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Biomedical subjects

J Chilcott

Publications and source records attributed to J Chilcott.

At least 19 recordsLinked to original sources
PubMed2006

Cost-effectiveness of oxaliplatin and capecitabine in the adjuvant treatment of stage III colon cancer.

For many years, the standard treatment for stage III colon cancer has been surgical resection followed by 5-fluorouracil in combination with folinic acid (5-FU/LV). Ongoing clinical trial evidence suggests that capecitabine and oxaliplatin (in combination with 5-FU/LV) may improve disease-free survival and overall survival when compared against 5-FU/LV alone in the adjuvant setting. This study evaluates the cost-effectiveness profiles of these two regimens in comparison to standard chemotherapy, using evidence from two international randomised controlled trials. Survival modelling techniques were employed to extrapolate survival curves from the two trials in order to estimate the long-term benefits of alternative treatment options over the remaining lifetime of patients. The health economic analysis suggests that capecitabine is expected to produce greater health gains at a lower cost than 5-FU/LV. Oxaliplatin in combination with 5-FU/LV is estimated to cost pounds 2970 per additional QALY gained when compared to 5-FU/LV alone. Future research should attempt to elucidate uncertainties concerning the optimal roles of capecitabine and/or oxaliplatin in the adjuvant setting in order to achieve the maximum level of clinical benefit.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

A systematic review and economic evaluation of magnetic resonance cholangiopancreatography compared with diagnostic endoscopic retrograde cholangiopancreatography.

OBJECTIVES: To compare the clinical and cost-effectiveness of magnetic resonance cholangiopancreatography (MRCP) with diagnostic endoscopic retrograde cholangiopancreatography (ERCP) for the investigation of biliary obstruction. DATA SOURCES: Electronic bibliographic databases, the reference lists of relevant articles and various health services research-related resources. REVIEW METHODS: The data sources were searched and selected studies were assessed using quality criteria. In total, 28 prospective diagnostic studies were identified reporting several suspected conditions plus one of patient satisfaction. Analyses were then performed to establish sensitivities, specificities, likelihood ratios and confidence intervals. The relative cost-effectiveness of adopting MRCP scanning in the investigation of the biliary tree was undertaken using a probabilistic economic model. RESULTS: The median sensitivity for choledocholithiasis (13 studies) was 93% and the median specificity 94%. The median likelihood ratio for a positive value was 15.75 and for a negative value 0.08. Reported sensitivities for malignancy were somewhat lower, ranging from 81 to 86%, and specificities ranged from 92 to 100%. There was some evidence that MRCP is an accurate diagnostic test in comparison to ERCP, although the quality of studies was moderate. Claustrophobia prevented at least some patients from having MRCP in ten of the 28 studies. The other 18 studies did not mention claustrophobia. The probability of avoiding unnecessary diagnostic ERCP is estimated at 30%. These patients could avoid the unnecessary risk of complications and death associated with diagnostic ERCP, and substantial cost saving would be gained. The overall expected cost saving associated with MRCP is GBP149; the overall expected gain in quality-adjusted life-year is estimated at 0.011. CONCLUSIONS: There is some evidence that MRCP is an accurate investigation compared with diagnostic ERCP, although the values for malignancy compared with choledocholithiasis were somewhat lower. The quality of studies was moderate. The limited evidence on patient satisfaction showed that patients preferred MRCP to diagnostic ERCP. The estimated clinical and economic impacts of diagnostic MRCP versus diagnostic ERCP are very favourable. The baseline estimate is that MRCP may both reduce cost and result in improved quality of life outcomes compared with diagnostic ERCP. Further research is suggested to compare MRCP and diagnostic ERCP with final diagnosis and also with the full range of target conditions; to examine patient satisfaction and ways of reducing problems with claustrophobia; to look at protocols to help identify who could most benefit from MRCP or ERCP; to assess the relative need and urgency of patient access to magnetic resonance imaging services, and also to determine how demand would affect availability and potential cost savings.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed2004

Clinical effectiveness and cost-effectiveness of neonatal screening for inborn errors of metabolism using tandem mass spectrometry: a systematic review.

OBJECTIVES: To evaluate the clinical and cost-effectiveness of tandem mass spectrometry (MS)-based neonatal screening for inborn errors of metabolism (IEM). DATA SOURCES: Fourteen electronic bibliographic databases covering biomedical, science, economic and grey literature, the reference lists of relevant articles and abstracts of conference proceedings and 18 health services research-related resources. REVIEW METHODS: This review is an update of two previous HTA reports of neonatal screening for IEM. These reports have been updated by a systematic review of published research (between 1995 and January 2002) on neonatal screening of inherited metabolic disorders using tandem MS. This was supplemented by a search for economic literature and the application of a modelling exercise to investigate the economics of using tandem MS within a neonatal screening programme in the UK. RESULTS: Evidence from the reviews of IEM found that the UK screening programme for phenylketonuria (PKU) was well established and there was universal agreement that neonatal screening for PKU was justified. Of the many other disorders that can be detected by tandem MS, the best candidate condition for a new screening programme was medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency. For many other IEM that can be detected by tandem MS, robust clinical evidence was limited. Cost-effectiveness analysis using economic modelling indicated that substituting the use of tandem MS for existing technologies for the screening of PKU alone could not be justified. However, results from the economic modelling indicate that the addition of screening for MCAD deficiency as part of a neonatal screening programme for PKU using tandem MS would be economically attractive. Using an operational range of 50,000-60,000 specimens per system per year, the mean incremental cost for PKU and MCAD deficiency screening combined using tandem MS from the model was -23,312 British pounds for each cohort of 100,000 neonates screened. This cost saving is associated with a mean incremental gain of 59 life-years. Additional economic modelling using the available evidence does not support including other inherited metabolic diseases within a neonatal screening programme at present. CONCLUSIONS: The evidence appears to support the introduction of tandem MS into a UK neonatal screening programme for PKU and MCAD deficiency combined. Tandem MS has the potential for simultaneous multi-disease screening using a single analytical technique. Although the marginal cost of extending the programme to include other conditions may be relatively small, the application of this new technology to PKU and MCAD deficiency screening does not imply the wholesale inclusion of all disorders detectable by tandem MS. It is suggested that the primary focus of further research should be on the long-term effectiveness of treatment strategies on adverse outcomes (disabilities and impairments) under conventional management and the potential impact of early diagnosis using tandem MS.

Cohort Studies↗
PubMed2004

Clinical effectiveness and cost-effectiveness of pioglitazone and rosiglitazone in the treatment of type 2 diabetes: a systematic review and economic evaluation.

OBJECTIVES: To evaluate the use of pioglitazone and rosiglitazone, in terms of both clinical and cost-effectiveness in the treatment of type 2 diabetes. DATA SOURCES: Electronic databases and the reference lists of relevant articles, in addition 14 health services research-related resources were consulted via the Internet. REVIEW METHODS: A systematic review of the literature, involving a range of databases, was performed to identify all papers relating to the glitazones. The methodological quality of the included randomised controlled trials (RCTs) was assessed using the Jadad method. A generic proforma for the critical appraisal of modelling studies in health economics was used in systematically reviewing the economic assessment studies identified. This was supplemented by a detailed review of the disease-specific factors within the studies. Where possible, key outcomes were compared. Readers should note that information from the sponsor's submission was submitted in confidence to the National Institute for Clinical Excellence (NICE). Such information was made available to the NICE Appraisals Committee, but has been removed from this version of the report. RESULTS: Of the 1272 studies identified, nine studies met the inclusion criteria. The clinical evidence available showed that glitazones reduce glycosylated haemoglobin by approximately 1%, and are more effective at higher doses than at lower doses. Glitazone treatment is associated with weight gain. No published data were available on the long-term effects of glitazone use. No prospective RCTs were found comparing pioglitazone to rosiglitazone, but the available evidence indicated that the two treatments had similar effects. There are no published economic studies on either pioglitazone or rosiglitazone. Economic evaluations for both glitazones were provided by the manufacturers. Sensitivity analyses undertaken by the assessment team suggest that the cost per quality-adjusted life-year (QALY) of rosiglitazone is most sensitive to dosage and treatment effect, that is, the effect of rosiglitazone on beta-cell function and insulin sensitivity. In the two scenarios where rosiglitazone is compared with metformin and sulfonylurea combination therapy, the cost-effectiveness of rosiglitazone switches from around 10,000 pounds per QALY to being dominated by the comparator strategy. Since the baseline estimate of cost-effectiveness is not robust to changes in the treatment effect and is reliant on the many assumptions included within the metabolic and long-term economic models, caution should be used in interpreting the baseline result. CONCLUSIONS: The clinical evidence available showed that glitazones can reduce glycosylated haemoglobin; however there were no peer-reviewed data available on the long-term effects of their use or any prospective RCTs found comparing pioglitazone with rosiglitazone. No published economic studies on either pioglitazone or rosiglitazone were found, although sensitivity analyses undertaken by the assessment team suggest that the cost per QALY of rosiglitazone is most sensitive to dosage and treatment effect. It is suggested that research already undertaken in this area should be published, preferably in peer-reviewed journals. Direct head-to-head comparisons of the glitazones in combination with metformin or sulfonylurea would be helpful. The current licence arrangements do not allow for routine use of the glitazones in triple oral combination therapy or in combination with insulin. Evidence is emerging of use of the glitazones within such combinations; therefore, prospective RCTs would be useful. These studies could examine short-term transition strategies and longer term management. The impact of the glitazones in delaying transfer to insulin and the impact on long-term outcomes should also be considered for investigation.

Adult↗
PubMed2004

Liquid-based cytology in cervical screening: an updated rapid and systematic review and economic analysis.

OBJECTIVES: To update an earlier published report reviewing the effectiveness and cost-effectiveness of liquid-based cytology (LBC). DATA SOURCES: Electronic bibliographic databases, relevant articles, sponsor submissions and various health services research-related resources. REVIEW METHODS: The selected data were reviewed and assessed with respect to the quality of the evidence. Pooled estimates of the parameters of interest were derived from the original and the updated studies. Meta-analyses were undertaken where appropriate. The mathematical model developed for the original rapid review of LBC was adapted to synthesise the updated data to estimate costs, survival and quality-adjusted survival of patients tested using LBC and using Papanicolaou (Pap) smear testing. Cost data from published sources were incorporated into the above model to allow economic, as well as clinical, implications of treatment to be assessed. The primary incremental cost-effectiveness ratio is the cost per life year gained (LYG), although estimates of the cost per quality-adjusted life-year (QALY) gained are also presented. A sensitivity analysis was undertaken to identify the key parameters that determine the cost-effectiveness of the treatments, with the objective of identifying how robust the results of the economic analysis are, given the current level of evidence. RESULTS: From the evidence available, it is likely that the LBC technique will reduce the number of false-negative test results. Modelling analyses undertaken as part of this study indicate that this would reduce the incidence of invasive cancer. There is now more evidence to support improvements emanating from the use of LBC screening in terms of a reduced number of unsatisfactory specimens and a decrease in the time needed to obtain the smear samples. The estimated annual gross cost of consumables and operating equipment, and other one-off conversion costs associated with introducing the new technique, will be between 17 British pounds and 38 British pounds million in England and Wales, depending on the LBC system and the configuration of the service. Analyses based on models of disease natural history, conducted in this study, showed that conventional Pap smear screening was extendedly dominated by LBC (LBC was always more cost-effective than conventional Pap smear testing over the same screening interval). Comparing LBC across alternative screening intervals gave a cost-effectiveness of under 10,000 British pounds per LYG when screening was undertaken every 3 years. The cost-effectiveness results were relatively stable under most conditions, although if screening outcomes such as borderline results and colposcopy are assumed to induce even small amounts of disutility then LBC screening at 5-yearly intervals may be the most cost-effective option. CONCLUSIONS: This updated analysis provides more certainty with regard to the potential cost-effectiveness of LBC compared with conventional Pap smear testing. However, there is uncertainty regarding the relative effectiveness (and cost-effectiveness) of the two main LBC techniques. Further research in the area of utility assessment may be worthwhile and possibly a full cost-effectiveness study of LBC based on a trial of its introduction in a low-prevalence population, although the results of the modelling analysis provide a robust argument that LBC is a cost-effective alternative to conventional cervical cancer screening. A randomised comparison of the two main techniques may also be useful.

Cost-Benefit Analysis↗
PubMed2004

Systematic review and economic evaluation of a long-acting insulin analogue, insulin glargine.

OBJECTIVES: To evaluate the use of insulin glargine in its licensed basal-bolus indication in terms of both clinical and cost-effectiveness. DATA SOURCES: Electronic databases. REVIEW METHODS: A systematic review of the literature, involving a range of databases, was performed to identify all papers relating to insulin glargine. RESULTS: Nineteen studies met the inclusion criteria but full reports were available for only six. For type 1 diabetes patients, insulin glargine appears to be more effective than neutral protamine Hagedorn (NPH) in reducing fasting blood glucose (FBG) but not in reducing glycosylated haemoglobin (HbA1c) and there is some evidence that both insulins are as effective as each other in both FBG and HbA1c control. For type 2 patients for whom oral antidiabetic agents provide inadequate glycaemic control, there is no evidence that insulin glargine is more effective than NPH in reducing either FBG or HbA1c and some evidence that both insulins are as effective as each other in both FBG and HbA1c control. Evidence for control of hypoglycaemia is equivocal. In studies where insulin glargine is demonstrated to be superior to NPH in controlling nocturnal hypoglycaemia, this may be only apparent when compared with once-daily NPH and not twice-daily NPH. Further, this superiority of glargine over NPH in the control of nocturnal hypoglycaemia may relate to one formulation of insulin glargine (HOE901[80]) and not another (HOE901[30]). There is no conclusive evidence that insulin glargine is superior to NPH in controlling symptomatic hypoglycaemia and severe hypoglycaemia. Insufficient data are available to conclude whether insulin glargine is different from each of the commonly used NPH dosing regimens: once daily and more than once daily. Given the lack of a published evidence base for the cost-effectiveness of insulin glargine, the economic review concentrates on a review of the industry submission and an amended model. Three economic models are provided in the submission, two relating to type 1 diabetes and one relating to type 2 diabetes. All three models compare the cost--utility of insulin glargine against NPH insulin. In general, the structures of the models are poor and in all three models, mistakes relating to assumptions and calculations have been made. The assessment team believe that the cost per QALY estimates generated by the Aventis model may be an underestimate for several reasons. The cost-effectiveness of insulin glargine in both type 1 and type 2 diabetes is highly sensitive to the amount of utility associated with reducing the fear of hypoglycaemia. CONCLUSIONS: The evidence suggests that, compared with NPH insulin, insulin glargine is effective in reducing the number of nocturnal hypoglycaemic episodes, especially when compared with once-daily NPH. There appears to be no improvement in long-term glycaemic control and therefore insulin glargine is unlikely to reduce the incidence of the long-term microvascular and cardiovascular complications of diabetes. Further research into insulin glargine is needed that addresses the quality of life issues associated with fear of hypoglycaemia and also the economic impact of balance of HbA1c control and incidence of hypoglycaemia achieved in practice. Studies examining the economic evidence on insulin glargine should be published.

Adult↗
PubMed2003

The cost-effectiveness of nCPAP treatment in patients with moderate-to-severe obstructive sleep apnoea.

The demand for diagnostic and therapeutic services for obstructive sleep apnoea syndrome (OSAS) showed marked growth during the 1990s. This paper analyses the long-term cost-effectiveness of nasal continuous positive airway pressure (nCPAP) treatment in comparison to conventional null treatment. A Markov model was used to represent the natural history of OSAS based upon published evidence. Utility values came from a survey of OSAS patients. Data on health costs were collected from hospitals in the Basque Country, Spain. The incremental cost-effectiveness ratio of nCPAP treatment is <6,000 Euros per quality-adjusted life year. On disaggregated analysis, nCPAP treatment accounts for 86% of incremental costs; 84% of incremental effectiveness is attributable to improved quality of life. Treatment of obstructive sleep apnoea syndrome with nasal continuous positive airway pressure has a cost-effectiveness that is in line with that of other commonly funded treatments such as antihypertensive drugs. The key clinical benefit of nasal continuous positive airway pressure treatment is improvement in the quality of life of patients with obstructive sleep apnoea syndrome. This benefit is also precisely the one for which the evidence base is strongest. The remaining uncertainties concerning the impact of nasal continuous positive airway pressure on long-term mortality have only a relatively small impact on the economics of treatment.

Adult↗
PubMed2003

The role of modelling in prioritising and planning clinical trials.

OBJECTIVES: To identify the role of modelling in planning and prioritising trials. The review focuses on modelling methods used in the construction of disease models and on methods for their analysis and interpretation. DATA SOURCES: Searches were initially developed in MEDLINE and then translated into other databases. REVIEW METHODS: Systematic reviews of the methodological and case study literature were undertaken. Search strategies focused on the intersection between three domains: modelling, health technology assessment and prioritisation. RESULTS: The review found that modelling can extend the validity of trials by: generalising from trial populations to specific target groups; generalising to other settings and countries; extrapolating trial outcomes to the longer term; linking intermediate outcome measures to final outcomes; extending analysis to the relevant comparators; adjusting for prognostic factors in trials; and synthesising research results. The review suggested that modelling may offer greatest benefits where the impact of a technology occurs over a long duration, where disease/technology characteristics are not observable, where there are long lead times in research, or for rapidly changing technologies. It was also found that modelling can inform the key parameters for research: sample size, trial duration and population characteristics. One-way, multi-way and threshold sensitivity analysis have been used in informing these aspects but are flawed. The payback approach has been piloted and while there have been weaknesses in its implementation, the approach does have potential. Expected value of information analysis is the only existing methodology that has been applied in practice and can address all these issues. The potential benefit of this methodology is that the value of research is directly related to its impact on technology commissioning decisions, and is demonstrated in real and absolute rather than relative terms; it assesses the technical efficiency of different types of research. Modelling is not a substitute for data collection. However, modelling can identify trial designs of low priority in informing health technology commissioning decisions. CONCLUSIONS: Good practice in undertaking and reporting economic modelling studies requires further dissemination and support, specifically in sensitivity analyses, model validation and the reporting of assumptions. Case studies of the payback approach using stochastic sensitivity analyses should be developed. Use of overall expected value of perfect information should be encouraged in modelling studies seeking to inform prioritisation and planning of health technology assessments. Research is required to assess if the potential benefits of value of information analysis can be realised in practice; on the definition of an adequate objective function; on methods for analysing computationally expensive models; and on methods for updating prior probability distributions.

Clinical Trials as Topic↗
PubMed2003

The clinical and cost-effectiveness of pulsatile machine perfusion versus cold storage of kidneys for transplantation retrieved from heart-beating and non-heart-beating donors.

OBJECTIVES: To evaluate the clinical and cost-effectiveness of machine perfusion (MP) compared to cold storage (CS), as a means of preserving kidneys prior to transplantation. Transplantation of kidneys from both heart-beating donors (HBDs) and non-heart-beating donors (NHBDs) is considered. Finally to review whether the use of MP can allow valid testing of kidney viability prior to transplantation. DATA SOURCES: Fifteen electronic bibliographic databases were searched. The reference lists of relevant articles and sponsor submissions were hand searched and various health service research-related resources were consulted via the Internet. REVIEW METHODS: A literature search was undertaken to identify relevant studies and a meta-analysis performed on the studies that had appropriate comparator groups and reported sufficient data. A structured review examined tests of viability of kidneys on MP. Economic modelling was used to determine the cost-effectiveness and cost-utility of MP. RESULTS: The meta-analysis suggested that the use of MP, as compared with CS, is associated with a relative risk of delayed graft function (DGF) of 0.804 (95% confidence limits 0.672 to 0.961). There was no evidence to suggest that this effect is different in kidneys taken from HBDs as opposed to NHBDs. Meta-analysis of 1-year graft survival data showed no significant effect, but the studies, even when aggregated, were severely underpowered with respect to the likely impact on graft survival. The size of effects demonstrated were in line with those predicted by an indirect model of graft survival based on the association of DGF with graft loss. The economic assessment indicated that it is unlikely that in the UK health setting complete cost recovery will be obtained from a reduction in the incidence of DGF. The probability that MP is cheaper and more effective than CS in the long term was estimated at around 80% for NHBD recipients and 50-60% for HBD recipients. Flow characteristics of the perfusate of kidneys undergoing MP may be an indicator of kidney viability, but data were inadequate to calculate the sensitivity and specificity of any test based on this. The concentration of alpha-glutathione-S-transferase (a marker of cell damage) in the perfusate may be the basis of a valid test. A threshold of 2800 micrograms/100 g gave a sensitivity of 93% and specificity of 33% (and hence a likelihood ratio of 1.41). CONCLUSIONS: The baseline analysis indicated that in the long-term MP would be expected to be cheaper and more effective than CS for both HBD and NHBD recipients. A definitive study of the clinical benefit of MP in order to establish its effect on DGF and longer term graft survival would be valuable, together with an economic evaluation of the benefits. While direct evidence relating to improvements in graft survival would be preferable, the small predicted improvement indicates that a very large sample size would be required. In addition to seeking direct evidence of the impact on DGF, research quantifying the impact of DGF on graft survival in this technology is required. Research is also needed to establish whether a valid test (or combination of tests) of kidney viability can be developed.

Cell Survival↗
PubMed2001

A systematic review of the clinical effectiveness of pioglitazone in the treatment of type 2 diabetes mellitus.

BACKGROUND: Pioglitazone is a member of a recently developed class of glucose-lowering agents, the thiazolidinediones, used in the treatment of type 2 diabetes mellitus. In the United States, it is approved for use both as monotherapy and in combination with metformin, a sulfonylurea, or insulin; in Europe, it is approved for use in combination with metformin or a sulfonylurea but not insulin. OBJECTIVE: This article presents a systematic review of the published literature on the effectiveness of pioglitazone in the treatment of type 2 diabetes, both as monotherapy and in combination with other antidiabetic agents. METHODS: The peer-reviewed English- and foreign-language literature was searched using MEDLINE, PubMED, EMBASE, Science Citation Index, the Cochrane Database of Systematic Reviews, the Cochrane Controlled Trials Register, the UK National Health Service Centre for Reviews and Dissemination databases, and the Office of Health Economics Health Economic Evaluations Database. Searches were not limited to specific publication types, study designs, dates, or languages. The latest search was performed in March 2001. For a trial to be included in the review, at least 1 outcome measure had to involve the effects of pioglitazone on glycemic control or cardiovascular risk factors, or its side effects. Because of the heterogeneity of studies, no formal meta-analysis was performed. RESULTS: Eleven studies met the inclusion criteria, 6 involving pioglitazone monotherapy and 5 involving combination therapy. Full reports were available for only 6 of the 11 studies. No studies directly compared pioglitazone with other antidiabetic drugs. Both as monotherapy and in combination therapy, pioglitazone produced decreases in blood glucose levels (up to 95 mg/dL) and glycosylated hemoglobin (up to 2.6%). At doses of > or = 30 mg/d, pioglitazone was associated with reductions in triglyceride levels (-30-70 mg/dL) and increases in high-density lipoprotein cholesterol (HDL-C) levels (-4-5 mg/dL). Pioglitazone treatment was associated with significant weight gain (up to 4 kg over 16 weeks). Adverse effects included mild edema (in up to 11.7% of patients) and a clinically nonsignificant decrease in hemoglobin concentrations. Abnormal results on liver function testing were no more common in treated patients than in control groups. CONCLUSIONS: Pioglitazone has been shown to reduce blood glucose levels in patients with type 2 diabetes. Although the observed decreases in triglyceride levels and increases in HDL-C levels could be expected to lead to a reduction in cardiovascular risk, the effects of weight gain may counteract this benefit. The evidence suggests that the preferred role for pioglitazone may be as an adjunct to metformin or a sulfonylurea in patients whose condition is not well controlled with monotherapy and for whom a metformin-sulfonylurea combination is contraindicated. There is a need for large-scale, long-term studies comparing the effectiveness of combination therapy that includes pioglitazone with that of other combinations of antidiabetic drugs.

Adult↗