The clinical and cost-effectiveness of implantable cardioverter defibrillators: a systematic review.

OBJECTIVES: To consider the clinical effectiveness and cost-effectiveness of implantable cardioverter defibrillators (ICDs) for arrhythmias. DATA SOURCES: Electronic databases. Manufacturer submissions. REVIEW METHODS: A systematic review of the literature on clinical and cost-effectiveness was undertaken. The quality of selected randomised controlled trials (RCTs) was assessed using the Jadad criteria, and of selected systematic reviews using criteria developed by the NHS Centre for Reviews and Dissemination. Economic evaluations were quality assessed by their internal validity (i.e. the methods used) using a series of relevant questions, and external validity (i.e. generalisability of the economic study to the population of interest) by modified standard criteria. The clinical effectiveness and cost-effectiveness of ICDs for arrhythmias were synthesised through a narrative review with full tabulation of results of all included studies. RESULTS: Eight RCTs, two systematic reviews and a meta-analysis met the inclusion criteria of the review. The RCTs were of variable quality, with most trials having a Jadad quality score of 1/5 or 2/5, owing to the nature of comparing a device with drug therapy and the impossibility of double-blinding. The outcome measure of interest was mortality, which was reported as all-cause mortality in most trials and sudden cardiac death in some trials. Eleven economic evaluations of ICDs for arrhythmias were identified. None were shown to have high internal and external validity. One unpublished study relevant to the UK was identified. The evidence suggests that ICDs reduce mortality in patients with previous ventricular arrest or symptomatic sustained ventricular arrhythmias, in patients who have not had a previous sudden cardiac episode or previous ventricular arrhythmia but have reduced left ventricular function due to coronary artery disease with asymptomatic non-sustained ventricular arrhythmia and sustained tachycardia that could be induced electrophysiologically, and in some patients with severe left ventricular dysfunction (ejection fraction 30%) after myocardial infarction. QoL data are inconsistent but suggest that there is impaired QoL in patients who received numerous shocks from implanted devices. Studies show that ICDs improve survival compared with drug treatment, but with considerably increased cost. Incremental cost per life-year gained ranges from 27,000 US dollars to 213,543 Can dollars and incremental cost per quality-adjusted life-year from 71,700 US dollars to 558,000 US dollars in the published literature. CONCLUSIONS: The use of ICDs in the UK is increasing, but the technology is still under-utilised compared with other developed countries. Extending the current indications to patients with prior myocardial infarction and depressed heart function would impact on costs and service provision. Further research is needed on the risk stratification of patients in whom ICDs are most likely to be clinically and cost-effective. An evaluation of shock frequency on QoL is also required.

Clinical effectiveness and cost-effectiveness of immediate angioplasty for acute myocardial infarction: systematic review and economic evaluation.

OBJECTIVES: To review the clinical evidence comparing immediate angioplasty with thrombolysis, and to consider whether it would be cost-effective. DATA SOURCES: Electronic databases. Experts in the field. REVIEW METHODS: For clinical effectiveness, a comprehensive review of randomised control trials (RCTs) was used for efficacy, and a selection of observational studies such as case series or audit data used for effectiveness in routine practice. RCTs of thrombolysis were used to assess the relative value of prehospital and hospital thrombolysis. Observational studies were used to assess the representativeness of patients in the RCTs, and to determine whether different groups have different capacity to benefit. Clinical effectiveness was synthesised through a narrative review with full tabulation of results of all included studies and a meta-analysis to provide a precise estimate of absolute clinical benefit. Consideration was given to the effect of the growing use of stents. The economic modelling adopted an NHS perspective to develop a decision-analytical model of cost-effectiveness focusing on opportunity costs over the short term (6 months). RESULTS: The results were consistent in showing an advantage of immediate angioplasty over hospital thrombolysis. The updated meta-analysis showed that mortality is reduced by about one-third, from 7.6% to 4.9% in the first 6 months, and by about the same in studies of up to 24 months. Reinfarction is reduced by over half, from 7.6% to 3.1%. Stroke is reduced by about two-thirds, from 2.3% with thrombolysis to 0.7% with percutaneous coronary intervention (PCI), with the difference being due to haemorrhagic stroke. The need for coronary artery bypass graft is reduced by about one-third, from 13.2% to 8.4%. Caution is needed in interpreting some of the older trials, as changes such as an increase in stenting and the use of the glycoprotein IIb/IIa inhibitors may improve the results of PCI. There is little evidence comparing prehospital thrombolysis with immediate PCI. Research on thrombolysis followed by PCI, known as 'facilitated PCI', is underway, but results are not yet available. Trials may be done in select centres and results may not be as good in lower volume centres, or out of normal working hours. In addition, much of the marginal mortality benefit of PCI over hospital thrombolysis may be lost if door-to-balloon time were more than an hour longer than door-to-needle time. Conversely, within the initial 6 hours, the later patients present, the greater the relative advantage of PCI. Results suggest that PCI is more cost-effective than thrombolysis, providing additional benefits in health status at some extra cost. In the longer term, the cost difference is expected to be reduced because of higher recurrence and reintervention rates among those who had thrombolysis. CONCLUSIONS: If both interventions were routinely available, the economic analysis favours PCI, given the assumptions of the model. However, very few units in England could offer a routine immediate PCI service at present, and there would be considerable resource implications of setting up such services. Without a detailed survey of existing provision, it is not possible to quantify the implications, but they include both capital and revenue: an increase in catheter laboratory provision and running costs. The greatest problem would be staffing, and that would take some years to resolve. A gradual incrementalist approach based on clinical networks, with transfer to centres able to offer PCI, may be used. In rural areas, one option may be to promote an increase in prehospital thrombolysis, with PCI for thrombolysis failures. There is a need for data on the long-term consequences of treatment, the quality of life of patients after treatment, and the effects of PCI following thrombolysis failure.

Systematic review of the Sugarbaker procedure for pseudomyxoma peritonei.

BACKGROUND: Pseudomyxoma peritonei, a rare progressive disease process within the peritoneum, is characterized by an abundance of mucinous fluid; if left untreated, the condition is fatal. The aim of this article is to assess the clinical effectiveness and costs of the Sugarbaker procedure for pseudomyxoma peritonei. METHODS: A systematic review of the literature up to April 2004 was undertaken, with modelling of costs. RESULTS: Five retrospective case-series reports met the inclusion criteria. Survival after operation was approximately 95 per cent at 2 years and 60-68 per cent at 10 years, with 41-52 per cent of patients having no evidence of disease at the end of follow-up. A Monte Carlo simulation model estimated the marginal cost for one patient over a maximum of 5 years to be about pound 9700 (standard deviation pound 1300). CONCLUSION: Evidence of the effectiveness of the Sugarbaker procedure for pseudomyxoma peritonei is limited in quantity and quality, but suggests there may be some benefit for patients. The marginal cost of the operation is about pound 9700, provided that trained and experienced staff are available to perform the procedure.

Pegylated interferon alpha-2a and -2b in combination with ribavirin in the treatment of chronic hepatitis C: a systematic review and economic evaluation.

OBJECTIVES: To assess the clinical-effectiveness and cost-effectiveness of pegylated interferon-alpha combined with ribavirin in the treatment of chronic hepatitis C. DATA SOURCES: Electronic databases, reference lists of retrieved reports, and the industry submissions to the National Institute for Clinical Excellence. REVIEW METHODS: Sources were rigorously searched and studies were selected that met the inclusion criteria of being randomised controlled trials (RCTs) involving comparisons between pegylated interferon-alpha plus ribavirin and non-pegylated interferon plus ribavirin (two trials) or pegylated interferon alone and non-pegylated interferon alone (four trials). The primary outcome in all trials was sustained virological response (SVR) at follow-up. The trials were generally of good quality, although reporting of methodological details could have been more thorough in places. A cost-effectiveness model followed a hypothetical cohort of 1000 individuals with chronic hepatitis C over a 30-year period. RESULTS: In the two trials that tested pegylated interferon plus ribavirin against non-pegylated interferon plus ribavirin the combined percentage of sustained virological response was 55%. The relative risk (RR) for remaining infected was reduced by 17% for pegylated interferon plus ribavirin compared with non-pegylated interferon plus ribavirin. Response to therapy varied according to viral genotype. Patients with genotype 1 had the lowest levels of sustained virological response and patients with genotype 2 or 3 had the highest. In the four trials that evaluated pegylated interferon monotherapy against non-pegylated interferon the combined sustained virological response rates were 31% for pegylated interferon and 14% for non-pegylated interferon. The RR for remaining infected with hepatitis C was reduced by 20% with the use of pegylated interferon. Patients with genotype 1 had the lowest levels of sustained virological response. There were also variations in sustained virological response according to other prognostic variables such as baseline viral load. Regimens involving pegylated interferon appear to be fairly well tolerated. Adverse events were been reported, but they did not differ substantially from levels of adverse events in regimens involving non-pegylated interferon. The incremental discounted cost per QALY for comparing no active treatment to 48 weeks of dual therapy with pegylated interferon and ribavirin (PEG + RBV) was 6045 pounds sterling. When moving from 48 weeks of dual therapy with non-pegylated interferon and ribavirin (IFN + RBV) to 48 weeks of dual therapy with PEG + RBV the figure was 12,123 pounds sterling. Subgroup analyses for dual PEG + RBV therapy demonstrated that the most favourable incremental discounted cost per QALY estimates were for patients infected with genotypes 2 and 3, and with low baseline viral load (3921 pounds sterling) compared with no active treatment. Results of one-way sensitivity analyses showed that the estimates varied according to differences in SVRs, drug costs and discount rates. In general estimates remained under 30,000 pounds sterling per QALY. The incremental discounted cost per QALY when moving from no active treatment to 48 weeks of monotherapy with pegylated interferon was 6484 pounds sterling. When moving from 48 weeks of monotherapy with IFN to 48 weeks of monotherapy with PEG the figure was 8404 pounds sterling. As with dual therapy, the lowest incremental cost per QALY was for patients with genotypes 2 and 3 and low baseline viral load, in the range 2641-4194 pounds sterling. The highest estimates were for patients with genotype 1 and high baseline viral load, around 30,000 pounds sterling. CONCLUSIONS: Well-designed RCTs show that patients treated with pegylated interferon, both as dual therapy and as monotherapy, experience higher sustained viral response rates than those treated with non-pegylated interferon. Patients with genotypes 2 and 3 experience the highest response, with rates in excess of 80%. Patients with the harder to treat genotype 1 nevertheless benefit, with up to 46% of patients experiencing an SVR in one of the trials. Pegylated interferon also appears to be relatively cost-effective in both monotherapy and dual therapy, with cost per QALY estimates remaining generally under 30,000 pounds sterling. The most favourable estimates were for patients with genotypes 2 and 3. Pegylated interferon is a relatively new intervention in the treatment of hepatitis C and therefore there are areas where further research is needed. These include: efficacies of therapy with PEG-alpha-2a vs PEG-alpha-2b; retreatment of previous non-responders using pegylated interferon; efficacy of treatments and long-term outcomes in patients who have other co-morbidities; prospective tests of rules governing stopping treatment; treating patients with acute hepatitis C; problems that may occur in a minority of patients with hepatitis C, such as cryoglobulinaemia and vasculitis; additional psychological effects on quality of life due to hepatitis C and also on the treatment of children and adolescents with hepatitis C.

Clinical effectiveness and costs of the Sugarbaker procedure for the treatment of pseudomyxoma peritonei.

OBJECTIVES: This systematic review examines the clinical and cost-effectiveness of the Sugarbaker procedure for treating pseudomyxoma peritonei (PMP) and the costs of the procedure in the UK. DATA SOURCES: Electronic databases, bibliographies of related papers and experts in the field were used as sources for English language studies available up to September 2002. REVIEW METHODS: Evidence of the clinical effectiveness of the Sugarbaker procedure for PMP was synthesised through a narrative review with full tabulation of results of all included studies. The economic modelling used a Monte-Carlo simulation model populated with UK price data to estimate likely UK costs. RESULTS: Five retrospective case-series reports assessing the Sugarbaker procedure met the inclusion criteria for the review, although they were found to be of poor quality when judged against standard criteria for assessing methodological standard. There appears to be some benefit for people with PMP who undergo treatment with the Sugarbaker procedure. Commonly reported complications of the Sugarbaker procedure were anastomotic leaks, fistula formation, wound infection, small bowel perforations/obstructions and pancreatitis. One costing study of poor methodological quality and set in the USA was found. This study, together with UK unit price data and expert advice, was used to populate a Monte-Carlo simulation model to estimate the marginal cost of operating a service to provide treatment for PMP using the Sugarbaker technique rather than standard treatment. The results of the Monte-Carlo simulation model showed that the cost for one patient over a maximum of 5 years would be about 9700 British pounds, with a standard deviation of about 1300 British pounds (although costs incurred in setting up the specific service or training the staff were not included). The US study showed a ten-fold higher cost. The Monte-Carlo analysis showed that the variation around the mean was not very high. The most likely factor influencing the variation of the costs was the length of procedure. No sensitivity analysis could be done of the alternative treatment. CONCLUSIONS: The economic results should be seen as merely an example of the likely marginal costs of the Sugarbaker procedure, as more information about the current alternative is required. Trained and experienced staff are required to implement the procedure and inevitably time and cost will be involved in developing the appropriate teams. Although the procedure requires some specialist equipment and maintenance, such as smoke evacuators, these should have limited effect on setting up the service. PMP is a relatively rare condition with approximately 50 new cases per year in the UK and the impact of an increase in the demand for services should be limited. Evidence is needed for the effectiveness of maximal cytoreductive surgery compared with surgical debulking, using different intraoperative intraperitoneal chemotherapy strategies, and for the effectiveness of treatments in patients who have residual disease following maximal efforts at cytoreduction. Further research involving high-quality prospective cohort studies with economic evaluations would be valuable.

The final phase in acute myeloid leukaemia (AML): a study of cause of death, place of death and type of care during the last week of life.

The aim of this study was to increase the knowledge of the final phase in acute myeloid leukaemia (AML), a period which entails many complex medical and psychosocial decisions. Data on cause and place of death were gathered through a retrospective review of medical and nursing records of 106 patients with AML who had died during 1995-1997. We focused on the actual phase of the disease and to what extent the patients were prescribed palliative care. With increased knowledge of the dying process in AML there are options to discuss which approach would be the most preferred final phase for an AML patient.

[Medical interests in gymnastics and athletics]. / Idrott, läkare och folkhälsa.

Since time immemorial authors have noticed the usefulness of physical activity. In the 18th century C von Linné was a spokesman for bodily exercise, and in the beginning of the 19th century P. H . Ling shaped the Swedish gymnastics and founded the Gymnastiska Centralinstitutet in 1813. He aimed at harmonious bodies according to the models of the classic antiquity. Many physicians, I. and F. Holmgren saw the value of the gymnastics. Completing the Ling gymnastics, there was a growing interest in physical performance, i.e., athletics. Above all, the contributions of the officer V. Balck, culminating at the olympic games in Stockholm 1912, made athletics a national movement. Since 1913 it receives an annual economic support from the state. Some physicians feared from overexertion in athletics but they appreciated physical performance. However, they demanded that you should be wholly full-grown prior to great exortions. An important part of the Ling program was remedial gymnastics which was more and more estimated after P. Haglund had asserted its value. T. Sjöstrand's studies became a good basis for evaluating the effect of physical training in both healthy and sick persons. It was not until the 1950s that the first studies, later confirmed, gave holds for the view that physical training was good for public health. But the average life span does not seem to be influenced by physical activities. Now and then training had earlier been used as therapy for disparate sorts of diseases but most rationally for disturbed functions of the locomotor system. Training became an important part of medical rehabilitation only after the second world war. Gymnastics and athletics at school have always had a solid support by physicians. The subject has nowadays so few hours that it cannot result in safe training habits for the future.

Domiciliary liquid oxygen versus concentrator treatment in chronic hypoxaemia: a cost-utility analysis.

Whether long-term oxygen therapy (LTOT) improves quality of life in chronic hypoxaemia has been questioned. LTOT with an oxygen concentrator (C/C) and gas cylinders for ambulation is considered cumbersome compared to mobile liquid oxygen equipment (L). The hypothesis for this study was that LTOT with liquid oxygen treatment (L) improves patients' health-related quality of life, but that it is also more expensive compared to concentrator (C/C) treatment. A prospective, randomized multicentre trial comparing C/C with L for LTOT was conducted during a six-month period. Fifty-one patients (29 on L and 22 on C/C) with chronic hypoxaemia, regularly active outside the home, participated in the study initially. Costs for oxygen were obtained from the pharmacies. Patient diaries and telephone contacts with members of the healthcare sector were used to estimate costs. Health-related quality of life was measured by the Sickness Impact Profile (SIP) and the EuroQol, instruments at the start and after 6 months. The average total cost per patient for group C/C for the six-month period was US$1,310, and for group L it was US$4,950. Health-related quality of life measured by the SIP instrument showed significant differences in favour of group L in the categories/dimensions of physical function, body care, ambulation, social interaction and total SIP score. In conclusion, liquid-oxygen treatment was more expensive compared to concentrator treatment. However, treatment effects showed that liquid oxygen had a better impact on quality of life.

Assistive technology selection: a study of participation of users with rheumatoid arthritis.

A new program based on improved user participation for the selection of assistive devices was implemented and its effectiveness and efficiency assessed. The intervention was compared with traditional routines. The study population comprised persons with rheumatoid arthritis who lived in two communities in Sweden. The selection process yielded increased user participation, user satisfaction, an increased number of prescriptions, and consequently also higher costs. The outcome measures showed more vague improvements. No improvement in functional ability was found regarding pain and difficulty with daily activities in the two study groups, but an increased use of assistive devices was found among women below 64 years in the intervention group (p = 0.001). Women below 64 years in the intervention group rated an improved health-related quality of life regarding both the total score (p = 0.017) and the underlying dimensions of physical function (p = 0.012). Even though the intervention yielded positive results on process-variables as increased user participation and an increased number of prescribed assistive devices, only women below 64 years showed an increased use of assistive devices in daily activities and an improved health related quality of life.

One-year economic consequences of accidents in a Swedish municipality.

The objectives of this study were to develop a system to calculate the economic consequences of accidents and to account for the economic consequences of all accidents during 1 year in a district. A total population injury survey was done in an area with a population of over 41,000. All accidents (N = 4926) occurring within a 12-month period and requiring medical care were noted. The costs (calculated at 1991 prices) to the health care service (outpatient care, including primary health care and hospital care) were SEK 23.7 million (US $3.59 million), to trade and industry SEK 79.7 million (US $12.08 million), and for health insurance SEK 9.1 million (US $1.38 million). The cost for society of uninsured people is not possible to estimate using loss of production. However, the time lost from "normal activities" was registered. If this time is valued at the same price as working hours, a welfare cost of SEK 43.1 million (US $6.53 million) should be added. In a forthcoming paper, an assessment of the cost-effectiveness of interventions against accidents will be published.

Assessment of rehabilitation technologies in stroke. Outcomes and costs.

Initial functional ability (Barthel Index, mean 57) was found to be an important predictor of functional ability 1 year after stroke (mean 80) and for costs during the period. On average the total cost for a stroke patient was about SEK 200,000; the main expense, accommodation, averaged about SEK 140,000, while assistive devices amounted to SEK 2,600. Those who use assistive devices, although having achieved a high functional ability, perceive and rate their life situation (Nottingham Health Profile) considerably more impaired than those without assistive devices.

Cost-utility analysis of assistive technologies in the European Commission's TIDE Program. Technology Initiative for Disabled and Elderly People.

Socioeconomic evaluation is an issue dealt with in the European Commission's research program TIDE. The principles of cost-utility analysis have been examined for usability in the assessment of rehabilitative technologies. A case study, the choice of a type of wheelchair, is described to demonstrate how estimates of utility can be derived and how cost-utility ratios can be used to guide decision making.

Cost analysis of different phases of acute myeloid leukaemia.

Priority lists have been formulated in several countries and cut-backs can be a threat to leukaemia treatment. We analysed the costs in different phases of disease for 54 conventionally treated patients with acute myeloid leukaemia. Thirty-two patients reached CR 1, seven patients are still alive as of May 1994. We found a cost per week and patient of 17,334 Swedish Crowns (SEK) (U.K. 1 pound = 10.57 and U.S. $1 = 5.91, 1990) in induction phase, 1854 in remission phase and 10,529 SEK in relapse phase. In the terminal phase 10% of the total cost was spent. The quality of life of the patients in relapse is discussed and palliative treatment is emphasized.

Costs over time in conventional treatment of acute myeloid leukaemia. A study exploring changes in treatment strategies over two decades.

OBJECTIVES: The aim was to analyse the consumption of different items in conventional treatment of acute myeloid leukaemia (AML) and their cost, in order to evaluate the economic consequences of new treatment strategies. DESIGN: Data on items of treatment were gathered retrospectively from case notes, including amount and date. Prices were gathered from price lists made up for internal billing/accounting. SETTING: The patients were all treated in a hospital with excellent treatment and service facilities. SUBJECTS: Seventy-three AML patients treated from 1973 to 1980, all since deceased, were compared with 54 patients treated from 1981 to 1988, of whom 14 were alive at the end of the observation period. INTERVENTIONS: The patients were treated according to randomized treatment protocols to achieve complete remission. Maintenance treatment or consolidation courses were given. In relapse, new induction treatment was given. MAIN OUTCOME MEASURES: Complete remission and survival were registered. The costs were divided into basic hospital costs and patient-specific costs. RESULTS: The mean total treatment cost for an AML patient in the 1970s was 211,138 SEK, and in 1980s 356,911 SEK. (UK 1 pound = 10.57 SEK, US$1 = 5.91 SEK 1990). All treatment costs increased between the periods: hospital costs by 20%, and patient-specific costs by 186%. Antibiotics, cytostatics and outpatient department costs had increased the most. The mean survival time almost doubled, and in the 1980s group there were several long-term survivors. CONCLUSIONS: The costs for AML treatment increased considerably from the 1970s to the 1980s. The effectiveness of these treatments increased as well, resulting in increased rate and duration of survival, and several patients were long-term survivors. It was not possible to identify the cost consequences of separate new technologies.