Economic evaluation of zinc and copper use in treating acute diarrhea in children: a randomized controlled trial Patel A B, Dhande L A, Rawat M S

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1 Economic evaluation of zinc and copper use in treating acute diarrhea in children: a randomized controlled trial Patel A B, Dhande L A, Rawat M S Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology The use of a daily dose of 40 mg zinc sulphate and 5 mg copper sulphate powder, dissolved in a litre of standard oral rehydration solution (ORS), to treat children aged 6 to 59 months with acute diarrhoea. This intervention was compared with 50 mg standard ORS powder dissolved in one litre of ORS. Type of intervention Treatment. Economic study type Cost-effectiveness analysis. Study population The study population comprised children aged 6 to 59 months with acute diarrhoea (i.e. more than 3 unformed stools in 24 hours and diarrhoea duration of less than 7 days). The exclusion criteria were those with intractable vomiting, prerenal or renal failure, respiratory distress, altered sensorium or any such co-morbid condition that precludes the use of ORS, and clinical signs of severe malnutrition. Setting The study setting was secondary care. The economic study was carried out at the Nagpur city's Government Medical College and Hospital, India. Dates to which data relate The effectiveness and resource use data appear to have been collected during the study, but the authors did not explicitly report the date of the study. The price year was Source of effectiveness data The effectiveness evidence was derived from a single study. Link between effectiveness and cost data The costing was carried out prospectively on the same sample of patients as that used in the effectiveness study. Study sample No sample size was determined in the planning phase of the study. In addition, no power calculations appear to have been performed. The patients were selected from children who presented at the Nagpur city's Government Medical College and Hospital with acute diarrhoea. A total of 220 children were enrolled in the study. The non participation rate Page: 1 / 6

2 was reported to be 9%, but no reasons for non-participation were given. One hundred and two children (58.8% male) were randomised to the trial group and 98 (48.9% male) to the control group. The mean age of the children was 21.2 (+/- 14.2) in the trial group and 21.4 (+/- 13.7) months in the control group. Study design This was a double-blinded randomised controlled trial (RCT) that was carried out in a single centre. Randomisation was performed by administering two identical coded waterproof sachets containing a group assignment once per day. The patients and the caregivers were blinded to the patient's treatment status. The duration of follow-up was the length of stay in the hospital. No loss to follow-up was reported. Analysis of effectiveness It appears that the analysis has been conducted on an intention to treat basis. The clinical outcomes in the analysis were: the duration of diarrhoea, the length of hospital stay, the proportion of children with diarrhoea for more than 4 days, the use of unscheduled intravenous fluids, the weight loss at discharge, and the presence of complications or mortality. Both the trial and control groups were comparable, with no statistically significant differences in baseline demographic characteristics or features of the diarrhoeal episode. Effectiveness results The clinical outcomes for the trial group versus control group, respectively, were as follows: mean duration of diarrhoea (+/- standard deviation), 4.34 (+/- 0.2) versus 4.48 (+/- 0.2), (p=0.3); length of hospital stay, 1.6 (+/- 0.2) versus 2 (+/- 0.2), (p=0.2); diarrhoea for more than 4 days, 39% versus 46% (odd ratio, OR=0.83, 95% confidence interval, CI: ; p=0.2); unscheduled IV use, 2% versus 5%, (OR 0.37, 95% CI: ; p=0.2); weight loss, 34% versus 44%, (OR 0.7, 95% CI: ; p=0.2); complications, 1 versus 6, (OR 0.15, 95% CI: ; p=0.05); mortality, 0 versus 2. Clinical conclusions This clinical study showed that micronutrient supplementation resulted in favourable health outcomes, but failed to reach significant levels. Micronutrient supplementation also resulted in clinically important reductions in rate of complications and mortality. Measure of benefits used in the economic analysis Page: 2 / 6

3 The measures of benefits used were the number of cases of diarrhoea (diarrhoea > 4 days) averted and the number of disability-adjusted life-years (DALYs) lost. The DALY was defined as an indicator of the time lived with a disability and the time lost due to premature mortality. This was estimated on the basis of actual age, the number of diarrhoea days, and disability weights ranging from 0.4 to 0.6 with death weighted as 1. A discount rate of 5% was used for the DALYs. Direct costs The direct medical costs were calculated from the perspectives of the patient and the government (provider). Such costs included visiting fees, medicines, outpatient visits, hospital stay, ORS used, antibiotics used, intravenous fluids used and laboratory tests. The direct non-medical costs were calculated from the perspective of the patient. These costs were for travel and food to the family and patient. The costs were calculated using a "micro-costing" procedure, and average variable costs were measured as a proxy for true marginal costs. Neither the quantity/cost boundary nor the sources of the costs were specifically reported, although the data seem to have come from hospital administrative sources. The data sources for non-medical costs were not reported. The costs of drugs were the manufacturer's wholesale price. Only the costs per patient treated were reported. Discounting was not reported because of the short time horizon. The price year was Statistical analysis of costs The costs of the two groups were compared statistically, although the authors did not report the statistical test used. Both univariate and multivariate linear regression were used to determine the impact of the interventions, and the pre and post randomisation variables in predicting the total mean costs. The cost-effectiveness of micronutrient supplementation was estimated using a nonparametric bootstrap method (1,000 replications), in order to assess the normality of this ratio and then construct the CIs. Indirect Costs The indirect costs were measured as the wages lost by employed parents or guardians attending to the child with diarrhoea. No other detail of the indirect costs was reported. Currency India rupees (Rs). These were converted to US dollars ($). The exchange rate was $1 = Rs36. Sensitivity analysis No sensitivity analysis was carried out. Estimated benefits used in the economic analysis The number of cases averted (diarrhoea > 4 days) was 63 (95% CI: 52-72) in the trial group and 52 (95% CI: 42-61) in the control group. When using micronutrient supplementation, there was a saving of 9 cases (diarrhoea > 4 days). The mean DALYs lost were 2.3 (95% CI: ) in the remaining patients of the trial group and 2.4 (95% CI: ) in the remaining patients of control group. There was a saving of 0.1 DALYs when using micronutrient supplementation. Cost results The mean total cost of treating a child with acute diarrhoea was Rs481 (+/- 44) in the trial group and Rs520.6 (+/- 54) in the control group, (p=0.6). There was a cost-saving of Rs40 when using micronutrient supplementation. The results from the linear regression model showed that there was a reduction in total cost with the use of micronutrients, but this failed to reach the necessary level of significance. Page: 3 / 6

4 The best sub-set linear regression showed that the grade of dehydration and the length of hospital stay were the most important predictors of total cost. Synthesis of costs and benefits The costs and benefits were not combined since the intervention was a dominant strategy (both more effective and less costly). The nonparametric bootstrap method showed that 62% of the bootstrap replications were in the quadrant where the treatment with the micronutrient supplements dominated. Authors' conclusions "Micronutrient supplementation had beneficial effects on rate of complications and mortality." Whilst it reduced the proportion of patients with diarrhoea for more than 4 days, it failed to reach traditional significance levels. CRD COMMENTARY - Selection of comparators The justification for choosing ORS as the comparator was clear, as it represented the routine practice. You should consider whether this is a widely used health technology in your own setting. Validity of estimate of measure of effectiveness The effectiveness data were derived from a single study. The study design, an RCT, was appropriate for the study question. The method of patient selection, blinding and the length of study were all reported, suggesting that the internal validity of the study is likely to be good. The study sample was taken from patients treated for acute diarrhoea at a hospital. The study sample should have been representative of all patients meeting the inclusion criteria, and the patient groups were shown to be comparable at analysis. Statistical analyses were conducted to ensure the credibility of the study. The main drawback of the effectiveness analysis was the absence of power calculations in determining the sample size. The sample size might have been too small. Hence, the study might not have had sufficient power to detect meaningful differences in outcomes between the two groups. Validity of estimate of measure of benefit The summary measures of benefit were appropriate as they reflected the impact of micronutrient supplementation on the children's health. However, the methods used to derive the disability weights were not explicitly reported in the current study. It is therefore not possible to comment on the quality of the estimates used. Validity of estimate of costs The perspectives adopted in the study were stated. The authors reported the cost components in detail and it appears that all the relevant categories of costs have been included in the economic analysis. The resource use quantities were taken from a single study. Actual financial costs, rather than economic costs, were used; the authors reported that the price paid for a service is a good reflection of the costs of producing the service in competitive markets which prevent both excess profits and negative expected profits. An extensive statistical analysis was undertaken, and this may improve the generalisability of the results. The costs and the quantities of resources used were not reported separately, thus the analysis could not be easily reworked for other settings. The prices were appropriately adjusted to reflect 1996 prices, which will enhance any future inflation exercises. Since all the costs were incurred during less than two years, the costs were appropriately not discount Other issues The authors compared their results with those from other studies from the USA and Indonesia. They noticed that the generalisability and external validity of their study were restricted, owing to the adopted measurement of outcomes (i.e. the proportion of diarrhoea > 4 days, which is an intermediate and proxy measure of diarrhoeal morbidity). Another Page: 4 / 6

5 limitation resulted from the adopted measurement of resources, which did not capture downstream resources such as rehospitalisation or resources used after discharge. Therefore, the total costs of acute diarrhoea might have been underestimated. The authors do not appear to have presented their results selectively and their conclusions reflected the scope of the analysis. The study enrolled children aged 6 months to 59 months with acute diarrhoea, but this was not clearly reflected in the authors' conclusions. Implications of the study This study suggested that the use of zinc and copper in treating children with acute diarrhoea is cost-effective, although further assessment in a larger and more varied population would be necessary to ensure the significance of the results. Source of funding The International Clinical Epidemiology network funded the writing of the manuscript. Bibliographic details Patel A B, Dhande L A, Rawat M S. Economic evaluation of zinc and copper use in treating acute diarrhea in children: a randomized controlled trial. Cost Effectiveness and Resource Allocation 2003; 1(7): E1-E10 PubMedID DOI /journal.pbio Other publications of related interest Avendano P, Matson D O, Long J, et al. Costs associated with office visits for diarrhea in infants and toddlers. Pediatric Infectious Disease Journal 1993;12: Garthright WE, Archer DL, Kvenberg JE. Estimates of incidence and costs of intestinal infectious diseases in the United States. Public Health Reports 1988;1003: Gutierrez GR, Tapia-Conyer R, Guiscafre H, et al. Impact of oral rehydration and selected public health interventions on reduction of mortality from childhood diarrheal diseases in Mexico. Bulletin of the World Health Organization 1996;74: Lerman SJ, Shepard DS, Cash RA. Treatment of diarrhea in Indonesian children: what it costs and who pays for it. Lancet 1985;21: Sazawal S, Black RE, Bhan MK, et al. Zinc supplementation in young children with acute diarrhoea in India. New England Journal of Medicine 1995;333: Indexing Status Subject indexing assigned by NLM MeSH Algorithms; Animals; Cell Line; Cloning, Molecular; Computational Biology /methods; DNA /chemistry; DNA, Intergenic; Humans; Lymphocytes /metabolism /pathology; Mice; Models, Genetic; Models, Statistical; Mutagenesis; Oligonucleotides /chemistry /genetics; Plasmids /metabolism; Protein Binding; Protein Sorting Signals; Recombination, Genetic; Software; T-Lymphocytes /immunology; VDJ Recombinases /physiology AccessionNumber Page: 5 / 6

6 Powered by TCPDF ( Date bibliographic record published 31/01/2006 Date abstract record published 31/01/2006 Page: 6 / 6