The REFER (REFer for EchocaRdiogram) protocol: a prospective validation of a clinical decision rule, NT-proBNP, or their combination, in the diagnosis of heart failure in primary care. Rationale and design

Tait, Lynda; Roalfe, Andrea; Mant, Jonathan; Cowie, Martin R.; Deeks, Jonathan J; Iles, Rachel; Barton, Pelham; Taylor, Clare; Derit, Marites; Hobbs, FD Richard

doi:10.1186/1471-2261-12-97

Cited by 13 publications

(15 citation statements)

References 49 publications

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“…The full methods for the study have been previously published elsewhere [8]. The clinical decision rule was developed from an Individual Patient Database meta-analysis of epidemiological studies of HF screening in primary care [9].…”

Section: Introductionmentioning

confidence: 99%

MICE or NICE? An economic evaluation of clinical decision rules in the diagnosis of heart failure in primary care

Monahan

Barton

Taylor

et al. 2017

International Journal of Cardiology

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BackgroundDetection and treatment of heart failure (HF) can improve quality of life and reduce premature mortality. However, symptoms such as breathlessness are common in primary care, have a variety of causes and not all patients require cardiac imaging. In systems where healthcare resources are limited, ensuring those patients who are likely to have HF undergo appropriate and timely investigation is vital.DesignA decision tree was developed to assess the cost-effectiveness of using the MICE (Male, Infarction, Crepitations, Edema) decision rule compared to other diagnostic strategies to identify HF patients presenting to primary care.MethodsData from REFER (REFer for EchocaRdiogram), a HF diagnostic accuracy study, was used to determine which patients received the correct diagnosis decision. The model adopted a UK National Health Service (NHS) perspective.ResultsThe current recommended National Institute for Health and Care Excellence (NICE) guidelines for identifying patients with HF was the most cost-effective option with a cost of £4400 per quality adjusted life year (QALY) gained compared to a “do nothing” strategy. That is, patients presenting with symptoms suggestive of HF should be referred straight for echocardiography if they had a history of myocardial infarction or if their NT-proBNP level was ≥ 400 pg/ml. The MICE rule was more expensive and less effective than the other comparators. Base-case results were robust to sensitivity analyses.ConclusionsThis represents the first cost-utility analysis comparing HF diagnostic strategies for symptomatic patients. Current guidelines in England were the most cost-effective option for identifying patients for confirmatory HF diagnosis. The low number of HF with Reduced Ejection Fraction patients (12%) in the REFER patient population limited the benefits of early detection.

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Section: Introductionmentioning

confidence: 99%

MICE or NICE? An economic evaluation of clinical decision rules in the diagnosis of heart failure in primary care

Monahan

Barton

Taylor

et al. 2017

International Journal of Cardiology

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“…One modification of a rule was identified. 19 Clinical settings for model development Candidate variables varied widely from five to 36. 19 Clinical settings for model development Candidate variables varied widely from five to 36.…”

Section: Resultsmentioning

confidence: 99%

A systematic review of clinical prediction rules for the diagnosis of chronic heart failure

et al. 2019

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Aims This study sought to review the literature for clinical prediction models for the diagnosis of patients with chronic heart failure in the community and to validate the models in a novel cohort of patients with a suspected diagnosis of chronic heart failure. Methods and results MEDLINE and Embase were searched from 1946 to Q4 2017. Studies were eligible if they contained at least one multivariable model for the diagnosis of chronic heart failure applicable to the primary care setting. The CHARMS checklist was used to evaluate models. We also validated models, where possible, in a novel cohort of patients with a suspected diagnosis of heart failure referred to a rapid access diagnostic clinic. In total, 5310 articles were identified with nine articles subsequently meeting the eligibility criteria. Three models had undergone internal validation, and four had undergone external validation. No clinical impact studies have been completed to date. Area under the curve (AUC) varied from 0.74 to 0.93 and from 0.60 to 0.65 in the novel cohort for clinical models alone with AUC up to 0.89 in combination with electrocardiogram and B‐type natriuretic peptide (BNP). The AUC for BNP was 0.86 (95% confidence interval 83.3–88.6%). Conclusions This review demonstrates that there are a number of clinical prediction rules relevant to the diagnosis of chronic heart failure in the literature. Clinical impact studies are required to compare the use of clinical prediction rules and biomarker strategies in this setting.

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“…NIHR Journals Library www.journalslibrary.nihr.ac.uk Chapter 2 The REFER study: methods T he full protocol for the REFer for EchocaRdiogram (REFER) study has been published previously 23 and a copy of the clinical record form used for each participant is available in Appendix 1.…”

Section: The Refer Study: Backgroundmentioning

confidence: 99%

“…The full methods for the REFER study have been published previously. 23 The CDR was developed from an individual patient data meta-analysis of epidemiological studies of heart failure screening in primary care, commissioned as a health technology assessment by NICE. 4 Briefly, primary care patients aged ≥ 55 years presenting to their GP with symptoms suggestive of heart failure were recruited across 28 central England practices in the UK.…”

Section: The Refer Study Data Setmentioning

confidence: 99%

The REFER (REFer for EchocaRdiogram) study: a prospective validation and health economic analysis of a clinical decision rule, NT-proBNP or their combination in the diagnosis of heart failure in primary care

et al. 2017

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Background Heart failure is a treatable condition but making a diagnosis can be challenging. Objective To evaluate the performance of a clinical decision rule (CDR) with or without a natriuretic peptide assay for identifying heart failure in symptomatic patients presenting to primary care. Design Prospective, observational, diagnostic validation study and economic evaluation. Setting Twenty-eight general practices in central England, UK. Participants Primary care patients aged ≥ 55 years presenting with recent new-onset shortness of breath, lethargy or peripheral ankle oedema of > 48 hours’ duration. Instrument The CDR included a clinical element (male, history of myocardial infarction, crepitations at the lung bases and oedema) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) blood test. The reference standard was an expert consensus panel of three cardiology specialists. Main outcome measure The main outcome measure was test performance of the CDR and the natriuretic peptide test alone, and in combination, in estimating sensitivity and specificity, positive predictive value (PPV) and negative predictive value (NPV) for a diagnosis of heart failure. Economic evaluation of a decision tree with a NHS/Personal Social Services perspective determined the cost per quality-adjusted life-year (QALY) gained. Results In total, 304 participants were recruited to the validation cohort. The mean age was 73.9 years (standard deviation 8.8 years) and 124 (40.8%) participants were male. In total, 104 [34.2%, 95% confidence interval (CI) 28.9% to 39.8%] had a confirmed diagnosis of heart failure. The CDR had a sensitivity of 90% (95% CI 83% to 95%), specificity of 46% (95% CI 39% to 53%), PPV of 46% (95% CI 39% to 53%) and NPV of 90% (95% CI 83% to 95%). NT-proBNP level alone with a cut-off point of < 400 pg/ml had a sensitivity of 77% (95% CI 68% to 85%) and specificity of 92% (95% CI 87% to 95%). At the lower cut-off point of 125 pg/ml, sensitivity was 94% (95% CI 88% to 98%) and specificity was 49% (95% CI 42% to 56%). The economic model results suggest that referring a patient for a confirmatory diagnosis if they have had a previous myocardial infarction or have a NT-proBNP level that is greater than a 400 pg/ml threshold (current practice in England) is the most cost-effective option, with a cost of £4400 per QALY gained compared with a do nothing strategy. The base-case results were robust to deterministic and probabilistic sensitivity analyses. Conclusions Natriuretic peptide testing alone performed as well as the validated CDR in determining which patients presenting with symptoms went on to have a diagnosis of heart failure. The current NT-proBNP cut-off point of 400 pg/ml used in the UK is too high and means that one in five patients with heart failure may not be appropriately referred for further investigation and diagnosis, but this threshold was cost-effective in the REFer for EchocaRdiogram (REFER) trial. The study found only three patients with heart failure with reduced ejection fraction (HFREF), which might limit the benefits of early detection. The other diagnostic strategies with lower NT-proBNP referral levels become more cost-effective as the proportion of HFREF patients increases. International consensus on the optimal cut-off point for natriuretic peptide testing in patients with symptoms suggestive of heart failure should be sought. Trial registration Current Controlled Trials ISRCTN17635379. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership.

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The REFER (REFer for EchocaRdiogram) protocol: a prospective validation of a clinical decision rule, NT-proBNP, or their combination, in the diagnosis of heart failure in primary care. Rationale and design

Cited by 13 publications

References 49 publications

MICE or NICE? An economic evaluation of clinical decision rules in the diagnosis of heart failure in primary care

MICE or NICE? An economic evaluation of clinical decision rules in the diagnosis of heart failure in primary care

A systematic review of clinical prediction rules for the diagnosis of chronic heart failure

The REFER (REFer for EchocaRdiogram) study: a prospective validation and health economic analysis of a clinical decision rule, NT-proBNP or their combination in the diagnosis of heart failure in primary care

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