantibodies were detected in virtually all patients with breast cancer, predominantly of the IgG1 and IgG3 isotypes. The profile detected in breast cancer sera showed distinctive features, such as antibodies targeting mitochondria, centrosomes, centromeres, nucleoli, cytoskeleton, and multiple nuclear dots. The majority of sera showing anti-mitochondrial antibodies did not react with the M2 component of pyruvate dehydrogenase, characteristic of primary biliary cirrhosis. Anti-centromere antibodies were mainly anti-CENP-B. ELISAs for extractable nuclear antigens and the assays for dsDNA were negative. CONCLUSIONS: The distinctive autoantibody profile detected in BC sera is the expression of tumor immunogenicity. Although some of these features resemble those in the rheumatic autoimmune diseases and primary biliary cirrhosis, the data suggest the involvement of an entirely different set of epithelial antigens in breast cancer. High titer autoantibodies targeting centrosomes, centromeres, and mitochondria were detected in a small group of healthy women with suspicious mammography assessment and no cancer by biopsy; this suggests that the process triggering autoantibody formation starts in the pre-malignant phase and that future studies using validated autoantibody panels may allow detection of breast cancer risk in asymptomatic women. Autoantibodies developing in breast cancer are not epiphenomena, but likely reflect an antigen-driven autoimmune response triggered by epitopes developing in the mammary gland during breast carcinogenesis. Our results support the validity of the multiple studies reporting association of autoantibodies with breast cancer. Results further suggest significant promise for the development of panels of breast cancer-specific, premalignant-phase autoantibodies, as well as studies on the autoantibody response to tumor associated antigens in the pathogenesis of cancer.

Histologic validation of vacuum sealed, formalin-free tissue preservation, and transport system.

We describe five validation trials of new vacuum sealing technologies that change the approach to the preanalytic "front end" of specimen transport, handling, and processing and illustrate their adaptation and integration into existing Lean laboratory operations with reduction in formalin use and personnel exposure to this toxic and potentially carcinogenic fixative. These trials provide histologic assessment by numerous pathologists of tissues processed in this new paradigm and define the financial advantages of applying this technology to the postanalytic or "back end" process of tissue storage. We conclude that the TisssueSAFE and SealSAFE vacuum sealing systems are both promising technologies for preserving fresh human specimens that can promote a safer environment by markedly reducing formalin use in operating room theaters and can minimize formalin use by laboratories.

Anti-centrosome antibodies in breast cancer are the expression of autoimmunity.

Centrosome abnormalities have been observed in nearly all human solid tumors, but their role in tumorigenesis is unclear. We have demonstrated that autoantibodies reacting with antigens in centrosomes are frequently found in BC sera. In this work, we attempted to characterize the centrosome antigens associated with BC. We immunoscreened a T7 cDNA library of BC proteins with BC sera, and the autoantigens identified were printed as a microarray and hybridized with BC and control sera. We used immunohistochemistry (IHC) to investigate the expression of the cloned autoantigens in BC tissue. Immunoscreening with BC sera led to the cloning of autoantibodies recognizing epitopes developing in a family of proteins located on centrosomes such as peri-centriolar material-1, isomorph CRA, stathmin1, HS actin gamma1, SUMO/sentrin peptidase 2, and ubiquitin-conjugating enzyme E2 variant 1. Antibody reactivity to these proteins that are associated with centrosome assembly and/or microtubule function was highly associated with the diagnosis of BC. IHC staining of formalin-fixed paraffin-embedded sections with specific antibodies showed that aurora and stathmin are expressed in BC. The discovery of autoantibodies to important centrosome antigens associated with BC suggests that this immune reactivity could be related to autoimmunity developing in BC. Our finding that some of these antibodies are also present in a group of healthy women suggests that breakdown of tolerance to centrosome proteins may occur early in breast carcinogenesis and that autoantibodies to centrosome antigens might be biomarkers of early BC.

Developing and pilot testing practical measures of preanalytic surgical specimen identification defects.

Accurate patient identification is a National Patient Safety Goal. Misidentification of surgical specimens is associated with increased morbidity, mortality, and costs of care. The authors developed 12 practical, process-based, standardized measures of surgical specimen identification defects during the preanalytic phase of pathology testing (from the operating room to the surgical pathology laboratory) that could be used to quantify the occurrence of these defects. The measures (6 container and 6 requisition identification defects) were developed by a panel of physicians, pathologists, nurses, and quality experts. A total of 69 hospitals prospectively collected data over 3 months. Overall, there were identification defects in 2.9% of cases (1780/60 501; 95% confidence interval [CI] = 2.0%-4.4%), 1.2% of containers (1018/81 656; 95% CI = 0.8%-2.0%), and 2.3% of requisitions (1417/61 245; 95% CI = 1.2%-4.6%). Future research is needed to evaluate if hospitals are able to use these measures to assess interventions meant to reduce the frequency of specimen identification defects and improve patient safety.

Study of amended reports to evaluate and improve surgical pathology processes.

BACKGROUND: : Amended surgical pathology reports record defects in the process of transforming tissue specimens into diagnostic information. OBJECTIVE: : Systematic study of amended reports tests 2 hypotheses: (a) that tracking amendment frequencies and the distribution of amendment types reveals relevant aspects of quality in surgical pathology's daily transformation of specimens into diagnoses and (b) that such tracking measures the effect, or lack of effect, of efforts to improve surgical pathology processes. MATERIALS AND METHODS: : We applied a binary definition of altered reports as either amendments or addenda and a taxonomy of defects that caused amendments as misidentifications, specimen defects, misinterpretations, and report defects. During the introduction of a LEAN process improvement approach-the Henry Ford Productions System-we followed trends in amendment rates and defect fractions to (a) evaluate specific interventions, (b) sort case-by-case root causes of misidentifications, specimen defects, and misinterpretations, and (c) audit the ongoing accuracy of the classification of changed reports. LEAN is the management and production system of the Toyota Motor Corporation that promotes continuous improvement; it considers wasted resources expended for purposes other than creating value for end customers and targets such expenditures for elimination. RESULTS: : Introduction of real-time editing of amendments saw annual amendment rates increase from 4.8/1000 to 10.1/1000 and then decrease in an incremental manner to 5.6/1000 as Henry Ford Productions System-specific interventions were introduced. Before introduction of HFPS interventions, about a fifth of the amendments were due to misidentifications, a 10th were due to specimen defects, a quarter due to misinterpretation, and almost half were due to report defects. During the period of the initial application of HFPS, the fraction of amendments due to misidentifications decreased as those due to report defects increased, in a statistically linked manner. As HFPS interventions took hold, misidentifications fell from 16% to 9%, specimen defect rates remained variable, ranging between 2% and 11%, and misinterpretations fell from 18% to 3%. Reciprocally, report defects rose from 64% to 83% of all amendment-causing defects. A case-by-case study of misidentifications, specimen defects, and misinterpretations found that (a) intervention at the specimen collection level had disappointingly little effect on patient misidentifications; (b) standardization of specimen accession and gross examination reduced only specimen defects surrounding ancillary testing; but (c) a double review of breast and prostate cases was associated with drastically reduced misinterpretation defects. Finally, audit of both amendments and addenda demonstrated that 10% of the so-called addenda actually qualified as amendments. DISCUSSION: : Monitored by the consistent taxonomy, rates of amended reports first rose, then fell. Examining specific defect categories provided information for evaluating specific LEAN interventions. Tracking the downward trend of amendment rates seemed to document the overall success of surgical pathology quality improvement efforts. Process improvements modestly decreased fractions of misidentifications and markedly decreased misinterpretation fractions. Classification integrity requires real time, independent editing of both amendments (changed reports) and addenda (addition to reports).

African ancestry and higher prevalence of triple-negative breast cancer: findings from an international study.

BACKGROUND: The study of breast cancer in women with African ancestry offers the promise of identifying markers for risk assessment and treatment of triple-negative disease. METHODS: African American and white American women with invasive cancer diagnosed at the Henry Ford Health System comprised the primary study population, and Ghanaian patients diagnosed and/or treated at the Komfo Anokye Teaching Hospital in Kumasi, Ghana constituted the comparison group. Formalin-fixed, paraffin-embedded specimens were transported to the University of Michigan for histopathology confirmation, and assessment of estrogen and progesterone receptors and HER-2/neu expression. RESULTS: The study population included 1008 white Americans, 581 African Americans, and 75 Ghanaians. Mean age at diagnosis was 48.0 years for Ghanaian, 60.8 years for African American, and 62.4 for white American cases (P=.002). Proportions of Ghanaian, African American, and white American cases with estrogen receptor-negative tumors were 76%, 36%, and 22%, respectively (P<.001), and proportions with triple-negative disease were 82%, 26%, and 16%, respectively (P<.001). All Ghanaian cases were palpable, locally advanced cancers; 57 (76%) were grade 3. A total of 147 American women were diagnosed as stage III or IV; of these, 67.5% (n=46) of African Americans and 44.6% (n=29) of white Americans were grade 3. Among palpable, grade 3 cancers, Ghanaians had the highest prevalence of triple-negative tumors (82.2%), followed by African Americans (32.8%) and white Americans (10.2%). CONCLUSIONS: Our study demonstrates progressively increasing frequency of estrogen receptor-negative and triple-negative tumors among breast cancer patients with white American, African American, and Ghanaian/African backgrounds. This pattern indicates a need for additional investigations correlating the extent of African ancestry and high-risk breast cancer subtypes.

Clinical performance of JAK2 V617F mutation detection assays in a molecular diagnostics laboratory: evaluation of screening and quantitation methods.

The presence of the JAK2 V617F mutation is now part of clinical diagnostic algorithms, and JAK2 status is routinely assessed when BCR/ABL- chronic myeloproliferative neoplasms (MPNs) are suspected. The aim of this study was to evaluate performance of 3 screening and 1 quantitative method for JAK2 V617F detection. For the study, 43 samples (27 bone marrow aspirates and 16 peripheral blood samples) were selected. The screening assays were the JAK2 Activating Mutation Assay (InVivoScribe, San Diego, CA), JAK2 MutaScreen kit (Ipsogen, Luminy Biotech, Marseille, France), and a home-brew melting curve analysis method. Ipsogen's JAK2 MutaQuant assay was used for quantification of mutant and wild-type alleles. The limit of detection was 1% for the kit-based screening methods and 10% for the melting curve method. The JAK2 MutaQuant assay demonstrated analytic sensitivity of 0.01%. All 4 methods detected cases of BCR/ABL- MPNs and gave negative results with BCR/ABL+ chronic myelogenous leukemia, multiple myeloma, myelodysplastic syndrome, and normal cases.

The Henry Ford production system: LEAN process redesign improves service in the molecular diagnostic laboratory: a paper from the 2008 William Beaumont hospital symposium on molecular pathology.

Accurate and timely molecular test results play an important role in patient management; consequently, there is a customer expectation of short testing turnaround times. Baseline data analysis revealed that the greatest challenge to timely result generation occurred in the preanalytic phase of specimen collection and transport. Here, we describe our efforts to improve molecular testing turnaround times by focusing primarily on redesign of preanalytic processes using the principles of LEAN production. Our goal was to complete greater than 90% of the molecular tests in less than 3 days. The project required cooperation from different laboratory disciplines as well as individuals outside of the laboratory. The redesigned processes involved defining and standardizing the protocols and approaching blood and tissue specimens as analytes for molecular testing. The LEAN process resulted in fewer steps, approaching the ideal of a one-piece flow for specimens through collection/retrieval, transport, and different aspects of the testing process. The outcome of introducing the LEAN process has been a 44% reduction in molecular test turnaround time for tissue specimens, from an average of 2.7 to 1.5 days. In addition, extending LEAN work principles to the clinician suppliers has resulted in a markedly increased number of properly collected and shipped blood specimens (from 50 to 87%). These continuous quality improvements were accomplished by empowered workers in a blame-free environment and are now being sustained with minimal management involvement.

The Henry Ford Production System: reduction of surgical pathology in-process misidentification defects by bar code-specified work process standardization.

Misidentification defects are a potential patient safety issue in medicine, including in the surgical pathology laboratory. In addressing the Joint Commission's national patient safety goal of accurate patient and specimen identification, we focused our lens internally on our own laboratory processes, with measurement tools designed to identify potential misidentification defects and their root causes. Based on this knowledge, aligned with our lean work culture in the Henry Ford Production System, we redesigned our surgical pathology laboratory workflow with simplified connections and pathways reinforced by a bar code technology innovation to specify and standardize work processes. We also adopted just-in-time prestain slide labeling with solvent-impervious, bar-coded slide labels at the microtome station, eliminating the loop-back pathway of poststain, batch slide matching, and labeling with adhesive paper labels. These changes have enabled us to dramatically reduce the overall misidentification case rate by approximately 62% with an approximate 95% reduction in the more common histologic slide misidentification defects while increasing technical throughput at the histology microtomy station by 125%.

Amended reports: development and validation of a taxonomy of defects.

Amended pathology reports produce rework, confusion, and distrust. To develop a reproducible amendment taxonomy we derived a classification from 141 amended reports, then validated it with 130 new cases before 4 observers independently reviewed 430 cases measuring agreement (k). Next, agreement in classifying 30 other amended reports in 7 institutions was measured. We further tracked amendment rates, defect categories, defect discoverers, and discovery mechanisms. In the 430-case validation set agreement was excellent (k = 0.8780 [range, 0.8416-0.9144]). Among the 7 institutions, agreement was good (k = 0.6235 [range, 0.3105-0.8975]). Amendment rates ranged from 2.6 to 4.8 per 1,000 reports. Misinterpretation fractions varied least (23%-29%). Misidentification fractions ranged more widely (20%-38%). Specimen defects were least frequent (4%-10%) and report defects most frequent (29%-48%). Misidentifications and report defects inversely correlated. Pathologists discovered most misinterpretations, and clinicians found most misidentifications. Conference review revealed 40% to 80% of misinterpretations. This taxonomy produced excellent reproducibility and good agreement across institutions.

The Henry ford production system: effective reduction of process defects and waste in surgical pathology.

By adopting a cultural transformation in its employees' approach to work and using manufacturing based continuous quality improvement methods, the surgical pathology division of Henry Ford Hospital, Detroit, MI, focused on reducing commonly encountered defects and waste in processes throughout the testing cycle. At inception, the baseline in-process defect rate was measured at nearly 1 in 3 cases (27.9%). After the year-long efforts of 77 workers implementing more than 100 process improvements, the number of cases with defects was reduced by 55% to 1 in 8 cases (12.5%), with a statistically significant reduction in the overall distribution of defects (P = .0004). Comparison with defects encountered in the pre-improvement period showed statistically significant reductions in pre-analytic (P = .0007) and analytic (P = .0002) test phase processes in the post-improvement period that included specimen receipt, specimen accessioning, grossing, histology slides, and slide recuts. We share the key improvements implemented that were responsible for the overall success in reducing waste and re-work in the broad spectrum of surgical pathology processes.