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Background: Fractional exhaled nitric oxide (FENO), a marker of eosinophilic airway inflammation, is easily measured by noninvasive means. The objective of this study was to determine the cost-effectiveness of FENO measurement using a hand-held monitor (NIOX MINO), at a reimbursement price of £23, for asthma diagnosis and management in the UK.
Methods: We constructed two decision trees to compare FENO measurement with standard diagnostic testing and guideline recommendations for management. For asthma diagnosis, we compared FENO measurement with lung function and reversibility testing, bronchial provocation and sputum eosinophil count. For asthma management, we evaluated the impact on asthma control, including inhaled corticosteroid use, exacerbations and hospitalizations, of monitoring with FENO measurement vs symptoms and lung function as in standard care. Resource use and health outcomes were evaluated over a 1-year time frame. Direct costs were calculated from a UK health-care payer perspective (2005 £).
Results: An asthma diagnosis using FENO measurement cost £43 less per patient as compared with standard diagnostic tests. Asthma management using FENO measurement instead of lung function testing resulted in annual cost-savings of £341 and 0.06 quality-adjusted life-years gained for patients with mild to severe asthma and cost-savings of £554 and 0.004 quality-adjusted life-years gained for those with moderate to severe asthma.
Conclusions: Asthma diagnosis based on FENO measurement with NIOX MINO alone is less costly and more accurate than standard diagnostic methods. Asthma management based on FENO measurement is less costly than asthma management based on standard guidelines and provides similar health benefits.
The costs of asthma to the United Kingdom National Health Service (UK NHS) were estimated at £750 million per year in 2000 (1) and to the UK overall, at over £2.3 billion per year in 2004 (2). Economic evaluations of asthma therapies and management strategies are thus an important component of decisions regarding best approaches to asthma care. Because a disproportionate share of asthma costs is attributable to patients with poorly controlled asthma (3–5), strategies aimed at improving asthma control could reduce costs as well as improve quality of life (QoL) of patients with asthma.
Asthma is characterized pathophysiologically by variable airway obstruction, airway inflammation and airway hyperresponsiveness. Assessments of airway inflammation can complement lung function testing for diagnosing and monitoring asthma; these include bronchial biopsy, bronchoalveolar lavage, induced sputum analysis and measurement of fractional exhaled nitric oxide (FENO). FENO is a marker of eosinophilic airway inflammation that correlates well with other measures of airway eosinophilia, such as sputum eosinophilia (6, 7), and can aid in asthma diagnosis as well as management (8–11).
The measurement of FENO differs from other means of assessing airway inflammation as it is noninvasive and easily performed and gives immediate and reproducible results (6, 12). Once primarily a research tool, measuring FENO is now more accessible to clinicians because of the development of an inexpensive hand-held FENO monitor (NIOX MINO®; Aerocrine AB, Solna, Sweden) (13, 14).
In the present day health economic environment, clinical tests must prove not only to be reliable and reproducible but also cost-effective. Our prior cost-effectiveness analysis of NIOX MINO in Germany found that, as compared with standard diagnostic and management procedures in that country, FENO measurement alone offered improved accuracy at slightly increased cost (€12 more per patient) for asthma diagnosis and similar health benefits at lower cost for asthma management (15). The objective of this study was to determine the cost-effectiveness of FENO measurement, using NIOX MINO, as compared with common clinical practice, for diagnosis and management of asthma in the UK.
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Results of our economic analysis indicate that measurement of FENO using NIOX MINO is a cost-effective alternative to standard testing for both asthma diagnosis and management in the UK. The cost of an asthma diagnosis made using FENO measurement was £43 less per patient, including the cost of false diagnoses, as compared with standard diagnostic tests. Asthma management using FENO measurement instead of lung function testing was a dominant strategy, resulting in annual cost-savings of £341 and 0.06 QALYs gained for patients with mild to severe asthma and cost-savings of £554 and 0.004 QALYs gained for those with moderate to severe asthma.
Varying our assumptions in the sensitivity analyses gave results consistent with the base-case analysis for both asthma diagnosis as well as management, indicating that the base-case models are robust. For asthma diagnosis, the cost of FENO measurement with NIOX MINO would have to triple to result in slightly greater costs (£3 more per patient) than with standard testing. Otherwise, NIOX MINO remained less expensive than standard diagnostic tests when we varied multiple parameters, including test sensitivity, specificity and costs. In addition, the cost of NIOX MINO was £102 less than the commonly used combination of reversibility testing followed by PEF charting (the latter added when reversibility testing is equivocal). Similarly, for asthma management, in the sensitivity analyses FENO measurement with NIOX MINO remained the dominant strategy in most cases.
In clinical practice, a diagnosis of asthma is typically made on the basis of history and physical findings, ideally supported by lung function and airway hyperresponsiveness testing (20). Thus, it is likely that, in practice, FENO measurement will be used in conjunction with other tests rather than as their replacement. We examined this scenario and found that the combination of FENO measurement plus lung function testing increased costs for diagnosing asthma by £42. The usefulness of this combination is supported by results of a recent study in which measurement of FENO, used in conjunction with spirometry, improved diagnostic confidence and therapeutic decision-making with regard to 94% of patients with nonspecific respiratory symptoms presenting in primary care (33).
The combination of FENO plus lung function testing for managing asthma was a hypothetical scenario, as there are no clinical studies from which to obtain precise data for the model. Use of this combination for managing asthma resulted in an incremental cost of £17 per patient per year and 0.059 QALYs gained, amounting to an incremental cost-effectiveness ratio of £279/QALY.
The findings of economic modelling are dependent on the assumptions contained in the model. Our goals in constructing our models were to compare FENO measurement with strategies recommended by BTS guidelines and used in clinical practice in the UK today (rather than with ideal practice without FENO measurement), as we believe these are the most relevant economic comparisons. We aimed to reflect the situation in a primary care setting, where most asthma is managed in the UK, as well as to use conservative assumptions to reach a conservative estimate of the cost-effectiveness of NIOX MINO in the UK. Our findings are thus specific to the UK.
Factors that are likely to be different between countries that could affect costs include the pattern of diagnostic tests as well as asthma treatments. In Germany, confirmation of an asthma diagnosis is often performed by office-based pulmonary specialists who use a battery of tests, including spirometry. In our analyses for Germany, to be conservative, we chose to use the cost of only spirometry (reimbursed at €8), and we found that asthma diagnosis based on FENO measurement alone (using NIOX MINO) offered improved accuracy at a cost of €12 more per patient than spirometry alone, while treatment decisions based on FENO measurement were less costly than those based on asthma management guidelines and provided similar health benefits (15).
There is currently no gold standard for diagnosing or managing asthma (17); moreover, comparative data on clinical testing for asthma are few. For our analyses, we derived sensitivity and specificity data for FENO measurement from the study by Smith et al. (6) and for PEF charting and other diagnostic testing from the study by Hunter et al. (21). While this resulted in an indirect comparison, the higher sensitivity and specificity values for PEF charting, and the low FEV1 reversibility cut point (2.9%), as reported by Hunter et al. (21), relative to other studies (6, 34), represented a conservative approach to the analysis. The management model applied risk reductions with FENO management from a population including patients with mild asthma (23), while the reductions were greatest in moderate to severe asthma, thus underestimating the benefits and again representing a conservative approach.
We were unable to examine asthma diagnosis and management strategies in a single economic model because data linking an improved diagnosis to treatment outcomes are not available. Moreover, the comparators and assumptions differed between the two models.
In the management model, the effect of FENO measurement on ICS dose was based on patients treated in primary care (10), while the impact on exacerbations was based on patients treated in secondary care (22, 23). We included both parameters in the model, thus assuming a mixed population utilizing both primary and secondary care resources. The follow-up periods in these studies were 1–1.5 years; a longer time frame might have allowed better stabilization of asthma control through seasonal fluctuations and thus better outcome assessments.
For the management model, we used the only data, to our knowledge, linking utilities to levels of asthma control (29). While this approach allowed us to calculate outcomes in terms of QALYs, a measure that can be compared across economic studies, it is associated with some uncertainty, both because of the difficulty in assessing the impact of exacerbations and hospitalizations on QoL and because of limited sensitivity of the EQ-5D for patients with mild asthma (29). Nonetheless, we believe that the slight gain in QALYs seen with FENO measurement for asthma management indicates at least a similar health effect to that of lung function testing.
Most economic analyses in asthma have examined alternatives for pharmacological therapy, while the cost-effectiveness of clinical tests for asthma has been little studied (35), and we found no other relevant comparators for the present study other than our German cost-effectiveness analysis (15). It would have been of interest to examine costs associated with the limited performance (sensitivity, specificity, reliability and validity) of existing measures; these data, however, are not available. We did not include indirect costs of asthma in our analyses because there are no applicable data on the impact of FENO measurement on indirect costs. Moreover, this is not required by UK payers. It is possible, however, that inclusion of indirect costs would strengthen our findings because of the added cost of lost productivity associated with asthma exacerbations and hospitalizations.
The application of FENO measurement in clinical practice can play an important role in diagnosing and assessing airway disease (12). This role will become better characterized with further study, in particular to define threshold values and cut-off points, use of individualized FENO profiles and use of differential flow analysis for identifying sites of airway inflammation (12, 36). With regard to cost-effectiveness, the results of our model need to be verified in practice, ideally prospectively and for a real-life primary care population, as only a small proportion of outpatients with asthma are eligible for enrolment in the typical randomized clinical trial (37, 38).
Our findings support the cost-effectiveness of FENO measurement for diagnosing and monitoring asthma in UK clinical practice. With the availability of a hand-held monitor (NIOX MINO), FENO measurement is now a practical alternative in day-to-day practice, as testing is noninvasive and simple to perform. In addition, FENO results can complement other findings, such as lung function testing, to provide a more complete picture of airway status.