John Nixon

The relationship between health care expenditure and health outcomes

The relationship between health care expenditure and health outcomes is of interest to policy makers in the light of steady increases in health care spending for most industrialised countries. However, establishing causal relationships is complex because, firstly, health care expenditure is only one of many quantitative and qualitative factors that contribute to health outcomes, and, secondly, measurement of health status is an imperfect process. This study reviews key findings and methodological approaches in this field and reports the results of our own empirical study of countries of the European Union. Our analysis examines life expectancy and infant mortality as the ‘output’ of the health care system, and various life-style, environmental and occupational factors as ‘inputs’. Econometric analyses using a fixed effects model are conducted on a panel data set for the former 15 members of the European Union over the period 1980–1995. The findings show that increases in health care expenditure are significantly associated with large improvements in infant mortality but only marginally in relation to life expectancy. The findings are generally consistent with those of several previous studies. Caveats and improvements for future research are presented.

Can economic evaluations be made more transferable

Several commentators have identified the lack of generalisability and transferability of economic evaluation results. The aims of this study were: (a) to develop a checklist to assess the level of generalisability and transferability of economic evaluations; (b) to assess the generalisability and transferability of economic evaluations between the UK and France using the checklist; (c) to identify reasons for any lack of transferability and generalisability; (d) to assess how the transferability and generalisability of economic evaluations can be improved; and (e) to outline ways in which databases of economic evaluations and journals can assist in this area. The checklist was developed using previous work and the templates of the NHS EED and CODECS databases. A sub-checklist of essential items was then derived. Validation of the two checklists was undertaken with Health Economists participating in the EURONHEED project. Economic evaluations involving the UK and France were then located and assessed using the checklist. A summary score for each study was calculated based on the percentage of correctly reported (applicable) points, and the results in the empirical analysis compared to identify differences. The extended checklist includes 42 items, and the sub-checklist 16 items. Twenty-five economic evaluations met the inclusion criteria for the empirical analysis. In the extended checklist the mean score was 66.9±13.6%. The results for the sub-checklist were very similar. The analysis revealed that costing, assessments of generalisability by the author(s), assessment of data variability, discounting, study population, and the reporting of effectiveness are areas that need more attention. Differences in cost-effectiveness results are often accounted for by price or organisational differences. The developed checklists are useful in assessing the generalisability and transferability of economic evaluations. In order to improve the generalisability and transferability of economic evaluations authors need to be more explicit and detailed in describing and reporting their studies. If they are to provide added value to their users, international databases of economic evaluations should systematically assess the generalisability and transferability of studies. Further research is in progress on producing a weighted version of the checklist.

Systematic review of the (cost-)effectiveness of spinal cord stimulation for people with failed back surgery syndrome

ObjectivesWe conducted a systematic review to assess the (cost)effectiveness of spinal cord stimulation (SCS) in relieving certain kinds of pain for people with chronic pain owing to failed back surgery syndrome (FBSS). MethodsWe considered randomized trials, controlled observational studies of adult patients with chronic pain owing to FBSS, and case series with at least 50 patients permanently implanted, at least 60% FBSS patients and at least 1-year follow-up. SCS was additional to usual care and compared with usual care. The primary outcome was reduction of pain. Medline, Embase, Lilacs, Cinahl, and Cochrane Library databases were searched from inception until September 2006. An update search was carried out in January 2008. ResultsFor the effectiveness analysis, 1 fully published randomized controlled trial, one randomized controlled trial with 6 month results (both of moderate quality), 1 retrospective cohort study, and 13 case series (all of low quality) were included. The mean period of follow-up was between 6 months and 8.8 years. These studies show that SCS is effective in the treatment of FBSS in terms of pain reduction. The effect was consistent in all analyzed studies. Improvements were also reported for other outcomes, such as quality of life and functional status. All the studies reported some complications, most of which were technical problems. In terms of cost-effectiveness, 3 studies met the inclusion criteria and offered the same conclusion that SCS is both more effective and less costly in the long-term, but there is an initial high cost associated with device implantation and maintenance.

Childhood obesity: should primary school children be routinely screened? A systematic review and discussion of the evidence

Background: Population monitoring has been introduced in UK primary schools in an effort to track the growing obesity epidemic. It has been argued that parents should be informed of their child’s results, but is there evidence that moving from monitoring to screening would be effective? We describe what is known about the effectiveness of monitoring and screening for overweight and obesity in primary school children and highlight areas where evidence is lacking and research should be prioritised. Design: Systematic review with discussion of evidence gaps and future research. Data sources: Published and unpublished studies (any language) from electronic databases (inception to July 2005), clinical experts, Primary Care Trusts and Strategic Health Authorities, and reference lists of retrieved studies. Review methods: We included any study that evaluated measures of overweight and obesity as part of a population-level assessment and excluded studies whose primary outcome measure was prevalence. Results: There were no trials assessing the effectiveness of monitoring or screening for overweight and obesity. Studies focussed on the diagnostic accuracy of measurements. Information on the attitudes of children, parents and health professionals to monitoring was extremely sparse. Conclusions: Our review found a lack of data on the potential impact of population monitoring or screening for obesity and more research is indicated. Identification of effective weight reduction strategies for children and clarification of the role of preventative measures are priorities. It is difficult to see how screening to identify individual children can be justified without effective interventions.

Summarising economic evaluations in systematic reviews: a new approach

Systematic reviews of healthcare interventions, which are aimed at informing health policy, increasingly include economic evaluations in addition to evaluations of clinical effectiveness.1–3 The challenge reviewers face is collating, appraising, and synthesising economic evidence in such a way that it is clearly helpful in making decisions about the effects and costs of competing alternatives. However, the methodology for summarising the findings of economic evaluations is not as well established as that applied to structured summaries of clinical evidence. The aim of this paper is to illustrate and discuss the relative merits of commonly used methods and to offer a new approach that makes interpreting the evidence easier for decision makers who require a clear overview of the findings. #### Summary points Systematic reviews of healthcare interventions are increasingly integrating clinical and economic evidence Methods are needed to summarise and convey clearly the findings of these reviews The methodology for summarising the results of economic evaluations is not well established Methods for summarising the results of economic evaluations include narratives, tables, the cost effectiveness plane, and permutation matrices A new hierarchical method offers an effective means of summarising the results of economic evaluations within a systematic review We describe well established methods that can be used to summarise the findings of a review of economic evaluations, namely narrative summaries, permutation matrices, and the cost effectiveness plane, and we give examples of how a permutation matrix has or could have been used in two published systematic reviews. Finally, a new method is described that presents the same information in a clear, concise, and hierarchical manner and which provides an effective tool for summarising the same results. The most elementary method of summarising the results of a review of economic evaluations is the narrative summary, which, in conjunction with a tabular approach to …

Immunologic and virologic studies of measles inclusion body encephalitis in an immunosuppressed host The relationship to subacute sclerosing panencephalitis

An immunosuppressed child with acute lymphoblastic leukemia in clinical remission developed measles inclusion body encephalitis (MIBE). Although measles antigen and nonbudding measles virus nucleocap-sids were detected in brain tissue, no virus was isolated. Immune precipitation of measles virus proteins with the patients serum showed no detectable antibody to virus M protein, a finding that has been reported in subacute sclerosing panencephalitis (SSPE). The virologic and immune precipitation studies suggest a similar virus mutation in MIBE and SSPE. The pathogenesis of the two diseases may also be similar.

THE U.K. NHS ECONOMIC EVALUATION DATABASE Economic Issues in Evaluations of Health Technology

OBJECTIVE The U.K. NHS Economic Evaluation Database (EED) project is commissioned to identify papers on economic evaluations of health technologies and to disseminate their findings to NHS decision makers by means of structured abstracts that are available through a public database and the Cochrane Library. This paper discusses current issues relating to the economic aspects of producing NHS EED abstracts. METHODS A review of NHS EED was undertaken between 1994 and 1999 to determine the methodologies adopted and issues that influence the usefulness of economic evaluations. Methods adopted to improve the quality of NHS EED abstracts are also reported. RESULTS Eighty-five percent of NHS EED abstracts are cost-effectiveness analyses (CEAs), 9.3% are cost-utility analyses (CUAs), and only 1.4% are cost-benefit analyses (CBAs). Of the total abstracts, 65.9% are based on single studies, 19.5% on reviews, 3.9% on estimates of effectiveness, and 10.7% on combinations of these sources. Models are utilized in 16.7% of CEAs, 60.2% of CUAs, and 20% of CBAs. Analyses of CBA studies reveal a degree of misuse of well-established definitions. NHS EED internal control mechanisms are reported that provide a means of ensuring that abstracts are based on sound academic principles. CONCLUSIONS Most economic evaluations are conducted by means of CEA, followed by CUA, while CBA accounts for an extreme minority of cases. Single studies form the principal source of effectiveness data, although models are widely used, principally in CUA. The structure of NHS EED abstracts provides decision makers with the principal results and an interpretation of the relative strengths and weaknesses of economic evaluations.

Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy

Objective: To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene. Methods: Patients with a phenotype suggestive of a motor, non–length-dependent neuronopathy predominantly affecting the lower limbs were identified at participating neuromuscular centers and referred for targeted sequencing of DYNC1H1. Results: We report a cohort of 30 cases of SMA-LED from 16 families, carrying mutations in the tail and motor domains of DYNC1H1, including 10 novel mutations. These patients are characterized by congenital or childhood-onset lower limb wasting and weakness frequently associated with cognitive impairment. The clinical severity is variable, ranging from generalized arthrogryposis and inability to ambulate to exclusive and mild lower limb weakness. In many individuals with cognitive impairment (9/30 had cognitive impairment) who underwent brain MRI, there was an underlying structural malformation resulting in polymicrogyric appearance. The lower limb muscle MRI shows a distinctive pattern suggestive of denervation characterized by sparing and relative hypertrophy of the adductor longus and semitendinosus muscles at the thigh level, and diffuse involvement with relative sparing of the anterior-medial muscles at the calf level. Proximal muscle histopathology did not always show classic neurogenic features. Conclusion: Our report expands the clinical spectrum of DYNC1H1-related SMA-LED to include generalized arthrogryposis. In addition, we report that the neurogenic peripheral pathology and the CNS neuronal migration defects are often associated, reinforcing the importance of DYNC1H1 in both central and peripheral neuronal functions.

ANO5 gene analysis in a large cohort of patients with anoctaminopathy: confirmation of male prevalence and high occurrence of the common exon 5 gene mutation

Limb girdle muscular dystrophy type 2L or anoctaminopathy is a condition mainly characterized by adult onset proximal lower limb muscular weakness and raised CK values, due to recessive ANO5 gene mutations. An exon 5 founder mutation (c.191dupA) has been identified in most of the British and German LGMD2L patients so far reported. We aimed to further investigate the prevalence and spectrum of ANO5 gene mutations and related clinical phenotypes, by screening 205 undiagnosed patients referred to our molecular service with a clinical suspicion of anoctaminopathy. A total of 42 unrelated patients had two ANO5 mutations (21%), whereas 14 carried a single change. We identified 34 pathogenic changes, 15 of which are novel. The c.191dupA mutation represents 61% of mutated alleles and appears to be less prevalent in non‐Northern European populations. Retrospective clinical analysis corroborates the prevalently proximal lower limb phenotype, the male predominance and absence of major cardiac or respiratory involvement. Identification of cases with isolated hyperCKaemia and very late symptomatic male and female subjects confirms the extension of the phenotypic spectrum of the disease. Anoctaminopathy appears to be one of the most common adult muscular dystrophies in Northern Europe, with a prevalence of about 20%–25% in unselected undiagnosed cases.

Guidelines for completing the EURONHEED transferability information checklists

The structure and methods to complete and derive a quality score from the European Network of Health Economic Evaluation Databases (EURONHEED) transferability information checklists for published economic evaluations were reported and discussed in a previous paper (Boulenger et al. in Eur J Health Econ 6, 334–346, 2005). Within the same paper, the use of the checklists was illustrated through their application to a sample of economic evaluations conducted in France and UK. The transferability information subchecklist, consisting of 16 items from the original 42-point checklist, and methods used to derive it, were validated among 16 health economists across Europe participating in the EURONHEED project. Recent correspondence with other researchers, however, indicates that the checklists are now being utilised in empirical work and the methodology of assessing transferability and generalisability. This supplementary paper provides full details of the guidelines that have been developed and recently updated by the authors, such that the overall and subchecklists can be more widely and consistently completed and utilised. We also briefly discuss associated issues such as weighting of items in the checklists and give further clarifications regarding what we consider the most appropriate applications of the checklists to be.