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Health Technology Assessment... 2000PROPOSED SERVICE: The service proposed is the use of implantable cardioverter defibrillators (ICDs) in the management of risk factors leading to sudden cardiac death... (Comparative Study)
Comparative Study Review
UNLABELLED
PROPOSED SERVICE: The service proposed is the use of implantable cardioverter defibrillators (ICDs) in the management of risk factors leading to sudden cardiac death (SCD). ICDs are similar in size to a pacemaker and are intended to prevent death due to life-threatening ventricular tachyarrhythmias.
EPIDEMIOLOGY AND BACKGROUND
SCD occurs in approximately 100,000 people annually in the UK and is usually due to ventricular tachyarrhythmia. Increasing numbers of people are surviving a first episode of ventricular tachyarrhythmia and are at high risk of further episodes. Standard treatments for those at high risk have been anti-arrhythmic drugs, catheter ablation or surgery and, increasingly, vasodilating beta-blockers.
METHODS
Electronic databases were searched for the period 1980-99. In addition, bibliographies of related papers were assessed for relevant studies, and experts were contacted to identify additional published and unpublished references. Studies were included if they were systematic reviews, meta-analyses or randomised controlled trials (RCTs) comparing ICDs with conventional therapy in people at high risk of SCD.
NUMBER AND QUALITY OF STUDIES AND DIRECTION OF EVIDENCE
Seven RCTs on effectiveness the majority of which were of good quality, eight cost-effectiveness analyses most of which were older studies and based on non-UK data, and two good-quality literature reviews one of which was a critical appraisal of the literature of effectiveness and cost-effectiveness of ICD therapy, and the other a review of the cost-effectiveness of ICD therapy. These showed changes in absolute risk of total mortality ranging from an increase of 1.7% to a reduction of 22.8% (relative risk reductions of -7% to +54%).
SUMMARY OF BENEFITS
Estimated benefits from RCT data are 0.23-0.8 additional years of life with ICD therapy compared with anti-arrhythmic drug therapy.
COSTS
Unit cost of ICDs (based on 1999/2000 prices), ranges from pound 12,500 to pound 22,000. Total discounted costs for 3 years range from pound 20,000 to pound 29,000. COST-EFFECTIVENESS: Cost-effectiveness estimates in the literature identified range from $11,000 to $146,000 per life-year saved. Using UK cost data from three hospitals and trial survival data from one RCT, the estimate of cost-effectiveness from this review ranges between pound 20,250 and pound 87,000 per life-year saved. COST-UTILITY: Cost per quality-adjusted life-year is estimated by the authors of this review at pound 21,300 to pound 108,800 (using survival data from one trial and quality-of-life indices derived from clinical opinion). These figures remain speculative until quality-of-life data from ongoing trials are available to inform future UK cost-effectiveness/utility analyses.
IMPLICATIONS
If implemented for indications supported by evidence from RCTs, ICDs may cost the NHS in excess of pound 24 million per annum.
FUTURE RESEARCH
Future research should include the use of British Pacing and Electrophysiological Group registries to assess the use of different types of ICD and current service provision.
Topics: Anti-Arrhythmia Agents; Cost-Benefit Analysis; Death, Sudden, Cardiac; Defibrillators, Implantable; Health Care Costs; Humans; Quality-Adjusted Life Years; Risk Factors; Tachycardia, Ventricular
PubMed: 11086270
DOI: No ID Found -
Health Technology Assessment... Nov 2006To assess the clinical and cost-effectiveness of oxaliplatin in combination with 5-fluorouracil/leucovorin (5-FU/LV), and capecitabine monotherapy (within their licensed... (Review)
Review
OBJECTIVES
To assess the clinical and cost-effectiveness of oxaliplatin in combination with 5-fluorouracil/leucovorin (5-FU/LV), and capecitabine monotherapy (within their licensed indications), as adjuvant therapies in the treatment of patients with Stage III (Dukes' C) colon cancer after complete surgical resection of the primary tumour, as compared with adjuvant chemotherapy with an established fluorouracil-containing regimen.
DATA SOURCES
Ten electronic bibliographic databases were searched from inception to January 2005. Searches were supplemented by hand searching relevant articles, sponsor and other submissions of evidence to the National Institute of Health and Clinical Excellence and conference proceedings.
REVIEW METHODS
A systematic review and meta-analysis (where appropriate) of clinical efficacy evidence and a cost-effectiveness review and economic modelling were carried out. Marginal costs, life years gained and cost-effectiveness acceptability curves were estimated. Probabilistic sensitivity analysis was used to generate information on the likelihood that each of the interventions was optimal.
RESULTS
Three randomised active-controlled trials, of varying methodological quality, were included in the review. The MOSAIC trial and NSABP C-07 study considered the addition of oxaliplatin to adjuvant treatment (albeit administered in different 5-FU/LV regimens) and the X-ACT study compared oral capecitabine with bolus 5-FU/LV alone. A review of the available evidence indicated that in patients with Stage III colon cancer, oxaliplatin in combination with an infusional de Gramont schedule of 5-FU/LV (FOLFOX4) was more effective in preventing and delaying disease recurrence than infusional 5-FU/LV alone (de Gramont regimen). Serious adverse events and treatment discontinuations due to toxicity were more evident with oxaliplatin-based regimens (FOLFOX4 and FLOX regimen) than infusional or bolus 5-FU/LV alone (de Gramont and Roswell Park regimen). Oral capecitabine was at least equivalent in disease-free survival to the bolus Mayo Clinic 5-FU/LV regimen for patients with resected Stage III colon cancer. Although, the safety and tolerability profile of capecitabine was superior to that of the Mayo Clinic 5-FU/LV regimen, it has not been evaluated in comparison with other less toxic 5-FU/LV regimens currently in common use in the UK. Based on the assumptions and survival analysis methods used, the cost-effectiveness analysis using economic modelling estimated that capecitabine was a dominating strategy and resulted in a cost-saving of approximately pound 3320 per patient in comparison with the Mayo Clinic 5-FU/LV regimen, while also providing an additional 0.98 quality-adjusted life-years (QALYs) over a 50-year model time horizon. Oxaliplatin in combination with 5-FU/LV (FOLFOX4 regimen) is estimated to cost an additional pound 2970 per QALY gained when compared with the de Gramont 5-FU/LV regimen and demonstrated superior survival outcomes with marginal costs. The uncertainty analysis suggests that both interventions have a high probability of being cost-effective at a threshold of both pound 20,000 and pound 30,000. An indirect comparison of the FOLFOX4 and Mayo Clinic 5-FU/LV regimens suggests that the use of FOLFOX4 in place of the Mayo Clinic 5-FU/LV regimen would cost an additional pound 5777 per QALY gained. An incremental cost-effectiveness ratio (ICER) is estimated to be approximately pound 13,000 per QALY gained from treatment with FOLFOX4 compared with capecitabine. However, if the Mayo Clinic and the de Gramont 5-FU/LV regimens are assumed to be equivalent in terms of effectiveness, the ICER of FOLFOX4 in comparison with capecitabine may be greater than pound 30,000 per QALY.
CONCLUSIONS
The evidence suggests that both capecitabine and FOLFOX4 are clinically effective and cost-effective in comparison with 5-FU/LV regimens (Mayo Clinic and de Gramont schedules). Further research is suggested into the effectiveness, tolerability, patient acceptability and costs of different oxaliplatin/fluoropyrimidine schedules in the adjuvant setting; the effects of treatment duration on efficacy; adverse events; resource data collection strategies and reporting of summary statistics; subgroups benefiting most from adjuvant chemotherapy; and methods for estimating mean survival.
Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents; Capecitabine; Colonic Neoplasms; Cost-Benefit Analysis; Deoxycytidine; Drug Therapy, Combination; Fluorouracil; Organoplatinum Compounds; Oxaliplatin; Treatment Outcome; United Kingdom
PubMed: 17049138
DOI: 10.3310/hta10410 -
Health Technology Assessment... Sep 2006To evaluate the clinical effectiveness, safety, tolerability and cost-effectiveness of etanercept and infliximab for the treatment of active and progressive psoriatic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To evaluate the clinical effectiveness, safety, tolerability and cost-effectiveness of etanercept and infliximab for the treatment of active and progressive psoriatic arthritis (PsA) in patients who have inadequate response to standard treatment, including disease-modifying antirheumatic drug (DMARD) therapy.
DATA SOURCES
Electronic databases were searched up to July 2004.
REVIEW METHODS
A systematic review evaluated the clinical efficacy and adverse effects of etanercept and infliximab. The efficacy of DMARDs in the treatment of PsA was also reviewed and treatments were compared using Bayesian evidence synthesis methods. Following evaluation of existing economic evaluations of etanercept and infliximab in PsA, a new economic model was developed (the York Model). This utilised the results from the evidence synthesis and data from a range of other sources.
RESULTS
Across the two trials, at 12 weeks, around 65% of patients treated with etanercept achieved an American College of Rheumatology (ACR) 20 {pooled relative risk (RR) 4.19 [95% confidence interval (CI) 2.74 to 6.42]}, demonstrating a basic degree of efficacy in terms of arthritis-related symptoms. In addition, around 45% of patients treated with etanercept achieved an ACR 50 [pooled RR 10.84 (95% CI 4.47 to 26.28)] and around 12% achieved an ACR 70 [pooled RR 16.28 (95% CI 2.20 to 120.54)], demonstrating a good level of efficacy. The subgroup analyses conducted in one trial revealed that the effect of etanercept was not dependent upon patients' concomitant use of methotrexate. In addition, almost 85% of patients treated with etanercept achieved a Psoriatic Arthritis Response Criteria (PsARC) [pooled RR 2.60 (95% CI 1.96 to 3.45). The Psoriatic Area and Severity Index (PASI) results indicate some beneficial effect on psoriasis at 12 weeks; however, the data are sparse. The statistically significant reduction (improvement) in Health Assessment Questionnaire (HAQ) score with etanercept compared with placebo indicates a beneficial effect of etanercept on function. Similar results were seen at 24 weeks, except that the results for PASI 75 and PASI 50 now achieved statistical significance and data for Total Sharp Score annualised rate of progression were available; this was statistically significantly lower in etanercept-treated patients than in placebo-treated patients. Uncontrolled follow-up of patients indicates that treatment benefit may be maintained for at least 50 weeks. At 16 weeks, 65% of patients treated with infliximab achieved an ACR 20 [RR 6.80 (95% CI 2.89 to 16.01)], demonstrating a basic degree of efficacy in terms of arthritis-related symptoms. This level of efficacy was not dependent upon patients' concomitant use of methotrexate. Almost half the patients treated with infliximab achieved an ACR 50 [RR 49.00 (95% CI 3.06 to 785.06)] and over one-quarter achieved an ACR 70 [RR 31.00 (95% CI 1.90 to 504.86)] compared with none of the placebo group, demonstrating a good level of efficacy. In addition, 75% of patients treated with infliximab achieved a PsARC [RR 3.55 (95% CI 2.05 to 6.13)]. The beneficial treatment effect on psoriasis was also statistically significant with a mean difference in percentage change from baseline in PASI of -5 (95% CI -6.8 to -3.3), as was the percentage improvement from baseline in HAQ score with infliximab compared with placebo [mean difference 51.4 (95% CI 48.08 to 54.72)], indicating a beneficial effect of infliximab on functional status. Uncontrolled data from all measures of joint disease, psoriasis and HAQ collected up to 50 weeks of follow-up reflect those at 16 weeks. There were no radiographic assessments, so nothing can be determined about the potential or otherwise of infliximab to delay the progression of joint disease. Using the York cost-effectiveness model, infliximab was consistently dominated by etanercept because of its higher acquisition and administration costs without superior effectiveness. The incremental cost per quality-adjusted life-year (QALY) gained of etanercept compared with palliative care ranged from 14,818 pounds (females, 40-year time horizon) to 49,374 pounds (males, 1-year time horizon) if it is assumed that, when patients eventually fail on biological therapy, their disability (in terms of HAQ score) deteriorates by the same amount as it improved when they initially respond to treatment (rebound equal to gain). Results for etanercept ranged from 25,443 pounds (females, 40-year time horizon) to 49,441 pounds (males, 1-year time horizon) per QALY gained under the assumption that, when patients fail on therapy, their disability level returns to what it would have been had they never responded (rebound equal to natural history).
CONCLUSIONS
The limited data available indicated that etanercept and infliximab are efficacious in the treatment of PsA with beneficial effects on both joint and psoriasis symptoms and on functional status. Short-term data indicated that etanercept can delay joint disease progression, but long-term data are needed. There are no controlled data as yet to indicate that infliximab can delay joint disease progression. Treatment with both etanercept and infliximab for 12 weeks demonstrated a significant degree of efficacy, with no statistically significant difference between them. For both drugs, adverse events were common with mild injection/infusion reactions being the main treatment-related effect. The York model indicated that etanercept is more cost-effective than infliximab as it has a lower cost with little difference in outcomes. The cost-effectiveness of etanercept is also sensitive to assumptions made about the extent of disease progression when patients are responding to therapy. The number of years for which a patient can be safely on biologicals is uncertain so these results should be considered with caution. Further research should include long-term controlled trials to confirm benefits, review adverse events and to explore further the implications of biologic therapy.
Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Arthritis, Psoriatic; Cost-Benefit Analysis; Etanercept; Humans; Immunoglobulin G; Infliximab; Receptors, Tumor Necrosis Factor; Recombinant Fusion Proteins; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 16948890
DOI: 10.3310/hta10310 -
Health Technology Assessment... 2000SECOND-LINE TREATMENT, PACLITAXEL (MEDIAN PROGRESSION-FREE SURVIVAL): The median progression-free survival in the paclitaxel arm was 3.5 months. This was significantly... (Review)
Review
SECOND-LINE TREATMENT, PACLITAXEL (MEDIAN PROGRESSION-FREE SURVIVAL): The median progression-free survival in the paclitaxel arm was 3.5 months. This was significantly longer than the mitomycin control arm (1.6 months, p = 0.026). BREAST CANCER - SECOND-LINE TREATMENT, PACLITAXEL (MEDIAN OVERALL SURVIVAL): The median length of overall survival in the paclitaxel arm was 12.7 months, compared with 8.4 months in the mitomycin arm. BREAST CANCER - SECOND-LINE TREATMENT, PACLITAXEL (QUALITY OF LIFE): Quality of life was not reported. BREAST CANCER - SECOND-LINE TREATMENT, PACLITAXEL (ECONOMIC EVALUATION): The only economic evaluation that compared paclitaxel with control (mitomycin) was submitted in confidence and has been removed from this report. Six economic evaluations involved comparisons of paclitaxel and docetaxel, which are given below. BREAST CANCER - SECOND-LINE TREATMENT, DOCETAXEL: Four randomised controlled Phase III trials were identified: 303 Study, 304 Study, Scand and Bonneterre. A total of 1092 patients were included. One of these was a preliminary report of a study before completion of accrual (Bonneterre). Patients in the 303 Study had previously received chemotherapy involving alkylating agents; those in the other three had received anthracyclines. There were six economic evaluations on docetaxel. BREAST CANCER - SECOND-LINE TREATMENT, DOCETAXEL (QUALITY OF TRIALS): The 303 and 304 Studies were analysed on an intention to treat basis; the Scand trial excluded a single patient. The length of follow-up ranged from 11 months (Scand) to 23 months (303 Study). At least two-thirds of the participants in these trials had died. The Scand study recommended cross-over to alternate treatment on objective signs of disease progression. Patients crossing over in this way were violating the randomisation; however, no details were given concerning whether or not such patients were censored. In the economic analyses, there were no direct comparisons for the estimation of benefits. BREAST CANCER - SECOND-LINE TREATMENT, DOCETAXEL (MEDIAN PROGRESSION-FREE SURVIVAL): The median progression-free survival in the docetaxel arm ranged from 4.75 months (304 Study) to 7 months (Bonneterre). Patients in the docetaxel arms of the 304 and Scand studies had significantly longer progression-free survivals than controls (4.75 months versus 2.75 months, p = 0.001; 6.3 months versus 3 months, p = 0.001). BREAST CANCER - SECOND-LINE TREATMENT, DOCETAXEL (MEDIAN OVERALL SURVIVAL): The median overall survival in the docetaxel arm ranged from 10.4 months (Scand) to 15 months (303 Study). Patients in the docetaxel arms of the 304 Study survived for significantly longer than the mitomycin plus vinblastine arm (11.4 months versus 8.7 months, p = 0.03). BREAST CANCER - SECOND-LINE TREATMENT, DOCETAXEL (QUALITY OF LIFE): Quality of life was evaluated in two of the trials: the 303 and 304 Studies. There were no significant differences between docetaxel and control in either of these trials in terms of global health status, although differences were apparent on some subscales. These did not appear to follow a consistent pattern across the trials. BREAST CANCER - SECOND-LINE TREATMENT, DOCETAXEL (ECONOMIC EVALUATIONS): All six of these involved comparisons of paclitaxel and docetaxel, where the range of cost-utility ratios for incremental quality-adjusted life-years (QALYs) gained was pound 1990-pound 2431. In addition, three analyses compared docetaxel and vinorelbine. The cost-utility ratio for incremental QALYs gained was pound 14,050 in the only one of these carried out in the UK. OVARIAN CANCER - FIRST-LINE TREATMENT, PACLITAXEL: Four randomised controlled Phase III trials were identified: EORTC, TITGANZ, E1193 and CA139-278. (ABSTRACT TRUNCATED)
Topics: Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cost-Benefit Analysis; Disease-Free Survival; Docetaxel; Female; Humans; Ovarian Neoplasms; Paclitaxel; Quality of Life; Survival Analysis; Taxoids
PubMed: 11074389
DOI: No ID Found -
Health Technology Assessment... Nov 2009To assess the clinical effectiveness and cost-effectiveness of glucosamine sulphate/hydrochloride and chondroitin sulphate in modifying the progression of osteoarthritis... (Review)
Review
The clinical effectiveness of glucosamine and chondroitin supplements in slowing or arresting progression of osteoarthritis of the knee: a systematic review and economic evaluation.
OBJECTIVE
To assess the clinical effectiveness and cost-effectiveness of glucosamine sulphate/hydrochloride and chondroitin sulphate in modifying the progression of osteoarthritis (OA) of the knee.
DATA SOURCES
Electronic databases were searched from 1950 to 2008 and included: MEDLINE and PubMed; EMBASE; Cochrane Library (including Cochrane Systematic Reviews Database, CENTRAL, DARE, NHS EED and HTA databases); Allied and Complementary Medicine (AMED); National Research Register (NRR); Web of Science Proceedings; Current Controlled Trials; and Clinical Trials.gov. Other sources included bibliographies of retrieved papers, registered but unpublished trials, internet searches and the Food Standards Agency website.
REVIEW METHODS
A search was conducted for systematic reviews of randomised controlled trials (RCTs), which were used to identify RCTs of at least 12 months' duration and updated with searches for primary studies. A cost-effectiveness model was constructed using cohort simulation and drawing on available evidence. Sensitivity analysis was undertaken and value of information analysis conducted. A review of studies of mechanism of action was carried out to explore the biological plausibility of the preparations.
RESULTS
Five systematic reviews and one clinical guideline met the inclusion criteria. They reported inconsistent conclusions with only modest effects on reported pain and function. A reduction in joint space narrowing was more consistently observed, but the effect size was small and the clinical significance uncertain. A separate review of eight primary trials of > 12 months' duration showed evidence of statistically significant improvements in joint space loss, pain and function for glucosamine sulphate, but the clinical importance of these differences was not clear. In two studies of glucosamine sulphate, the need for knee arthroplasty was reduced from 14.5% to 6.3% at 8 years' follow-up. For other preparations of glucosamine, chondroitin and combination therapy, there was less evidence to support a clinical effect. Cost-effectiveness modelling was restricted to glucosamine sulphate. Over a lifetime horizon the incremental cost per quality-adjusted life-year (QALY) gain for adding glucosamine sulphate to current care was estimated to be 21,335 pounds. Deterministic sensitivity analysis suggested that the cost-effectiveness of glucosamine sulphate therapy was particularly dependent on the magnitude of the quality of life (QoL) gain, the change in knee arthroplasty probability with therapy and the discount rate. At a cost per QALY gained threshold of 20,000 pounds, the likelihood that glucosamine sulphate is more cost-effective than current care is 0.43, while at a threshold of 30,000 pounds, the probability rises to 0.73. Probabilistic sensitivity analysis showed that estimates were imprecise and subject to a degree of decision uncertainty. Value of information analysis demonstrated the need for further research. Several biologically plausible mechanisms of action for glucosamine sulphate and chondroitin were proposed.
CONCLUSIONS
There was evidence that glucosamine sulphate shows some clinical effectiveness in the treatment of OA of the knee. No trial data came from the UK and caution should be exercised in generalising the findings to the UK health-care setting. Cost-effectiveness was not conclusively demonstrated. There was evidence to support the potential clinical impact of glucosamine sulphate. The value of information analysis identified three research priorities: QoL, structural outcomes and knee arthroplasty. The biological mechanism of glucosamine sulphate and chondroitin remains uncertain and, in particular, the proposal that the active substance may be sulphate should be explored further.
Topics: Aged; Chondroitin Sulfates; Cost-Benefit Analysis; Disease Progression; Female; Glucosamine; Humans; Male; Middle Aged; Osteoarthritis, Knee; Randomized Controlled Trials as Topic; United Kingdom
PubMed: 19903416
DOI: 10.3310/hta13520 -
Health Technology Assessment... Jun 2006To determine the most effective diagnostic strategy for the investigation of microscopic and macroscopic haematuria in adults. (Review)
Review
OBJECTIVES
To determine the most effective diagnostic strategy for the investigation of microscopic and macroscopic haematuria in adults.
DATA SOURCES
Electronic databases from inception to October 2003, updated in August 2004.
REVIEW METHODS
A systematic review was undertaken according to published guidelines. Decision analytic modelling was undertaken, based on the findings of the review, expert opinion and additional information from the literature, to assess the relative cost-effectiveness of plausible alternative tests that are part of diagnostic algorithms for haematuria.
RESULTS
A total of 118 studies met the inclusion criteria. No studies that evaluated the effectiveness of diagnostic algorithms for haematuria or the effectiveness of screening for haematuria or investigating its underlying cause were identified. Eighteen out of 19 identified studies evaluated dipstick tests and data from these suggested that these are moderately useful in establishing the presence of, but cannot be used to rule out, haematuria. Six studies using haematuria as a test for the presence of a disease indicated that the detection of microhaematuria cannot alone be considered a useful test either to rule in or rule out the presence of a significant underlying pathology (urinary calculi or bladder cancer). Forty-eight of 80 studies addressed methods to localise the source of bleeding (renal or lower urinary tract). The methods and thresholds described in these studies varied greatly, precluding any estimate of a 'best performance' threshold that could be applied across patient groups. However, studies of red blood cell morphology that used a cut-off value of 80% dysmorphic cells for glomerular disease reported consistently high specificities (potentially useful in ruling in a renal cause for haematuria). The reported sensitivities were generally low. Twenty-eight studies included data on the accuracy of laboratory tests (tumour markers, cytology) for the diagnosis of bladder cancer. The majority of tumour marker studies evaluated nuclear matrix protein 22 or bladder tumour antigen. The sensitivity and specificity ranges suggested that neither of these would be useful either for diagnosing bladder cancer or for ruling out patients for further investigation (cystoscopy). However, the evidence remains sparse and the diagnostic accuracy estimates varied widely between studies. Fifteen studies evaluating urine cytology as a test for urinary tract malignancies were heterogeneous and poorly reported. The calculated specificity values were generally high, suggesting some possible utility in confirming malignancy. However, the evidence suggests that urine cytology has no application in ruling out malignancy or excluding patients from further investigation. Fifteen studies evaluated imaging techniques [computed tomography (CT), intravenous urography (IVU) or ultrasound scanning (US)] to detect the underlying cause of haematuria. The target condition and the reference standard varied greatly between these studies. The diagnostic accuracy data for several individual studies appeared promising but meaningful comparison of the available imaging technologies was impossible. Eight studies met the inclusion criteria but addressed different parts of the diagnostic chain (e.g. screening programmes, laboratory investigations, full urological work-up). No single study addressed the complete diagnostic process. The review also highlighted a number of methodological limitations of these studies, including their lack of generalisability to the UK context. Separate decision analytic models were therefore developed to progress estimation of the optimal strategy for the diagnostic management of haematuria. The economic model for the detection of microhaematuria found that immediate microscopy following a positive dipstick test would improve diagnostic efficiency as it eliminates the high number of false positives produced by dipstick testing. Strategies that use routine microscopy may be associated with high numbers of false results, but evidence was lacking regarding the accuracy of routine microscopy and estimates were adopted for the model. The model for imaging the upper urinary tract showed that US detects more tumours than IVU at one-third of the cost, and is also associated with fewer false results. For any cause of haematuria, CT was shown to have a mean incremental cost-effectiveness ratio of pounds sterling 9939 in comparison with the next best option, US. When US is followed up with CT for negative results with persistent haematuria, it dominates the initial use of CT alone, with a saving of pounds sterling 235,000 for the evaluation of 1000 patients. The model for investigation of the lower urinary tract showed that for low-risk patients the use of immediate cystoscopy could be avoided if cystoscopy were used for follow-up patients with a negative initial test using tumour markers and/or cytology, resulting in a saving of pounds sterling 483,000 for the evaluation of 1000 patients. The clinical and economic impact on delayed detection of both upper and lower urinary tract tumours through the use of follow-up testing should be evaluated in future studies.
CONCLUSIONS
There are insufficient data currently available to derive an evidence-based algorithm of the diagnostic pathway for haematuria. A hypothetical algorithm based on the opinion and practice of clinical experts in the review team, other published algorithms and the results of economic modelling is presented in this report. This algorithm is presented, for comparative purposes, alongside current US and UK guidelines. The ideas contained in these algorithms and the specific questions outlined should form the basis of future research. Quality assessment of the diagnostic accuracy studies included in this review highlighted several areas of deficiency.
Topics: Algorithms; Cost-Benefit Analysis; Diagnostic Tests, Routine; Hematuria; Humans; State Medicine; United Kingdom
PubMed: 16729917
DOI: 10.3310/hta10180 -
Health Technology Assessment... Jun 2008To assess the clinical effectiveness and cost-effectiveness of minimal incision approaches to total hip replacement (THR) for arthritis of the hip. (Review)
Review
A systematic review of the clinical effectiveness and cost-effectiveness and economic modelling of minimal incision total hip replacement approaches in the management of arthritic disease of the hip.
OBJECTIVES
To assess the clinical effectiveness and cost-effectiveness of minimal incision approaches to total hip replacement (THR) for arthritis of the hip.
DATA SOURCES
Major electronic databases were searched from 1966 to 2007. Relevant websites were also examined and experts in the field were consulted.
REVIEW METHODS
Studies of minimal (one or two) incision THR compared with standard THR were assessed for inclusion in the review of clinical effectiveness. A systematic review of economic evaluations comparing a minimal incision approach to standard THR was also performed and the estimates from the systematic review of clinical effectiveness were incorporated into an economic model. Utilities data were sourced to estimate quality-adjusted life-years (QALYs). Due to lack of data, no economic analysis was conducted for the two mini-incision surgical method.
RESULTS
Nine randomised controlled trials (RCTs), 17 non-randomised comparative studies, six case series and one registry were found to be useful for the comparison of single mini-incision THR with standard THR. One RCT compared two mini-incision THR with standard THR, and two RCTs, five non-randomised comparative studies and two case series compared two mini-incision with single mini-incision THR. The RCTs were of moderate quality. Most had fewer than 200 patients and had a follow-up period of less than 1 year. The single mini-incision THR may have some perioperative advantages, e.g. blood loss [weighted mean difference (WMD) -57.71 ml, p<0.01] and shorter operative time, of uncertain practical significance. It may also offer a shorter recovery period and greater patient satisfaction. Evidence on long-term outcomes (especially revision) is too limited to be useful. Lack of data prevented subgroup analysis. With respect to the two-incision approach, data were suggestive of shorter recovery compared with single-incision THR, but conclusions must be treated with caution. The costs to the health service, per patient, of single mini-incision THR depend upon assumptions made, but are similar at one year (7060 pounds sterling vs 7350 pounds sterling for standard THR). For a 40-year time horizon the costs were 11,618 pounds sterling for mini-incision and 11,899 pounds sterling for standard THR. Two existing economic evaluations were identified, but they added little, if any, value to the current evidence base owing to their limited quality. In the economic model, mini-incision THR was less costly and provided slightly more QALYs in both the 1- and 40-year analyses. The mean QALYs at 1 year were 0.677 for standard THR and 0.695 for mini-incision THR. At 40 years, the mean QALYs were 8.463 for standard THR and 8.480 for mini-incision. At 1 year the probabilistic sensitivity analyses indicate that mini-incision THR has a 95% probability of being cost-effective if society's willingness to pay for a QALY were up to 50,000 pounds sterling. This is reduced to approximately 55% for the 40-year analysis. The results were driven by the assumption of a 1-month earlier return to usual activities and a decreased hospital length of stay and operation duration following mini-incision THR. If mini-incision THR actually required more intensive use of resources it would become approximately 200 pounds sterling more expensive and would only be cost-effective (cost per QALY>30,000 pounds sterling) if recovery was 1.5 weeks faster. A threshold analysis around risk of revision showed, using the same cost per QALY threshold, mini-incision THR would have to have no more than a 7.5% increase in revisions compared with standard THR for it to be no longer considered cost-effective (one more revision for every 200 procedures performed). Further sensitivity analysis involved relaxing assumptions of equal long-term outcomes where possible. and broadly similar results to the base-case analysis were found in this and further sensitivity analyses.
CONCLUSIONS
Compared with standard THR, minimal incision THR has small perioperative advantages in terms of blood loss and operation time. It may offer a shorter hospital stay and quicker recovery. It appears to have a similar procedure cost to standard THR, but evidence on its longer term performance is very limited. Further long-term follow-up data on costs and outcomes including analysis of subgroups of interest to the NHS would strengthen the current economic evaluation.
Topics: Arthroplasty, Replacement, Hip; Cost-Benefit Analysis; Decision Making; Female; Humans; Male; Meta-Analysis as Topic; Models, Economic; Osteoarthritis, Hip; Quality of Life; Randomized Controlled Trials as Topic; Technology Assessment, Biomedical
PubMed: 18513467
DOI: 10.3310/hta12260 -
Journal of Viral Hepatitis Feb 2007Standard treatments for chronic hepatitis B (CHB) include interferon-alpha (IFN-alpha) and lamivudine (LAM), but these are associated with adverse effects and viral... (Review)
Review
Standard treatments for chronic hepatitis B (CHB) include interferon-alpha (IFN-alpha) and lamivudine (LAM), but these are associated with adverse effects and viral resistance, respectively. The aim of this systematic review and economic evaluation was to assess the clinical effectiveness and cost-effectiveness of two alternative drugs for the treatment of adults with CHB: adefovir dipivoxil (ADV) and pegylated IFN-alpha-2a. We searched electronic databases, including Cochrane Systematic Reviews and Medline, for literature that met criteria defined in a research protocol. Retrieved articles were independently assessed for inclusion by two reviewers. We developed a Markov state transition model to estimate the cost-effectiveness (cost-utility) of pegylated IFN-alpha-2a and of ADV compared with nonpegylated IFN-alpha-2a, LAM and best supportive care. Seven randomized controlled trials and two systematic reviews met the inclusion criteria for our review of clinical effectiveness. ADV was significantly more effective than placebo or ongoing LAM in reducing levels of hepatitis B virus (HBV) DNA. Rates of hepatitis B e antigen (HBeAg) seroconversion were higher among patients receiving ADV than either placebo or ongoing LAM. Patients treated with pegylated IFN-alpha-2a, either as monotherapy or in combination with LAM, showed significantly reduced HBV DNA levels compared with patients treated with LAM monotherapy. HBeAg seroconversion rates at follow-up were significantly higher for pegylated IFN-alpha-2a patients than for those receiving LAM monotherapy. Results of our cost-effectiveness analysis demonstrate that incremental costs per quality adjusted life year (QALY) for a range of comparisons were between 5,994 and 16,569 British Pound, and within the range considered by NHS decision-makers to represent good value for money.
Topics: Adenine; Antiviral Agents; Cost-Benefit Analysis; England; Hepatitis B e Antigens; Hepatitis B, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Lamivudine; Organophosphonates; Polyethylene Glycols; Randomized Controlled Trials as Topic; Recombinant Proteins; Wales
PubMed: 17244247
DOI: 10.1111/j.1365-2893.2006.00808.x -
Health Technology Assessment... Feb 2010To assess the effectiveness and cost-effectiveness of schools-based skills-building behavioural interventions to encourage young people to adopt and maintain safer... (Review)
Review
The effectiveness and cost-effectiveness of behavioural interventions for the prevention of sexually transmitted infections in young people aged 13-19: a systematic review and economic evaluation.
OBJECTIVES
To assess the effectiveness and cost-effectiveness of schools-based skills-building behavioural interventions to encourage young people to adopt and maintain safer sexual behaviour and to prevent them from acquiring sexually transmitted infections (STIs).
DATA SOURCES
Electronic bibliographic databases (e.g. MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, CINAHL, PsycINFO, CCRCT, NHS EED and DARE) were searched for the period 1985 to March 2008. Bibliographies of systematic reviews and related papers were screened and experts contacted to identify additional published and unpublished references.
REVIEW METHODS
A systematic review of effectiveness and economic evaluation of cost-effectiveness were carried out. A descriptive map of studies that met inclusion criteria was produced, and keywords were developed and systematically applied to these studies to identify a policy-relevant subset of studies for the systematic review. Outcome data for variables including sexual behaviour were extracted. An economic model was developed to compare the costs and consequences of the behavioural interventions. A Bernoulli statistical model was constructed to describe the probability of STI infection.
RESULTS
There were few significant differences between the interventions and comparators in terms of changes in sexual behaviour outcomes, although there were some significant differences for knowledge and some measures of self-efficacy. The studies included in this review conducted relatively short follow-up assessments at a time when many young people were becoming sexually active. It is therefore possible that favourable behaviour change may have occurred, and become more cost-effective, with time, as sexual activity becomes more routine in young people's lives. The quality of the intervention provider influenced whether or not young people found the interventions to be acceptable and engaging; enthusiasm and considerable expertise were important for effective class management and delivery of skills-building activities, and a supportive school culture was also helpful. Recognition of young people's individual needs in relation to sexual health was another important factor. No conclusions could be drawn on the impact of the interventions on sexual health inequalities due to a lack of relevant data on socioeconomic status, gender and ethnicity. The results of the economic evaluation were considered to be illustrative, mainly due to the uncertainty of the effect of intervention on behavioural outcomes. The results were most sensitive to changes in parameter values for the intervention effect, the transmission probability of STIs and the number of sexual partners. The costs of teacher-led and peer-led behavioural interventions, based on the resources estimated from the relevant randomised controlled trials in our systematic review, were 4.30 pounds and 15 pounds per pupil, respectively. Teacher-led interventions were more cost-effective than peer-led interventions due to the less frequent need for training. The incremental cost-effectiveness of the teacher-led and peer-led interventions was 20,223 pounds and 80,782 pounds per quality-adjusted life-year gained, respectively. An analysis of individual parameters revealed that future research funding should focus on assessing the intervention effect for condom use from a school-based intervention.
CONCLUSIONS
School-based behavioural interventions for the prevention of STIs in young people can bring about improvements in knowledge and increased self-efficacy, but the interventions did not significantly influence sexual risk-taking behaviour or infection rates. Future investigation should include long-term follow-up to assess the extent to which safer sexual behaviour is adopted and maintained into adulthood, and prospective cohort studies are needed to look at the parameters that describe the transmission of STIs between partners. Funding should focus on the effectiveness of the interventions on influencing behaviour.
Topics: Adolescent; Adolescent Behavior; Cost-Benefit Analysis; Female; Humans; Male; Risk Reduction Behavior; Safe Sex; Schools; Sex Education; Sexually Transmitted Diseases; United Kingdom; Young Adult
PubMed: 20178696
DOI: 10.3310/hta14070 -
Health Technology Assessment... Apr 2007To assess the effectiveness and cost-effectiveness of epoetin alpha, epoetin beta and darbepoetin alpha (referred to collectively in this report as epo) in anaemia... (Review)
Review
A systematic review and economic evaluation of epoetin alpha, epoetin beta and darbepoetin alpha in anaemia associated with cancer, especially that attributable to cancer treatment.
OBJECTIVES
To assess the effectiveness and cost-effectiveness of epoetin alpha, epoetin beta and darbepoetin alpha (referred to collectively in this report as epo) in anaemia associated with cancer, especially that attributable to cancer treatment.
DATA SOURCES
Electronic databases were searched from 2000 (1996 in the case of darbepoetin alpha) to September 2004.
REVIEW METHODS
Using a recently published Cochrane review as the starting point, a systematic review of recent randomised controlled trials (RCTs) comparing epo with best standard was conducted. Inclusion, quality assessment and data abstraction were undertaken in duplicate. Where possible, meta-analysis was employed. The economic assessment consisted of a systematic review of past economic evaluations, an assessment of economic models submitted by the manufacturers of the three epo agents and development of a new individual sampling model (the Birmingham epo model).
RESULTS
In total 46 RCTs were included within this systematic review, 27 of which had been included in the Cochrane systematic review. All 46 trials compared epo plus supportive care for anaemia (including transfusions), with supportive care for anaemia (including transfusions), alone. Haematological response (defined as an improvement by 2 g/dl(-1)) had a relative risk of 3.4 [95% confidence interval (CI) 3.0 to 3.8, 22 RCTs] with a response rate for epo of 53%. The trial duration was most commonly 16-20 weeks. There was little statistical heterogeneity in the estimate of haematological response, and there were no important differences between the subgroups examined. Haemoglobin (Hb) change showed a weighted mean difference of 1.63 g/dl(-1) (95% CI 1.46 to 1.80) in favour of epo. Treatment with erythropoietin in patients with cancer-induced anaemia reduces the number of patients who receive a red blood cell transfusion (RBCT) by an estimated 18%. Health-related quality of life (HRQoL) data were analysed using vote counting and qualitative assessment and a positive effect was observed in favour of an improved HRQoL for patients on epo. Published information on side-effects was of poor quality. New trials provided further evidence of side-effects with epo, particularly thrombic events, but it is still unclear whether these could be accounted for by chance alone. The results of the previous Cochrane review had suggested a survival advantage for epo (HR 0.84, 95% CI 0.69 to 1.02), based on 19 RCTs. The update, based on 28 RCTs, suggests no difference (HR 1.03, 95% CI 0.88 to 1.21). Subgroup analysis suggested some explanations for this heterogeneity, but it is difficult to draw firm conclusions without access to the substantial amounts of missing or unpublished data, or more detailed results from some of the trials with heterogeneous patient populations. The conclusions are, however, broadly in line with those of a Food and Drug Administration (FDA) safety briefing, which recommended that patients with a haemoglobin above 12 g/dl(-1) should not be treated; the target rate of rise in Hb should not be too great, and further carefully conducted trials are required to determine which subgroups of patients may be harmed by the use of these products, in particular through the stimulation of tumour activity. Five published economic evaluations identified from the literature had inconsistent results, with estimates ranging from a cost per quality-adjusted life-year (QALY) under pound 10,000 through to epo being less effective and more costly than standard care. The more favourable evaluations assumed a survival advantage for epo. The three company models submitted each relied on assumed survival gains to achieve relatively low cost per QALY, from pound 13,000 to pound 28,000, but generated estimates from pound 84,000 to pound 159,000 per QALY when no survival gain was assumed. Each of these models relied on Hb levels alone driving utility, and each assumed gradual normalisation of Hb in the standard treatment arm after the end of treatment. The Birmingham epo model followed the company models in regard to the relationship between Hb levels and utility, and also assumed normalisation in the base case. With no survival gain, the incremental cost per QALY was pound 150,000, falling to pound 40,000 when the lower, more favourable, confidence interval for survival was used.
CONCLUSIONS
Epo is effective in improving haematological response and reducing RBCT requirements, and appears to have a positive effect on HRQoL. The incidence of side-effects and effects on survival remains highly uncertain. However, if there is no impact on survival, it seems highly unlikely that epo would be considered a cost-effective use of healthcare resources. The main target for further research should be improving estimates of impact on survival, initially through more detailed secondary research, such as the individual patient data meta-analysis started by the Cochrane group. Further trials may be required, and have been recommended by the FDA, although many trials are in progress, completed but unreported or awaiting mature follow-up. The Birmingham epo model developed as part of this project contains new features that improve its flexibility in exploring different scenarios; further refinement and validation would therefore be of assistance. Finally, further research to resolve uncertainty about other parameters, particularly quality of life, adverse events, and the rate of normalisation, would also be beneficial.
Topics: Anemia; Antineoplastic Agents; Cost-Benefit Analysis; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Recombinant Proteins; Survival Analysis; Treatment Outcome
PubMed: 17408534
DOI: 10.3310/hta11130