Improved implementation of medical tests - barriers and opportunities.

Applying the concept of a value proposition to medical testing is just one of the many ways to identify and monitor the value of tests. A key part of this concept focusses on processes that should take place after a test is introduced into routine local practice, namely test implementation. This process requires identification of the clinical pathway, the stakeholders and the benefits or disbenefits that accrue to those stakeholders. There are various barriers and challenges to test implementation. Implementation requires the process of clinical audit which involves measurement of outcomes external to the laboratory but this is not widely performed in laboratory medicine. A second key challenge is that implementation requires liaison with stakeholders outside of the laboratory including clinicians and other healthcare professional such as finance managers. Many laboratories are remote from clinical care and other stakeholders making such liaison difficult. The implementation process is based on data which again will be primarily on processes outside of the laboratory. However the recent enthusiasm for so-called real world data and new data mining techniques may represent opportunities that will facilitate better test implementation. A final barrier is that a range of new tools not currently in the education curriculum of the laboratory professional is required for implementation such as those of preparing a business case to support the introduction of a test and health economic analysis. The professional bodies in laboratory medicine could assist with education in these areas.

The value proposition for point-of-care testing in healthcare: HbA1c for monitoring in diabetes management as an exemplar.

Point-of-care testing (POCT) is a key enabling technology for disruptive and transformative innovation in healthcare, allowing tests to be performed quickly and close to the patient. This results in faster clinical decision making and new, more efficient models of care, with clinical, process and economic benefits potentially accruing to all stakeholders. Recognised barriers to the adoption of new technology such as POCT include poor understanding of current practice and thus the unmet need, the challenges of process change, and reluctance to disinvest in redundant resources resulting from improved pathway efficiency. Major contributors to this problem include a background of funding, organisation and management of healthcare that fails to recognise the complexity of a multiple stakeholder health economy seeking to become more outcomes-based and value driven. We examine the concept of a structured value proposition as a generic tool to achieve better adoption of POCT using as an example, the evidence that is available for the rapid measurement of glycated haemoglobin (HbA1c) in the management of diabetes. We highlight the key components of the value proposition, identifying the impact of the test result on all stakeholders and the metrics which are required to define current practice (e.g. a laboratory-based HbA1c testing service), in order to develop the business case and the implementation plan required to demonstrate effective adoption of a POCT-based service. We conclude that the value proposition helps to identify the potential benefits to be gained from using POCT, and the stakeholders to whom they accrue.

Improving the quality of point-of-care testing.

Background: It is suggested that new models of primary care should have better access to test results through the use of point-of-care testing (POCT). Objective: To determine whether quality management of POCT leads to better results. Methods: A comprehensive search of the literature on quality management of POCT in primary care, where the impact of participation in quality management programmes had been investigated with relevant outcome measures. Results: Three databases were systematically searched using key words relevant to POCT and quality management, covering from 1945 to January 2017. Titles and abstracts were reviewed for relevance and papers selected for review and data extraction. Five observational studies were found in which the performance of POCT for specific analytes in external quality assurance (EQA) programmes was used to assess improvement over a period of time, varying from 3.5 to 15 years. The tests monitored were HbA1c, urine albumin, C-reactive protein, glucose and haemoglobin. In each case, the performance of the test against defined analytical criteria was used to judge improvement in performance. Different summary performance criteria were used, including the imprecision of results over a period of time (two studies) and meeting defined target values for bias and imprecision of measurement (three studies). Performance improved with time and was associated with regular participation in EQA schemes and with the use of internal quality control (IQC) procedures. Conclusions: These findings indicate that adoption of quality management for POCT, including participation in IQC and EQA, with the support of laboratory medicine professionals, will improve the quality of the results 'produced'.

International definition of a point-of-care test in family practice: a modified e-Delphi procedure.

Background: The use of point-of-care tests (POCTs) in family practice is increasing, and the term POCT is often used in medical literature and clinical practice. Yet, no widely supported definition by several professional fields exists. Objective: To reach consensus on an international definition of a POCT in family practice. Methods: We performed a modified international e-Delphi procedure of four rounds among expert panel members from different professional backgrounds-family practitioners, laboratory specialists, policymakers, researchers and manufacturers. Results: Of 27 panel members from seven different countries, 26 participated in all rounds. Most panel members were active in POCT research or policymaking and 70% worked in family medicine. After choosing important components, structuring of answers and feedback, the following definition was chosen as the best or second best definition by 81% of panel members: a point-of-care test in family practice is a test to support clinical decision making, which is performed by a qualified member of the practice staff nearby the patient and on any part of the patient's body or its derivatives, during or very close to the time of consultation, to help the patient and physician to decide upon the best suited approach, and of which the results should be known at the time of the clinical decision making. Conclusion: The definition emerging from this study can inform family practitioners, laboratory specialists, policymakers and manufacturers on the most widely supported and recognized definition and could act as a clear starting point for the organization and execution of professional point-of-care testing in family practice worldwide.

Performance of point-of-care HbA1c test devices: implications for use in clinical practice - a systematic review and meta-analysis.

BACKGROUND: Point-of-care (POC) devices could be used to measure hemoglobin A1c (HbA1c) in the doctors' office, allowing immediate feedback of results to patients. Reports have raised concerns about the analytical performance of some of these devices. We carried out a systematic review and meta-analysis using a novel approach to compare the accuracy and precision of POC HbA1c devices. METHODS: Medline, Embase and Web of Science databases were searched in June 2015 for published reports comparing POC HbA1c devices with laboratory methods. Two reviewers screened articles and extracted data on bias, precision and diagnostic accuracy. Mean bias and variability between the POC and laboratory test were combined in a meta-analysis. Study quality was assessed using the QUADAS2 tool. RESULTS: Two researchers independently reviewed 1739 records for eligibility. Sixty-one studies were included in the meta-analysis of mean bias. Devices evaluated were A1cgear, A1cNow, Afinion, B-analyst, Clover, Cobas b101, DCA 2000/Vantage, HemoCue, Innovastar, Nycocard, Quo-Lab, Quo-Test and SDA1cCare. Nine devices had a negative mean bias which was significant for three devices. There was substantial variability in bias within devices. There was no difference in bias between clinical or laboratory operators in two devices. CONCLUSIONS: This is the first meta-analysis to directly compare performance of POC HbA1c devices. Use of a device with a mean negative bias compared to a laboratory method may lead to higher levels of glycemia and a lower risk of hypoglycaemia. The implications of this on clinical decision-making and patient outcomes now need to be tested in a randomized trial.

Point-of-care testing in UK primary care: a survey to establish clinical needs.

BACKGROUND: A number of point-of-care diagnostic tests are commercially available in the UK, however, not much is known regarding GPs' desire for these tests or the clinical areas of interest. OBJECTIVE: We sought to establish for which conditions point-of-care tests (POCTs) would be most helpful to UK GPs for diagnosis, reduction of referrals, and monitoring of chronic conditions. METHODS: A total of 1635 regionally representative GPs were invited to complete an online cross-sectional survey between 31 September and 16 October 2012. RESULTS: A total of 1109 (68%) GPs responded to the survey. The most frequently cited conditions were urinary tract infections for diagnosis (47% of respondents), pulmonary embolism/deep vein thrombosis for referral reduction (47%) and international normalized ratio/anticoagulation for monitoring (49%). CONCLUSIONS: This survey has identified the conditions for which UK GPs would find POCTs most helpful. Comments by respondents suggest that quite radical system-level adjustments will be required to allow primary care clinicians to capitalize on the potential benefits of POCTs.

Controlling pharmaceutical crystallization with designed polymeric heteronuclei.

To investigate the hypothesis that molecules acting as crystallization inhibitors in solution could be transformed into crystallization promoters, additives were synthesized that mimic the pharmaceuticals acetaminophen and mefenamic acid and also possess polymerizable functionality. It was found that, in solution, these additives face-selectively inhibit crystal growth and lead to overall slower crystal appearance. In contrast, when the tailor-made additives were incorporated into an insoluble polymer, the induction time for the onset of crystal formation for both pharmaceuticals was substantially decreased. This approach now allows for the synthesis of tailor-made polymers that decrease the induction time for crystal appearance and may find application in compounds that are resistant to crystallization or in improving the fidelity of heteronucleation approaches to solid form discovery.

Diagnostic accuracy of point-of-care tests for detecting albuminuria: a systematic review and meta-analysis.

BACKGROUND: Experts recommend screening for albuminuria in patients at risk for kidney disease. PURPOSE: To systematically review evidence about the diagnostic accuracy of point-of-care (POC) tests for detecting albuminuria in individuals for whom guidelines recommend such detection. DATA SOURCES: Cochrane Library, EMBASE, Medion database, MEDLINE, and Science Citation Index from 1963 through 5 December 2013; hand searches of other relevant journals; and reference lists. STUDY SELECTION: Cross-sectional studies, published in any language, that compared the accuracy of machine-read POC tests of urinary albumin-creatinine ratio with that of laboratory measurement. DATA EXTRACTION: Two independent reviewers extracted study data and assessed study quality using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool. DATA SYNTHESIS: Sixteen studies (n = 3356 patients) that evaluated semiquantitative or quantitative POC tests and used random urine samples collected in primary or secondary ambulatory care settings met inclusion criteria. Pooling results from a bivariate random-effects model gave sensitivity and specificity estimates of 76% (95% CI, 63% to 86%) and 93% (CI, 84% to 97%), respectively, for the semiquantitative test. Sensitivity and specificity estimates for the quantitative test were 96% (CI, 78% to 99%) and 98% (CI, 93% to 99%), respectively. The negative likelihood ratios for the semiquantitative and quantitative tests were 0.26 (CI, 0.16 to 0.40) and 0.04 (CI, 0.01 to 0.25), respectively. LIMITATION: Accuracy estimates were based on data from single-sample urine measurement, but guidelines require that diagnosis of albuminuria be based on at least 2 of 3 samples collected in a 6-month period. CONCLUSION: A negative semiquantitative POC test result does not rule out albuminuria, whereas quantitative POC testing meets required performance standards and can be used to rule out albuminuria. PRIMARY FUNDING SOURCE: None.

Investigation of apparent non-albuminuric proteinuria in a primary care population.

BACKGROUND: There is debate as to whether using the urinary albumin- or protein-to-creatinine ratio (ACR or PCR) should be the primary test for proteinuria. Whilst albuminuria (increased ACR) in the absence of proteinuria (increased PCR) may be expected in some patients, the converse (i.e., proteinuria in the absence of albuminuria) is more unusual and its cause and significance are unclear. We investigated the nature of such apparent non-albuminuric proteinuria in a primary care population of patients. METHODS: ACR and PCR were measured in 569 urine samples from patients who either had chronic kidney disease or were at increased risk of the condition. Samples with apparent proteinuria (PCR ≥23 mg/mmol/≥200 mg/g) but no albuminuria (ACR <3.4 mg/mmol/<30 mg/g) were classified as 'discrepant' (37% of proteinuric samples, 6% of all samples); 27 of these samples were available for further analyses. The further analyses included electrophoresis, repeat measurement, immunoassays for markers of tubular proteinuria and use of alternative albumin and total protein methods. RESULTS: Electrophoresis did not identify significant proteinuria in the discrepant samples. The only evidence of tubular proteinuria following measurement of three urinary markers of the condition was a mildly increased α1-microglobulin-to-creatinine ratio in 10 of the 27 discrepant samples analysed, four of which also had a raised ß-trace protein-to-creatinine ratio. Use of an alternative urinary total protein method resulted in significantly lower PCRs and 17 of the 27 samples were no longer classified as proteinuric. CONCLUSIONS: We were unable to confirm the cause of a raised PCR without albuminuria in these patients and suspect that in most cases it is artefactual.

Primary care clinicians' attitudes towards point-of-care blood testing: a systematic review of qualitative studies.

BACKGROUND: Point-of-care blood tests are becoming increasingly available and could replace current venipuncture and laboratory testing for many commonly used tests. However, at present very few have been implemented in most primary care settings. Understanding the attitudes of primary care clinicians towards these tests may help to identify the barriers and facilitators to their wider adoption. We aimed to systematically review qualitative studies of primary care clinicians' attitudes to point-of-care blood tests. METHODS: We systematically searched Medline, Embase, ISI Web of Knowledge, PsycINFO and CINAHL for qualitative studies of primary care clinicians' attitudes towards point-of-care blood tests in high income countries. We conducted a thematic synthesis of included studies. RESULTS: Our search identified seven studies, including around two hundred participants from Europe and Australia. The synthesis generated three main themes: the impact of point-of-care testing on decision-making, diagnosis and treatment; impact on clinical practice more broadly; and impact on patient-clinician relationships and perceived patient experience. Primary care clinicians believed point-of-care testing improved diagnostic certainty, targeting of treatment, self-management of chronic conditions, and clinician-patient communication and relationships. There were concerns about test accuracy, over-reliance on tests, undermining of clinical skills, cost, and limited usefulness. CONCLUSIONS: We identified several perceived benefits and barriers regarding point-of-care tests in primary care. These imply that if point-of-care tests are to become more widely adopted, primary care clinicians require evidence of their accuracy, rigorous testing of the impact of introduction on patient pathways and clinical practice, and consideration of test funding.

The diagnostic accuracy of a urine albumin-creatinine ratio point-of-care test for detection of albuminuria in primary care.

BACKGROUND: Albuminuria is an important sign of chronic kidney disease and is detected routinely by measurement of urinary albumin-creatinine ratio (ACR). A Siemens CLINITEK test designed for use at the point of care is available that can semiquantitatively measure ACR. STUDY DESIGN: Diagnostic accuracy study evaluating a urinary ACR point-of-care test. SETTING & PARTICIPANTS: The semiquantitative ACR test was evaluated at the point of care in a representative primary care population (those with or at increased risk of chronic kidney disease) of 642 patients under standard operational conditions and compared with the reference standard of ACR measurement in the clinical laboratory. INDEX TEST: The point-of-care CLINITEK semiquantitative ACR test. This test uses dye-binding and catalytic assays for albumin and creatinine, respectively, on a Microalbumin 9 strip, which is read by the CLINITEK Status Analyzer, and ACR is calculated automatically. REFERENCE TEST: Laboratory measurement of albumin and creatinine on an Abbott Architect analyzer by immunoturbidimetric and enzymatic assays, respectively, and calculation of ACR. RESULTS: The prevalence of albuminuria (laboratory ACR≥30 mg/g) in the study population was 20.2%. Sensitivity and specificity of the point-of-care test for detecting albuminuria were 83.2% and 80.0%, respectively. Positive and negative predictive values were 51.2% and 95.0%, respectively; positive and negative likelihood ratios were 4.16 and 0.21, respectively. Twenty-three (3.6%) samples measured at the point of care were not analyzed in the central laboratory for a variety of reasons, including laboratory reception data entry errors. LIMITATIONS: Our sensitivity calculation is accurate to an approximately 8% CI. CONCLUSIONS: The instrument-read reagent strip test was a poor rule-in test for albuminuria at the point of care, as evidenced by the low positive predictive value, but was a reasonable rule-out test. Observed sensitivity was lower than reported in earlier laboratory-based studies. This decreased diagnostic accuracy needs to be balanced against the potential advantages of a point-of-care testing approach.

Health economic evaluations of medical tests: Translating laboratory information into value - A case study example.

Health-care providers and funders are focused on identifying value in all their services and that includes laboratories. This means that in order to gain a share of scarce resources, laboratory professionals must also understand and assess the value of tests and that includes their economic impact. This can be assessed using health economic modelling tools which, when used in conjunction with a detailed value proposition for the test, can translate laboratory information into value. While a variety of health economic assessment tools are available, this review will focus on the use of decision analytic models which essentially compare the outcomes from pathways with and without the new test, the value of which is being assessed. A step-by-step framework is provided to guide laboratory professionals through the essential steps of conducting the evaluation. Initial steps include mapping the clinical pathway, understanding the goal of the evaluation, identifying the key stakeholders and their needs and determining a suitable analytical model. Following collection of the actual data, the validity of the model must be checked, and the robustness of the outcomes tested through sensitivity analysis. The last step is to translate the findings into measures of value which can then inform appropriate decisions by the stakeholders. This review of basic health economic modelling should enable laboratory professionals to have an understanding of how modelling can be applied to tests in their own environment and help deliver their potential value.

How to Realize the Benefits of Point-of-Care Testing at the General Practice: A Comparison of Four High-Income Countries.

BACKGROUND: In some countries, such as the Netherlands and Norway, point-of-care testing (POCT) is more widely implemented in general practice compared to countries such as England and Australia. To comprehend what is necessary to realize the benefits of POCT, regarding its integration in primary care, it would be beneficial to have an overview of the structure of healthcare operations and the transactions between stakeholders (also referred to as value networks). The aim of this paper is to identify the current value networks in place applying to POCT implementation at general practices in England, Australia, Norway and the Netherlands and to compare these networks in terms of seven previously published factors that support the successful implementation, sustainability and scale-up of innovations. METHODS: The value networks were described based on formal guidelines and standards published by the respective governments, organizational bodies and affiliates. The value network of each country was validated by at least two relevant stakeholders from the respective country. RESULTS: The analysis revealed that the biggest challenge for countries with low POCT uptake was the lack of effective communication between the several organizations involved with POCT as well as the high workload for general practitioners (GPs) aiming to implement POCT. It is observed that countries with a single national authority responsible for POCT have a better uptake as they can govern the task of POCT roll-out and management and reduce the workload for GPs by assisting with set-up, quality control, training and support. CONCLUSION: Setting up a single national authority may be an effective step towards realizing the full benefits of POCT. Although it is possible for day-to-day operations to fall under the responsibility of the GP, this is only feasible if support and guidance are readily available to ensure that the workload associated with POCT is limited and as low as possible.

Point-of-care testing for Hb A1c in the management of diabetes: a systematic review and metaanalysis.

BACKGROUND: The measurement of hemoglobin A(1c) (Hb A(1c)) is employed in monitoring of patients with diabetes. Use of point-of-care testing (POCT) for Hb A(1c) results at the time of the patient consultation potentially provides an opportunity for greater interaction between patient and caregiver, and more effective care. OBJECTIVE: To perform a systematic review of current trials to determine whether POCT for Hb A(1c), compared with conventional laboratory testing, improves outcomes for patients with diabetes. METHODS: Searches were undertaken on 4 electronic databases and bibliographies from, and hand searches of, relevant journal papers. Only randomized controlled trials were included. The primary outcome measures were change in Hb A(1c) and treatment intensification. Metaanalyses were performed on the data obtained. RESULTS: Seven trials were found. There was a nonsignificant reduction of 0.09% (95% CI -0.21 to 0.02) in the Hb A(1c) in the POCT compared to the standard group. Although data were collected on the change in proportion of patients reaching a target Hb A(1c) of <7.0%, treatment intensification and heterogeneity in the populations studied and how measures were reported precluded pooling of data and metaanalysis. Positive patient satisfaction was also reported in the studies, as well as limited assessments of costs. CONCLUSIONS: There is an absence of evidence in clinical trial data to date for the effectiveness of POCT for Hb A(1c) in the management of diabetes. In future studies attention to trial design is needed to ensure appropriate selection and stratification of patients, collection of outcome measures, and action taken upon Hb A(1c) results when produced.

Point-of-Care Testing for D-Dimer in the Diagnosis of Venous Thromboembolism in Primary Care: A Narrative Review.

Venous thromboembolism (VTE) is regarded as a significant cause of mortality and disability, affecting 1-2 per 1000 people annually, presenting with a relatively wide range of symptoms, which can pose a diagnostic challenge. Historically, people in whom VTE is suspected will have been taken to hospital for diagnosis and treatment; however, a high proportion of patients are found not to have VTE. Concerns have been expressed about potential delays in treatment, with the risk of additional morbidity and disability, and death. Diagnostic strategies are typically based on the use of a clinical prediction rule to determine the pre-test probability, complemented with a measurement of D-dimer, with confirmation by imaging assessment. This narrative review explores the literature on the use of point-of-care testing (POCT) for the measurement of D-dimer, as part of a clinical decision rule, for the diagnosis of deep vein thrombosis (DVT) and pulmonary embolism (PE) in the primary care setting. In the two main prospective management (validation) studies that included D-dimer POCT or similar technologies, with a total cohort of 1600 participants, DVT was ruled out in 49% of patients, with a false negative rate of 1.4%, whereas PE was ruled out in 45% of patients, with a false negative rate of 1.5%. This suggests that uptake of POCT D-dimer in primary care has the potential to reduce the number of referrals to hospitals for imaging confirmatory investigation, with consequent cost savings. Thus, adopting POCT for D-dimer in primary care can offer clinical and cost benefits, particularly when quantitative POCT assays are being used. Furthermore, POCT should be undertaken in collaboration with the local laboratories to ensure the harmonisation of D-dimer methods and quality assurance to improve the diagnosis of VTE.

Implementation of medical tests in a Value-Based healthcare environment: A framework for delivering value.

Significant variation in the utilisation of medical tests is known to have an adverse impact on health outcomes and analysis of this variation is an important tool for quality assurance in healthcare. The introduction of a new medical test into a care pathway requires two distinct processes, termed adoption and implementation. One cause of the unwarranted variation in the use of medical tests is poor adoption and implementation. Adoption is the decision to acquire a technology and make it available to the users and is supported with evidence of clinical and cost effectiveness. Implementation is delivering the benefits promised in the business case, based on evidence of the impact of a test on each stakeholder involved in delivering the care pathway. The business case will have identified the benefits delivered to all stakeholders, as set out in a value proposition, and according to the quality domains typically addressed in quality improvement, namely clinical, process and structure (resource utilisation) outcomes. The outcome measures extend beyond those of clinical and cost effectiveness required for adoption. We describe an implementation framework which is designed to document the changes to the care pathway, the resource inputs and the expected outcomes with associated quality metrics.

Roots, development and future directions of laboratory medicine.

Laboratory medicine has evolved from basic scientific observation and good experimental practice, with a strong emphasis on establishing the mechanisms of disease processes, linked with biomarker discovery, and development of analytical technologies. That evolution is set to move on apace with the mapping of the human genome. However, laboratory medicine is not solely based on robust basic science, but also on the translation of that knowledge into establishing the clinical utility of a marker, translation into evidence of the impact on health outcomes, as well as transformational change to integrate this new knowledge into the delivery of better care for patients. This translational research and the focus on transformational change are crucial in demonstrating value-for-money in the laboratory medicine service.

Prioritisation criteria for the selection of new diagnostic technologies for evaluation.

BACKGROUND: Currently there is no framework for those involved in the identification, evaluation and prioritisation of new diagnostic technologies. Therefore we aimed to develop prioritisation criteria for the assessment of new diagnostic technologies, by gaining international consensus on not only which criteria should be used, but also their relative importance. METHODS: A two-round Delphi process was used to generate consensus amongst an international panel of twenty-six experts on priority criteria for diagnostic health technology assessment. Participants represented a range of health care and related professions, including government, industry, health services and academia. RESULTS: Based on the responses to the first questionnaire 18 criteria were placed into three categories: high, intermediate and moderate priority. For 16 of the 18 criteria, agreement with the categorisation of the criteria into the high, intermediate and moderate categories was high at > or = 70% (10 had agreement > or = 80%). A further questionnaire and panel discussion reduced the criteria to 16 and two categories; seven were classified as high priority and nine intermediate. CONCLUSIONS: This study proposes an objective structure of prioritisation criteria to use when assessing new diagnostic technologies, based on an expert consensus process. The value of these criteria is that no one single component should be used as the decisive driver for prioritisation of new diagnostic technologies for adoption in healthcare settings. Future studies should be directed at establishing the value of these prioritisation criteria across a range of healthcare settings.