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A value proposition for natriuretic peptide measurement in the assessment of patients with suspected acute heart failure
Journal Pre-proofs A value proposition for natriuretic peptide measurement in the assessment of patients with suspected acute heart failure Maurice O'Kane, David Porter, Michael McCann, Paul Jülicher, Robert Christenson, Michael Oellerich, Christopher P Price, Andrew St John PII: DOI: Reference:
S0009-8981(19)32051-0 https://doi.org/10.1016/j.cca.2019.09.023 CCA 15861
To appear in:
Clinica Chimica Acta
Received Date: Accepted Date:
14 September 2019 18 September 2019
Please cite this article as: M. O'Kane, D. Porter, M. McCann, P. Jülicher, R. Christenson, M. Oellerich, C.P. Price, A. St John, A value proposition for natriuretic peptide measurement in the assessment of patients with suspected acute heart failure, Clinica Chimica Acta (2019), doi: https://doi.org/10.1016/j.cca.2019.09.023
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© 2019 Published by Elsevier B.V.
A value proposition for natriuretic peptide measurement in the assessment of patients with suspected acute heart failure
Maurice O’Kane,1,2 David Porter,1,2 Michael McCann,3 Paul Jülicher,4 Robert Christenson , 5 Michael Oellerich,6 Christopher P Price,7 Andrew St John8
1
Clinical Chemistry Laboratory, Altnagelvin Hospital , Londonderry, N. Ireland, UK
2
Centre for Personalised Medicine: Clinical Decision Making and Patient Safety, C-TRIC, Altnagelvin Hospital, Londonderry, N. Ireland 3
Letterkenny Institute of Technology, Letterkenny, Republic of Ireland
4
Laboratories of Pathology, University of Maryland Medical Centre, 22 South Green Street, Baltimore, MD 21201, USA 5
Health Economics and Outcomes Research, Medical Affairs, Abbott Laboratories, Wiesbaden, Germany 6
Department of Clinical Pharmacology, University Medicine Göttingen (UMG),Kreuzbergring 36, 37075 Göttingen, Germany 7
Barts and the London School of Medicine and Dentistry, Queen Mary University of London,, United Kingdom 8
ARC Consulting, Perth, W. Australia
Correspondence to Dr Maurice O’Kane: [email protected] Acknowledgements: The contribution of authors MOK, DP and MMcC to this work was supported in part by the European Union’s INTERREG VA Programme, managed by the Special EU Programmes Body (SEUPB). The views and opinions expressed in this document do not necessarily reflect those of the European Commission or the Special EU Programmes Body (SEUPB).
This paper includes work on behalf of the Committee for the Value Proposition in Laboratory Medicine of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC).
1
Abstract There is robust clinical trial evidence supporting the role of natriuretic peptides [NPs] in the assessment of patients presenting with suspected acute heart failure [AHF]. Despite the fact that clinical guidelines have for some time advocated NP measurement, the availability and uptake of NP testing in acute care services remains patchy and incomplete. The reasons for this are multifactorial but are underpinned by compartmentalised management and budget structures within complex healthcare delivery organisations. This paper outlines a value proposition for NP testing in the acute care setting which crosses the continuum of services and budgets. It articulates the expected benefits to each stakeholder in terms of efficiency of processes, clinical outcomes and cost effectiveness. It describes a pathway to implementation and suggests metrics that may be used to measure the effectiveness of introduction of NP testing. It is hoped that the value proposition will facilitate the uptake of NT testing by fostering collaboration between laboratory, clinical, management and finance teams and by informing the development of business cases.
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Background Acute heart failure [AHF] is a syndrome which refers to the rapid onset of the features of heart failure and may occur de novo or as is more commonly the case against a background of known heart failure [decompensated heart failure]. 1 With a lifetime risk of ~ 20% for developing AHF, it is now among the most frequent causes of hospital admission on the > 65 year old age group. 2 It is a condition associated with significant morbidity and has a mortality rate of approximately 17 - 25% in the 12 months following diagnosis.1,3
The diagnosis of heart failure is challenging because the presenting clinical features are not specific and may overlap with other cardiorespiratory conditions. Even following careful clinical assessment by an experienced clinician including chest X ray and ECG, the diagnosis may be uncertain in 30-50% of cases. 4-6 The benefits of early diagnosis and treatment in improving patient outcomes are well established. 6-9 There is now a very strong body of evidence supporting the measurement of natriuretic peptides [NPs] in the assessment of patients with suspected acute heart failure.4 NPs investigated for clinical use include B-type natriuretic peptide [BNP], N-terminal-pro-B-type natriuretic peptide [NTproBNP] and mid-regional-pro-A-type natriuretic peptide [MRproANP]. An increased NP concentration has high sensitivity for the diagnosis AHF i.e. a NP concentration below the ‘rule-out cutoff’ has a high negative predictive value in ruling out AHF as a cause of the patient’s symptoms and redirects the physician towards alternative diagnoses. The specificity of NP for AHF is more modest and confirmatory echocardiography will be required in patients with raised NP concentrations. The measurement of NP is recommended as an essential test in the assessment of patients with suspected acute heart failure in a range of international clinical practice guidelines.1,10-12 However, despite the robust clinical trial evidence pointing to the clinical utility of NP measurement, the adoption of NP testing by medical laboratories remains patchy and incomplete. A recently published survey of European and North American laboratories found that of the respondents only 67% of European and 58% of North American laboratories offered NP measurements. 13,14
In the UK a recent ‘National Confidential Enquiry on Patient Outcome and Death: Failure to Function - a review of the care received by patients who died in hospital following an admission with acute heart failure’ showed that of the participating hospitals, 15.8% did not have access to NP measurement; furthermore NP measurements were performed in only 17.9% of patients with a 3
new diagnosis of acute heart failure.15 There was therefore evidence of incomplete availability of NP measurement on the one hand and on the other hand, apparent underutilisation of NP measurement where it was available to clinical teams. The reasons for underutilisation of NPs in the acute care setting remain unclear but may relate at least in part to the additional cost to the laboratory of providing a 24 hours/7 days a week NP measurement service, 4, 13-14 the failure to incorporate NP measurement into clinical care pathways, or the failure by clinical teams to adhere to the care pathway. Regardless of the reasons, this failure to incorporate NP measurement into clinical practice means that the proven benefits of NP measurement are not being realised.
A particular challenge facing laboratories in many countries in introducing new tests is that the funding model may operate on a cost per test basis in the context of a laboratory budget that is siloed. 16 The introduction of a new test will require investment in the laboratory budget, yet the benefits [clinical, process, financial] may accrue to a separate clinical service and budget. Furthermore, the accrual of the clinical benefit may occur at a time point distant from the testing episode. Defining and quantifying the value of a test to support investment decisions requires a broad approach across the continuum of healthcare services and budgets.
Recent years have seen the development of the concept of a ‘value proposition’ for laboratory medicine 16 This is a paradigm borrowed from the business world which aims to describe the value of a new product or service to the customer, over and above that which is currently available. A value proposition for a laboratory test defines the benefits of introducing a test into a clinical care pathway; these benefits may accrue to a variety of stakeholders including patients, clinical staff, laboratories, finance departments and management teams [including commissioners of health services and purchasers]. The value of the test in question may cover a range of outcomes including improved clinical outcomes for patients, an enhanced patient experience, more efficient processes or financial benefits, all of which are detailed in the value proposition. It is hoped that the articulation of a value proposition will act as a driver that will facilitate the introduction of new evidence based tests into laboratories and their incorporation into care pathways. The aim of this paper is to develop a value proposition for the use of NP measurement in the assessment of patients with suspected AHF. The value proposition does not address the role of NPs as prognostic markers or their use as treatment targets. The structure of the value proposition follows that outlined previously by Price, St John and colleagues. 16,17 This framework describes the
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unmet clinical need that the test will address, the patient population which will benefit, the characteristics of the test and its clinical utility, the expected outcomes, the location of the test, a consideration of the quality of the evidence, the benefits and disadvantages to identified stakeholders, resource requirements, a consideration of reimbursement and a proposed implementation plan including measures that will indicate successful adoption.
Methods There is a large body of clinical trial evidence, subsequently synthesised in systematic reviews/metanalyses on the clinical value of NP measurement in the assessment of patients with suspected AHF. 4,10 This has been incorporated into best practice guidelines, which advocate the role of NP measurement as ‘ a rule-out test’ and position it in the care pathway for the assessment and clinical management of patients.1,10-12 The purpose of the present paper is not therefore to provide a further review of the evidence base but rather to extract the salient features relevant to the value proposition.
1. Unmet clinical need The unmet clinical need is the early exclusion or inclusion of a diagnosis of AHF in the acute care setting. Patients with AHF present with a range of symptoms and clinical signs which may overlap with other cardiorespiratory conditions. Even with careful clinical assessment by experienced clinicians including ECG and chest X Ray, the diagnosis may be uncertain in 30-50 % of patients. Misdiagnosis of AHF may result in inappropriate treatment and increased mortality.8,9 The early exclusion of AHF allows consideration of alternative diagnoses to explain the patient’s symptoms. Conversely, prompt diagnosis of AHF is important as there is evidence that early administration of treatment is associated with reduction in hospital mortality [OR 0.87] and the adjusted odds of death is increased 6.8% for every 6 hours delay in treatment. 8,9,18 2. Patient population that will benefit The patient population under consideration are those attending for acute medical care with clinical features in particular dyspnoea, suggestive of a diagnosis of AHF. For the most part these patients will present to emergency departments or other acute care facilities.
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3. Laboratory test The laboratory tests under consideration for this value proposition are the natriuretic peptides BNP, NTproBNP and MR proANP, all of which have been investigated for clinical use. Of these BNP and NTproBNP are more widely available and have been more studied than MRproANP. BNP and NTproBNP are also commercially available as point-of care tests. Based on clinical trial evidence the European Society of Cardiology has defined the following ‘ruleout cut-offs’ , which make acute heart failure unlikely: 1 NTproBNP < 300ng /L BNP < 100ng/L MR-proAMP < 120pmol/L Age dependent cut-offs for NTproBNP to ‘rule in’ AHF have also been proposed: > 450ng/L for patients < 50nyears, > 900 ng/L for patients 50-75 years and 1800ng/L > 75 year although these have not been universally incorporated into best practice clinical guidelines. 18 Individual NP assays are offered by a number of manufacturers on different analytical platforms. Agreement is better between NTproBNP assays [all of which use antibodies and calibrators from a single manufacturer] than for BNP assays. 19,20
4. Test intervention utility The clinical utility of the test is the ability of NP measurement to exclude or confirm a diagnosis of AHF as the cause of the patient’s symptoms.1,5,6,21-23 NPs have high sensitivity [in the range 95% to 99%] for the diagnosis of AHF and this therefore makes it an excellent ‘rule out’ test: using the ‘rule out’ cut-off thresholds given in section 3 above, NPs have a pooled negative predictive value of 94% to 98% in patients presenting at an acute care setting with symptoms suggestive of AHF. 4 The pooled positive predictive value of NP s at these cutoffs was 63% to 64%. NPs have more modest specificity [in the range 43 to 63% for BNP or NTproBNP and 40-98% for MRproANP].10 Increased NP concentrations may be found in a range of other cardiac and noncardiac conditions including acute coronary syndrome, pulmonary embolism, myocarditis, cerebral infract, subarachnoid haemorrhage ,ascites, renal impairment, sepsis, thyrotoxicosis, ketoacidosis.
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Patients with raised NP concentrations therefore require echocardiography or other cardiac imaging to confirm a diagnosis of AHF and to establish aetiology. The use of BNP and NTproBNP measurements was consistently associated with reduced hospitalisation rates and reduced length of hospital stay for up to 12 months after the index presentation.10 For example in the B-Type Natriuretic Peptide for Acute Shortness of Breath Evaluation [BASEL] Study, a diagnostic strategy involving rapid measurement of BNP was associated with a reduced hospitalisation rate v. standard care [75% v 85%], reduced requirement for intensive care [15% v. 24%] and reduced length of hospital stay [8 v. 11 days].6 Some studies have also shown that the use of BNP or NTproBNP is associated with reduced mortality at 30 and 180 days. 10,28,29,31 In the BASEL study for example the all cause mortality was 20 v. 23% in favour of a diagnostic strategy incorporating BNP measurement. 6 Expected outcomes The incorporation of NP measurement in the assessment of patients allows AHF to be excluded as a diagnosis with a high degree of certainty and allows more expeditious clinical management of patients presenting with suspected AHF. 1,10-12 This will result in more rapid patient triage and treatment with improved clinical outcomes and more effective use of resources through increased triage efficiency and reduced hospitalisation including a reduced need for intensive care.
Location where test performed NP measurement may be provided as a central laboratory test servicing the Emergency Department or other acute or urgent care facility which will be the primary site of assessment of patients presenting with clinical features suggestive of AHF. To contribute maximally to patient care, NP test results should be available rapidly, ideally within one hour. 10 BNP and NTproBNP are available as point-of care tests and deliver a result within 15 to 20 minutes. Quality of evidence available There has been extensive research on the clinical utility of NP measurements in patients presenting with suspected AHF, in particular for NTproBNP and BNP. There have been fewer studies with MRproANP and accordingly the evidence is base is less robust. Studies have varied in quality of design and reporting with variation in the accuracy of the outcome measurements obtained. The largest metanalysis undertaken considered specifically those studies 7
which took place in an acute care setting using an acceptable reference standard for the diagnosis of AHF and in a consecutive or randomised cohort of patients. 4 The individual studies were also graded for the risk of bias for a number of study design and reporting quality categories. The results of this metanalysis can therefore be regarded as robust: ·
For BNP a metanalysis of high quality evidence from 19 studies [6950 participants] showed a pooled sensitivity and specificity for the diagnosis of AHF using a cut off of <100ng/L of 95% [SD 1%] and 63% [SD 6%]. 4,10
·
·
For NTproBNP a metanalysis of high quality evidence from 10 studies [3349 participants] showed a pooled sensitivity and specificity using a cut off of < 300ng/L of 99% [SD 1%] and 43% [SD 10%].4,10 For MRproANP the evidence base is much smaller; high quality evidence from four studies [2557participants] showed a sensitivity of 84-98% and a specificity of 40 -98%.4,10
Some studies investigated the impact of NP testing when used in conjunction with a pre-specified treatment regimen. 5,6 27 In addition to diagnostic accuracy, studies have reported on the impact of NP testing on a range of clinical and other outcomes:
Clinical evidence NP measurement has high sensitivity for AHF and accordingly a NP concentration below the rule-out threshold in patients with acute dyspnoea excludes a diagnosis of AHF with a high degree of certainty. NP measurement is associated with a reduced time to administration of appropriate treatment [as per discharge diagnosis] of 63 minutes v. 90 minutes, 6 reduced hospitalisation, reduced requirement for intensive care and reduced length of stay. There is evidence from some [but not all] studies of reduction in all cause mortality up to 180 days post presentation.10 The use of NP is associated with fewer false negatives [2.3% v. 9.4%] compared with conventional assessment not involving NP measurement, although more frequent false positives [19.8% v. 12.2%]. In some modelling analyses this has suggested the need for a greater number of echocardiograms [668 v 592 per 1 000 patients]. 3
Economic evidence Several economic evaluations have demonstrated the cost effectiveness of NP testing. 5, 24-28 The BASEL study suggested that total treatment costs at 180 days were reduced by ~ 25%. The reduction in cost is driven primarily by reduced hospitalisation, reduced requirement for intensive care,
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reduced length of hospital stay and reduced readmission rate. A Markov modelling analysis considered the cost of adoption of NP testing alone and NP testing combined with specialist outreach care of AHF patients. It concluded that strategies using NP testing with or without specialist care were more expensive, however both were cost effective with NP testing combined with specialist care being the most cost effective strategy at £2 883 [2017 price] per Quality Adjusted Life Year gained. 3 The more modest specificity of NP as a diagnostic test means that patients with increased NP concentration require echocardiogram for confirmation of diagnosis and to investigate aetiology. The impact of NP testing on echocardiography in patients with AHF is complex. The high negative predictive value may result in a reduced numbers of echocardiographs in patients with NP results below the ‘rule out’ cut-off. For patients presenting with acute dyspnoea, approximately one third will be considered on clinical assessment alone to have low probability of AHF and would not therefore be referred for echocardiography. However a diagnostic pathway that combines NP measurement in conjunction with clinical assessment in all patients will generate additional false positive results [due to the more modest specificity of NP] and true positive results and there may therefore be an increase in the total number of echocardiographs overall. 6. Nevertheless, diagnostic strategies incorporating NP testing remain cost effective. 3,10 8
Part of the care pathway in which the test will be used
NP should be measured as part of the initial clinical assessment of patients presenting with symptoms and signs suggestive of acute heart failure. This will predominantly be in ED or other acute care facilities. Patients with NP concentrations above the rule out cut -off may require echocardiography to confirm the diagnosis and which may also provide information as to the aetiology of the AHF. 9
Benefits / Disadvantages to each of the stakeholders involved in delivering and receiving the care ·
Patients: more rapid diagnosis of the cause of their symptoms, more rapid administration of appropriate treatment, reduced hospitalisation, reduced requirement for intensive care, shorter length of hospital stay, reduced readmission within the first year following presentation. Assessment strategies incorporating NP testing are associated with fewer false negatives than clinical assessment alone. Even for these patients, expert opinion suggests that up to 80% will have a correct diagnosis of AHF made during the admission and for the
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remaining 20%, within 3 months of presentation. NP testing presents minimal risk to patients.
·
Medical Laboratories: need to provide a rapid turnaround time NP service; this will incur additional cost and technologist time
·
Clinical staff: more rapid patient triage, more rapid administration of appropriate treatment, reduced length of hospital stay, reduced re- hospitalisation rates, reduced intensive care requirement, reduced readmission rate in the first year. To derive maximum benefit NP measurement must be incorporated into a clinical care pathway which offers protocol driven, evidence based care to patients with AHF. This may require the reorganisation of the delivery of clinical care to AHF patients.
·
Cardiac imaging services: some modelling analyses have suggested that NP testing in patients presenting with clinical features suggestive of AHF may be associated overall with an increase in requirement for echocardiography.
·
Healthcare provider: improved efficiency of patient triage, reduced hospitalisation, reduced intensive care requirement, reduced rehospitalisation rates. To accrue all these benefits there will be a need to implement a laboratory NP testing service available on a 24 hours / 7 days per week basis with rapid turnaround and to configure clinical teams that can deliver high quality evidence based care to AHF patients.
10 Potential limitations and risks that might be associated with introduction of the test, and a proposed mitigation strategy The introduction of an AHF assessment strategy incorporating NP testing presents minimal risks to patients. The rate of false negative assessment i.e. incorrectly excluding a diagnosis of heart failure, is lower than with strategies which do not include NP testing. Even for these patients the great majority will have the correct diagnosis established during the same admission. 10 Another potential risk is a possible increase in echocardiography requests due both to the high sensitivity and more modest specificity of NPs for AHF] which has been suggested by some modelling studies. 3, 10 Furthermore there is a risk that where the clinical pathway is not adhered to that patients may inappropriately be referred for echocardiography where the NP concentration falls below the ‘rule out’ cut off; this risk can be mitigated by audit to ensuring the adherence to care pathway protocols. 10
11
Resource/activity contributed by each of the service lines involved in the care pathway ·
The laboratory service will be required to establish and deliver a 24 hour / 7 days per week NP assay service within an appropriately rapid test turn-around time.
·
Emergency departments / acute care facilities will have to develop a new clinical care pathway for the assessment and management of suspected AHF patients incorporating NP testing. This must include protocol driven, evidence based, management of AHF and might require reorganisation of care delivery e.g. a dedicated acute heart failure outreach team.
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Statement of reimbursement required for delivering the care pathway
Economic modelling suggests that the use of NP assays is maximally cost effective when incorporated into a care pathway offering specialist care for AHF patients. Additional expenditure may be required for establishment of a rapid turnaround, 24hour /7 days a week NP laboratory service and for reconfiguring clinical teams to ensure the delivery of high quality evidence based care to AHF patients.
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A proposed implementation plan including metrics for monitoring appropriate adoption
The benefit to patients of NP measurement derives from testing followed by the delivery of appropriate high quality care.
The implementation plan will therefore comprise three major elements:
(a) Establishment of rapid turnaround 24 ours /7 days a week laboratory NP measurement service with appropriate rule out cut- offs for AHF (b) The development of a clinical diagnostic pathway [incorporating NP measurement] for patients presenting with symptoms suggestive of AHF (c) The development of a clinical guideline based care pathway to allow specialist care of patients with AHF. This may require the reorganisation of existing treatment pathways and clinical teams.
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Table 1 outlines metrics that might be considered in assessing the outcomes of implementation of NP testing. Some of these will be easy to measure, in particular those relating to the laboratory and clinical processes. It is recognised that the measurement, analysis and interpretation of economic outcomes may be more challenging but these are an important component of the value proposition. Summary of the value proposition The provision of a 24 hour / 7 days a week NP service will produce value and benefits arising from more efficient patient triage, more rapid diagnosis and treatment, shorter length of hospital stay and reduced requirement for intensive care.
Discussion
Abundant evidence from carefully designed, high quality clinical trials has accumulated over the last 20 years confirming the clinical utility of NP measurement in patients with suspected AHF.4 While NP has been incorporated into numerous best practice clinical guidelines,1,10,12,13 the fact that the availability and uptake of NP testing remains patchy and incomplete points to major challenges in the process for the adoption of new evidence based tests into routine practice.13,15 We can only speculate as to the reasons for this but they may relate to cost and to challenges in disrupting and replacing existing clinical practice. An overarching factor however is the complex nature of large healthcare organisations in which healthcare delivery is too often compartmentalised and fragmented, where activity and investment in one sector e.g. laboratory medicine is considered in isolation from activity and investment in other sectors e.g. a clinical service. This may be a particular challenge where investment in one service budget results in benefits that accrue to another service and budget or where a change in one service requires change of practice in another service to maximise benefit for patients. Any decision therefore to introduce a new laboratory test maybe challenging and requires collaboration across a range of laboratory, clinical, organisational and budgetary boundaries.
This paper presents a value proposition for NP in the assessment of patients presenting with clinical features suggestive of AHF to the Emergency Department or other acute / urgent care facility. The value proposition does not seek to favour one particular NP test over another but acknowledges the greater evidence base and wider availability of BNP and NTproBNP over MRproANP. Using robust 12
data from clinical trials and metanalyses which have informed best practice clinical guidelines, it articulates and where possible quantifies the benefits that will accrue from NP testing to each of the stakeholders involved in service delivery including patients. The key benefits include more rapid patient triage and treatment, reduced hospitalisation, reduced requirement for intensive care and reduced length of hospital stay. 3, 10 A central element of the value proposition is that it places NP testing in a clinical care pathway that includes patient clinical management in addition to diagnosis. For any diagnostic test, the value to the patient relates not only to the diagnostic performance of the test but also to the quality of clinical care subsequent to testing. For NP, the combination of NP measurement with specialist heart failure management delivers much greater cost effectiveness than NP testing alone. 3,10 This is a clear example of how the introduction of a new laboratory test may require the disruption and reorganisation of existing care delivery to maximise the benefits of testing. It also makes a cogent argument for the need to consider laboratory testing in the context of the totality of clinical care pathways and for closer collaboration between laboratory and clinical services. As such, we believe that the value proposition will be of relevance to patients and organisations advocating for patients, policy makers, health care delivery organisations, clinical teams and laboratory medicine specialists.
Perhaps more so than for many other tests used in laboratory medicine, the development of a value proposition for NPs has been relatively straightforward given the high quality of evidence generated over 20 years regarding the diagnostic utility of the test and its impact on outcomes. This makes it all the more disappointing and surprising that uptake remains incomplete and points to the need for tools, such as the present value proposition, that will enable healthcare organisations to adopt new evidence based tests in a more timely manner. An important next step will be for laboratorians and other relevant stakeholders to test the various elements of the value proposition by using it to support the introduction and implementation of NP testing for acute care services where this is not already in place. For services which already have NP testing as part of the care pathway for patients presenting with features of AHF, the various elements outlined in Table 1 may be used to assess the effectiveness and the impact of NP testing in this patient group.
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Table 1 Measures for monitoring the adoption of a NP measurement in the assessment of patients with suspected Acute Heart Failure
Laboratory
Number of NP measurements performed per unit time for patients with suspected acute heart failure Median NP turnaround time
Clinical
Number of patients with suspected AHF per unit time Number /proportion of patients with suspected AHF who have NP testing performed as part of the initial assessment Number / proportion of patients with positive NP test result who have AHF confirmed at echocardiogram Number / proportion of NP positive and negative patients who are admitted to hospital Number / proportion of patients with negative NP results who are referred for echocardiography Triage time in acute care facility /ED to confirm or exclude a diagnosis of AHF Time from presentation to administration of treatment appropriate to diagnosis Number / proportion of patients with negative NP result who have a final discharge diagnosis of AHF Number / proportion of NP positive patients who receive intensive care Median length of hospital stay [days] Rehospitalisation within 180 days with a diagnosis of AHF
Cardiac imaging
No of transthoracic echocardiograms in patients with suspected AHF
Economic
Reduced hospital admissions Reduced length of stay Reduced readmission within 180 days
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Highlights
Natriuretic peptide [NP] measurement is underutilised in acute heart failure assessment A value proposition is presented for NP in acute heart failure
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S0009-8981(19)32051-0 https://doi.org/10.1016/j.cca.2019.09.023 CCA 15861
To appear in:
Clinica Chimica Acta
Received Date: Accepted Date:
14 September 2019 18 September 2019
Please cite this article as: M. O'Kane, D. Porter, M. McCann, P. Jülicher, R. Christenson, M. Oellerich, C.P. Price, A. St John, A value proposition for natriuretic peptide measurement in the assessment of patients with suspected acute heart failure, Clinica Chimica Acta (2019), doi: https://doi.org/10.1016/j.cca.2019.09.023
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© 2019 Published by Elsevier B.V.
A value proposition for natriuretic peptide measurement in the assessment of patients with suspected acute heart failure
Maurice O’Kane,1,2 David Porter,1,2 Michael McCann,3 Paul Jülicher,4 Robert Christenson , 5 Michael Oellerich,6 Christopher P Price,7 Andrew St John8
1
Clinical Chemistry Laboratory, Altnagelvin Hospital , Londonderry, N. Ireland, UK
2
Centre for Personalised Medicine: Clinical Decision Making and Patient Safety, C-TRIC, Altnagelvin Hospital, Londonderry, N. Ireland 3
Letterkenny Institute of Technology, Letterkenny, Republic of Ireland
4
Laboratories of Pathology, University of Maryland Medical Centre, 22 South Green Street, Baltimore, MD 21201, USA 5
Health Economics and Outcomes Research, Medical Affairs, Abbott Laboratories, Wiesbaden, Germany 6
Department of Clinical Pharmacology, University Medicine Göttingen (UMG),Kreuzbergring 36, 37075 Göttingen, Germany 7
Barts and the London School of Medicine and Dentistry, Queen Mary University of London,, United Kingdom 8
ARC Consulting, Perth, W. Australia
Correspondence to Dr Maurice O’Kane: [email protected] Acknowledgements: The contribution of authors MOK, DP and MMcC to this work was supported in part by the European Union’s INTERREG VA Programme, managed by the Special EU Programmes Body (SEUPB). The views and opinions expressed in this document do not necessarily reflect those of the European Commission or the Special EU Programmes Body (SEUPB).
This paper includes work on behalf of the Committee for the Value Proposition in Laboratory Medicine of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC).
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Abstract There is robust clinical trial evidence supporting the role of natriuretic peptides [NPs] in the assessment of patients presenting with suspected acute heart failure [AHF]. Despite the fact that clinical guidelines have for some time advocated NP measurement, the availability and uptake of NP testing in acute care services remains patchy and incomplete. The reasons for this are multifactorial but are underpinned by compartmentalised management and budget structures within complex healthcare delivery organisations. This paper outlines a value proposition for NP testing in the acute care setting which crosses the continuum of services and budgets. It articulates the expected benefits to each stakeholder in terms of efficiency of processes, clinical outcomes and cost effectiveness. It describes a pathway to implementation and suggests metrics that may be used to measure the effectiveness of introduction of NP testing. It is hoped that the value proposition will facilitate the uptake of NT testing by fostering collaboration between laboratory, clinical, management and finance teams and by informing the development of business cases.
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Background Acute heart failure [AHF] is a syndrome which refers to the rapid onset of the features of heart failure and may occur de novo or as is more commonly the case against a background of known heart failure [decompensated heart failure]. 1 With a lifetime risk of ~ 20% for developing AHF, it is now among the most frequent causes of hospital admission on the > 65 year old age group. 2 It is a condition associated with significant morbidity and has a mortality rate of approximately 17 - 25% in the 12 months following diagnosis.1,3
The diagnosis of heart failure is challenging because the presenting clinical features are not specific and may overlap with other cardiorespiratory conditions. Even following careful clinical assessment by an experienced clinician including chest X ray and ECG, the diagnosis may be uncertain in 30-50% of cases. 4-6 The benefits of early diagnosis and treatment in improving patient outcomes are well established. 6-9 There is now a very strong body of evidence supporting the measurement of natriuretic peptides [NPs] in the assessment of patients with suspected acute heart failure.4 NPs investigated for clinical use include B-type natriuretic peptide [BNP], N-terminal-pro-B-type natriuretic peptide [NTproBNP] and mid-regional-pro-A-type natriuretic peptide [MRproANP]. An increased NP concentration has high sensitivity for the diagnosis AHF i.e. a NP concentration below the ‘rule-out cutoff’ has a high negative predictive value in ruling out AHF as a cause of the patient’s symptoms and redirects the physician towards alternative diagnoses. The specificity of NP for AHF is more modest and confirmatory echocardiography will be required in patients with raised NP concentrations. The measurement of NP is recommended as an essential test in the assessment of patients with suspected acute heart failure in a range of international clinical practice guidelines.1,10-12 However, despite the robust clinical trial evidence pointing to the clinical utility of NP measurement, the adoption of NP testing by medical laboratories remains patchy and incomplete. A recently published survey of European and North American laboratories found that of the respondents only 67% of European and 58% of North American laboratories offered NP measurements. 13,14
In the UK a recent ‘National Confidential Enquiry on Patient Outcome and Death: Failure to Function - a review of the care received by patients who died in hospital following an admission with acute heart failure’ showed that of the participating hospitals, 15.8% did not have access to NP measurement; furthermore NP measurements were performed in only 17.9% of patients with a 3
new diagnosis of acute heart failure.15 There was therefore evidence of incomplete availability of NP measurement on the one hand and on the other hand, apparent underutilisation of NP measurement where it was available to clinical teams. The reasons for underutilisation of NPs in the acute care setting remain unclear but may relate at least in part to the additional cost to the laboratory of providing a 24 hours/7 days a week NP measurement service, 4, 13-14 the failure to incorporate NP measurement into clinical care pathways, or the failure by clinical teams to adhere to the care pathway. Regardless of the reasons, this failure to incorporate NP measurement into clinical practice means that the proven benefits of NP measurement are not being realised.
A particular challenge facing laboratories in many countries in introducing new tests is that the funding model may operate on a cost per test basis in the context of a laboratory budget that is siloed. 16 The introduction of a new test will require investment in the laboratory budget, yet the benefits [clinical, process, financial] may accrue to a separate clinical service and budget. Furthermore, the accrual of the clinical benefit may occur at a time point distant from the testing episode. Defining and quantifying the value of a test to support investment decisions requires a broad approach across the continuum of healthcare services and budgets.
Recent years have seen the development of the concept of a ‘value proposition’ for laboratory medicine 16 This is a paradigm borrowed from the business world which aims to describe the value of a new product or service to the customer, over and above that which is currently available. A value proposition for a laboratory test defines the benefits of introducing a test into a clinical care pathway; these benefits may accrue to a variety of stakeholders including patients, clinical staff, laboratories, finance departments and management teams [including commissioners of health services and purchasers]. The value of the test in question may cover a range of outcomes including improved clinical outcomes for patients, an enhanced patient experience, more efficient processes or financial benefits, all of which are detailed in the value proposition. It is hoped that the articulation of a value proposition will act as a driver that will facilitate the introduction of new evidence based tests into laboratories and their incorporation into care pathways. The aim of this paper is to develop a value proposition for the use of NP measurement in the assessment of patients with suspected AHF. The value proposition does not address the role of NPs as prognostic markers or their use as treatment targets. The structure of the value proposition follows that outlined previously by Price, St John and colleagues. 16,17 This framework describes the
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unmet clinical need that the test will address, the patient population which will benefit, the characteristics of the test and its clinical utility, the expected outcomes, the location of the test, a consideration of the quality of the evidence, the benefits and disadvantages to identified stakeholders, resource requirements, a consideration of reimbursement and a proposed implementation plan including measures that will indicate successful adoption.
Methods There is a large body of clinical trial evidence, subsequently synthesised in systematic reviews/metanalyses on the clinical value of NP measurement in the assessment of patients with suspected AHF. 4,10 This has been incorporated into best practice guidelines, which advocate the role of NP measurement as ‘ a rule-out test’ and position it in the care pathway for the assessment and clinical management of patients.1,10-12 The purpose of the present paper is not therefore to provide a further review of the evidence base but rather to extract the salient features relevant to the value proposition.
1. Unmet clinical need The unmet clinical need is the early exclusion or inclusion of a diagnosis of AHF in the acute care setting. Patients with AHF present with a range of symptoms and clinical signs which may overlap with other cardiorespiratory conditions. Even with careful clinical assessment by experienced clinicians including ECG and chest X Ray, the diagnosis may be uncertain in 30-50 % of patients. Misdiagnosis of AHF may result in inappropriate treatment and increased mortality.8,9 The early exclusion of AHF allows consideration of alternative diagnoses to explain the patient’s symptoms. Conversely, prompt diagnosis of AHF is important as there is evidence that early administration of treatment is associated with reduction in hospital mortality [OR 0.87] and the adjusted odds of death is increased 6.8% for every 6 hours delay in treatment. 8,9,18 2. Patient population that will benefit The patient population under consideration are those attending for acute medical care with clinical features in particular dyspnoea, suggestive of a diagnosis of AHF. For the most part these patients will present to emergency departments or other acute care facilities.
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3. Laboratory test The laboratory tests under consideration for this value proposition are the natriuretic peptides BNP, NTproBNP and MR proANP, all of which have been investigated for clinical use. Of these BNP and NTproBNP are more widely available and have been more studied than MRproANP. BNP and NTproBNP are also commercially available as point-of care tests. Based on clinical trial evidence the European Society of Cardiology has defined the following ‘ruleout cut-offs’ , which make acute heart failure unlikely: 1 NTproBNP < 300ng /L BNP < 100ng/L MR-proAMP < 120pmol/L Age dependent cut-offs for NTproBNP to ‘rule in’ AHF have also been proposed: > 450ng/L for patients < 50nyears, > 900 ng/L for patients 50-75 years and 1800ng/L > 75 year although these have not been universally incorporated into best practice clinical guidelines. 18 Individual NP assays are offered by a number of manufacturers on different analytical platforms. Agreement is better between NTproBNP assays [all of which use antibodies and calibrators from a single manufacturer] than for BNP assays. 19,20
4. Test intervention utility The clinical utility of the test is the ability of NP measurement to exclude or confirm a diagnosis of AHF as the cause of the patient’s symptoms.1,5,6,21-23 NPs have high sensitivity [in the range 95% to 99%] for the diagnosis of AHF and this therefore makes it an excellent ‘rule out’ test: using the ‘rule out’ cut-off thresholds given in section 3 above, NPs have a pooled negative predictive value of 94% to 98% in patients presenting at an acute care setting with symptoms suggestive of AHF. 4 The pooled positive predictive value of NP s at these cutoffs was 63% to 64%. NPs have more modest specificity [in the range 43 to 63% for BNP or NTproBNP and 40-98% for MRproANP].10 Increased NP concentrations may be found in a range of other cardiac and noncardiac conditions including acute coronary syndrome, pulmonary embolism, myocarditis, cerebral infract, subarachnoid haemorrhage ,ascites, renal impairment, sepsis, thyrotoxicosis, ketoacidosis.
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Patients with raised NP concentrations therefore require echocardiography or other cardiac imaging to confirm a diagnosis of AHF and to establish aetiology. The use of BNP and NTproBNP measurements was consistently associated with reduced hospitalisation rates and reduced length of hospital stay for up to 12 months after the index presentation.10 For example in the B-Type Natriuretic Peptide for Acute Shortness of Breath Evaluation [BASEL] Study, a diagnostic strategy involving rapid measurement of BNP was associated with a reduced hospitalisation rate v. standard care [75% v 85%], reduced requirement for intensive care [15% v. 24%] and reduced length of hospital stay [8 v. 11 days].6 Some studies have also shown that the use of BNP or NTproBNP is associated with reduced mortality at 30 and 180 days. 10,28,29,31 In the BASEL study for example the all cause mortality was 20 v. 23% in favour of a diagnostic strategy incorporating BNP measurement. 6 Expected outcomes The incorporation of NP measurement in the assessment of patients allows AHF to be excluded as a diagnosis with a high degree of certainty and allows more expeditious clinical management of patients presenting with suspected AHF. 1,10-12 This will result in more rapid patient triage and treatment with improved clinical outcomes and more effective use of resources through increased triage efficiency and reduced hospitalisation including a reduced need for intensive care.
Location where test performed NP measurement may be provided as a central laboratory test servicing the Emergency Department or other acute or urgent care facility which will be the primary site of assessment of patients presenting with clinical features suggestive of AHF. To contribute maximally to patient care, NP test results should be available rapidly, ideally within one hour. 10 BNP and NTproBNP are available as point-of care tests and deliver a result within 15 to 20 minutes. Quality of evidence available There has been extensive research on the clinical utility of NP measurements in patients presenting with suspected AHF, in particular for NTproBNP and BNP. There have been fewer studies with MRproANP and accordingly the evidence is base is less robust. Studies have varied in quality of design and reporting with variation in the accuracy of the outcome measurements obtained. The largest metanalysis undertaken considered specifically those studies 7
which took place in an acute care setting using an acceptable reference standard for the diagnosis of AHF and in a consecutive or randomised cohort of patients. 4 The individual studies were also graded for the risk of bias for a number of study design and reporting quality categories. The results of this metanalysis can therefore be regarded as robust: ·
For BNP a metanalysis of high quality evidence from 19 studies [6950 participants] showed a pooled sensitivity and specificity for the diagnosis of AHF using a cut off of <100ng/L of 95% [SD 1%] and 63% [SD 6%]. 4,10
·
·
For NTproBNP a metanalysis of high quality evidence from 10 studies [3349 participants] showed a pooled sensitivity and specificity using a cut off of < 300ng/L of 99% [SD 1%] and 43% [SD 10%].4,10 For MRproANP the evidence base is much smaller; high quality evidence from four studies [2557participants] showed a sensitivity of 84-98% and a specificity of 40 -98%.4,10
Some studies investigated the impact of NP testing when used in conjunction with a pre-specified treatment regimen. 5,6 27 In addition to diagnostic accuracy, studies have reported on the impact of NP testing on a range of clinical and other outcomes:
Clinical evidence NP measurement has high sensitivity for AHF and accordingly a NP concentration below the rule-out threshold in patients with acute dyspnoea excludes a diagnosis of AHF with a high degree of certainty. NP measurement is associated with a reduced time to administration of appropriate treatment [as per discharge diagnosis] of 63 minutes v. 90 minutes, 6 reduced hospitalisation, reduced requirement for intensive care and reduced length of stay. There is evidence from some [but not all] studies of reduction in all cause mortality up to 180 days post presentation.10 The use of NP is associated with fewer false negatives [2.3% v. 9.4%] compared with conventional assessment not involving NP measurement, although more frequent false positives [19.8% v. 12.2%]. In some modelling analyses this has suggested the need for a greater number of echocardiograms [668 v 592 per 1 000 patients]. 3
Economic evidence Several economic evaluations have demonstrated the cost effectiveness of NP testing. 5, 24-28 The BASEL study suggested that total treatment costs at 180 days were reduced by ~ 25%. The reduction in cost is driven primarily by reduced hospitalisation, reduced requirement for intensive care,
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reduced length of hospital stay and reduced readmission rate. A Markov modelling analysis considered the cost of adoption of NP testing alone and NP testing combined with specialist outreach care of AHF patients. It concluded that strategies using NP testing with or without specialist care were more expensive, however both were cost effective with NP testing combined with specialist care being the most cost effective strategy at £2 883 [2017 price] per Quality Adjusted Life Year gained. 3 The more modest specificity of NP as a diagnostic test means that patients with increased NP concentration require echocardiogram for confirmation of diagnosis and to investigate aetiology. The impact of NP testing on echocardiography in patients with AHF is complex. The high negative predictive value may result in a reduced numbers of echocardiographs in patients with NP results below the ‘rule out’ cut-off. For patients presenting with acute dyspnoea, approximately one third will be considered on clinical assessment alone to have low probability of AHF and would not therefore be referred for echocardiography. However a diagnostic pathway that combines NP measurement in conjunction with clinical assessment in all patients will generate additional false positive results [due to the more modest specificity of NP] and true positive results and there may therefore be an increase in the total number of echocardiographs overall. 6. Nevertheless, diagnostic strategies incorporating NP testing remain cost effective. 3,10 8
Part of the care pathway in which the test will be used
NP should be measured as part of the initial clinical assessment of patients presenting with symptoms and signs suggestive of acute heart failure. This will predominantly be in ED or other acute care facilities. Patients with NP concentrations above the rule out cut -off may require echocardiography to confirm the diagnosis and which may also provide information as to the aetiology of the AHF. 9
Benefits / Disadvantages to each of the stakeholders involved in delivering and receiving the care ·
Patients: more rapid diagnosis of the cause of their symptoms, more rapid administration of appropriate treatment, reduced hospitalisation, reduced requirement for intensive care, shorter length of hospital stay, reduced readmission within the first year following presentation. Assessment strategies incorporating NP testing are associated with fewer false negatives than clinical assessment alone. Even for these patients, expert opinion suggests that up to 80% will have a correct diagnosis of AHF made during the admission and for the
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remaining 20%, within 3 months of presentation. NP testing presents minimal risk to patients.
·
Medical Laboratories: need to provide a rapid turnaround time NP service; this will incur additional cost and technologist time
·
Clinical staff: more rapid patient triage, more rapid administration of appropriate treatment, reduced length of hospital stay, reduced re- hospitalisation rates, reduced intensive care requirement, reduced readmission rate in the first year. To derive maximum benefit NP measurement must be incorporated into a clinical care pathway which offers protocol driven, evidence based care to patients with AHF. This may require the reorganisation of the delivery of clinical care to AHF patients.
·
Cardiac imaging services: some modelling analyses have suggested that NP testing in patients presenting with clinical features suggestive of AHF may be associated overall with an increase in requirement for echocardiography.
·
Healthcare provider: improved efficiency of patient triage, reduced hospitalisation, reduced intensive care requirement, reduced rehospitalisation rates. To accrue all these benefits there will be a need to implement a laboratory NP testing service available on a 24 hours / 7 days per week basis with rapid turnaround and to configure clinical teams that can deliver high quality evidence based care to AHF patients.
10 Potential limitations and risks that might be associated with introduction of the test, and a proposed mitigation strategy The introduction of an AHF assessment strategy incorporating NP testing presents minimal risks to patients. The rate of false negative assessment i.e. incorrectly excluding a diagnosis of heart failure, is lower than with strategies which do not include NP testing. Even for these patients the great majority will have the correct diagnosis established during the same admission. 10 Another potential risk is a possible increase in echocardiography requests due both to the high sensitivity and more modest specificity of NPs for AHF] which has been suggested by some modelling studies. 3, 10 Furthermore there is a risk that where the clinical pathway is not adhered to that patients may inappropriately be referred for echocardiography where the NP concentration falls below the ‘rule out’ cut off; this risk can be mitigated by audit to ensuring the adherence to care pathway protocols. 10
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Resource/activity contributed by each of the service lines involved in the care pathway ·
The laboratory service will be required to establish and deliver a 24 hour / 7 days per week NP assay service within an appropriately rapid test turn-around time.
·
Emergency departments / acute care facilities will have to develop a new clinical care pathway for the assessment and management of suspected AHF patients incorporating NP testing. This must include protocol driven, evidence based, management of AHF and might require reorganisation of care delivery e.g. a dedicated acute heart failure outreach team.
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Statement of reimbursement required for delivering the care pathway
Economic modelling suggests that the use of NP assays is maximally cost effective when incorporated into a care pathway offering specialist care for AHF patients. Additional expenditure may be required for establishment of a rapid turnaround, 24hour /7 days a week NP laboratory service and for reconfiguring clinical teams to ensure the delivery of high quality evidence based care to AHF patients.
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A proposed implementation plan including metrics for monitoring appropriate adoption
The benefit to patients of NP measurement derives from testing followed by the delivery of appropriate high quality care.
The implementation plan will therefore comprise three major elements:
(a) Establishment of rapid turnaround 24 ours /7 days a week laboratory NP measurement service with appropriate rule out cut- offs for AHF (b) The development of a clinical diagnostic pathway [incorporating NP measurement] for patients presenting with symptoms suggestive of AHF (c) The development of a clinical guideline based care pathway to allow specialist care of patients with AHF. This may require the reorganisation of existing treatment pathways and clinical teams.
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Table 1 outlines metrics that might be considered in assessing the outcomes of implementation of NP testing. Some of these will be easy to measure, in particular those relating to the laboratory and clinical processes. It is recognised that the measurement, analysis and interpretation of economic outcomes may be more challenging but these are an important component of the value proposition. Summary of the value proposition The provision of a 24 hour / 7 days a week NP service will produce value and benefits arising from more efficient patient triage, more rapid diagnosis and treatment, shorter length of hospital stay and reduced requirement for intensive care.
Discussion
Abundant evidence from carefully designed, high quality clinical trials has accumulated over the last 20 years confirming the clinical utility of NP measurement in patients with suspected AHF.4 While NP has been incorporated into numerous best practice clinical guidelines,1,10,12,13 the fact that the availability and uptake of NP testing remains patchy and incomplete points to major challenges in the process for the adoption of new evidence based tests into routine practice.13,15 We can only speculate as to the reasons for this but they may relate to cost and to challenges in disrupting and replacing existing clinical practice. An overarching factor however is the complex nature of large healthcare organisations in which healthcare delivery is too often compartmentalised and fragmented, where activity and investment in one sector e.g. laboratory medicine is considered in isolation from activity and investment in other sectors e.g. a clinical service. This may be a particular challenge where investment in one service budget results in benefits that accrue to another service and budget or where a change in one service requires change of practice in another service to maximise benefit for patients. Any decision therefore to introduce a new laboratory test maybe challenging and requires collaboration across a range of laboratory, clinical, organisational and budgetary boundaries.
This paper presents a value proposition for NP in the assessment of patients presenting with clinical features suggestive of AHF to the Emergency Department or other acute / urgent care facility. The value proposition does not seek to favour one particular NP test over another but acknowledges the greater evidence base and wider availability of BNP and NTproBNP over MRproANP. Using robust 12
data from clinical trials and metanalyses which have informed best practice clinical guidelines, it articulates and where possible quantifies the benefits that will accrue from NP testing to each of the stakeholders involved in service delivery including patients. The key benefits include more rapid patient triage and treatment, reduced hospitalisation, reduced requirement for intensive care and reduced length of hospital stay. 3, 10 A central element of the value proposition is that it places NP testing in a clinical care pathway that includes patient clinical management in addition to diagnosis. For any diagnostic test, the value to the patient relates not only to the diagnostic performance of the test but also to the quality of clinical care subsequent to testing. For NP, the combination of NP measurement with specialist heart failure management delivers much greater cost effectiveness than NP testing alone. 3,10 This is a clear example of how the introduction of a new laboratory test may require the disruption and reorganisation of existing care delivery to maximise the benefits of testing. It also makes a cogent argument for the need to consider laboratory testing in the context of the totality of clinical care pathways and for closer collaboration between laboratory and clinical services. As such, we believe that the value proposition will be of relevance to patients and organisations advocating for patients, policy makers, health care delivery organisations, clinical teams and laboratory medicine specialists.
Perhaps more so than for many other tests used in laboratory medicine, the development of a value proposition for NPs has been relatively straightforward given the high quality of evidence generated over 20 years regarding the diagnostic utility of the test and its impact on outcomes. This makes it all the more disappointing and surprising that uptake remains incomplete and points to the need for tools, such as the present value proposition, that will enable healthcare organisations to adopt new evidence based tests in a more timely manner. An important next step will be for laboratorians and other relevant stakeholders to test the various elements of the value proposition by using it to support the introduction and implementation of NP testing for acute care services where this is not already in place. For services which already have NP testing as part of the care pathway for patients presenting with features of AHF, the various elements outlined in Table 1 may be used to assess the effectiveness and the impact of NP testing in this patient group.
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Table 1 Measures for monitoring the adoption of a NP measurement in the assessment of patients with suspected Acute Heart Failure
Laboratory
Number of NP measurements performed per unit time for patients with suspected acute heart failure Median NP turnaround time
Clinical
Number of patients with suspected AHF per unit time Number /proportion of patients with suspected AHF who have NP testing performed as part of the initial assessment Number / proportion of patients with positive NP test result who have AHF confirmed at echocardiogram Number / proportion of NP positive and negative patients who are admitted to hospital Number / proportion of patients with negative NP results who are referred for echocardiography Triage time in acute care facility /ED to confirm or exclude a diagnosis of AHF Time from presentation to administration of treatment appropriate to diagnosis Number / proportion of patients with negative NP result who have a final discharge diagnosis of AHF Number / proportion of NP positive patients who receive intensive care Median length of hospital stay [days] Rehospitalisation within 180 days with a diagnosis of AHF
Cardiac imaging
No of transthoracic echocardiograms in patients with suspected AHF
Economic
Reduced hospital admissions Reduced length of stay Reduced readmission within 180 days
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Highlights
Natriuretic peptide [NP] measurement is underutilised in acute heart failure assessment A value proposition is presented for NP in acute heart failure
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