The Diagnosis of Urinary Tract Infection in Young Children DUTY Study Clinical Rule: economic evaluation

Accepted/In Press date: 16 January 2017

e-pub ahead of print date: 22 February 2017

Published date: April 2017

Additional Information: Summary of findings We evaluated the cost-effectiveness of a two-step clinical rule using symptoms, signs and dipstick test results to select children for urine sampling and antibiotic treatment. Compared to GPs’ clinical judgement, the DUTY5% clinical rule could substantially reduce urine sampling, achieving lower costs and equivalent patient outcomes. DUTY points-based rules are more cost-effective than clinical judgement at high specificity thresholds (DUTY?5, DUTY?6) and could be used where it is infeasible to estimate the DUTY coefficient-based score. Our findings suggest that urine sampling should be more carefully targeted, rather than increased, but do not support the use of dipstick testing in children at intermediate risk of UTI. The benefits of immediate dipstick-guided treatment were counterbalanced by imperfect test specificity resulting in more antibiotic prescriptions in children without UTI. Strengths and limitations Our model was based on individual patient data from a large, rigorously conducted, prospective diagnostic cohort study. Therefore, most of the parameters underlying the short-term model come from a consistent, high-quality data source. In the DUTY study, urine samples were analysed by both health service and research laboratories providing more accurate estimates of the prevalence of UTI and contamination. Furthermore, we were able to model the impact of false negative laboratory results and antibiotic resistance on the efficiency of UTI diagnosis. Our results are based on evidence from children in whom clean catch samples were collected and are not necessarily generalizable to younger children where nappy pads are generally used for sampling. The ‘clinical judgement’ diagnostic strategy aimed to represent current practice, based on clinicians’ responses to questions about working diagnoses and testing and treatment plans. However, DUTY study participation may have sensitised clinicians to the possibility of UTI, leading to an over-estimate of urine sampling rates. While this would not alter our conclusion that selected symptoms and signs can help primary care clinicians to target urine sampling, it does strengthen the interpretation that high specificity diagnostic strategies (e.g. DUTY 5%, DUTY?5) are most likely to be cost-effective in diagnosing and treating UTI. Some of the evidence underlying the model was imprecise and potentially biased. For example, there is no RCT-based evidence on the effect of antibiotics in young children with UTI. The evidence underlying the long-term model is based on observational associations between recurrent UTI and renal disease which continues to evolve: the RIVUR trial comparing daily trimethoprim–sulfamethoxazole prophylaxis to placebo in children with VUR recently reported a 50% reduction in recurrent UTI, but no trend for reduced incidence of renal scarring(25). Similarly, the choice of sampling distribution for some parameters, in particular costs and utilities, was based on convention rather than primary data introducing subjectivity into the probabilistic sensitivity analysis. Our model did not include other potential long-term consequences of UTI such as pregnancy-related complications or hypertension where the causal role of UTI is debated and difficult to ascertain(26, 27). It is possible that other long-term consequences of UTI exist. Identifying and including these would favour more sensitive strategies. However, our conclusions were insensitive to different assumptions about the long-term sequelae of UTI. The model results are dominated by the short-term costs of testing and treating rather than long-term sequelae because most children presenting to primary care do not have UTI, most children with UTI will not develop ESRD, and each strategy only has a small impact on the proportion of children treated appropriately. The large number of risk thresholds and the multiple ways of using dipstick testing and laboratory culture to guide treatment, produce an almost unlimited number of potential management strategies. We evaluated some which closely reflect current practice, but other unevaluated strategies could prove more cost-effective. We did not quantify the societal costs of antibiotic resistance. Current methods may underestimate the cost of antibiotic resistance and accurate estimation may not be possible.(4) Given increasing levels of resistance and the paucity of new antibiotics, the inclusion of these costs would further strengthen the case for high specificity diagnostic strategies that limit prescriptions to those most likely to have a UTI. Results in context with other studies As far as we are aware, this is the first study to evaluate the cost-effectiveness of a clinical rule to identify children with UTI in primary care. Previous work has assessed the most cost-effective test or series of tests for diagnosing UTI rather than evaluating which children should be considered at risk of UTI. An economic model evaluating testing strategies for children with suspected UTI concluded that either presumptive treatment or treatment based on positive dipstick nitrites and leukocyte and MCUG were optimal(2). Our findings suggest that waiting for a positive laboratory culture is more cost-effective in children at ‘intermediate risk’ of UTI. The differences in findings are likely to be partly due to the inclusion of serendipitous treatment and detailed daily symptom resolution rates in our model. Clinical and research implications Each year large numbers of young children present to primary care with acute illness. Therefore, even small modifications to diagnostic strategies for common conditions such as UTI will have a large impact on aggregate costs and workload. Our findings demonstrate the need for clinicians to base the decision to collect a urine sample on symptoms and signs known to be predictive of UTI in primary care rather than on personal judgement, or evidence derived from secondary care. Our results also illustrate the trade-off between the small but certain short-term costs of UTI diagnosis and treatment against the important but less certain benefits of detecting and treating UTI, and potentially preventing renal disease. Our findings suggest that clinicians should select low-cost, high specificity, diagnostic strategies. A GP requesting urine samples in children using the DUTY5% strategy, would sample 4.8% of all acutely unwell children, and request a sample in 58% of children who have UTI at a testing and antibiotic cost of £1.22 per child. Where symptoms and signs are routinely recorded in electronic records, this process could be automated. However, in settings where resources do not permit this, a GP using DUTY?5 strategy would sample 6.7% of all acutely unwell children, including 53% of children who have UTI, at a testing and antibiotic cost of £1.57 per child. Both strategies are more cost-effective than clinical judgement alone. Our research does not support the routine use of dipstick testing to guide treatment. However this conclusion is based on weak evidence about the effect of antibiotics. Trial evidence comparing the cost-effectiveness of management strategies in women with suspected UTI concluded that all strategies achieved similar symptom control and that dipstick test guided management was likely, albeit with considerable uncertainty, to be cost-effective(28, 29). A similar trial of management strategies in infants is needed. Studies of parent-reported quality of life and disutility of UTI symptoms in young children would enable more precise estimates of short-term benefits of antibiotics. Long-term epidemiological study designs are needed to better quantify and understand the association between childhood UTI and renal disease. Conclusions The DUTY coefficient and points scores were more cost-effective than GPs’ clinical judgement in selecting children for urine sampling and treatment for UTI. Small differences between strategies in cost-effectiveness are important given the large number of urine samples collected in children. High specificity thresholds, such as DUTY?5, are simple to implement and likely to be most cost-effective than clinical judgement. Our findings do not support the routine use of dipstick testing, but trial evidence is needed to compare the cost-effectiveness of various management strategies.

Organisations: Primary Care & Population Sciences

Local EPrints ID: 404971

URI: http://eprints.soton.ac.uk/id/eprint/404971

DOI: doi:10.1016/j.jval.2017.01.003

ISSN: 1098-3015

PURE UUID: 69889a7b-b410-4dc1-90e3-99287ce284cf

ORCID for Kim Harman: orcid.org/0000-0002-5173-7753

Date deposited: 25 Jan 2017 14:41

Last modified: 15 Mar 2024 06:15