The role of laboratory medicine in a value-based healthcare system: the example of heart failure patient management in the Italian context.

OBJECTIVE: As of today, healthcare systems worldwide face severe challenges that undermine their sustainability. The value-based healthcare (VBHC) approach has been proposed as a strategic and methodological framework to ensure the delivery of the best patient outcomes with economic efficiency. Through the illustrative example of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) for heart failure (HF) patient management in the context of the Italian National Healthcare system, this article explores the role that in vitro diagnostics (IVDs) can play in enabling value-based care models. SUBJECTS AND METHODS: 14 healthcare professionals representing the relevant professional figures involved in HF patient management met to revise the current HF patient journey and design a new care pathway that, leveraging on BNP/NT-proBNP, reflects the VBHC principles. RESULTS: The literature recognizes the dosage of BNP/NT-proBNP as the gold stan-dard for diagnosing HF. However, as of today, these IVDs are not employed at their full potential regarding HF patient management. A new patient journey is proposed so that patients are diagnosed early and properly monitored in the aftermath of hospitalization, improving outcomes at contained costs. CONCLUSIONS: As testified by the example of HF patient management in Italy, laboratory medicine can represent a lever for adopting value-based care models. Still, large-scale adoption of VBHC will call for structural reforms that revise how healthcare delivery is organized, measured, and reimbursed.

Quality indicators to detect pre-analytical errors in laboratory testing.

The identification of reliable quality indicators (QIs) is a crucial step in enabling users to quantify the quality of laboratory services. The current lack of attention to extra-laboratory factors is in stark contrast to the body of evidence pointing to the multitude of errors that continue to occur, particularly in the pre-analytical phase. The ISO 15189: 2012 standard for laboratory accreditation defines the pre-analytical phase, and recognizes the need to evaluate, monitor and improve all the procedures and processes in the initial phase of the testing cycle, including those performed in the phase of requesting tests and collecting samples, the so-called "pre-pre-analytical phase". Therefore, QIs should allow the identification of errors and non-conformities that can occur in all steps of the pre-analytical phase. Traditionally, pre-analytical errors are grouped into identification and sample problems. However, appropriate test requesting and complete request forms are now recognized as fundamental components in providing valuable laboratory services. The model of QIs developed by the Working Group of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) includes indicators related to both identification and sample problems as well as all other pre-analytical defects, including those in test requesting and request forms. It, moreover, provides the framework (with objective criteria) necessary for promoting the harmonization of available QIs in the pre-analytical phase.

An integrated system for monitoring the quality of sample transportation.

OBJECTIVES: Due to the consolidation of laboratory testing facilities, there is an increasing need for systems able to assure quality and safety in biological sample transportation, although little evidence on this aspect is available in literature. DESIGN AND METHODS: An integrated system for sample transportation, implemented and monitored over a five-year period by our team, consists of secondary and tertiary containers, a device for temperature and time recording, and a system manager allowing the acceptance or rejection of biological samples through the immediate visualization and validation of registered data. RESULTS: Data collected between 2009 and October 2011, after a preliminary phase for optimizing the temperature inside the containers, demonstrated the frequency of transportations at an acceptable temperature (<20 °C) had increased and that of transportations at an excessively high temperature (>25 °C) had decreased by ~80%. CONCLUSIONS: The integrated system and related operating instructions allow improvement in the quality of sample transportation over time.

External Quality Assessment Schemes: need for recognised requirements.

Programs for Accreditation of clinical laboratories consider participation in External Quality Assessment Schemes (EQAS) a key element in the evaluation of testing procedures and improving them. One of the main functions of EQAS is to assess whether laboratories perform tests competently. It is therefore of utmost importance for laboratories to participate in EQAS that are in line with formally recognised requirements. Specific proposals have been made on how to design and execute EQAS by International Working Groups, but there seems to be no consensus on the best strategies to use and quality specifications to set out. The Clinical Pathology Accreditation (CPA) Program for EQA Scheme Accreditation (CPA-EQA) is the only program in Europe to provide a formal recognition of the quality of EQAS activities. The present paper reports on the experience of the Centre of Biomedical Research which is following an accreditation process for their own schemes in line with the CPA-EQA program and a proposal to set requirements that Italian schemes must follow to be recognised as valid and effective.

Assessment of package inserts for diagnostic kits.

To assure the quality of service in laboratory medicine, it is necessary to implement a quality system which comprises the entire testing process. The use of quality reagents is an important aspect of the process. Despite the fact that it is the responsibility of the laboratory to ensure the quality of the analytical system (including reagents) and since it is impossible to evaluate all commercial diagnostic kits, the laboratory often depends on statements issued by the manufacturer to select the most appropriate diagnostics for a particular laboratory. In this study we report the results of the analysis of information provided in 887 package inserts enclosed in the more widely used commercial diagnostic kits, following the Standard for the labelling of clinical laboratory materials of the European Committee for Clinical Laboratory Standards (ECCLS). Only a third of these were in agreement with the guidelines of ECCLS Standard, reporting complete and correct information. We believe that it is necessary to implement a constructive cooperation between manufacturers of diagnostic materials and clinical laboratories to produce a more uniform approach to improvements in laboratory quality assurance.

New and traditional serum markers of bone metabolism in the detection of skeletal metastases.

OBJECTIVES: The evaluation of "new" and "traditional" markers of osteoblastic and osteoclastic activity, in patients with bone metastases. DESIGN AND METHODS: Our series consist of 40 patients with clinical, radiological, and scintigraphic evidence of bone metastases, and 40 age-matched healthy subjects. In all samples, traditional markers were evaluated by measuring total alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TrACP) activity, and osteocalcin (BGP) concentration. To assess new biochemical bone markers, bone isoenzyme of alkaline phosphatase (ALP-B) activity, carboxyterminal propeptide of type I procollagen (PICP), and carboxyterminal telopeptide of type I collagen (ICTP) concentrations were measured. RESULTS: Our findings showed that the best diagnostic efficiency is provided by ICTP (0.94) followed by total ALP (0.90), ALP-B (0.80), and TrACP (0.76). The efficiency of BGP and PICP was, instead, very low (0.64 and 0.60, respectively). CONCLUSION: Our results confirm the utility of the new serum markers such as ALP-B and ICTP assays in detecting bone metastases.

Serum bone alkaline phosphatase in the follow-up of skeletal metastases.

The efficacy of bone alkaline phosphatase (ALP) isoenzyme measurement, using a lectin precipitation method, in confirming metastatic sites was assessed in 65 patients with cancer and skeletal (n = 44), hepatic (n = 15) or lymph node (n = 6) metastases; the control group consisted of 33 healthy adults. In all subjects, total ALP activity and osteocalcin were also assayed. Our results confirm that isoenzyme analysis is more specific than total enzymatic activity measurement in the identification of bone metastases: the mean for total ALP values was increased in all patients, while significantly high mean values of bone fraction (p < 0.05 by ANOVA) were observed only in patients with bone secondaries. In the serial monitoring of 9 patients with skeletal metastases, bone ALP values correlate with pain symptomatology: a progressive decrease in bone isoenzyme activity was observed in patients with a complete remission of pain after radiotherapy, while a progressive increase in activity was observed in the presence of increased bone pain. The measurement of bone isoenzyme activity is useful in screening for skeletal metastases; levels appear to correlate with the course of bone symptomatology, thus providing useful objective evidence of response to treatment.

Monitoring skeletal cancer metastases with the bone isoenzyme of tissue unspecific alkaline phosphatase.

The efficacy of bone alkaline phosphatase (ALP) isoenzyme measurement using lectin precipitation in confirming metastatic bone lesions was compared with total ALP and osteocalcin assay in serum. Sixty-five patients with cancer and metastases to bone (n = 44), liver (n = 15) or lymph nodes (n = 6) as well as 33 healthy adults were studied. Assay of bone ALP is as sensitive but more specific than assay of total ALP in the identification of bone metastases. On the other hand, bone ALP did not correlate with osteocalcin, as is the case in other bone diseases. In the serial monitoring of nine patients with skeletal metastases, bone ALP correlated well with the presence of pain and the progression or regression of metastatic spread.

Precipitation method for separating and quantifying bone and liver alkaline phosphatase isoenzymes.

We evaluated a method for quantifying bone isoenzyme of alkaline phosphatase (ALP) which utilizes wheat-germ lectin to precipitate this fraction. In precision studies, CVs ranged from 3.2 to 11.4% (within-day) and from 3.7 to 11.5% (day-to-day). The assay procedure was linear to 1100 U/L and was easily adapted to automated kinetic measurement. Comparison of the precipitation method with an affinity electrophoretic method, which utilizes cellulose acetate as a support, demonstrated a satisfactory coefficient of correlation (r = 0.886). The reference range was determined in sera from 188 healthy adult subjects. The distribution of bone ALP values was also studied in 73 healthy children and in 30 healthy adolescents. To evaluate the clinical applicability of the method, the bone isoenzyme was determined in samples from several groups of subjects (pregnant women, patients with hepatobiliary diseases, patients with hepatocellular carcinoma without skeletal involvement, and patients with bone, liver or lymph node metastases). We found the method suitable for routine determination of bone alkaline phosphatase and for the screening of bone metastases. Because of its technical simplicity and satisfactory analytical performance, it can be used instead of the heat-inactivation procedure.

High-performance liquid chromatography for cyclosporin measurement: comparison with radioimmunoassay.

The large inter-patient variability in cyclosporin pharmacokinetics coupled with the agent's narrow therapeutic index with adverse effects resulting from supratherapeutic levels, necessitates individualization of drug dosage and therapeutic monitoring of cyclosporin blood levels. The performance of a liquid chromatographic method for the measurement of cyclosporin was evaluated and the results obtained by this method and by a specific radioimmunoassay were correlated. The method described is sensitive, selective, reproducible and easier to perform than other chromatographic methods. It is suitable for the daily measurement of cyclosporin in batches of up to 40 samples and the results correlate well with another chromatographic method and with the specific radioimmunoassay.

Importance of control materials in quality assessment of cyclosporine determination.

The importance of control materials in intralaboratory quality assessment of cyclosporine A determination was analyzed. Two types of control materials and a human pool serum were evaluated. The first material was a two-level lyophilized cyclosporine human whole blood control (TLCC); the other was a tri-level therapeutic drug monitoring control (TDMC). The drug was determined in all specimens by both tritiated and iodinated radioimmunoassay. The coefficients of variation obtained in TLCC samples were significantly lower in comparison with the TDMC samples and similar to that of the human pool.