Jim Chilcott

Pulsatile machine perfusion vs. cold storage of kidneys for transplantation: a rapid and systematic review

Abstract: Objective: To identify and prioritize key areas for further research in kidney preservation systems.

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.

Modelling the cost effectiveness of interferon beta and glatiramer acetate in the management of multiple sclerosis. Commentary: evaluating disease modifying treatments in multiple sclerosis.

Abstract Objective: To evaluate the cost effectiveness of four disease modifying treatments (interferon betas and glatiramer acetate) for relapsing remitting and secondary progressive multiple sclerosis in the United Kingdom. Design: Modelling cost effectiveness. Setting: UK NHS. Participants: Patients with relapsing remitting multiple sclerosis and secondary progressive multiple sclerosis. Main outcome measures: Cost per quality adjusted life year gained. Results: The base case cost per quality adjusted life year gained by using any of the four treatments ranged from £42 000 (

Option appraisal of population-based colorectal cancer screening programmes in England

66 469; €61 630) to £98 000 based on efficacy information in the public domain. Uncertainty analysis suggests that the probability of any of these treatments having a cost effectiveness better than £20 000 at 20 years is below 20%. The key determinants of cost effectiveness were the time horizon, the progression of patients after stopping treatment, differential discount rates, and the price of the treatments. Conclusions: Cost effectiveness varied markedly between the interventions. Uncertainty around point estimates was substantial. This uncertainty could be reduced by conducting research on the true magnitude of the effect of these drugs, the progression of patients after stopping treatment, the costs of care, and the quality of life of the patients. Price was the key modifiable determinant of the cost effectiveness of these treatments. What is already known on this topic Interferon beta and glatiramer acetate are the only disease modifying therapies used to treat multiple sclerosis Economic evaluations of these drugs have had flaws in the specification of the course of the disease, efficacy, duration of treatment, mortality, and the analysis of uncertainty None of the existing estimates of cost effectiveness can be viewed as robust What this study adds The cost per quality adjusted life year gained is unlikely to be less than £40 000 for interferon beta or glatiramer acetate Experience after stopping treatment is a key determinant of the cost effectiveness of these therapies Key factors affecting point estimates of cost effectiveness are the cost of interferon beta and glatiramer acetate, the effect of these therapies on disease progression, and the time horizon evaluated

Ezetimibe monotherapy for cholesterol lowering in 2,722 people: systematic review and meta-analysis of randomized controlled trials

Objectives: To estimate the effectiveness, cost-effectiveness and resource impact of faecal occult blood testing (FOBT) and flexible sigmoidoscopy (FSIG) screening options for colorectal cancer to inform the Department of Health’s policy on bowel cancer screening in England. Methods: We developed a state transition model to simulate the life experience of a cohort of individuals without polyps or cancer through to the development of adenomatous polyps and malignant carcinoma and subsequent death in the general population of England. The costs, effects and resource impact of five screening options were evaluated: (a) FOBT for individuals aged 50–69 (biennial screening); (b) FOBT for individuals aged 60–69 (biennial screening); (c) once-only FSIG for individuals aged 55; (d) once-only FSIG for individuals aged 60; and (e) once-only FSIG for individuals aged 60, followed by FOBT for individuals aged 61–70 (biennial screening). Results: The model suggests that screening using FSIG with or without FOBT may be cost-saving and may produce additional benefits compared with a policy of no screening. The marginal cost-effectiveness of FOBT options compared to a policy of no screening is estimated to be below £3000 per quality adjusted life year gained. Conclusions: Screening using FOBT and/or FSIG is potentially a cost-effective strategy for the early detection of colorectal cancer. However, the practical feasibility of alternative screening programmes is inevitably limited by current pressures on endoscopy services.

Calculating Partial Expected Value of Perfect Information via Monte Carlo Sampling Algorithms

Objectives.  To study the evidence on the efficacy and safety of ezetimibe monotherapy for the treatment of primary (heterozygous familial and non‐familial) hypercholesterolaemia.

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

Partial expected value of perfect information (EVPI) calculations can quantify the value of learning about particular subsets of uncertain parameters in decision models. Published case studies have used different computational approaches. This article examines the computation of partial EVPI estimates via Monte Carlo sampling algorithms. The mathematical definition shows 2 nested expectations, which must be evaluated separately because of the need to compute a maximum between them. A generalized Monte Carlo sampling algorithm uses nested simulation with an outer loop to sample parameters of interest and, conditional upon these, an inner loop to sample remaining uncertain parameters. Alternative computation methods and shortcut algorithms are discussed and mathematical conditions for their use considered. Maxima of Monte Carlo estimates of expectations are biased upward, and the authors show that the use of small samples results in biased EVPI estimates. Three case studies illustrate 1) the bias due to maximization and also the inaccuracy of shortcut algorithms 2) when correlated variables are present and 3) when there is nonlinearity in net benefit functions. If relatively small correlation or nonlinearity is present, then the shortcut algorithm can be substantially inaccurate. Empirical investigation of the numbers of Monte Carlo samples suggests that fewer samples on the outer level and more on the inner level could be efficient and that relatively small numbers of samples can sometimes be used. Several remaining areas for methodological development are set out. A wider application of partial EVPI is recommended both for greater understanding of decision uncertainty and for analyzing research priorities.

Modelling the cost effectiveness of interferon beta and glatiramer acetate in the management of multiple sclerosis

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.

The Multiple Sclerosis Risk Sharing Scheme Monitoring Study--early results and lessons for the future.

Abstract Objective: To evaluate the cost effectiveness of four disease modifying treatments (interferon betas and glatiramer acetate) for relapsing remitting and secondary progressive multiple sclerosis in the United Kingdom. Design: Modelling cost effectiveness. Setting: UK NHS. Participants: Patients with relapsing remitting multiple sclerosis and secondary progressive multiple sclerosis. Main outcome measures: Cost per quality adjusted life year gained. Results: The base case cost per quality adjusted life year gained by using any of the four treatments ranged from £42 000 (

Gaussian Process Modeling in Conjunction with Individual Patient Simulation Modeling: A Case Study Describing the Calculation of Cost-Effectiveness Ratios for the Treatment of Established Osteoporosis

66 469; €61 630) to £98 000 based on efficacy information in the public domain. Uncertainty analysis suggests that the probability of any of these treatments having a cost effectiveness better than £20 000 at 20 years is below 20%. The key determinants of cost effectiveness were the time horizon, the progression of patients after stopping treatment, differential discount rates, and the price of the treatments. Conclusions: Cost effectiveness varied markedly between the interventions. Uncertainty around point estimates was substantial. This uncertainty could be reduced by conducting research on the true magnitude of the effect of these drugs, the progression of patients after stopping treatment, the costs of care, and the quality of life of the patients. Price was the key modifiable determinant of the cost effectiveness of these treatments. What is already known on this topic Interferon beta and glatiramer acetate are the only disease modifying therapies used to treat multiple sclerosis Economic evaluations of these drugs have had flaws in the specification of the course of the disease, efficacy, duration of treatment, mortality, and the analysis of uncertainty None of the existing estimates of cost effectiveness can be viewed as robust What this study adds The cost per quality adjusted life year gained is unlikely to be less than £40 000 for interferon beta or glatiramer acetate Experience after stopping treatment is a key determinant of the cost effectiveness of these therapies Key factors affecting point estimates of cost effectiveness are the cost of interferon beta and glatiramer acetate, the effect of these therapies on disease progression, and the time horizon evaluated