Is hydrotherapy cost-effective? A randomised controlled trial of combined hydrotherapy programmes compared with physiotherapy land techniques in children with juvenile idiopathic arthritis.

OBJECTIVES: To compare the effects of combined hydrotherapy and land-based physiotherapy (combined) with land-based physiotherapy only (land) on cost, health-related quality of life (HRQoL) and outcome of disease in children with juvenile idiopathic arthritis (JIA). Also to determine the cost-effectiveness of combined hydrotherapy and land-based physiotherapy in JIA. DESIGN: A multicentre randomised controlled, partially blinded trial was designed with 100 patients in a control arm receiving land-based physiotherapy only (land group) and 100 patients in an intervention arm receiving a combination of hydrotherapy and land-based physiotherapy (combined group). SETTING: Three tertiary centres in the UK. PARTICIPANTS: Patients aged 4-19 years diagnosed more than 3 months with idiopathic arthritides, onset before their 16th birthday, stable on medication with at least one active joint. INTERVENTIONS: Patients in the combined and land groups received 16 1-hour treatment sessions over 2 weeks followed by local physiotherapy attendances for 2 months. MAIN OUTCOME MEASURES: Disease improvement defined as a decrease of > or =30% in any three of six core set variables without there being a 30% increase in more than one of the remaining three variables was used as the primary outcome measure and assessed at 2 months following completion of intervention. Health services resource use (in- and outpatient care, GP visits, drugs, interventions, and investigations) and productivity costs (parents' time away from paid work) were collected at 6 months follow-up. HRQoL was measured at baseline and 2 and 6 months following intervention using the EQ-5D, and quality-adjusted life-years (QALYs) were calculated. Secondary outcome measures at 2 and 6 months included cardiovascular fitness, pain, isometric muscle strength and patient satisfaction. RESULTS: Seventy-eight patients were recruited into the trial and received treatment. Two months after intervention 47% patients in the combined group and 61% patients in the land group had improved disease with 11 and 5% with worsened disease, respectively. The analysis showed no significant differences in mean costs and QALYs between the two groups. The combined group had slightly lower mean costs (-6.91 pounds Sterling) and lower mean QALYs (-0.0478, 95% confidence interval -0.11294 to 0.0163 based on 1000 bootstrap replications). All secondary measures demonstrated a mean improvement in both groups, with the combined group showing greater improvements in physical aspects of HRQoL and cardiovascular fitness. CONCLUSIONS: JIA is a disease in which a cure is not available. This research demonstrates a beneficial effect from both combined hydrotherapy and land-based physiotherapy treatment and land-based physiotherapy treatment alone in JIA without any exacerbation of disease, indicating that treatments are safe. The caveat to the results of the cost-effectiveness and clinical efficacy analysis is that the restricted sample size could have prevented a true difference being detected between the groups. Nevertheless, there appears to be no evidence to justify the costs of building pools or initiating new services specifically for use in this disease. However, this conclusion may not apply to patients with unremitting active disease who could not be entered into the trial because of specified exclusion criteria. For this group, hydrotherapy or combined treatment may still be the only physiotherapy option. Further research is suggested into: the investigation and development of appropriate and sensitive outcome measures for use in future hydrotherapy and physiotherapy trials of JIA; preliminary studies of methodologies in complex interventions such as physiotherapy and hydrotherapy to improve recruitment and ensure protocol is acceptable to patients and carers; hydrotherapy in the most common paediatric user group, children with neurological dysfunction, ensuring appropriate outcome measures are available and methodologies previously tried; patient satisfaction and compliance in land-based physiotherapy and hydrotherapy and European studies of hydrotherapy in rare disorders such as JIA.

Cost-effectiveness of alternative strategies for the initial medical management of non-ST elevation acute coronary syndrome: systematic review and decision-analytical modelling.

OBJECTIVES: To identify and prioritise key areas of clinical uncertainty regarding the medical management of non-ST elevation acute coronary syndrome (ACS) in current UK practice. DATA SOURCES: Electronic databases. Consultations with clinical advisors. Postal survey of cardiologists. REVIEW METHODS: Potential areas of important uncertainty were identified and 'decision problems' prioritised. A systematic literature review was carried out using standard methods. The constructed decision model consisted of a short-term phase that applied the results of the systematic review and a long-term phase that included relevant information from a UK observational study to extrapolate estimated costs and effects. Sensitivity analyses were undertaken to examine the dependence of the results on baseline parameters, using alternative data sources. Expected value of information analysis was undertaken to estimate the expected value of perfect information associated with the decision problem. This provided an upper bound on the monetary value associated with additional research in the area. RESULTS: Seven current areas of clinical uncertainty (decision problems) in the drug treatment of unstable angina patients were identified. The agents concerned were clopidogrel, low molecular weight heparin, hirudin and intravenous glycoprotein antagonists (GPAs). Twelve published clinical guidelines for unstable angina or non-ST elevation ACS were identified, but few contained recommendations about the specified decision problems. The postal survey of clinicians showed that the greatest disagreement existed for the use of small molecule GPAs, and the greatest uncertainty existed for decisions relating to the use of abciximab (a large molecule GPA). Overall, decision problems concerning the GPA class of drugs were considered to be the highest priority for further study. Selected papers describing the clinical efficacy of treatment were divided into three groups, each representing an alternative strategy. The strategy involving the use of GPAs as part of the initial medical management of all non-ST elevation ACS was the optimal choice, with an incremental cost-effectiveness ratio (ICER) of 5738 pounds per quality-adjusted life-year (QALY) compared with no use of GPAs. Stochastic analysis showed that if the health service is willing to pay 10,000 pounds per additional QALY, the probability of this strategy being cost-effective was around 82%, increasing to 95% at a threshold of 50,000 pounds per QALY. A sensitivity analysis including an additional strategy of using GPAs as part of initial medical management only in patients at particular high risk (as defined by age, ST depression or diabetes) showed that this additional strategy was yet more cost-effective, with an ICER of 3996 pounds per QALY compared with no treatment with GPA. Value of information analysis suggested that there was considerable merit in additional research to reduce the level of uncertainty in the optimal decision. At a threshold of 10,000 pounds per QALY, the maximum potential value of such research in the base case was calculated as 12.7 million pounds per annum for the UK as a whole. Taking account of the greater uncertainty in the sensitivity analyses including clopidogrel, this figure was increased to approximately 50 million pounds. CONCLUSIONS: This study suggests the use of GPAs in all non-ST elevation ACS patients as part of their initial medical management. Sensitivity analysis showed that virtually all of the benefit could be realised by treating only high-risk patients. Further clarification of the optimum role of GPAs in the UK NHS depends on the availability of further high-quality observational and trial data. Value of information analysis derived from the model suggests that a relatively large investment in such research may be worthwhile. Further research should focus on the identification of the characteristics of patients who benefit most from GPAs as part of medical management, the comparison of GPAs with clopidogrel as an adjunct to standard care, follow-up cohort studies of the costs and outcomes of high-risk non-ST elevation ACS over several years, and exploring how clinicians' decisions combine a normative evidence-based decision model with their own personal behavioural perspective.

Review of guidelines for good practice in decision-analytic modelling in health technology assessment.

OBJECTIVES: To identify existing guidelines and develop a synthesised guideline plus accompanying checklist. In addition to provide guidance on key theoretical, methodological and practical issues and consider the implications of this research for what might be expected of future decision-analytic models. DATA SOURCES: Electronic databases. REVIEW METHODS: A systematic review of existing good practice guidelines was undertaken to identify and summarise guidelines currently available for assessing the quality of decision-analytic models that have been undertaken for health technology assessment. A synthesised good practice guidance and accompanying checklist was developed. Two specific methods areas in decision modelling were considered. The first method's topic is the identification of parameter estimates from published literature. Parameter searches were developed and piloted using a case-study model. The second topic relates to bias in parameter estimates; that is, how to adjust estimates of treatment effect from observational studies where there are risks of selection bias. A systematic literature review was conducted to identify those studies looking at quantification of bias in parameter estimates and the implication of this bias. RESULTS: Fifteen studies met the inclusion criteria and were reviewed and consolidated into a single set of brief statements of good practice. From this, a checklist was developed and applied to three independent decision-analytic models. Although the checklist provided excellent guidance on some key issues for model evaluation, it was too general to pick up on the specific nuances of each model. The searches that were developed helped to identify important data for inclusion in the model. However, the quality of life searches proved to be problematic: the published search filters did not focus on those measures specific to cost-effectiveness analysis and although the strategies developed as part of this project were more successful few data were found. Of the 11 studies meeting the criteria on the effect of selection bias, five concluded that a non-randomised trial design is associated with bias and six studies found 'similar' estimates of treatment effects from observational studies or non-randomised clinical trials and randomised controlled trials (RCTs). One purpose of developing the synthesised guideline and checklist was to provide a framework for critical appraisal by the various parties involved in the health technology assessment process. First, the guideline and checklist can be used by groups that are reviewing other analysts' models and, secondly, the guideline and checklist could be used by the various analysts as they develop their models (to use it as a check on how they are developing and reporting their analyses). The Expert Advisory Group (EAG) that was convened to discuss the potential role of the guidance and checklist felt that, in general, the guidance and checklist would be a useful tool, although the checklist is not meant to be used exclusively to determine a model's quality, and so should not be used as a substitute for critical appraisal. CONCLUSIONS: The review of current guidelines showed that although authors may provide a consistent message regarding some aspects of modelling, in other areas conflicting attributes are presented in different guidelines. In general, the checklist appears to perform well, in terms of identifying those aspects of the model that should be of particular concern to the reader. The checklist cannot, however, provide answers to the appropriateness of the model structure and structural assumptions, as these may be seen as a general problem with generic checklists and do not reflect any shortcoming with the synthesised guidance and checklist developed here. The assessment of the checklist, as well as feedback from the EAG, indicated the importance of its use in conjunction with a more general checklist or guidelines on economic evaluation. Further methods research into the following areas would be valuable: the quantification of selection bias in non-controlled studies and in controlled observational studies; the level of bias in the different non-RCT study designs; a comparison of results from RCTs with those from other non-randomised studies; assessment of the strengths and weaknesses of alternative ways to adjust for bias in a decision model; and how to prioritise searching for parameter estimates.

A pilot study on the use of decision theory and value of information analysis as part of the NHS Health Technology Assessment programme.

OBJECTIVES: To demonstrate the benefits of using appropriate decision-analytic methods and value of information analysis (DA-VOI). Also to establish the feasibility and implications of applying these methods to inform the prioritisation process of the NHS Health Technology Assessment (HTA) programme, and possibly extending their use therein. DATA SOURCES: Three research topics that were considered by the HTA panels in the September 2002 and February 2003 prioritisation rounds. REVIEW METHODS: A brief and non-technical overview of DA-VOI methods was circulated to the panels and Prioritisation Strategy Group (PSG). For each case study the results were presented to the panels and the PSG in the form of brief case-study reports. Feedback on the DA-VOI analysis and its presentation was obtained in the form of completed questionnaires from panel members, and reports from panel senior lecturers and PSG members. RESULTS: Although none of the research topics identified met all of the original selection criteria for inclusion as case studies in the pilot, it was possible to construct appropriate decision-analytic models and conduct probabilistic analysis for each topic. In each case, the tasks were completed within the time-frame required by the existing HTA research prioritisation process. The brief case-study reports provided a description of the decision problem, a summary of the current evidence base and a characterisation of decision uncertainty in the form of cost-effectiveness acceptability curves. Estimates of value of information for the decision problem were presented for relevant patient groups and clinical settings, as well as the value of information associated with particular model inputs. The implications for the value of research in each of the areas were presented in general terms. Details were also provided on what the analysis suggested regarding the design of any future research in terms of features such as the relevant patient groups and comparators, and whether experimental design was likely to be required. CONCLUSIONS: The pilot study showed that, even with very short timelines, it is possible to undertake DA-VOI that can feed into the priority-setting process that has been developed for the HTA programme. There are however a number of areas that need to be established at the beginning of the process, such as clarification of the nature of the decision problem for which additional research is being considered, explicitness about which existing data should be used and how data that exhibit particular weaknesses should be down-weighted in the analysis. Other areas, including optimum application of researcher time, integrating the vignette (a summary of the clinical problem and existing evidence) and the use of DA-VOI, training, use of sensitivity analyses, and deployment of clinical expertise, are also considered in terms of the potential implementation of DA-VOI within the HTA programme. Recommendations for further research include how literature searching should focus on those variables to which the model's results are most sensitive and with the highest expected value of perfect information; methods of evidence synthesis (multiple parameter synthesis) to consider the evidence surrounding multiple comparators and networks of evidence; and ways in which the value of sample information can be used by the NHS HTA programme and other research funders to decide on the most efficient design of new evaluative research. There is also a need for an analytical framework to be developed that can jointly address the question of whether additional resources would better be devoted to additional research or interventions to change clinical practice.