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A high-dose preparation of lactobacilli and bifidobacteria in the prevention of antibiotic-associated and Clostridium difficile diarrhoea in older people admitted to hospital: a multicentre, randomised, double-blind, placebo-controlled, parallel arm trial (PLACIDE) |
Allen SJ, Wareham K, Wang D, Bradley C, Sewell B, Hutchings H, Harris W, Dhar A, Brown H, Foden A, Gravenor MB, Mack D, Phillips CJ |
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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. CRD summary This study evaluated the clinical effectiveness and cost-effectiveness of a high-dose, multi-strain probiotic to prevent diarrhoea due to antibiotics or Clostridium difficile, in hospitalised people aged 65 years or older. The conclusion was that similar outcomes and the lack of cost-effectiveness meant that further research was needed. The analysis was well done and well reported and the conclusion seems appropriate. There was considerable uncertainty in the results and little difference in the costs and effectiveness. Type of economic evaluation Cost-effectiveness analysis, cost-utility analysis Study objective This study aimed to evaluate the clinical effectiveness and cost-effectiveness of a high-dose, multi-strain probiotic to prevent diarrhoea due to antibiotics or Clostridium difficile, in people aged 65 years or older, who were admitted to hospital and were taking antibiotics. Interventions A course of 21 capsules of a high-dose, multi-strain preparation of lactobacilli and bifidobacteria was compared with placebo capsules. Methods Analytical approach:The cost-effectiveness analysis was based on a clinical trial with subgroups of patients at different risk levels. The time horizon was eight weeks, which was the trial follow-up period. The authors stated that their study adopted a UK NHS perspective. Effectiveness data:The effectiveness data were from a multicentre, randomised, double-blind, placebo-controlled, parallel-arm trial. This trial recruited 2,981 patients from five hospitals in the UK. The outcomes were assessed by research nurses who followed up participants daily during their hospital stay and then weekly up to eight weeks after recruitment. The main effectiveness data were the occurrence of antibiotic-associated diarrhoea within eight weeks and of Clostridium difficile diarrhoea within 12 weeks of recruitment. Monetary benefit and utility valuations:Patients in the clinical trial completed EQ-5D questionnaires at the start and after four and eight weeks. These responses were used to derive utility scores for each patient at each time point. The Short Form (SF-12) Health Survey was also completed by the patients. Measure of benefit:Two measures of benefit were used: quality-adjusted life-years (QALYs) and the number of cases of diarrhoea averted. Cost data:The costs were based on data from the clinical trial. The resources used by the patients were recorded prospectively, and collected routinely during the trial. The costs included bacterial preparation, related staff time, treatment of adverse events, the assessment of cases of diarrhoea, and diarrhoea management. The unit costs were from published sources, including NHS Reference Costs, and clinical and finance staff. Missing data were imputed, using the weighted cost method, from known cost histories. All costs were reported in UK £. The price year was 2011. Analysis of uncertainty:Probabilistic sensitivity analysis was conducted by simultaneously varying all parameters to evaluate the overall uncertainty in the cost-effectiveness estimate. The results were presented in cost-effectiveness acceptability curves. One-way sensitivity analyses were conducted for a range of cost parameters. Results There were six more cases of antibiotic-associated diarrhoea with the probiotics, than with placebo (p=0.72), and there were five fewer cases of Clostridium difficile diarrhoea (p=0.35). The incremental QALYs for the probiotics compared with placebo were 0.0004 (95% CI -0.0006 to 0.0014). The mean cost per patient was £8,020.11 with probiotics and £8,011.37 with placebo (p=0.98). The cost per case of diarrhoea averted was not analysed as the study did not find any difference in diarrhoea frequency between the groups. The incremental cost per QALY gained was £22,701. The likelihood that the probiotic was cost-effective at a willingness-to-pay threshold of £20,000 per QALY gained was 48%. The results were not sensitive to variation in the cost parameters and assumptions, apart from the inclusion of only the implementation costs for the probiotics. In this case, the incremental cost per QALY gained was £189,662. Authors' conclusions The authors concluded that the similar outcomes and lack of cost-effectiveness of the probiotic meant that further investigation should be conducted. CRD commentary Interventions:The interventions were described. It was not entirely clear if no probiotic was current practice. It is useful, from a decision-maker's point of view, to include current practice as a comparator. Effectiveness/benefits:The clinical trial was well described and appears to have been well conducted. The authors gave some information that suggested that the best available evidence was used. The health outcomes appear to have been appropriately captured using the EQ-5D questionnaire. Costs:The perspective was clearly stated and the appropriate costs appear to have been included. It was not clear why the authors focused on the analysis of probiotic implementation costs only in their discussion. Both the resource use and the unit costs were from sources appropriate to the study setting and population. The costing methods generally appear to have been good. Analysis and results:The analytic methods and the results were well reported. Uncertainty in the cost-effectiveness estimate was evaluated appropriately. The authors compared their results with those of related studies, and there seems to have been a justification for basing their analysis on one clinical trial. There was little difference in the cost and QALY outcomes, and whether or not further research is needed depends on the potential gain from that research. Concluding remarks:The analysis was well done and well reported, and the authors' conclusions appear to be appropriate. There was considerable uncertainty in the results, with little difference in the cost and QALY outcomes. Funding Funded by the NIHR Health Technology Assessment programme, UK. Bibliographic details Allen SJ, Wareham K, Wang D, Bradley C, Sewell B, Hutchings H, Harris W, Dhar A, Brown H, Foden A, Gravenor MB, Mack D, Phillips CJ. A high-dose preparation of lactobacilli and bifidobacteria in the prevention of antibiotic-associated and Clostridium difficile diarrhoea in older people admitted to hospital: a multicentre, randomised, double-blind, placebo-controlled, parallel arm trial (PLACIDE) Health Technology Assessment 2013; 17(57): 1-139 Indexing Status Subject indexing assigned by NLM MeSH Aged; Aged, 80 and over; Anti-Bacterial Agents /adverse effects /classification /economics; Bifidobacterium /physiology; Clostridium difficile; Comorbidity; Cost-Benefit Analysis; Diarrhea /chemically induced /economics /microbiology /prevention & Double-Blind Method; Enterocolitis, Pseudomembranous /chemically induced /economics /prevention & Female; Great Britain; Humans; Inpatients /statistics & Lactobacillus /physiology; Male; Outcome Assessment (Health Care); Probiotics /administration & Prospective Studies; Quality-Adjusted Life Years; control; control; dosage /adverse effects /economics; numerical data AccessionNumber 22013052650 Date bibliographic record published 20/12/2013 Date abstract record published 23/01/2014 |
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