Cost analysis of smear microscopy and the Xpert assay for tuberculosis diagnosis: average turnaround time.

INTRODUCTION: Rapid and accurate tuberculosis detection is critical for improving patient diagnosis and decreasing tuberculosis transmission. Molecular assays can significantly increase laboratory costs; therefore, the average time and economic impact should be evaluated before implementing a new technology. The aim of this study was to evaluate the cost and average turnaround time of smear microscopy and Xpert assay at a university hospital. METHODS: The turnaround time and cost of the laboratory diagnosis of tuberculosis were calculated based on the mean cost and activity based costing (ABC). RESULTS: The average turnaround time for smear microscopy was 16.6 hours while that for Xpert was 24.1 hours. The Xpert had a mean cost of USD 17.37 with an ABC of USD 10.86, while smear microscopy had a mean cost of USD 13.31 with an ABC of USD 6.01. The sensitivity of smear microscopy was 42.9% and its specificity was 99.1%, while the Xpert assay had a sensitivity of 100% and a specificity of 96.7%. CONCLUSIONS: The Xpert assay has high accuracy; however, the turnaround time and cost of smear microscopy were lower than those of Xpert.

Cost analysis of smear microscopy and the Xpert assay for tuberculosis diagnosis: average turnaround time

Abstract INTRODUCTION: Rapid and accurate tuberculosis detection is critical for improving patient diagnosis and decreasing tuberculosis transmission. Molecular assays can significantly increase laboratory costs; therefore, the average time and economic impact should be evaluated before implementing a new technology. The aim of this study was to evaluate the cost and average turnaround time of smear microscopy and Xpert assay at a university hospital. METHODS: The turnaround time and cost of the laboratory diagnosis of tuberculosis were calculated based on the mean cost and activity based costing (ABC). RESULTS: The average turnaround time for smear microscopy was 16.6 hours while that for Xpert was 24.1 hours. The Xpert had a mean cost of USD 17.37 with an ABC of USD 10.86, while smear microscopy had a mean cost of USD 13.31 with an ABC of USD 6.01. The sensitivity of smear microscopy was 42.9% and its specificity was 99.1%, while the Xpert assay had a sensitivity of 100% and a specificity of 96.7%. CONCLUSIONS: The Xpert assay has high accuracy; however, the turnaround time and cost of smear microscopy were lower than those of Xpert.

Context-Specific Economic Evaluation for Molecular Pathology Tests: An Application in Colorectal Cancer in the West of Scotland.

OBJECTIVES: The cost-effectiveness of molecular pathology testing is highly context dependent. The field is fast-moving, and national health technology assessment may not be relevant or timely for local decision makers. This study illustrates a method of context-specific economic evaluation that can be carried out in a limited timescale without extensive resources. METHODS: We established a multi-disciplinary group including an oncologist, pathologists and a health economist. We set out diagnostic and treatment pathways and costs using registry data, health technology assessments, guidelines, audit data, and estimates from the group. Sensitivity analysis varied input parameters across plausible ranges. The evaluation setting was the West of Scotland and UK NHS perspective was adopted. The evaluation was assessed against the AdHopHTA checklist for hospital-based health technology assessment. RESULTS: A context-specific economic evaluation could be carried out on a timely basis using limited resources. The evaluation met all relevant criteria in the AdHopHTA checklist. Health outcomes were expected to be at least equal to the current strategy. Annual cost savings of £637,000 were estimated resulting primarily from a reduction in the proportion of patients receiving intravenous infusional chemotherapy regimens. The result was not sensitive to any parameter. The data driving the main cost saving came from a small clinical audit. We recommended this finding was confirmed in a larger population. CONCLUSIONS: The method could be used to evaluate testing changes elsewhere. The results of the case study may be transferable to other jurisdictions where the organization of cancer services is fragmented.

Cost-effectiveness of molecular diagnostic assays for the therapy of severe sepsis and septic shock in the emergency department.

OBJECTIVES: Sepsis presents a major burden to the emergency department (ED). Because empiric inappropriate antimicrobial therapy (IAAT) is associated with increased mortality, rapid molecular assays may decrease IAAT and improve outcomes. We evaluated the cost-effectiveness of molecular testing as an adjunct to blood cultures in patients with severe sepsis or septic shock evaluated in the ED. METHODS: We developed a decision analysis model with primary outcome the incremental cost-effectiveness ratio expressed in terms of deaths averted. Costs were dependent on the assay price and the patients' length of stay (LOS). Three base-case scenarios regarding the difference in LOS between patients receiving appropriate (AAT) and IAAT were described. Sensitivity analyses regarding the assay cost and sensitivity, and its ability to guide changes from IAAT to AAT were performed. RESULTS: Under baseline assumptions, molecular testing was cost-saving when the LOS differed by 4 days between patients receiving IAAT and AAT (ICER -$7,302/death averted). Our results remained robust in sensitivity analyses for assay sensitivity≥52%, panel efficiency≥39%, and assay cost≤$270. In the extreme case that the LOS of patients receiving AAT and IAAT was the same, the ICER remained≤$20,000/death averted for every studied sensitivity (i.e. 0.5-0.95), panel efficiency≥34%, and assay cost≤$313. For 2 days difference in LOS, the bundle approach was dominant when the assay cost was≤$135 and the panel efficiency was≥77%. CONCLUSIONS: The incorporation of molecular tests in the management of sepsis in the ED has the potential to improve outcomes and be cost-effective for a wide range of clinical scenarios.

A portable nucleic acid detection system using natural convection combined with a smartphone.

The development of portable nucleic acid diagnostic devices has the potential to expand the availability of molecular diagnostics into low-resource settings. One of the promising solutions for rapid and simple DNA amplification is the use of Rayleigh-Bernard natural convection which is caused by a buoyancy-driven thermal gradient of liquid when heated from below. This natural convection avoids the use of the complex and sophisticated hardware that is required for precise maintenance of temperature cycles in conventional PCR. We have developed a stand-alone convective PCR (cPCR) device linked to a smartphone for rapid detection of nucleic acids using natural convection heating. The device amplifies multiple DNA samples simultaneously using a custom-made heat block controlled by Bluetooth wireless communication. The entire device is highly portable, user-friendly, battery-operated and can provide target DNA amplification in less than 30 min. A detection limit of 2.8 × 103 copies of a segment of lambda DNA was obtained when the two different fluorescently-tagged amplicons were collected magnetically and detected using the smartphone fluorescence reader. Thus, the combination of cPCR and multiplex fluorescence-based detection on a smartphone provides new opportunities for the development of affordable and portable molecular diagnostic devices for point-of-care situations or remote clinical settings.

Xpert MRSA screening in surgical patient flow; time for a rethink for hub-and-spoke laboratory models?

The move towards pathology networks and hub-and-spoke models of medical laboratory service provision has significantly changed the flow of samples, and the impact of results on patients, over recent years. At the same time advances in technology, including rapid, simple to use molecular platforms, are changing the way microbiology results can be utilized. Like many other medical microbiology laboratories, we struggle with this balance for many different sample types and test requests. Work published by Neilson et al. in Journal of Medical Microbiology last year looked at this balance for methicillin-resistant Staphylococcus aureus (MRSA) genotypic diagnostics and suggested significant cost savings when a whole-healthcare economy perspective was adopted. However, as with all changes, implementing MRSA molecular diagnostics in different clinical settings must be considered carefully. We add to this discussion in our accompanying letter, detailing our experience (in a hub-and-spoke medical microbiology laboratory setting) of 'rapid' MRSA molecular diagnostics for day-case surgery where pre-operative assessment had been missed, exploring the impact and costs of these tests. We find no impact on patient care, but at considerable additional cost. We hope this will add a cautionary note to those considering implementing molecular microbiology diagnostics, and reopen the debate on where, in hub-and-spoke laboratory models, such devices should be situated.

Using the EPIDEM Model of Quality Improvement to Increase Value of BCR-ABL1 Tests.

Objectives: As pathologists and laboratorians, we can enhance patient care by promoting the appropriate ordering of diagnostic tests. Our goal was to improve the ordering of BCR-ABL1 tests by using the EPIDEM model of quality improvement. Methods: We applied the EPIDEM model, which emphasizes understanding local context, culture, and resources, to explore inappropriate BCR-ABL1 ordering, promote and implement a new reflexive testing strategy in-house, document and evaluate effectiveness, and make stepwise modifications. Results: Multiple quality improvement interventions correlated with cost savings and decreased total errors and incorrect orders for both BCR-ABL1 major and minor positive patients. Furthermore, our laboratory built stronger collaborative relationships with colleagues within and outside of pathology. Conclusions: Our molecular pathology laboratory successfully used the EPIDEM model of quality improvement to improve the ordering of BCR-ABL1 tests and promote better patient care by focusing on educational efforts and modification of laboratory workflow.

Meeting the challenges of implementing rapid genomic testing in acute pediatric care.

PURPOSE: The purpose of the study was to implement and prospectively evaluate the outcomes of a rapid genomic diagnosis program at two pediatric tertiary centers. METHODS: Rapid singleton whole-exome sequencing (rWES) was performed in acutely unwell pediatric patients with suspected monogenic disorders. Laboratory and clinical barriers to implementation were addressed through continuous multidisciplinary review of process parameters. Diagnostic and clinical utility and cost-effectiveness of rWES were assessed. RESULTS: Of 40 enrolled patients, 21 (52.5%) received a diagnosis, with median time to report of 16 days (range 9-109 days). A result was provided during the first hospital admission in 28 of 36 inpatients (78%). Clinical management changed in 12 of the 21 diagnosed patients (57%), including the provision of lifesaving treatment, avoidance of invasive biopsies, and palliative care guidance. The cost per diagnosis was AU$13,388 (US$10,453). Additional cost savings from avoidance of planned tests and procedures and reduced length of stay are estimated to be around AU$543,178 (US$424,101). The clear relative advantage of rWES, joint clinical and laboratory leadership, and the creation of a multidisciplinary "rapid team" were key to successful implementation. CONCLUSION: Rapid genomic testing in acute pediatrics is not only feasible but also cost-effective, and has high diagnostic and clinical utility. It requires a whole-of-system approach for successful implementation.

The History and Impact of Molecular Coding Changes on Coverage and Reimbursement of Molecular Diagnostic Tests: Transition from Stacking Codes to the Current Molecular Code Set Including Genomic Sequencing Procedures.

Changes in coding and coverage generate an uncertain reimbursement environment for molecular pathology laboratories. We analyzed our experience with two representative molecular oncology tests: a T-cell receptor (TCR) ß rearrangement test and a large (467-gene) cancer next-generation sequencing panel, the Columbia Combined Cancer Panel (CCCP). Before 2013, the TCR ß test was coded using stacked current procedural terminology codes and subsequently transitioned to a tier 1 code. CCCP was coded using a combination of tier 1 and 2 codes until 2015, when a new Genomic Sequencing Procedure code was adopted. A decrease in reimbursement of 61% was observed for the TCR ß test on moving from stacking to tier 1 codes. No initial increase in total rejection rate was observed, but a subsequent increase in rejection rates in 2015 and 2016 was noted. The CCCP test showed a similar decrease (48%) in reimbursement after adoption of the new Genomic Sequencing Procedure code and was accompanied by a sharp increase in rejection rates both on implementation of the new code and over time. Changes in coding can result in substantial decreases in reimbursement. This may be a barrier to patient access because of the high cost of molecular diagnostics. Revisions to the molecular code set will continue. These findings help laboratories and manufacturers prepare for the financial impact and advocate appropriately.

Data-Driven Iterative Refinement of Bone Marrow Testing Protocols Leads to Progressive Improvement in Cytogenetic and Molecular Test Utilization.

OBJECTIVES: To determine the effect of iterative refinement of standard ordering protocols on test utilization and results for bone marrow biopsy specimens. METHODS: Eighteen months of test utilization and result data were used to revise the protocols that determine cytogenetic and molecular test selection on bone marrow specimens and then compared with data obtained following protocol revision. RESULTS: Revision of protocols resulted in reduction in total tests and associated charges, due to a decrease in tests both concordant and discordant with the protocols. These reductions only occurred in diseases for which revisions were made and were limited to cases in which reflex testing was performed. There was an increase in the fraction of positive tests, which was also limited to reflex testing. CONCLUSIONS: Data-driven iterative revision of protocols further improves test utilization and performance, while reducing cost. Analysis of testing data can be used to continuously improve test ordering decisions.

Could molecular pathology testing in lung cancer be more cost-effective?

AIMS: EGFR and ALK analysis is routinely undertaken prior to targeted treatment of non-squamous non-small cell lung carcinoma (NSCLC). Increasingly, limited resources require molecular pathology services to be cost-effective without detriment to patient care. METHODS: Data from an audit of molecular pathology testing in the South East Scotland Cancer Network (SCAN) network have been used to explore different testing strategies with the aim of reducing costs; including investigation of thyroid transcription factor 1 (TTF1) expression as a negative predictor for EGFR mutations. RESULTS: TTF1 immunohistochemistry had a high negative predictive value for EGFR mutations (99%). Reflex testing all non-squamous NSCLC, as expected, had the highest costs, whereas limiting testing to those who might be considered for treatment would lead to a cost reduction of only 7.5%; however, a serial testing model could save 32.7%. CONCLUSIONS: Testing only patients being considered for EGFR and ALK inhibitors represented small savings; more significant savings would be achievable if testing algorithms used known associations between clinical biomarkers.

[From biomarkers to clinical decision support]. / Biomarkerek hálózatától a klinikai döntéstámogatásig.

The rapidly accumulating, heterogeneous, numerous biomedical data and the increasing knowledge represent both the key areas and the major bottleneck in the complete realization of personalized medicine. Traditional clinical aims as well as decision-making processes in drug research need systems-based integration of data and their analyses, which require a wide range of new mathematical approaches and application of information technologies. In the world of biomarkers, all such tasks correspond to three types of biomarkers, namely, endpoint, target and diagnostic biomarkers, which together form a complex network. To decipher the networks, probabilistic graphical models are introduced. Briefly, the authors illustrate their use for exploration and visualization of direct dependencies among biomarkers. Finally, construction of decision networks and their application to structural and quantitative optimization of biomarkers are discussed to provide a novel type of supporting tools for clinical practice.

Current projects in Pre-analytics: where to go?

The current clinical practice of tissue handling and sample preparation is multifaceted and lacks strict standardisation: this scenario leads to significant variability in the quality of clinical samples. Poor tissue preservation has a detrimental effect thus leading to morphological artefacts, hampering the reproducibility of immunocytochemical and molecular diagnostic results (protein expression, DNA gene mutations, RNA gene expression) and affecting the research outcomes with irreproducible gene expression and post-transcriptional data. Altogether, this limits the opportunity to share and pool national databases into European common databases. At the European level, standardization of pre-analytical steps is just at the beginning and issues regarding bio-specimen collection and management are still debated. A joint (public-private) project entitled on standardization of tissue handling in pre-analytical procedures has been recently funded in Italy with the aim of proposing novel approaches to the neglected issue of pre-analytical procedures. In this chapter, we will show how investing in pre-analytics may impact both public health problems and practical innovation in solid tumour processing.

The future of laboratory medicine - a 2014 perspective.

Predicting the future is a difficult task. Not surprisingly, there are many examples and assumptions that have proved to be wrong. This review surveys the many predictions, beginning in 1887, about the future of laboratory medicine and its sub-specialties such as clinical chemistry and molecular pathology. It provides a commentary on the accuracy of the predictions and offers opinions on emerging technologies, economic factors and social developments that may play a role in shaping the future of laboratory medicine.