Jackie Bryant

The clinical effectiveness and cost-effectiveness of long-term weight management schemes for adults: a systematic review.

OBJECTIVE To assess the long-term clinical effectiveness and cost-effectiveness of multicomponent weight management schemes for adults in terms of weight loss and maintenance of weight loss. DATA SOURCES Bibliographic databases were searched from inception to December 2009, including the Cochrane Library, MEDLINE (Ovid), EMBASE (Ovid), and MEDLINE In-Process & Other Non-Indexed Citations. Bibliographies of related papers were screened, key conferences and symposia were searched and experts were contacted to identify additional published and unpublished references. REVIEW METHODS For the clinical effectiveness review, two reviewers independently screened titles and abstracts for eligibility. Inclusion criteria were applied to the full text of retrieved papers by one reviewer and checked by a second reviewer using a pre-piloted inclusion flow chart. The studies were long-term randomised controlled trials (RCTs) of adult participants who were classified by body mass index as overweight or obese. Interventions were multicomponent weight management programmes (including diet, physical activity and behaviour change strategies) that assessed weight measures. Programmes that involved the use of over-the-counter medicines licensed in the UK were also eligible. For the cost-effectiveness review two reviewers independently screened studies for inclusion. Cost-effectiveness, cost-utility, cost-benefit or cost-consequence analyses were eligible. Data were extracted using a standardised and pre-piloted data extraction form. The quality of included studies was assessed using standard criteria. Studies were synthesised through a narrative review with full tabulation of results. RESULTS A total of 3358 references were identified, of which 12 were included in the clinical effectiveness review. Five RCTs compared multicomponent interventions with non-active comparator groups. In general, weight loss appeared to be greater in the intervention groups than in the comparator groups. Two RCTs compared multicomponent interventions that focused on the diet component. In these studies there were no statistically significant differences in weight loss between interventions. Four RCTs compared multicomponent interventions that focused on the physical activity component. There was little consistency in the pattern of results seen, in part owing to the differences in the interventions. In one RCT the intervention focused on the goal-setting interval and it appeared that weight loss was greatest in those given daily goals compared with weekly goals. Overall, where measured, it appeared that most groups began to regain weight at further follow-up. Of the 419 studies identified in the cost-effectiveness searches, none met the full inclusion criteria. Two economic evaluations are described in our review; however, caution is required in their interpretation, as they did not meet all inclusion criteria. Lifetime chronic disease models were used in these studies and the models included the costs and benefits of avoiding chronic illness. Both studies found the interventions to be cost-effective, with estimates varying between -£473 and £7200 (US

CLINICAL AND COST-EFFECTIVENESS OF DONEPEZIL, RIVASTIGMINE, AND GALANTAMINE FOR ALZHEIMER'S DISEASE

12,640) per quality-adjusted life-year gained; methodological omissions from these studies were apparent and caution is therefore required in the interpretation of these results. CONCLUSIONS Long-term multicomponent weight management interventions were generally shown to promote weight loss in overweight or obese adults. Weight changes were small however and weight regain was common. There were few similarities between the included studies; consequently an overall interpretation of the results was difficult to make. There is some evidence that weight management interventions are likely to be cost-effective, although caution is required as there were some limitations in the two cost-evaluation studies described. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Bortezomib for the treatment of multiple myeloma patients.

OBJECTIVES Systematic review of the clinical and cost-effectiveness of donepezil, rivastigmine, and galantamine for people suffering from Alzheimers disease. METHODS Sixteen electronic databases (including MEDLINE, the Cochrane Library, and Embase) and bibliographies of related papers were searched for published/unpublished English language studies, and experts and pharmaceutical companies were consulted for additional information. Randomized controlled trials (RCTs) and economic studies were selected. Clinical effectiveness was assessed on measurement scales assessing progression of Alzheimers disease on the persons global health, cognition, functional ability, behavior and mood, and quality of life. Cost-effectiveness was presented as incremental cost per year spent in a nonsevere state (by Mini Mental Health State Examination) or quality-adjusted life-year. RESULTS Twelve of 15 RCTs included were judged to be of good quality. Although donepezil had beneficial effects in Alzheimers patients on global health and cognition, rivastigmine on global health, and galantamine on global health, cognition, and functional scales, these improvements were small and may not be clinically significant. Measures of quality of life and behavior and mood were rarely assessed. Adverse effects were usually mild and transient. Cost-effectiveness base case estimates ranged from 2,415 Pounds savings to 49,476 Pounds additional cost (1997 prices) per unit of effect for donepezil and a small savings for rivastigmine. Estimates were not considered robust or generalizable. CONCLUSIONS Donepezil, rivastigmine, and galantamine appear to have some clinical effect for people with Alzheimers disease, although the extent to which these translate into real differences in everyday life remains unclear. Due to the nature of current economic studies, cost-effectiveness remains uncertain and the impact on different care sectors has been inadequately investigated. Further research is needed to establish the actual benefits of acetylcholinesterase inhibitors (AChEls) for people with Alzheimers disease and their caregivers, the relationship of these changes to clinical management, and careful prospective evaluation of resource and budgetary consequences.

Systematic review of the Sugarbaker procedure for pseudomyxoma peritonei

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of bortezomib for the treatment of multiple myeloma patients at first relapse and beyond, in accordance with the licensed indication, based upon the evidence submission from Ortho Biotech to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The outcomes stated in the manufacturers definition of the decision problem were time to disease progression, response rate, survival and quality of life. The literature searches for clinical and cost-effectiveness studies were adequate and the one randomised controlled trial (RCT) included was of reasonable quality. Results from the RCT suggest that bortezomib increases survival and time to disease progression compared with high-dose dexamethasone (HDD) in multiple myeloma patients who have had a relapse after one to three treatments. Cost-effectiveness analysis based on the same trial and an observational study was reasonable and gave an estimated cost per life-year gained of 30,750 pounds, which ranged from 27,957 pounds to 36,747 pounds on sensitivity analysis. An attempt was made to replicate the results of the manufacturers model and to compare the results to the Kaplan-Meier survival curve presented in the manufacturers submission. In addition, a one-way sensitivity analysis and a probabilistic sensitivity analysis were undertaken, as well as additional scenario analyses. Based on these analyses the ERG suggests that the cost-effectiveness results presented in the manufacturers submission may underestimate the cost per life-year gained for bortezomib therapy (versus high-dose dexamethasone) when potential UK practice and scenarios are considered. The guidance issued by NICE in June 2006 as a result of the STA states that bortezomib monotherapy for the treatment of relapsed multiple myeloma is clinically effective compared with HDD but has not been shown to be cost-effective and is not recommended for the treatment of progressive multiple myeloma in patients who have received at least one previous therapy and who have undergone, or are unsuitable for, bone marrow transplantation.

Immunomodulatory drugs for multiple sclerosis: a systematic review of clinical and cost effectiveness

Pseudomyxoma peritonei, a rare progressive disease process within the peritoneum, is characterized by an abundance of mucinous fluid; if left untreated, the condition is fatal. The aim of this article is to assess the clinical effectiveness and costs of the Sugarbaker procedure for pseudomyxoma peritonei.

Clinical and cost-effectiveness of left ventricular assist devices as destination therapy for people with end-stage heart failure: a systematic review and economic evaluation.

Uncertainties about the clinical and cost effectiveness of immunomodulatory drugs for multiple sclerosis (MS), as well as concerns about funding treatment, continue to influence their use. The National Institute for Clinical Excellence (NICE) in England and Wales has been appraising the evidence on the clinical and cost effectiveness of IFN-β and glatiramer to provide guidance to the NHS. It has proved a difficult task. This paper is an update of our systematic review which assesses the evidence on the clinical and cost effectiveness of a range of immunomodulatory drugs for MS, including azathioprine, IFN-β, cladribine, cyclophosphamide, glatiramer, intravenous immunoglobulin (IVIg), methotrexate and mitoxantrone. Searches of electronic databases (such as Medline, Embase and the Cochrane Library) and bibliographies of related papers, as well as consultation with experts, for systematic reviews of randomised controlled trials (RCTs) and direct reports of RCTs revealed 26 studies of clinical effectiveness and eight economic evaluations that met the criteria for inclusion. The quality of the evidence was often poor, affected by methodological limitations. Evidence on the clinical effectiveness of immunomodulatory drugs showed some clinical effect, with reductions in relapse rates and/or progression to disability for people with MS. However, benefits from these drugs may be lessened by side effects. Assessment of cost effectiveness was limited to IFN-β and glatiramer, showing that any benefit from these drugs was achieved at very high cost. The inadequacies in the evidence of clinical and cost effectiveness on some immunomodulatory drugs for the treatment of people with MS necessitate further rigorous RCTs and comparative economic evaluations of different alternatives.

Systematic review of immunomodulatory drugs for the treatment of people with multiple sclerosis: Is there good quality evidence on effectiveness and cost?

OBJECTIVES The clinical and cost-effectiveness of left ventricular assist devices as destination therapy for people with end-stage heart failure is assessed through a systematic review and economic evaluation. METHODS Systematic review was performed of randomized controlled trials, quasiexperimental studies, case series, and case studies identified through searching eighteen electronic databases, bibliographies, and consultation with experts and manufacturers. Studies assessed survival, functional capacity, and quality of life. Cost-effectiveness was assessed through a 5-year decision analytic model to estimate the incremental cost-effectiveness ratio for using left ventricular assist devices compared with usual care. RESULTS Six studies met the inclusion criteria, showing that left ventricular assist devices appear beneficial, improving survival and quality of life. Adverse events are a serious concern. The economic evaluation showed that left ventricular assist devices had a cost per quality adjusted life year of 170,616 pounds. Sensitivity analysis showed that the cost-effectiveness was not sensitive to changes in costs or utility. CONCLUSIONS Although left ventricular assist devices appear clinically effective as destination therapy, it is unlikely they will be cost-effective unless costs decrease or the benefits of their use increase.

Cost-effectiveness of left ventricular-assist devices in end-stage heart failure

OBJECTIVE To review the clinical effectiveness and costs of a range of disease modifying drugs in multiple sclerosis. Drugs included are azathioprine, cladribine, cyclophosphamide, intravenous immunoglobulin, methotrexate, and mitoxantrone. METHODS Electronic databases and bibliographies of related papers were searched for randomised controlled trials (RCTs) and systematic reviews, and experts and pharmaceutical companies were contacted for further information. Inclusion and quality criteria were assessed, data extraction undertaken by one reviewer and checked by a second reviewer, with discrepancies being resolved through discussion. Costs were obtained and cost-effectiveness papers sought. RESULTS Seventeen studies met the inclusion criteria for the review. Evidence for the clinical effectiveness of the drugs showed some reductions in relapse rates and/or progression to disability for people with MS, although benefits may be lessened by wide ranging side effects. Annual drug costs/patient are estimated to range from £60 to £10 200. No cost effectiveness studies were found. CONCLUSION Evidence for the effectiveness of these drugs in multiple sclerosis is problematic because there are few good quality trials for each drug. Trials often have methodological limitations and use different treatment regimes, patient groups, and outcome measures. Well conducted trials using outcome measures with clinical significance for groups of patients with different types of multiple sclerosis and long term follow up are needed if the evidence base of treatment for the disease is to be improved.

Clinical effectiveness and cost-effectiveness of implantable cardioverter defibrillators for arrhythmias: A systematic review and economic evaluation

With a limited supply of donor hearts, individuals with end-stage heart failure have been offered hope through the use of mechanical devices. Left ventricular-assist devices (LVADs) are a technology designed to work in parallel with the heart but have yet to see widespread use since uncertainty remains as to the cost–effectiveness of this evolving new technology. We have systematically reviewed evidence of cost–effectiveness for LVADs in the bridge-to-transplant and long-term chronic support indications. A total of 18 studies reporting costs were identified. Of these, only four studies reported results in cost–effectiveness terms; two in cost per life-year saved and two in cost per quality-adjusted life-year (QALY). The majority of the other studies were simple cost summations (cost per day or incremental cost) without consideration of efficacy. In the bridge-to-transplant indication, a Danish abstract reported a cost per life-year saved of DKK270k (US

Dasatinib, high dose imatinib and nilotinib for the treatment of imatinib-resistant chronic myeloid leukaemia: a systematic review and economic evaluation

48,000), a UK study reported a cost per QALY of GB£39,787 (US